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Gastritis

2026-07-25T21:51:37Z

Mikael Häggström: /* Acute gastritis */ Threshold

{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}

Inflammation of the [[stomach]]. If biopsy is at the esophagus, evaluate as '''[[gastroesophageal junction]]'''.
{{Comprehensiveness}}
==Microscopy evaluation==
[[File:Histopathology of mucosal plasma cell infiltrate in chronic gastritis.jpg|thumb|Mucosal plasma cell infiltrate in '''mild chronic gastritis'''.]]
Look for chronic or acute gastritis. If either is present, still look for the other.
===Chronic gastritis===
*'''Chronic gastritis'''<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachchronicgastritis.html|title=Stomach - Gastritis - Chronic gastritis|author=Elliot Weisenberg|website=PathologyOutlines}} Topic Completed: 1 August 2012. Minor changes: 31 August 2020</ref>
:*Presence of '''plasma cells''', '''lymphocytes''', and occasionally lymphoid '''follicles'''. Scattered single plasma cells and lymphocytes is normal, and the threshold is subjective, but one definition of chronic gastritis is when seeing chronic inflammation at 4x magnification (as increased dots separating glands)<ref>{{cite web|url=http://www.azpath.org/uploads/2/6/3/8/2638612/voltaggio_-_gastritis_presentation.pdf|title=Gastritis: A Pattern Based Approach|author=Lysandra Voltaggio, Johns Hopkins Department of Pathology|website=Arizona Society of Pathologists|date=2018-10-31}}</ref> Eosinophils and neutrophils may be present.
:*'''Reduced mucin''' in the cytoplasm
:*'''Enlargement''' of nuclei and nucleoi
:*'''Subnuclear vacuolation''' in antral glands or pits (which is PAS negative)
:*'''Intestinal metaplasia''': with partial replacement of the mucosa of the antrum and body with metaplastic goblet cells of intestinal morphology, absorptive cells and Paneth cells.
<gallery mode=packed heights=210>
File:Updated Sydney System for visual classification of gastritis.png|thumb|340px|Updated Sydney System for visual classification of gastritis.<ref name=Carrasco/>
File:Moderate superficial chronic gastritis.jpg|'''Moderate''' gastritis.
File:Histopathology of antral mucosa with atrophy.png|In '''intestinal metaplasia''' (seen at bottom of this antral mucosa), also look for '''atrophy''' as pictured.<ref name=Carrasco/><ref group=note>The combination of atrophy and gastritis (especially when deeper than submucosal) helps the clinician to potentially make a diagnosis of atrophic gastritis.</ref>
File:Histopathology of fundic mucosa with atrophy.png|Extensive atrophy of oxyntic glands in fundus/corpus causes '''pseudo-pyloric metaplasia'''.<ref name=Carrasco/>
</gallery>
When there is at least {{Moderate-begin}}mild or{{Moderate-end}} moderate gastritis, especially if relatively superficial, also evaluate as a [[stomach biopsy for Helicobacter pylori|stomach biopsy for '''Helicobacter pylori''']].

===Acute gastritis===
[[File:Histopathology of mild active gastritis, annotated.jpg|thumb|230px|Histopathology of '''mild active gastritis''', with intraepithelial neutrophils (white arrows) as well as in lamina propria (black arrows).]]
*'''Mild acute gastritis:'''<ref name=PathologyOutlinesAcute>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachacutegastritis.html|title=Stomach - Gastritis - Acute gastritis|author=Elliot Weisenberg|website=pathologyOutlines}} Topic Completed: 1 August 2012. Minor changes: 31 August 2020</ref>
:*Modest '''edema''' of lamina propria
:*'''Vascular congestion'''
:*Scattered '''neutrophils'''. Even a few unequivocal neutrophils in the lamina propria or epithelium constitute gastritis.
:*Mucosal '''hemorrhage'''
:*Intact epithelium
<gallery mode=packed heights=210px>
File:Histopathology of early acute superficial gastritis.png|Early acute superficial gastritis: Marked neutrophilic infiltrates appear in the mucous neck region and lamina with a pit micoabscess.<ref name=Carrasco>{{cite journal| author=Carrasco G, Corvalan AH| title=Helicobacter pylori-Induced Chronic Gastritis and Assessing Risks for Gastric Cancer. | journal=Gastroenterol Res Pract | year= 2013 | volume= 2013 | issue= | pages= 393015 | pmid=23983680 | doi=10.1155/2013/393015 | pmc=3745848 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23983680 }} [https://www.researchgate.net/publication/256190376_Helicobacter_pylori-Induced_Chronic_Gastritis_and_Assessing_Risks_for_Gastric_Cancer Figures - available via license: Creative Commons Attribution 3.0 Unported]</ref>
</gallery>
*'''Moderate to severe acute gastritis''':<ref name=PathologyOutlinesAcute/>
:*'''Loss of superficial epithelium''' above the muscularis mucosa
:*'''Hemorrhage'''
:*Variable infiltrate with '''neutrophils'''
:*Fibrinopurulent luminal '''exudate'''
:*Nearby epithelium may show '''regenerative''' changes

===Microscopy report===
*'''Mild and/or chronic gastritis''' and '''severity'''
:*{{Moderate-begin}}If present, state if positive or negative for '''''Helicobacter pylori''''' organisms.{{Moderate-end}}
Chronic gastritis without neutrophils is preferably also termed "inactive".

Example:
{|class=wikitable
| {{Moderate-begin}}Stomach, biopsy:{{Moderate-end}}
*{{Moderate-begin}}Gastric antral/oxyntic mucosa with{{Moderate-end}} mild chronic {{Moderate-begin}}inactive{{Moderate-end}} gastritis{{Comprehensive-begin}}, non-specific{{Comprehensive-end}}
*{{Moderate-begin}}Negative for ''Helicobacter pylori'' organisms on H&E sections.{{Moderate-end}}
|}
{{Bottom}}

Peripheral blood smear

2026-07-24T17:15:14Z

Mikael Häggström: /* White blood cells */

{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
Look at and comment separately on white blood cells, red blood cells and platelets. You generally don't need to aim for a perfect report, because for most purposes, a peripheral smear is a relatively simple screening test, and clinicians may opt to perform for example flow cytometry and/or a bone marrow biopsy if they want a better evaluation.
{{Comprehensiveness|otherlegend=yes}}
==Oil immersion microscopy==
This is preferred for light microscopy of peripheral blood smears in order to achieve a very high magnification. First use low or medium power to center on suspicious cells, or where red or white blood cells are best appreciated. Put a drop of immersion oil on the location and switch to the immersion objective. Then, whenever there's oil on a slide, always think twice before switching between objectives so as to avoid getting oil on any of your dry objectives (which is a bit tedious to clean off).

==Red blood cells==
===Automated values===
When available, automatic quantification of mean corpuscular volume (MCV) and red blood cell (RBC) distribution width (RDW), usually as part of CBC panel, generally decides whether you will call the sample "'''normocytic'''" versus "microcytic"/"macrocytic" and/or "anisocytotic", even if it is not clearly visible in the microscope. If automated values are not available, compare RBC sizes to lymphocyte nuclei, which should normally be the same size. If mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) are normal, but you still see multiple RBCs with central pallor greater than 50% of the diameter, you can report it as ''"Increased central pallor"'', and you may add ''"indicating iron deficiency"'' if it is compatible with the clinical history.

Automated values can be graded as follows:<ref name=HongKong>Unless otherwise specified in table, reference is: - {{cite web|url=http://www.hkimls.org/qapeduhsm-rbc-mor.htm|title=Hong Kong Medical Technology Association - Quality Assurance Programme - Haematology and Serology, Prepared by HKMTAQAP Haematology & Serology Panel on November 2002.}}</ref>
{|class=wikitable
|-
! Interpretation
! Mild
! Moderate
! Marked
|-
| Microcytosis ||MCV : 70 - 79||MCV : 60 - 69||MCV <60
|-
| Macrocytosis ||MCV : 100 - 115||MCV : 115 - 125||MCV >125
|-
| Hypochromasia||MCH : 23 - 26||MCH : 21 - 23||MCH <20
|-
| Anisocytosis||RDW: 14.5<ref name=MrLabTest>{{cite web|url=https://www.mrlabtest.com/high-RDW-blood.htm|website=MrLabTest|title=High RDW level in the blood}} Last update: 12/01/2021</ref> or 16<ref name=HongKong/> - 18||RDW : 18 - 22<ref name=HongKong/> or 26<ref name=MrLabTest/> ||RDW > 22<ref name=HongKong/> or 26<ref name=MrLabTest/>
|}

===Morphologic findings===
Look for poikilocytosis (red blood cells of abnormal shapes). These are counted as a percentage of visible red blood cells:<ref name=HongKong/>
{|class=wikitable
|-
|
! Image
! Rare/Occasional
! Moderate amount of
! Many/Abundant
|-
! Polychromasia
| [[File:Peripheral blood smear with polychromasia.jpg|90px]]
|3 - 5%||5 - 25%||>25%
|-
! Spherocytes
| [[File:Micrograph of a spherocyte.jpg|90px]]
|1 - 5%||5 - 25%||>25%
|-
! Schistocytes
| [[File:Micrograph of schistocytes.jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Target cells (codocytes)
| [[File:Micrograph of a target cell.jpg|90px]]
|up to 3%||3 - 25%||>25%
|-
! Tear drop cells
| [[File:Micrograph of a tear drop cell (dacrocyte).jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Burr cells (echinocytes)
| [[File:Micrograph of an echinocyte on a peripheral blood smear.jpg|90px]]
|1 - 3% || 3 - 10%|| >10%
|-
! Sickle cells (drepanocytes)
| [[File:Micrograph of a sickle cell.jpg|90px]]
|3 - 5%||5 - 25%||>25%
|-
! Elliptocytes
| [[File:Micrograph of an elliptocyte on a peripheral blood smear 02.jpg|90px]]
|1 - 5%||5 - 25%||>25%
|-
! Basophilic stipplings
| [[File:Micrograph of a red blood cell with basophilic stippling.jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Howell Jolly bodies
| [[File:Micrograph of a Howell–Jolly body in a red blood cell.jpg|90px]]
|up to 1%||2 - 3 %||>3%
|-
|}
;Burr cells versus spur cells
<gallery mode="packed" heights="150">
File:Micrograph of an echinocyte on a peripheral blood smear.jpg|'''Burr cell''' (echinocyte)
File:Human blood film with acanthocytes 02.jpg|'''Spur cell''' (acanthocyte)
</gallery>
Burr cells are distinguished from spur cells by having more equally distributed and rounded projections. They are usually [[Artifacts|artifactual]]. However, they may also be caused by renal insufficiency, so if this is present, a report may include "Occasional/Multiple echinocytes, consistent with renal insufficiency".

;Intraerythrocytic findings
<gallery mode="packed" heights="150">
File:Micrograph of a red blood cells with an overlying platelet on a peripheral blood smear.jpg|When seeing what appears to a platelet overlying a red blood cells (as pictured), confirm that there is a halo.
File:Human blood film with babesia.jpg|Otherwise, make sure it is not '''babesia''' (pictured) or malaria (images below).
</gallery>
<gallery mode="packed" heights="250">
File:Blood stages of P. falciparum over 48h.jpg|'''Malaria''', showing appearance at different intraerythrocytic blood stages.
File:Thick blood film with Plasmodium falciparum rings and schizonts.png|If '''malaria''' is suspected, also make a thick blood film.
</gallery>

===Platelets===
If CBC is performed, use count to determine whether platelets are "normal in number" or whether there is "thrombocytopenia" or "thrombocytosis". If no CBC, count platelets within a high power oil immersed field, which should normally be 8 to 20.

[[File:Micrograph of a giant platelet.jpg|thumb|200px|A '''giant platelet'''.]]
'''Large platelets''' are those with a diameter greater than 4 microns. '''Giant platelets''' are those with a diameter greater than 7 microns (larger than a normal red blood cell).<ref name=ash2016>{{cite web|url=https://imagebank.hematology.org/image/60931/giant-platelets?type=upload|title=Giant platelets|website=American Society of Hematology|author=Teresa Scordino|date=2016-12-02}}</ref> Example report:
{|class=wikitable
| Numerous large and giant platelets{{Moderate-begin}}, suggesting an increased platelet turnover{{Moderate-end}}{{Comprehensive-begin}} such as in immune thrombocytopenic purpura. They may also be present in myeloproliferative neoplasms, myelodysplasia, and some congenital thrombocytopenia syndromes, including Bernard-Soulier syndrome and MYH9-related disorders.<ref name=ash2016/>{{Comprehensive-end}}
|}

In '''thrombocytopenia''' from automatic counting, look in particular for:
*'''Clumping''' of platelets (which can cause a falsely low automatic platelet count). If present, check with the lab if it was sent in EDTA (which may cause artefactual clumping) and ask to have a blood sample sent in sodium citrate instead. Also, look for satellitosis (platelets attached around white blood cells).
*'''Schistocytes''' among red blood cells.

===White blood cells===
[[File:Monoblast, promonocyte and monocyte.jpg|thumb|400px|Comparison of monoblast, promonocyte and monocyte. {{further|Suspected blasts on peripheral blood smear}}]]
A common practice is to evaluate at least 100 white blood cells. Look for:
<gallery mode="packed" heights="190">
File:Myeloblast with Auer rod.jpg|thumb|'''Blast cells''', generally having large nucleus, immature chromatin, a prominent nucleolus, scant cytoplasm and few or no cytoplasmic granules. This example has an Auer rod (to the left of the nucleus). {{further|Suspected blasts on peripheral blood smear}}
File:Hypersegmented neutrophil.jpg|'''Hypersegmented neutrophils'''. This is abnormal when more than half of neutrophils have at least 4 segments, or more than 5% of neutrophils have more than 5 segments.<ref name="Glassy 1998 p. ">{{cite book | last=Glassy | first=Eric | title=Color atlas of hematology : an illustrated field guide based on proficiency testing | publisher=College of American Patholgists | publication-place=Northfield, Ill | year=1998 | isbn=978-0-930304-66-9 | oclc=40976106 | page=}}</ref>
File:Prolymphocyte in peripheral blood smear.png|In patients with known chronic lymphocytic leukemia, estimate the percentage of '''prolymphocytes''', which are medium-sized lymphocytes with prominent nucleoli.<ref>{{cite web|url=https://imagebank.hematology.org/image/19922/prolymphocytes-in-pll?type=upload|title=prolymphocytes in PLL|website=American Society of Hematology|date=2013-07-16}}</ref> A percentage of less than 5% can be reported as such.
File:Smudge cell in a peripheral blood smear.jpg|When '''smudge cells''' constitute more than 10% of white blood cells, or in patients with CLL, a separate smear with a drop of serum albumin to every four or five drops of blood should be made to stabilize cell membranes.<ref>{{cite web|url=http://www.captodayonline.com/Archives/0610/0610_qa.html|title=Q & A|website=CAP Today|author=Fredrick L. Kiechle}} June 2010</ref> A semi-quantification of different cell lines should then be made on the albumin slide, whereas white and red blood cell morphology should still be made on the original slide, since it is altered by albumin.
</gallery>

{| class="wikitable" style="text-align:center; vertical-align:middle;"
|+ Atypical/Reactive lymphocytes:<ref name="Nozaka2023">{{cite journal
|last1=Nozaka |first1=Hiroyuki
|last2=Kushibiki |first2=Mihoko
|last3=Kamata |first3=Kosuke
|last4=Yamagata |first4=Kazufumi
|title=Classifying Microscopic Images of Reactive Lymphocytosis Using Two-Step Tandem AI Models
|journal=Applied Sciences
|year=2023
|volume=13
|issue=9
|page=5296
|doi=10.3390/app13095296
|doi-access=free
}} "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."</ref>
! rowspan="2" | Morphological feature
! colspan="3" | Atypical lymphocyte — Downey's categorization —
|-
! Type I (monocyte-like)
! Type II (plasma cell-like) - Most common
! Type III (lymphoblast-like)
|-
! Typical morphology
| [[File:Type 1 atypical lymphocyte.png|180px|center|Type I (monocyte-like) atypical lymphocyte]]
| [[File:Type 2 atypical lymphocyte.png|180px|center|Type II (plasma cell-like) atypical lymphocyte]]
| [[File:Type 3 atypical lymphocyte.png|180px|center|Type III (lymphoblast-like) atypical lymphocyte]]
|-
! Size
| ≥16 µm
| ≥16 µm
| ≥16 µm
|-
! Nuclear features
| style="text-align:left;" |
* Kidney-shaped or segmented
| style="text-align:left;" |
* Fine nucleus
* Nucleolus (±)
| style="text-align:left;" |
* Agglutinated chromatin
* Nucleolus (±)
|-
! Cytoplasm
| style="text-align:left;" |
* Strongly basophilic
* Vacuoles (±)
| style="text-align:left;" |
* Strongly basophilic
| style="text-align:left;" |
* Strongly basophilic
|-
! Intracytoplasmic granules
| —
| Azurophilic granules (±)
| —
|}

==Report==
Example report:
{|class=wikitable
| Normochromic normocytic red blood cells. Red blood cells show <normal morphology / anisopoikilocytosis with occasional ___>. {{Comment-begin}}If thrombocytopenia, also add "Schistocytes are not significantly increased" if applicable.{{Comment-end}}

{{Finding-begin}}Leukocytosis with neutrophilia / lymphocytosis.{{Finding-end}} White blood cells show no left shift or blasts.

Platelets show no evidence of clumping, and show normal granularity.

{{Moderate-begin}}Causes of the above findings include ___.{{Moderate-end}}
|}
{{Bottom}}

Peripheral blood smear

2026-07-24T17:14:03Z

Mikael Häggström: /* White blood cells */ or reactive

{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
Look at and comment separately on white blood cells, red blood cells and platelets. You generally don't need to aim for a perfect report, because for most purposes, a peripheral smear is a relatively simple screening test, and clinicians may opt to perform for example flow cytometry and/or a bone marrow biopsy if they want a better evaluation.
{{Comprehensiveness|otherlegend=yes}}
==Oil immersion microscopy==
This is preferred for light microscopy of peripheral blood smears in order to achieve a very high magnification. First use low or medium power to center on suspicious cells, or where red or white blood cells are best appreciated. Put a drop of immersion oil on the location and switch to the immersion objective. Then, whenever there's oil on a slide, always think twice before switching between objectives so as to avoid getting oil on any of your dry objectives (which is a bit tedious to clean off).

==Red blood cells==
===Automated values===
When available, automatic quantification of mean corpuscular volume (MCV) and red blood cell (RBC) distribution width (RDW), usually as part of CBC panel, generally decides whether you will call the sample "'''normocytic'''" versus "microcytic"/"macrocytic" and/or "anisocytotic", even if it is not clearly visible in the microscope. If automated values are not available, compare RBC sizes to lymphocyte nuclei, which should normally be the same size. If mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) are normal, but you still see multiple RBCs with central pallor greater than 50% of the diameter, you can report it as ''"Increased central pallor"'', and you may add ''"indicating iron deficiency"'' if it is compatible with the clinical history.

Automated values can be graded as follows:<ref name=HongKong>Unless otherwise specified in table, reference is: - {{cite web|url=http://www.hkimls.org/qapeduhsm-rbc-mor.htm|title=Hong Kong Medical Technology Association - Quality Assurance Programme - Haematology and Serology, Prepared by HKMTAQAP Haematology & Serology Panel on November 2002.}}</ref>
{|class=wikitable
|-
! Interpretation
! Mild
! Moderate
! Marked
|-
| Microcytosis ||MCV : 70 - 79||MCV : 60 - 69||MCV <60
|-
| Macrocytosis ||MCV : 100 - 115||MCV : 115 - 125||MCV >125
|-
| Hypochromasia||MCH : 23 - 26||MCH : 21 - 23||MCH <20
|-
| Anisocytosis||RDW: 14.5<ref name=MrLabTest>{{cite web|url=https://www.mrlabtest.com/high-RDW-blood.htm|website=MrLabTest|title=High RDW level in the blood}} Last update: 12/01/2021</ref> or 16<ref name=HongKong/> - 18||RDW : 18 - 22<ref name=HongKong/> or 26<ref name=MrLabTest/> ||RDW > 22<ref name=HongKong/> or 26<ref name=MrLabTest/>
|}

===Morphologic findings===
Look for poikilocytosis (red blood cells of abnormal shapes). These are counted as a percentage of visible red blood cells:<ref name=HongKong/>
{|class=wikitable
|-
|
! Image
! Rare/Occasional
! Moderate amount of
! Many/Abundant
|-
! Polychromasia
| [[File:Peripheral blood smear with polychromasia.jpg|90px]]
|3 - 5%||5 - 25%||>25%
|-
! Spherocytes
| [[File:Micrograph of a spherocyte.jpg|90px]]
|1 - 5%||5 - 25%||>25%
|-
! Schistocytes
| [[File:Micrograph of schistocytes.jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Target cells (codocytes)
| [[File:Micrograph of a target cell.jpg|90px]]
|up to 3%||3 - 25%||>25%
|-
! Tear drop cells
| [[File:Micrograph of a tear drop cell (dacrocyte).jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Burr cells (echinocytes)
| [[File:Micrograph of an echinocyte on a peripheral blood smear.jpg|90px]]
|1 - 3% || 3 - 10%|| >10%
|-
! Sickle cells (drepanocytes)
| [[File:Micrograph of a sickle cell.jpg|90px]]
|3 - 5%||5 - 25%||>25%
|-
! Elliptocytes
| [[File:Micrograph of an elliptocyte on a peripheral blood smear 02.jpg|90px]]
|1 - 5%||5 - 25%||>25%
|-
! Basophilic stipplings
| [[File:Micrograph of a red blood cell with basophilic stippling.jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Howell Jolly bodies
| [[File:Micrograph of a Howell–Jolly body in a red blood cell.jpg|90px]]
|up to 1%||2 - 3 %||>3%
|-
|}
;Burr cells versus spur cells
<gallery mode=packed heights=150>
File:Micrograph of an echinocyte on a peripheral blood smear.jpg|'''Burr cell''' (echinocyte)
File:Human blood film with acanthocytes 02.jpg|'''Spur cell''' (acanthocyte)
</gallery>
Burr cells are distinguished from spur cells by having more equally distributed and rounded projections. They are usually [[Artifacts|artifactual]]. However, they may also be caused by renal insufficiency, so if this is present, a report may include "Occasional/Multiple echinocytes, consistent with renal insufficiency".

;Intraerythrocytic findings
<gallery mode=packed heights=150>
File:Micrograph of a red blood cells with an overlying platelet on a peripheral blood smear.jpg|When seeing what appears to a platelet overlying a red blood cells (as pictured), confirm that there is a halo.
File:Human blood film with babesia.jpg|Otherwise, make sure it is not '''babesia''' (pictured) or malaria (images below).
</gallery>
<gallery mode=packed heights=250>
File:Blood stages of P. falciparum over 48h.jpg|'''Malaria''', showing appearance at different intraerythrocytic blood stages.
File:Thick blood film with Plasmodium falciparum rings and schizonts.png|If '''malaria''' is suspected, also make a thick blood film.
</gallery>

===Platelets===
If CBC is performed, use count to determine whether platelets are "normal in number" or whether there is "thrombocytopenia" or "thrombocytosis". If no CBC, count platelets within a high power oil immersed field, which should normally be 8 to 20.

[[File:Micrograph of a giant platelet.jpg|thumb|200px|A '''giant platelet'''.]]
'''Large platelets''' are those with a diameter greater than 4 microns. '''Giant platelets''' are those with a diameter greater than 7 microns (larger than a normal red blood cell).<ref name=ash2016>{{cite web|url=https://imagebank.hematology.org/image/60931/giant-platelets?type=upload|title=Giant platelets|website=American Society of Hematology|author=Teresa Scordino|date=2016-12-02}}</ref> Example report:
{|class=wikitable
| Numerous large and giant platelets{{Moderate-begin}}, suggesting an increased platelet turnover{{Moderate-end}}{{Comprehensive-begin}} such as in immune thrombocytopenic purpura. They may also be present in myeloproliferative neoplasms, myelodysplasia, and some congenital thrombocytopenia syndromes, including Bernard-Soulier syndrome and MYH9-related disorders.<ref name=ash2016/>{{Comprehensive-end}}
|}

In '''thrombocytopenia''' from automatic counting, look in particular for:
*'''Clumping''' of platelets (which can cause a falsely low automatic platelet count). If present, check with the lab if it was sent in EDTA (which may cause artefactual clumping) and ask to have a blood sample sent in sodium citrate instead. Also, look for satellitosis (platelets attached around white blood cells).
*'''Schistocytes''' among red blood cells.

===White blood cells===
[[File:Monoblast, promonocyte and monocyte.jpg|thumb|400px|Comparison of monoblast, promonocyte and monocyte. {{further|Suspected blasts on peripheral blood smear}}]]
A common practice is to evaluate at least 100 white blood cells. Look for:
<gallery mode=packed heights=190>
File:Myeloblast with Auer rod.jpg|thumb|'''Blast cells''', generally having large nucleus, immature chromatin, a prominent nucleolus, scant cytoplasm and few or no cytoplasmic granules. This example has an Auer rod (to the left of the nucleus). {{further|Suspected blasts on peripheral blood smear}}
File:Hypersegmented neutrophil.jpg|'''Hypersegmented neutrophils'''. This is abnormal when more than half of neutrophils have at least 4 segments, or more than 5% of neutrophils have more than 5 segments.<ref name="Glassy 1998 p. ">{{cite book | last=Glassy | first=Eric | title=Color atlas of hematology : an illustrated field guide based on proficiency testing | publisher=College of American Patholgists | publication-place=Northfield, Ill | year=1998 | isbn=978-0-930304-66-9 | oclc=40976106 | page=}}</ref>
File:Prolymphocyte in peripheral blood smear.png|In patients with known chronic lymphocytic leukemia, estimate the percentage of '''prolymphocytes''', which are medium-sized lymphocytes with prominent nucleoli.<ref>{{cite web|url=https://imagebank.hematology.org/image/19922/prolymphocytes-in-pll?type=upload|title=prolymphocytes in PLL|website=American Society of Hematology|date=2013-07-16}}</ref> A percentage of less than 5% can be reported as such.
File:Smudge cell in a peripheral blood smear.jpg|When '''smudge cells''' constitute more than 10% of white blood cells, or in patients with CLL, a separate smear with a drop of serum albumin to every four or five drops of blood should be made to stabilize cell membranes.<ref>{{cite web|url=http://www.captodayonline.com/Archives/0610/0610_qa.html|title=Q & A|website=CAP Today|author=Fredrick L. Kiechle}} June 2010</ref> A semi-quantification of different cell lines should then be made on the albumin slide, whereas white and red blood cell morphology should still be made on the original slide, since it is altered by albumin.
</gallery>

{| class="wikitable" style="text-align:center; vertical-align:middle;"
|+ Atypical/Reactive lymphocytes:<ref name="Nozaka2023">{{cite journal
|last1=Nozaka |first1=Hiroyuki
|last2=Kushibiki |first2=Mihoko
|last3=Kamata |first3=Kosuke
|last4=Yamagata |first4=Kazufumi
|title=Classifying Microscopic Images of Reactive Lymphocytosis Using Two-Step Tandem AI Models
|journal=Applied Sciences
|year=2023
|volume=13
|issue=9
|page=5296
|doi=10.3390/app13095296
|doi-access=free
}} "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."</ref>
! rowspan="2" | Morphological feature
! colspan="3" | Atypical lymphocyte — Downey's categorization —
|-
! Type I (monocyte-like)
! Type II (plasma cell-like) - Most common
! Type III (lymphoblast-like)
|-
! Size
| ≥16 µm
| ≥16 µm
| ≥16 µm
|-
! Nuclear features
| style="text-align:left;" |
* Kidney-shaped or segmented
| style="text-align:left;" |
* Fine nucleus
* Nucleolus (±)
| style="text-align:left;" |
* Agglutinated chromatin
* Nucleolus (±)
|-
! Cytoplasm
| style="text-align:left;" |
* Strongly basophilic
* Vacuoles (±)
| style="text-align:left;" |
* Strongly basophilic
| style="text-align:left;" |
* Strongly basophilic
|-
! Intracytoplasmic granules
| —
| Azurophilic granules (±)
| —
|-
! Typical morphology
| [[File:Type 1 atypical lymphocyte.png|180px|center|Type I (monocyte-like) atypical lymphocyte]]
| [[File:Type 2 atypical lymphocyte.png|180px|center|Type II (plasma cell-like) atypical lymphocyte]]
| [[File:Type 3 atypical lymphocyte.png|180px|center|Type III (lymphoblast-like) atypical lymphocyte]]
|}

==Report==
Example report:
{|class=wikitable
| Normochromic normocytic red blood cells. Red blood cells show <normal morphology / anisopoikilocytosis with occasional ___>. {{Comment-begin}}If thrombocytopenia, also add "Schistocytes are not significantly increased" if applicable.{{Comment-end}}

{{Finding-begin}}Leukocytosis with neutrophilia / lymphocytosis.{{Finding-end}} White blood cells show no left shift or blasts.

Platelets show no evidence of clumping, and show normal granularity.

{{Moderate-begin}}Causes of the above findings include ___.{{Moderate-end}}
|}
{{Bottom}}

Peripheral blood smear

2026-07-24T17:12:38Z

Mikael Häggström: /* White blood cells */ +Atypical lymphs

{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
Look at and comment separately on white blood cells, red blood cells and platelets. You generally don't need to aim for a perfect report, because for most purposes, a peripheral smear is a relatively simple screening test, and clinicians may opt to perform for example flow cytometry and/or a bone marrow biopsy if they want a better evaluation.
{{Comprehensiveness|otherlegend=yes}}
==Oil immersion microscopy==
This is preferred for light microscopy of peripheral blood smears in order to achieve a very high magnification. First use low or medium power to center on suspicious cells, or where red or white blood cells are best appreciated. Put a drop of immersion oil on the location and switch to the immersion objective. Then, whenever there's oil on a slide, always think twice before switching between objectives so as to avoid getting oil on any of your dry objectives (which is a bit tedious to clean off).

==Red blood cells==
===Automated values===
When available, automatic quantification of mean corpuscular volume (MCV) and red blood cell (RBC) distribution width (RDW), usually as part of CBC panel, generally decides whether you will call the sample "'''normocytic'''" versus "microcytic"/"macrocytic" and/or "anisocytotic", even if it is not clearly visible in the microscope. If automated values are not available, compare RBC sizes to lymphocyte nuclei, which should normally be the same size. If mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) are normal, but you still see multiple RBCs with central pallor greater than 50% of the diameter, you can report it as ''"Increased central pallor"'', and you may add ''"indicating iron deficiency"'' if it is compatible with the clinical history.

Automated values can be graded as follows:<ref name=HongKong>Unless otherwise specified in table, reference is: - {{cite web|url=http://www.hkimls.org/qapeduhsm-rbc-mor.htm|title=Hong Kong Medical Technology Association - Quality Assurance Programme - Haematology and Serology, Prepared by HKMTAQAP Haematology & Serology Panel on November 2002.}}</ref>
{|class=wikitable
|-
! Interpretation
! Mild
! Moderate
! Marked
|-
| Microcytosis ||MCV : 70 - 79||MCV : 60 - 69||MCV <60
|-
| Macrocytosis ||MCV : 100 - 115||MCV : 115 - 125||MCV >125
|-
| Hypochromasia||MCH : 23 - 26||MCH : 21 - 23||MCH <20
|-
| Anisocytosis||RDW: 14.5<ref name=MrLabTest>{{cite web|url=https://www.mrlabtest.com/high-RDW-blood.htm|website=MrLabTest|title=High RDW level in the blood}} Last update: 12/01/2021</ref> or 16<ref name=HongKong/> - 18||RDW : 18 - 22<ref name=HongKong/> or 26<ref name=MrLabTest/> ||RDW > 22<ref name=HongKong/> or 26<ref name=MrLabTest/>
|}

===Morphologic findings===
Look for poikilocytosis (red blood cells of abnormal shapes). These are counted as a percentage of visible red blood cells:<ref name=HongKong/>
{|class=wikitable
|-
|
! Image
! Rare/Occasional
! Moderate amount of
! Many/Abundant
|-
! Polychromasia
| [[File:Peripheral blood smear with polychromasia.jpg|90px]]
|3 - 5%||5 - 25%||>25%
|-
! Spherocytes
| [[File:Micrograph of a spherocyte.jpg|90px]]
|1 - 5%||5 - 25%||>25%
|-
! Schistocytes
| [[File:Micrograph of schistocytes.jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Target cells (codocytes)
| [[File:Micrograph of a target cell.jpg|90px]]
|up to 3%||3 - 25%||>25%
|-
! Tear drop cells
| [[File:Micrograph of a tear drop cell (dacrocyte).jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Burr cells (echinocytes)
| [[File:Micrograph of an echinocyte on a peripheral blood smear.jpg|90px]]
|1 - 3% || 3 - 10%|| >10%
|-
! Sickle cells (drepanocytes)
| [[File:Micrograph of a sickle cell.jpg|90px]]
|3 - 5%||5 - 25%||>25%
|-
! Elliptocytes
| [[File:Micrograph of an elliptocyte on a peripheral blood smear 02.jpg|90px]]
|1 - 5%||5 - 25%||>25%
|-
! Basophilic stipplings
| [[File:Micrograph of a red blood cell with basophilic stippling.jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Howell Jolly bodies
| [[File:Micrograph of a Howell–Jolly body in a red blood cell.jpg|90px]]
|up to 1%||2 - 3 %||>3%
|-
|}
;Burr cells versus spur cells
<gallery mode=packed heights=150>
File:Micrograph of an echinocyte on a peripheral blood smear.jpg|'''Burr cell''' (echinocyte)
File:Human blood film with acanthocytes 02.jpg|'''Spur cell''' (acanthocyte)
</gallery>
Burr cells are distinguished from spur cells by having more equally distributed and rounded projections. They are usually [[Artifacts|artifactual]]. However, they may also be caused by renal insufficiency, so if this is present, a report may include "Occasional/Multiple echinocytes, consistent with renal insufficiency".

;Intraerythrocytic findings
<gallery mode=packed heights=150>
File:Micrograph of a red blood cells with an overlying platelet on a peripheral blood smear.jpg|When seeing what appears to a platelet overlying a red blood cells (as pictured), confirm that there is a halo.
File:Human blood film with babesia.jpg|Otherwise, make sure it is not '''babesia''' (pictured) or malaria (images below).
</gallery>
<gallery mode=packed heights=250>
File:Blood stages of P. falciparum over 48h.jpg|'''Malaria''', showing appearance at different intraerythrocytic blood stages.
File:Thick blood film with Plasmodium falciparum rings and schizonts.png|If '''malaria''' is suspected, also make a thick blood film.
</gallery>

===Platelets===
If CBC is performed, use count to determine whether platelets are "normal in number" or whether there is "thrombocytopenia" or "thrombocytosis". If no CBC, count platelets within a high power oil immersed field, which should normally be 8 to 20.

[[File:Micrograph of a giant platelet.jpg|thumb|200px|A '''giant platelet'''.]]
'''Large platelets''' are those with a diameter greater than 4 microns. '''Giant platelets''' are those with a diameter greater than 7 microns (larger than a normal red blood cell).<ref name=ash2016>{{cite web|url=https://imagebank.hematology.org/image/60931/giant-platelets?type=upload|title=Giant platelets|website=American Society of Hematology|author=Teresa Scordino|date=2016-12-02}}</ref> Example report:
{|class=wikitable
| Numerous large and giant platelets{{Moderate-begin}}, suggesting an increased platelet turnover{{Moderate-end}}{{Comprehensive-begin}} such as in immune thrombocytopenic purpura. They may also be present in myeloproliferative neoplasms, myelodysplasia, and some congenital thrombocytopenia syndromes, including Bernard-Soulier syndrome and MYH9-related disorders.<ref name=ash2016/>{{Comprehensive-end}}
|}

In '''thrombocytopenia''' from automatic counting, look in particular for:
*'''Clumping''' of platelets (which can cause a falsely low automatic platelet count). If present, check with the lab if it was sent in EDTA (which may cause artefactual clumping) and ask to have a blood sample sent in sodium citrate instead. Also, look for satellitosis (platelets attached around white blood cells).
*'''Schistocytes''' among red blood cells.

===White blood cells===
[[File:Monoblast, promonocyte and monocyte.jpg|thumb|400px|Comparison of monoblast, promonocyte and monocyte. {{further|Suspected blasts on peripheral blood smear}}]]
A common practice is to evaluate at least 100 white blood cells. Look for:
<gallery mode=packed heights=190>
File:Myeloblast with Auer rod.jpg|thumb|'''Blast cells''', generally having large nucleus, immature chromatin, a prominent nucleolus, scant cytoplasm and few or no cytoplasmic granules. This example has an Auer rod (to the left of the nucleus). {{further|Suspected blasts on peripheral blood smear}}
File:Hypersegmented neutrophil.jpg|'''Hypersegmented neutrophils'''. This is abnormal when more than half of neutrophils have at least 4 segments, or more than 5% of neutrophils have more than 5 segments.<ref name="Glassy 1998 p. ">{{cite book | last=Glassy | first=Eric | title=Color atlas of hematology : an illustrated field guide based on proficiency testing | publisher=College of American Patholgists | publication-place=Northfield, Ill | year=1998 | isbn=978-0-930304-66-9 | oclc=40976106 | page=}}</ref>
File:Prolymphocyte in peripheral blood smear.png|In patients with known chronic lymphocytic leukemia, estimate the percentage of '''prolymphocytes''', which are medium-sized lymphocytes with prominent nucleoli.<ref>{{cite web|url=https://imagebank.hematology.org/image/19922/prolymphocytes-in-pll?type=upload|title=prolymphocytes in PLL|website=American Society of Hematology|date=2013-07-16}}</ref> A percentage of less than 5% can be reported as such.
File:Smudge cell in a peripheral blood smear.jpg|When '''smudge cells''' constitute more than 10% of white blood cells, or in patients with CLL, a separate smear with a drop of serum albumin to every four or five drops of blood should be made to stabilize cell membranes.<ref>{{cite web|url=http://www.captodayonline.com/Archives/0610/0610_qa.html|title=Q & A|website=CAP Today|author=Fredrick L. Kiechle}} June 2010</ref> A semi-quantification of different cell lines should then be made on the albumin slide, whereas white and red blood cell morphology should still be made on the original slide, since it is altered by albumin.
</gallery>

{| class="wikitable" style="text-align:center; vertical-align:middle;"
|+ Atypical lymphocytes:<ref name="Nozaka2023">{{cite journal
|last1=Nozaka |first1=Hiroyuki
|last2=Kushibiki |first2=Mihoko
|last3=Kamata |first3=Kosuke
|last4=Yamagata |first4=Kazufumi
|title=Classifying Microscopic Images of Reactive Lymphocytosis Using Two-Step Tandem AI Models
|journal=Applied Sciences
|year=2023
|volume=13
|issue=9
|page=5296
|doi=10.3390/app13095296
|doi-access=free
}} "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."</ref>
! rowspan="2" | Morphological feature
! colspan="3" | Atypical lymphocyte — Downey's categorization —
|-
! Type I (monocyte-like)
! Type II (plasma cell-like) - Most common
! Type III (lymphoblast-like)
|-
! Size
| ≥16 µm
| ≥16 µm
| ≥16 µm
|-
! Nuclear features
| style="text-align:left;" |
* Kidney-shaped or segmented
| style="text-align:left;" |
* Fine nucleus
* Nucleolus (±)
| style="text-align:left;" |
* Agglutinated chromatin
* Nucleolus (±)
|-
! Cytoplasm
| style="text-align:left;" |
* Strongly basophilic
* Vacuoles (±)
| style="text-align:left;" |
* Strongly basophilic
| style="text-align:left;" |
* Strongly basophilic
|-
! Intracytoplasmic granules
| —
| Azurophilic granules (±)
| —
|-
! Typical morphology
| [[File:Type 1 atypical lymphocyte.png|180px|center|Type I (monocyte-like) atypical lymphocyte]]
| [[File:Type 2 atypical lymphocyte.png|180px|center|Type II (plasma cell-like) atypical lymphocyte]]
| [[File:Type 3 atypical lymphocyte.png|180px|center|Type III (lymphoblast-like) atypical lymphocyte]]
|}

==Report==
Example report:
{|class=wikitable
| Normochromic normocytic red blood cells. Red blood cells show <normal morphology / anisopoikilocytosis with occasional ___>. {{Comment-begin}}If thrombocytopenia, also add "Schistocytes are not significantly increased" if applicable.{{Comment-end}}

{{Finding-begin}}Leukocytosis with neutrophilia / lymphocytosis.{{Finding-end}} White blood cells show no left shift or blasts.

Platelets show no evidence of clumping, and show normal granularity.

{{Moderate-begin}}Causes of the above findings include ___.{{Moderate-end}}
|}
{{Bottom}}

Cervical cytology

2026-07-23T14:35:34Z

Mikael Häggström: /* Main conditions to exclude or confirm */ Tip

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
'''[[Cytology]]''' of the '''[[cervix]]''':</noinclude>
==Clinical information==
It is not necessary to look through more than readily available reports from previous cervical cytologies.

==Magnification==
While being fairly new to cervical cytology, preferably start looking at a high magnification such as 20x objective (with 10x eye piece). For suspicious findings, you may magnify up to maximum. On the other hand, once the pattern feels repetitive you can try switching to a slightly lower magnification such as 10x.

==Adequacy==
Adequacy should always be stated, either as "Satisfactory" or "Unsatisfactory". For estimating the number of cells, determine the following:
*The area of your field of view at high power (see the [[Evaluation]] chapter)
*The total size of the relevant area on the microscope slide. A ThinPrep is about 360 mm2.
*Look at 10 representative high power fields (HPFs) within that area, and calculate the average number of cells per high power field.
[[File:Adequacy counting of pap test.jpg|thumb|240px|HPF example on a ThinPrep (about 360 mm2). If 10 fields gives a total of 40 cells, it will be 4 cells per HPF. The area of this field is 0.23 mm2. Therefore, total cellularity is estimated to be: 4 cells * 360mm2 / 0.23mm2 = 6260 cells.]]
<gallery mode=packed heights=180px>
File:Adequacy counting for cervical Pap tests.png|You may count 10 fields either across the slide, or 5 fields in each direction.<ref name=eurocytology>{{cite web|url=https://www.eurocytology.eu/en/course/1142|title=Criteria for adequacy of a cervical cytology sample|website=EuroCytology|accessdate=2022-08-29}}</ref>
</gallery>
{|
|valign=center| Total number of cells = Average number of cells per HPF * || Total size of area HPF area
|}

Conventional smear cellularity should be at least 8,000 cells. Liquid-based cytology cellularity should be at least 5,000 cells. Also a conventional smear is inadequate if >75% of cells are obscured by blood, exudate or air-drying artefact.<ref name=eurocytology/>

Eventually you will be able to tell when most cases are adequate or inadequate without performing a detailed calculation.

===Transformation zone presence===
[[File:Cytology of cervical squamous metaplasia.png|thumb|290px|'''Squamous metaplasia''' also counts as endocervix. Typical features are annotated. Pap stain.]]
State whether the endocervical/transformation zone is present or absent. Count an endocervical component as present if there are 10 or more endocervical or squamous metaplastic cells.<ref name="CibasDucatman">{{cite book | last=Cibas | first=Edmund S. | last2=Ducatman | first2=Barbara S. | title=Cytology : diagnostic principles and clinical correlates | publication-place=Philadelphia, PA | date=2021 | isbn=978-0-323-63637-7 | oclc=1138033641 | page=9}}</ref>
<gallery mode=packed heights=190>
File:Cytology of endocervical cells.jpg|Endocervical cells can be viewed from the side as nuclear polarity (margination towards the same side as others) in a “picket-fence” configuration.
File:Cytology of sheets of endocervical cells.jpg|Sheets of endocervical cells have a honeycomb pattern.
</gallery>
In patients with previous '''hysterectomy''', simply report glandular or squamous metaplastic cells as such, rather than stating the presence of a transformation zone, since they are likely vaginal in origin in such patients.<ref name="pmid10726617">{{cite journal| author=Ramirez NC, Sastry LK, Pisharodi LR| title=Benign glandular and squamous metaplastic-like cells seen in vaginal Pap smears of post hysterectomy patients: incidence and patient profile. | journal=Eur J Gynaecol Oncol | year= 2000 | volume= 21 | issue= 1 | pages= 43-8 | pmid=10726617 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10726617 }} </ref>

==Very common findings==
<gallery mode=packed heights=200>
File:Reportable and non-reportable acute inflammation in cervical cytology.jpg|For reporting, '''acute inflammation''' should be a background of ample dispersed neutrophils, and not only aggregates of neutrophils with cells or mucus.
File:Normal vaginal flora versus bacterial vaginosis on Pap stain.jpg|Vaginal squamous cell with normal vaginal flora versus bacterial vaginosis on Pap stain. Normal vaginal flora (left) is predominantly rod-shaped ''Lactobacilli'', whereas in bacterial vaginosis (right) there are '''clue cells''', covered in bacteria. A significant amount of clue cells can be reported as "Shift in vaginal flora suggestive of bacterial vaginosis".
File:Candida, Liquid-based Pap (3952574619).jpg|Candida, seen as pseudohyphae.
</gallery>

==Main conditions to exclude or confirm==
'''Squamous atypia''', seen mainly as cells with increased nucleus/cytoplasm ratio, nuclear hyperchromasia and irregular nuclear outline.

If the slide has been previously marked by a cytotechnologist or other previewer, grade the marked cells first. Then, you only need to look for worse findings on the rest of the slide.
<gallery mode=packed heights=220>
File:Atipia de células escamosas (ASCUS, ASC) (9392112063).jpg|'''Atypical squamous cells of undetermined significance (ASCUS)''', with only few slightly atypical cells
File:Cytopathology of low-grade squamous intraepithelial lesion (LSIL).png|'''Low-grade squamous intraepithelial lesion (LSIL)''', here compared to an unremarkable intermediate squamous cell.
File:Cytology of High-Grade SIL, ThinPrep.jpg|'''High-grade squamous intraepithelial lesion (HSIL)''', showing even more prominent features, and decreased cytoplasm, causing a high nuclear/cytoplasmic ratio.
File:Cytopathology of keratinizing squamous cell carcinoma.png|Cytopathology of '''squamous cell carcinoma, keratinizing variant''', with typical features.<ref>- Image annotated by Mikael Häggström - Reference for entries: {{cite web|url=https://www.pathologyoutlines.com/topic/cervixSCC.html|title=Cervix - Squamous cell carcinoma and variants|author=Gulisa Turashvili, M.D., Ph.D.|website=Pathology Outlines}} Last author update: 24 September 2020. Last staff update: 4 April 2022. - Source image from National Cancer Institute (Public Domain)</ref> Pap stain.
File:ThinPrep Pap smear HPV.jpeg|LSIL and '''changes consistent with human papillomavirus''' (HPV), which is the presence of koilocytes, which show perinuclear cavitation, binucleation, nuclear hyperchromasia, and nuclear enlargement.
</gallery>
[[File:Cytopathology of nonkeratinizing squamous cell carcinoma.png|thumb|350px|Cytopathology of squamous cell carcinoma, nonkeratinizing variant, with typical features.<ref>- Image annotated by Mikael Häggström - Reference for entries: {{cite web|url=https://www.pathologyoutlines.com/topic/cervixSCC.html|title=Cervix - Squamous cell carcinoma and variants|author=Gulisa Turashvili, M.D., Ph.D.|website=Pathology Outlines}} Last author update: 24 September 2020. Last staff update: 4 April 2022. - Source image by Ravi Mehrotra, Anurag Gupta, Mamta Singh and Rahela Ibrahim (Creative Commons Attribution 2.0 Generic license.)</ref> Pap stain. Necrotic debris (dirty background) is a feature that generally makes a HSIL case "suspicious for invasive squamous cell carcinoma".<ref name="pmid34345247">{{cite journal| author=Alrajjal A, Pansare V, Choudhury MSR, Khan MYA, Shidham VB| title=Squamous intraepithelial lesions (SIL: LSIL, HSIL, ASCUS, ASC-H, LSIL-H) of Uterine Cervix and Bethesda System. | journal=Cytojournal | year= 2021 | volume= 18 | issue= | pages= 16 | pmid=34345247 | doi=10.25259/Cytojournal_24_2021 | pmc=8326095 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34345247 }} </ref> In contrast to the more distinct keratinizing variant, these findings are overall less specific, and most can be seen in other cancers such as [[adenocarcinoma]] as well (which, however, tends to have fine chromatin)<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/lungtumoradenocarcinoma.html|title=Adenocarcinoma overview|website=Pathology Outlines|author=Authors: Caroline I.M. Underwood, M.D., Alexis Musick, B.S., Carolyn Glass, M.D., Ph.D.}} Last staff update: 19 July 2022</ref>]]
<gallery mode=packed heights=220>
File:Glycogenated cervical squamous cells.tif|Distinguish HPV-changes from '''glycogenated''' squamous cells. Glycogen confers a yellowish color to the cytoplasm. It can look like the perinuclear cavitation of koilocytes, but has more rounded edges.
</gallery>
===Clinical implication===
If you are uncertain of the degree of dysplasia, it can be useful to look up how much difference it will likely make for the management of the patient. You may make an Internet search for the management of abnormal cervical screening in your region (such as [https://app.asccp.org/ The ASCCP tool] for management in the US). A change from close follow-up to colposcopy is not that big of a deal, but if one of the alternatives will lead to a diagnostic excision, make sure that the case is looked upon by commensurate expertise.
<noinclude>

==Other findings==
<gallery mode=packed heights=220>
File:Pap smear showing clamydia in the vacuoles 500x H&E.jpg|'''Chlamydia trachomatis''', with granular cytoplasm with multiple intracytoplasmic inclusions with central small coccoid bodies.
</gallery>
</noinclude>

==Report==
Example in a normal case:
{|class=wikitable
| Cervical/endocervical ThinPrep:
:Negative for intraepithelial lesion or malignancy (NILM).
|}
<noinclude>{{Bottom}}</noinclude>

Gastritis

2026-07-17T03:39:14Z

Mikael Häggström: /* Microscopy report */ sections

{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}

Inflammation of the [[stomach]]. If biopsy is at the esophagus, evaluate as '''[[gastroesophageal junction]]'''.
{{Comprehensiveness}}
==Microscopy evaluation==
[[File:Histopathology of mucosal plasma cell infiltrate in chronic gastritis.jpg|thumb|Mucosal plasma cell infiltrate in '''mild chronic gastritis'''.]]
Look for chronic or acute gastritis. If either is present, still look for the other.
===Chronic gastritis===
*'''Chronic gastritis'''<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachchronicgastritis.html|title=Stomach - Gastritis - Chronic gastritis|author=Elliot Weisenberg|website=PathologyOutlines}} Topic Completed: 1 August 2012. Minor changes: 31 August 2020</ref>
:*Presence of '''plasma cells''', '''lymphocytes''', and occasionally lymphoid '''follicles'''. Scattered single plasma cells and lymphocytes is normal, and the threshold is subjective, but one definition of chronic gastritis is when seeing chronic inflammation at 4x magnification (as increased dots separating glands)<ref>{{cite web|url=http://www.azpath.org/uploads/2/6/3/8/2638612/voltaggio_-_gastritis_presentation.pdf|title=Gastritis: A Pattern Based Approach|author=Lysandra Voltaggio, Johns Hopkins Department of Pathology|website=Arizona Society of Pathologists|date=2018-10-31}}</ref> Eosinophils and neutrophils may be present.
:*'''Reduced mucin''' in the cytoplasm
:*'''Enlargement''' of nuclei and nucleoi
:*'''Subnuclear vacuolation''' in antral glands or pits (which is PAS negative)
:*'''Intestinal metaplasia''': with partial replacement of the mucosa of the antrum and body with metaplastic goblet cells of intestinal morphology, absorptive cells and Paneth cells.
<gallery mode=packed heights=210>
File:Updated Sydney System for visual classification of gastritis.png|thumb|340px|Updated Sydney System for visual classification of gastritis.<ref name=Carrasco/>
File:Moderate superficial chronic gastritis.jpg|'''Moderate''' gastritis.
File:Histopathology of antral mucosa with atrophy.png|In '''intestinal metaplasia''' (seen at bottom of this antral mucosa), also look for '''atrophy''' as pictured.<ref name=Carrasco/><ref group=note>The combination of atrophy and gastritis (especially when deeper than submucosal) helps the clinician to potentially make a diagnosis of atrophic gastritis.</ref>
File:Histopathology of fundic mucosa with atrophy.png|Extensive atrophy of oxyntic glands in fundus/corpus causes '''pseudo-pyloric metaplasia'''.<ref name=Carrasco/>
</gallery>
When there is at least {{Moderate-begin}}mild or{{Moderate-end}} moderate gastritis, especially if relatively superficial, also evaluate as a [[stomach biopsy for Helicobacter pylori|stomach biopsy for '''Helicobacter pylori''']].

===Acute gastritis===
[[File:Histopathology of mild active gastritis, annotated.jpg|thumb|230px|Histopathology of '''mild active gastritis''', with intraepithelial neutrophils (white arrows) as well as in lamina propria (black arrows).]]
*'''Mild acute gastritis:'''<ref name=PathologyOutlinesAcute>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachacutegastritis.html|title=Stomach - Gastritis - Acute gastritis|author=Elliot Weisenberg|website=pathologyOutlines}} Topic Completed: 1 August 2012. Minor changes: 31 August 2020</ref>
:*Modest '''edema''' of lamina propria
:*'''Vascular congestion'''
:*Scattered '''neutrophils'''
:*Mucosal '''hemorrhage'''
:*Intact epithelium
<gallery mode=packed heights=210px>
File:Histopathology of early acute superficial gastritis.png|Early acute superficial gastritis: Marked neutrophilic infiltrates appear in the mucous neck region and lamina with a pit micoabscess.<ref name=Carrasco>{{cite journal| author=Carrasco G, Corvalan AH| title=Helicobacter pylori-Induced Chronic Gastritis and Assessing Risks for Gastric Cancer. | journal=Gastroenterol Res Pract | year= 2013 | volume= 2013 | issue= | pages= 393015 | pmid=23983680 | doi=10.1155/2013/393015 | pmc=3745848 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23983680 }} [https://www.researchgate.net/publication/256190376_Helicobacter_pylori-Induced_Chronic_Gastritis_and_Assessing_Risks_for_Gastric_Cancer Figures - available via license: Creative Commons Attribution 3.0 Unported]</ref>
</gallery>
*'''Moderate to severe acute gastritis''':<ref name=PathologyOutlinesAcute/>
:*'''Loss of superficial epithelium''' above the muscularis mucosa
:*'''Hemorrhage'''
:*Variable infiltrate with '''neutrophils'''
:*Fibrinopurulent luminal '''exudate'''
:*Nearby epithelium may show '''regenerative''' changes

===Microscopy report===
*'''Mild and/or chronic gastritis''' and '''severity'''
:*{{Moderate-begin}}If present, state if positive or negative for '''''Helicobacter pylori''''' organisms.{{Moderate-end}}
Chronic gastritis without neutrophils is preferably also termed "inactive".

Example:
{|class=wikitable
| {{Moderate-begin}}Stomach, biopsy:{{Moderate-end}}
*{{Moderate-begin}}Gastric antral/oxyntic mucosa with{{Moderate-end}} mild chronic {{Moderate-begin}}inactive{{Moderate-end}} gastritis{{Comprehensive-begin}}, non-specific{{Comprehensive-end}}
*{{Moderate-begin}}Negative for ''Helicobacter pylori'' organisms on H&E sections.{{Moderate-end}}
|}
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Gastritis

2026-07-17T03:38:48Z

Mikael Häggström: /* Microscopy report */ in

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Inflammation of the [[stomach]]. If biopsy is at the esophagus, evaluate as '''[[gastroesophageal junction]]'''.
{{Comprehensiveness}}
==Microscopy evaluation==
[[File:Histopathology of mucosal plasma cell infiltrate in chronic gastritis.jpg|thumb|Mucosal plasma cell infiltrate in '''mild chronic gastritis'''.]]
Look for chronic or acute gastritis. If either is present, still look for the other.
===Chronic gastritis===
*'''Chronic gastritis'''<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachchronicgastritis.html|title=Stomach - Gastritis - Chronic gastritis|author=Elliot Weisenberg|website=PathologyOutlines}} Topic Completed: 1 August 2012. Minor changes: 31 August 2020</ref>
:*Presence of '''plasma cells''', '''lymphocytes''', and occasionally lymphoid '''follicles'''. Scattered single plasma cells and lymphocytes is normal, and the threshold is subjective, but one definition of chronic gastritis is when seeing chronic inflammation at 4x magnification (as increased dots separating glands)<ref>{{cite web|url=http://www.azpath.org/uploads/2/6/3/8/2638612/voltaggio_-_gastritis_presentation.pdf|title=Gastritis: A Pattern Based Approach|author=Lysandra Voltaggio, Johns Hopkins Department of Pathology|website=Arizona Society of Pathologists|date=2018-10-31}}</ref> Eosinophils and neutrophils may be present.
:*'''Reduced mucin''' in the cytoplasm
:*'''Enlargement''' of nuclei and nucleoi
:*'''Subnuclear vacuolation''' in antral glands or pits (which is PAS negative)
:*'''Intestinal metaplasia''': with partial replacement of the mucosa of the antrum and body with metaplastic goblet cells of intestinal morphology, absorptive cells and Paneth cells.
<gallery mode=packed heights=210>
File:Updated Sydney System for visual classification of gastritis.png|thumb|340px|Updated Sydney System for visual classification of gastritis.<ref name=Carrasco/>
File:Moderate superficial chronic gastritis.jpg|'''Moderate''' gastritis.
File:Histopathology of antral mucosa with atrophy.png|In '''intestinal metaplasia''' (seen at bottom of this antral mucosa), also look for '''atrophy''' as pictured.<ref name=Carrasco/><ref group=note>The combination of atrophy and gastritis (especially when deeper than submucosal) helps the clinician to potentially make a diagnosis of atrophic gastritis.</ref>
File:Histopathology of fundic mucosa with atrophy.png|Extensive atrophy of oxyntic glands in fundus/corpus causes '''pseudo-pyloric metaplasia'''.<ref name=Carrasco/>
</gallery>
When there is at least {{Moderate-begin}}mild or{{Moderate-end}} moderate gastritis, especially if relatively superficial, also evaluate as a [[stomach biopsy for Helicobacter pylori|stomach biopsy for '''Helicobacter pylori''']].

===Acute gastritis===
[[File:Histopathology of mild active gastritis, annotated.jpg|thumb|230px|Histopathology of '''mild active gastritis''', with intraepithelial neutrophils (white arrows) as well as in lamina propria (black arrows).]]
*'''Mild acute gastritis:'''<ref name=PathologyOutlinesAcute>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachacutegastritis.html|title=Stomach - Gastritis - Acute gastritis|author=Elliot Weisenberg|website=pathologyOutlines}} Topic Completed: 1 August 2012. Minor changes: 31 August 2020</ref>
:*Modest '''edema''' of lamina propria
:*'''Vascular congestion'''
:*Scattered '''neutrophils'''
:*Mucosal '''hemorrhage'''
:*Intact epithelium
<gallery mode=packed heights=210px>
File:Histopathology of early acute superficial gastritis.png|Early acute superficial gastritis: Marked neutrophilic infiltrates appear in the mucous neck region and lamina with a pit micoabscess.<ref name=Carrasco>{{cite journal| author=Carrasco G, Corvalan AH| title=Helicobacter pylori-Induced Chronic Gastritis and Assessing Risks for Gastric Cancer. | journal=Gastroenterol Res Pract | year= 2013 | volume= 2013 | issue= | pages= 393015 | pmid=23983680 | doi=10.1155/2013/393015 | pmc=3745848 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23983680 }} [https://www.researchgate.net/publication/256190376_Helicobacter_pylori-Induced_Chronic_Gastritis_and_Assessing_Risks_for_Gastric_Cancer Figures - available via license: Creative Commons Attribution 3.0 Unported]</ref>
</gallery>
*'''Moderate to severe acute gastritis''':<ref name=PathologyOutlinesAcute/>
:*'''Loss of superficial epithelium''' above the muscularis mucosa
:*'''Hemorrhage'''
:*Variable infiltrate with '''neutrophils'''
:*Fibrinopurulent luminal '''exudate'''
:*Nearby epithelium may show '''regenerative''' changes

===Microscopy report===
*'''Mild and/or chronic gastritis''' and '''severity'''
:*{{Moderate-begin}}If present, state if positive or negative for '''''Helicobacter pylori''''' organisms.{{Moderate-end}}
Chronic gastritis without neutrophils is preferably also termed "inactive".

Example:
{|class=wikitable
| {{Moderate-begin}}Stomach, biopsy:{{Moderate-end}}
*{{Moderate-begin}}Gastric antral/oxyntic mucosa with{{Moderate-end}} mild chronic {{Moderate-begin}}inactive{{Moderate-end}} gastritis{{Comprehensive-begin}}, non-specific{{Comprehensive-end}}
*{{Moderate-begin}}Negative for ''Helicobacter pylori'' organisms on H&E slide.{{Moderate-end}}
|}
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Starting pathology - Copies

2026-07-17T00:48:36Z

Mikael Häggström: Recommended

<noinclude>
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It is recommended that you keep an offline copy of this work on devices you regularly use for pathology workups. To get a printable version of this handbook (which can also be downloaded for offline use), go to patholines.org, click [[Starting pathology (handbook)|'''Starting pathology''' (handbook)]], and click [https://patholines.org/index.php?title=Starting_pathology&printable=yes Printable version] in the left hand menu.<ref group=note>The printable version URL is: http://patholines.org/index.php?title=Starting_pathology&printable=yes The recommended letter format version in Firefox is scale 100%, or Google Chrome scale 135%. To save it for offline use, choose to print it as a PDF file. Google Chrome gives you a smaller file size than Firefox (about 30 MB compared to about 240 MB in Firefox, but also slightly less image quality).</ref> A normal color printer and normal paper is sufficient, and you can keep the pages together in a binder. If you want even better quality, use color printer paper, or google a "copy shop" for a color print delivery or in-store pickup (possibly as a photo book). If you are not intending to practice in clinical pathology (or laboratory medicine) then you may skip printing the "Clinical pathology" part.
[[File:Scary FBI logo.jpg|thumb|200px|Scary FBI logos like this are often copy-pasted into works, but do not change your copyrights.]]
This handbook is released under the ''[https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC-BY 4.0)] license'', meaning that you may reuse any of its content (such as in scholarly articles or other publications of yours), but you should mention its author ({{MH top}}). Also, many images are ''[[Public Domain]]'', that is, without any restrictions. The status of each image, and its creator(s), is seen on its description page (found by clicking the image at Patholines.org). This handbook is published in the United States, and the United States copyright law holds that "''In no case does copyright protection for an original work of authorship extend to any idea, procedure, process, system, method of operation, concept, principle, or discovery, regardless of the form in which it is described, explained, illustrated, or embodied in such work.''".<ref>{{cite web|url=https://www.copyright.gov/title17/title17.pdf|title=Copyright Law OF THE United States and Related Laws Contained in Title 17 of the United States Code|website=U.S. Copyright Office}} May 2021</ref><ref>{{cite web|url=https://www.law.cornell.edu/uscode/text/17/102|title=17 U.S. Code § 102 - Subject matter of copyright: In general|website=Cornell Law School, Legal Information Institute|accessdate=2022-01-11}}</ref> Hence, you can use any texts, tables and graphs herein as Public Domain, and defend such usage by stating that it describes anatomical, physiological and pathological processes and systems. Hence, in practice, the attribution as per above when using texts, tables and graphs from this handbook is a polite request rather than a legal requirement.<ref>{{cite web|url=https://deepblue.lib.umich.edu/bitstream/handle/2027.42/83329/copyrightability_of_tables_charts_and_graphs.pdf|title=Copyrightability of Tables, Charts and Graphs|website=Deep Blue Repositories, University of Michigan Library|accessdate=2022-01-07}}</ref>{{Further|Patholines:Copyright}}<noinclude>
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Peripheral blood smear

2026-07-16T23:05:05Z

Mikael Häggström: /* White blood cells */ number

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Look at and comment separately on white blood cells, red blood cells and platelets. You generally don't need to aim for a perfect report, because for most purposes, a peripheral smear is a relatively simple screening test, and clinicians may opt to perform for example flow cytometry and/or a bone marrow biopsy if they want a better evaluation.
{{Comprehensiveness|otherlegend=yes}}
==Oil immersion microscopy==
This is preferred for light microscopy of peripheral blood smears in order to achieve a very high magnification. First use low or medium power to center on suspicious cells, or where red or white blood cells are best appreciated. Put a drop of immersion oil on the location and switch to the immersion objective. Then, whenever there's oil on a slide, always think twice before switching between objectives so as to avoid getting oil on any of your dry objectives (which is a bit tedious to clean off).

==Red blood cells==
===Automated values===
When available, automatic quantification of mean corpuscular volume (MCV) and red blood cell (RBC) distribution width (RDW), usually as part of CBC panel, generally decides whether you will call the sample "'''normocytic'''" versus "microcytic"/"macrocytic" and/or "anisocytotic", even if it is not clearly visible in the microscope. If automated values are not available, compare RBC sizes to lymphocyte nuclei, which should normally be the same size. If mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) are normal, but you still see multiple RBCs with central pallor greater than 50% of the diameter, you can report it as ''"Increased central pallor"'', and you may add ''"indicating iron deficiency"'' if it is compatible with the clinical history.

Automated values can be graded as follows:<ref name=HongKong>Unless otherwise specified in table, reference is: - {{cite web|url=http://www.hkimls.org/qapeduhsm-rbc-mor.htm|title=Hong Kong Medical Technology Association - Quality Assurance Programme - Haematology and Serology, Prepared by HKMTAQAP Haematology & Serology Panel on November 2002.}}</ref>
{|class=wikitable
|-
! Interpretation
! Mild
! Moderate
! Marked
|-
| Microcytosis ||MCV : 70 - 79||MCV : 60 - 69||MCV <60
|-
| Macrocytosis ||MCV : 100 - 115||MCV : 115 - 125||MCV >125
|-
| Hypochromasia||MCH : 23 - 26||MCH : 21 - 23||MCH <20
|-
| Anisocytosis||RDW: 14.5<ref name=MrLabTest>{{cite web|url=https://www.mrlabtest.com/high-RDW-blood.htm|website=MrLabTest|title=High RDW level in the blood}} Last update: 12/01/2021</ref> or 16<ref name=HongKong/> - 18||RDW : 18 - 22<ref name=HongKong/> or 26<ref name=MrLabTest/> ||RDW > 22<ref name=HongKong/> or 26<ref name=MrLabTest/>
|}

===Morphologic findings===
Look for poikilocytosis (red blood cells of abnormal shapes). These are counted as a percentage of visible red blood cells:<ref name=HongKong/>
{|class=wikitable
|-
|
! Image
! Rare/Occasional
! Moderate amount of
! Many/Abundant
|-
! Polychromasia
| [[File:Peripheral blood smear with polychromasia.jpg|90px]]
|3 - 5%||5 - 25%||>25%
|-
! Spherocytes
| [[File:Micrograph of a spherocyte.jpg|90px]]
|1 - 5%||5 - 25%||>25%
|-
! Schistocytes
| [[File:Micrograph of schistocytes.jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Target cells (codocytes)
| [[File:Micrograph of a target cell.jpg|90px]]
|up to 3%||3 - 25%||>25%
|-
! Tear drop cells
| [[File:Micrograph of a tear drop cell (dacrocyte).jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Burr cells (echinocytes)
| [[File:Micrograph of an echinocyte on a peripheral blood smear.jpg|90px]]
|1 - 3% || 3 - 10%|| >10%
|-
! Sickle cells (drepanocytes)
| [[File:Micrograph of a sickle cell.jpg|90px]]
|3 - 5%||5 - 25%||>25%
|-
! Elliptocytes
| [[File:Micrograph of an elliptocyte on a peripheral blood smear 02.jpg|90px]]
|1 - 5%||5 - 25%||>25%
|-
! Basophilic stipplings
| [[File:Micrograph of a red blood cell with basophilic stippling.jpg|90px]]
|up to 2%||2 - 25%||>25%
|-
! Howell Jolly bodies
| [[File:Micrograph of a Howell–Jolly body in a red blood cell.jpg|90px]]
|up to 1%||2 - 3 %||>3%
|-
|}
;Burr cells versus spur cells
<gallery mode=packed heights=150>
File:Micrograph of an echinocyte on a peripheral blood smear.jpg|'''Burr cell''' (echinocyte)
File:Human blood film with acanthocytes 02.jpg|'''Spur cell''' (acanthocyte)
</gallery>
Burr cells are distinguished from spur cells by having more equally distributed and rounded projections. They are usually [[Artifacts|artifactual]]. However, they may also be caused by renal insufficiency, so if this is present, a report may include "Occasional/Multiple echinocytes, consistent with renal insufficiency".

;Intraerythrocytic findings
<gallery mode=packed heights=150>
File:Micrograph of a red blood cells with an overlying platelet on a peripheral blood smear.jpg|When seeing what appears to a platelet overlying a red blood cells (as pictured), confirm that there is a halo.
File:Human blood film with babesia.jpg|Otherwise, make sure it is not '''babesia''' (pictured) or malaria (images below).
</gallery>
<gallery mode=packed heights=250>
File:Blood stages of P. falciparum over 48h.jpg|'''Malaria''', showing appearance at different intraerythrocytic blood stages.
File:Thick blood film with Plasmodium falciparum rings and schizonts.png|If '''malaria''' is suspected, also make a thick blood film.
</gallery>

===Platelets===
If CBC is performed, use count to determine whether platelets are "normal in number" or whether there is "thrombocytopenia" or "thrombocytosis". If no CBC, count platelets within a high power oil immersed field, which should normally be 8 to 20.

[[File:Micrograph of a giant platelet.jpg|thumb|200px|A '''giant platelet'''.]]
'''Large platelets''' are those with a diameter greater than 4 microns. '''Giant platelets''' are those with a diameter greater than 7 microns (larger than a normal red blood cell).<ref name=ash2016>{{cite web|url=https://imagebank.hematology.org/image/60931/giant-platelets?type=upload|title=Giant platelets|website=American Society of Hematology|author=Teresa Scordino|date=2016-12-02}}</ref> Example report:
{|class=wikitable
| Numerous large and giant platelets{{Moderate-begin}}, suggesting an increased platelet turnover{{Moderate-end}}{{Comprehensive-begin}} such as in immune thrombocytopenic purpura. They may also be present in myeloproliferative neoplasms, myelodysplasia, and some congenital thrombocytopenia syndromes, including Bernard-Soulier syndrome and MYH9-related disorders.<ref name=ash2016/>{{Comprehensive-end}}
|}

In '''thrombocytopenia''' from automatic counting, look in particular for:
*'''Clumping''' of platelets (which can cause a falsely low automatic platelet count). If present, check with the lab if it was sent in EDTA (which may cause artefactual clumping) and ask to have a blood sample sent in sodium citrate instead. Also, look for satellitosis (platelets attached around white blood cells).
*'''Schistocytes''' among red blood cells.

===White blood cells===
[[File:Monoblast, promonocyte and monocyte.jpg|thumb|400px|Comparison of monoblast, promonocyte and monocyte. {{further|Suspected blasts on peripheral blood smear}}]]
A common practice is to evaluate at least 100 white blood cells. Look for:
<gallery mode=packed heights=190>
File:Myeloblast with Auer rod.jpg|thumb|'''Blast cells''', generally having large nucleus, immature chromatin, a prominent nucleolus, scant cytoplasm and few or no cytoplasmic granules. This example has an Auer rod (to the left of the nucleus). {{further|Suspected blasts on peripheral blood smear}}
File:Hypersegmented neutrophil.jpg|'''Hypersegmented neutrophils'''. This is abnormal when more than half of neutrophils have at least 4 segments, or more than 5% of neutrophils have more than 5 segments.<ref name="Glassy 1998 p. ">{{cite book | last=Glassy | first=Eric | title=Color atlas of hematology : an illustrated field guide based on proficiency testing | publisher=College of American Patholgists | publication-place=Northfield, Ill | year=1998 | isbn=978-0-930304-66-9 | oclc=40976106 | page=}}</ref>
File:Prolymphocyte in peripheral blood smear.png|In patients with known chronic lymphocytic leukemia, estimate the percentage of '''prolymphocytes''', which are medium-sized lymphocytes with prominent nucleoli.<ref>{{cite web|url=https://imagebank.hematology.org/image/19922/prolymphocytes-in-pll?type=upload|title=prolymphocytes in PLL|website=American Society of Hematology|date=2013-07-16}}</ref> A percentage of less than 5% can be reported as such.
File:Smudge cell in a peripheral blood smear.jpg|When '''smudge cells''' constitute more than 10% of white blood cells, or in patients with CLL, a separate smear with a drop of serum albumin to every four or five drops of blood should be made to stabilize cell membranes.<ref>{{cite web|url=http://www.captodayonline.com/Archives/0610/0610_qa.html|title=Q & A|website=CAP Today|author=Fredrick L. Kiechle}} June 2010</ref> A semi-quantification of different cell lines should then be made on the albumin slide, whereas white and red blood cell morphology should still be made on the original slide, since it is altered by albumin.
</gallery>

==Report==
Example report:
{|class=wikitable
| Normochromic normocytic red blood cells. Red blood cells show <normal morphology / anisopoikilocytosis with occasional ___>. {{Comment-begin}}If thrombocytopenia, also add "Schistocytes are not significantly increased" if applicable.{{Comment-end}}

{{Finding-begin}}Leukocytosis with neutrophilia / lymphocytosis.{{Finding-end}} White blood cells show no left shift or blasts.

Platelets show no evidence of clumping, and show normal granularity.

{{Moderate-begin}}Causes of the above findings include ___.{{Moderate-end}}
|}
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Gastroesophageal junction

2026-07-16T18:33:10Z

Mikael Häggström: dysplasia

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{{Endoscopic biopsies}}
{{Comprehensiveness}}</noinclude>
==Microscopic examination==
The main findings to look for are:
*'''[[Barrett's esophagus|Intestinalized mucosa]]''' ([[Barrett's esophagus]])
*(Reflux) '''esophagitis'''.
*'''Gastritis'''. {{Further|Stomach|linebreak=no}}
*'''[[Esophageal adenocarcinoma]]'''

===Barrett's esophagus===
The main diagnostic sign of Barrett's esophagus is the presence of '''goblet cells'''. A true goblet cell should have rounded shape, clear to bluish cytoplasmic mucin, and be randomly scattered.<ref name=PathologyOutlines-Barrett>{{cite web|url=http://www.pathologyoutlines.com/topic/esophagusBarrettsgeneral.html|title=Esophagus - Premalignant - Barrett esophagus|author=Dipti M. Karamchandani}} Topic Completed: 19 March 2020, Minor changes: 29 June 2020</ref> The mucin usually indents the nucleus.<ref name=PathologyOutlines-Barrett/>
<gallery mode=packed heights=220>
File:Histopathology of Barrett's esophagus, annotated.jpg|Histopathology of '''[[Barrett's esophagus]]''', showing intestinalized epithelium with goblet cells, as opposed to normal stratified squamous epithelium of the esophagus, and pseudostratified columnar epithelium of the fundus of the stomach. H&E stain.
File:Histopathology of goblet cells (annotated) and foveolar cells in incomplete Barrett's esophagus.jpg|In '''incomplete''' intestinal metaplasia, there are both foveolar cells and goblet cells, the latter (indicated by arrows) usually having a slightly bluish color compared to the apical cytoplasm of foveolar cells. An occasional but specific sign of goblet cells is crescent shaped nuclei (seen in middle one).
</gallery>

{{further|Barrett's esophagus}}

{{Esophagitis}}

===Report===
{{Moderate-begin}}Document the '''type of mucosa''':
*If both gastric and squamous mucosa is present in the same fragment, report as "'''Gastroesophageal junctional mucosa with...'''"
*If not, report the presence of '''squamous''' and/or '''gastric mucosa'''.{{Moderate-end}}

Examples:
{|class=wikitable
| {{Moderate-begin}}GE junction, biopsy:{{Moderate-end}} Squamous mucosa without significant histopathologic changes. {{Moderate-begin}}Negative for gastric mucosa or intestinalized (Barrett's) mucosa.{{Moderate-end}} {{Comprehensive-begin}}Negative for dysplasia and malignancy.{{Comprehensive-end}}
|}

{|class=wikitable
| {{Moderate-begin}}GE junction, biopsy:{{Moderate-end}} Gastroesophageal junctional mucosa with '''chronic inflammation''' and reactive changes{{Moderate-begin}}, non-specific. Negative for intestinalized (Barrett's) mucosa.{{Moderate-end}}{{Comprehensive-begin}}, dysplasia, and malignancy{{Comprehensive-end}}.
|}

In case of multiple signs of reflux esophagitis:
{|class=wikitable
| {{Moderate-begin}}GE junction, biopsy:{{Moderate-end}} Gastroesophageal junctional mucosa with changes consistent with '''reflux esophagitis'''. {{Moderate-begin}}Negative for intestinalized (Barrett's) mucosa{{Moderate-end}}{{Comprehensive-begin}}, dysplasia, and malignancy{{Comprehensive-end}}.
|}
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Stomach

2026-07-16T03:33:16Z

Mikael Häggström: /* Microscopy report */ english

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{{Endoscopic biopsies}}
==Presentations==
:*[[Gastric polyp]]
:*[[Stomach biopsy for Helicobacter pylori]]
:*[[Stomach tumor]]
:*[[Gastric sleeve]]
{{Comprehensiveness}}</noinclude>
==Microscopic evaluation==
Generally screen for:
<gallery mode=packed heights=200>
File:Histopathology of gastric adenoma and adenocarcinoma.jpg|Gastric '''adenomas''' and '''adenocarcinomas'''. {{further|Stomach tumor}}
File:Histopathology of mucosal plasma cell infiltrate in chronic gastritis.jpg|thumb|'''[[Gastritis]]''', with neutrophils indicating acute gastritis, and plasma cells (pictured) indicating chronic gastritis.<ref name=PathologyOutlinesAcute>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachacutegastritis.html|title=Stomach - Gastritis - Acute gastritis|author=Elliot Weisenberg|website=pathologyOutlines}} Topic Completed: 1 August 2012. Minor changes: 31 August 2020</ref><ref>{{cite web|url=https://www.pathologyoutlines.com/topic/stomachchronicgastritis.html|title=Stomach - Gastritis - Chronic gastritis|author=Elliot Weisenberg|website=PathologyOutlines}} Topic Completed: 1 August 2012. Minor changes: 31 August 2020</ref>
File:Histopathology of reactive gastropathy, annotated.jpg|thumb|'''Reactive gastropathy''', which is a triad of:<ref name=pmid16939055>{{Cite journal | last1 = Genta | first1 = RM. | title = Differential diagnosis of reactive gastropathy. | journal = Semin Diagn Pathol | volume = 22 | issue = 4 | pages = 273-83 | month = Nov | year = 2005 | doi = | PMID = 16939055 }}</ref> - '''Foveolar hyperplasia''' (black arrow), generally seen as a tortuosity in the "neck" region of the gastric glands. - Scant acute and chronic '''inflammatory''' cells (white arrow). - '''Smooth muscle hyperplasia''' (black oval)
File:Helicobacter pylori, Gastric Mucosa, H&E (390307642).jpg|{{Comprehensive-begin}}Look for '''[[Helicobacter pylori]]''' even without signs of gastritis.{{Comprehensive-end}}<ref group=note>H. pylori is very unlikely without gastritis or reactive changes.</ref>
</gallery>

===Microscopy report===
Example in case of normal findings:
{|class=wikitable
| {{Moderate-begin}}Stomach, biopsy:{{Moderate-end}} Gastric {{Moderate-begin}}oxyntic/antral{{Moderate-end}} mucosa without significant histopathologic changes. {{Moderate-begin}}Negative for ''Helicobacter {{Comprehensive-begin}}pylori{{Comprehensive-end}}'' organisms on H&E slide.{{Moderate-end}}
|}
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Endometrial polyp

2026-07-16T02:00:40Z

Mikael Häggström: /* Microscopic evaluation */ corrected

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{{Comprehensiveness}}
{{Fixation - standard}}
{{Fixation - general notes}}
==Microscopic evaluation==
The main objectives are:
*Making a '''diagnosis''' of endometrioid polyp. An endometrial polyp may be diagnosed in the presence of 2 of the following 3:
:*Thick-walled vessels
:*Collagenous stroma
:*Epithelium on at least 3 sides
*Look for signs of '''atypia or malignancy'''.
<gallery mode=packed heights=200>
File:Histopathology of non-complex endometrial polyp without atypia.jpg|'''Endometrial polyp''' (without atypia), with a thick-walled blood vessel in middle - typical of endometrial polyps. Glands are may be cystic but have unremarkable linings.
File:Histopathology of non-complex endometrial polyp without atypia, with tubal metaplasia.jpg|'''Endometrial polyp''' (without atypia), with tubal metaplasia (black arrow, showing ciliated epithelium) and a thick-walled blood vessel (white arrow). The stroma is hemorrhagic in this case.
File:Myometrium versus endometrial stroma versus endometrial polyp stroma.jpg|Myometrium (smooth muscle cells) versus endometrial stroma (more cellular) versus '''endometrial polyp stroma''' (more collagenous).{{MH}}
File:Histopathology of endometrial intraepithelial neoplasia (EIN).jpg|'''Atypia''' (mainly seen as signs of '''endometrial intraepithelial neoplasia''' ('''EIN'''), which has the following criteria:<ref name="OwingsQuick2014">{{cite journal|last1=Owings|first1=Richard A.|last2=Quick|first2=Charles M.|title=Endometrial Intraepithelial Neoplasia|journal=Archives of Pathology & Laboratory Medicine|volume=138|issue=4|year=2014|pages=484–491|issn=1543-2165|doi=10.5858/arpa.2012-0709-RA}}</ref> - Architectural gland crowding - Altered cytology relative to background glands - Minimum size of 1 mm - Exclusion of adenocarcinoma - Exclusion of mimics Mitoses should also preferably be seen.
File:Histopathology of Serous carcinoma arising in endometrial polyp.jpg|'''[[Endometrial adenocarcinoma]]'''<ref>{{cite journal|last1=Stewart|first1=Colin J.R.|last2=Crum|first2=Christopher P.|last3=McCluggage|first3=W. Glenn|last4=Park|first4=Kay J.|last5=Rutgers|first5=Joanne K.|last6=Oliva|first6=Esther|last7=Malpica|first7=Anais|last8=Parkash|first8=Vinita|last9=Matias-Guiu|first9=Xavier|last10=Ronnett|first10=Brigitte M.|title=Guidelines to Aid in the Distinction of Endometrial and Endocervical Carcinomas, and the Distinction of Independent Primary Carcinomas of the Endometrium and Adnexa From Metastatic Spread Between These and Other Sites|journal=International Journal of Gynecological Pathology|volume=38|year=2019|pages=S75–S92|issn=0277-1691|doi=10.1097/PGP.0000000000000553}} - "Figures - available via license: Creative Commons Attribution 4.0 International"</ref> arising in an endometrial polyp. These are most commonly endometrioid, in which case low-grade carcinoma is distinguished from hyperplasia with atypia by the presence of glandular crowding with endometrial stromal exclusion, and significant cribriform, confluent glandular, labyrinthine, papillary/villoglandular, or non-squamous solid architecture.<ref name="RabbanGilks2019">{{cite journal|last1=Rabban|first1=Joseph T.|last2=Gilks|first2=C. Blake|last3=Malpica|first3=Anais|last4=Matias-Guiu|first4=Xavier|last5=Mittal|first5=Khush|last6=Mutter|first6=George L.|last7=Oliva|first7=Esther|last8=Parkash|first8=Vinita|last9=Ronnett|first9=Brigitte M.|last10=Staats|first10=Paul|last11=Stewart|first11=Colin J.R.|last12=McCluggage|first12=W. Glenn|title=Issues in the Differential Diagnosis of Uterine Low-grade Endometrioid Carcinoma, Including Mixed Endometrial Carcinomas|journal=International Journal of Gynecological Pathology|volume=38|year=2019|pages=S25–S39|issn=0277-1691|doi=10.1097/PGP.0000000000000512}}</ref>
File:Histopathology of a leiomyoma with fascicular growth.jpg|Subserosal pedunculated uterine '''leiomyomas''' may present as endometrial polyps. They typically show smooth muscle in a fascicular pattern<ref>{{cite web|url=http://www.pathologyoutlines.com/topic/uterusleiomyoma.html|title=Uterus - Stromal tumors - Leiomyoma|author=Mohamed Mokhtar Desouki|website=pathology Outlines}} Topic Completed: 1 August 2011. Revised: 15 December 2019</ref> {{further|Smooth muscle tumor|linebreak=no}}
</gallery>

==Reporting==
Most importantly:
*Benign versus malignant {{Moderate-begin}}or presence or absence of atypia.{{Moderate-end}}
*{{Comprehensive-begin}}The size of the polyp.{{Comprehensive-end}}
*{{Comprehensive-begin}}The type of epithelium at both the surface and gland coverings.{{Comprehensive-end}}

Example of a minimal report:
{|class=wikitable
| Benign endometrial polyp.
|}
{{Reporting}}
{{Bottom}}

Template:Mitotic count in invasive breast cancer

2026-07-14T16:33:22Z

Mikael Häggström: Table

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}</noinclude>[[File:Mitosis appearances in breast cancer.jpg|thumb|Mitosis appearances in breast cancer]]
{{edit|Template:Mitotic count in invasive breast cancer}} 
Mitotic figures are counted only at the periphery of the tumor, and counting should begin in the most mitotically active areas, and in at least 10 high-power fields (HPFs). If you know that the area of your high power field is about 0.2mm2, then you may score mitotic count as follows:<ref name=cap-invasive>{{cite web|url=https://documents.cap.org/protocols/Breast.Invasive_4.7.0.1.REL_CAPCP.pdf|title=Protocol for the Examination of Resection Specimens from Patients with Invasive Carcinoma of the Breast Version: 4.7.0.1 - Table 1. Score Categories According to Field Diameter and Mitotic Count|website=College of American Pathologists}} Protocol Posting Date: September 2022</ref>
*'''1 point''': ≤7 mitoses per 10 HPFs
*'''2 points''': 8 to 14 mitoses per 10 HPFs
*'''3 points''': ≥15 mitoses per 10 HPFs
If you have a significant different HPF area or you are not sure, count 10 HPFs and calculate the number of mitoses per mm2 ({{further|Evaluation#Counts per mm2}}):
*'''1 point''': ≤3 mitoses per mm2
*'''2 points''': 4 to 7 mitoses per mm2
*'''3 points''': ≥7 mitoses per mm2
A table of counts for various HPF sizes is available in notes below.<ref group="note">
{| class="wikitable"
|+ Table 1. Score categories according to field diameter and mitotic count
! rowspan="2" | Field diameter (mm)
! rowspan="2" | Area (mm²)
! colspan="3" | Number of mitoses per 10 fields corresponding to:
|-
! Score 1
! Score 2
! Score 3
|-
| 0.40 || 0.125 || ≤4 || 5 to 9 || ≥10
|-
| 0.41 || 0.132 || ≤4 || 5 to 9 || ≥10
|-
| 0.42 || 0.139 || ≤5 || 6 to 10 || ≥11
|-
| 0.43 || 0.145 || ≤5 || 6 to 10 || ≥11
|-
| 0.44 || 0.152 || ≤5 || 6 to 11 || ≥12
|-
| 0.45 || 0.159 || ≤5 || 6 to 11 || ≥12
|-
| 0.46 || 0.166 || ≤6 || 7 to 12 || ≥13
|-
| 0.47 || 0.173 || ≤6 || 7 to 12 || ≥13
|-
| 0.48 || 0.181 || ≤6 || 7 to 13 || ≥14
|-
| 0.49 || 0.189 || ≤6 || 7 to 13 || ≥14
|-
| 0.50 || 0.196 || ≤7 || 8 to 14 || ≥15
|-
| 0.51 || 0.204 || ≤7 || 8 to 14 || ≥15
|-
| 0.52 || 0.212 || ≤7 || 8 to 15 || ≥16
|-
| 0.53 || 0.221 || ≤8 || 9 to 16 || ≥17
|-
| 0.54 || 0.229 || ≤8 || 9 to 16 || ≥17
|-
| 0.55 || 0.238 || ≤8 || 9 to 17 || ≥18
|-
| 0.56 || 0.246 || ≤8 || 9 to 17 || ≥18
|-
| 0.57 || 0.255 || ≤9 || 10 to 18 || ≥19
|-
| 0.58 || 0.264 || ≤9 || 10 to 19 || ≥20
|-
| 0.59 || 0.273 || ≤9 || 10 to 19 || ≥20
|-
| 0.60 || 0.283 || ≤10 || 11 to 20 || ≥21
|-
| 0.61 || 0.292 || ≤10 || 11 to 21 || ≥22
|-
| 0.62 || 0.302 || ≤11 || 12 to 22 || ≥23
|-
| 0.63 || 0.312 || ≤11 || 12 to 22 || ≥23
|-
| 0.64 || 0.322 || ≤11 || 12 to 23 || ≥24
|-
| 0.65 || 0.332 || ≤12 || 13 to 24 || ≥25
|-
| 0.66 || 0.342 || ≤12 || 13 to 24 || ≥25
|-
| 0.67 || 0.353 || ≤12 || 13 to 25 || ≥26
|-
| 0.68 || 0.363 || ≤13 || 14 to 26 || ≥27
|-
| 0.69 || 0.374 || ≤13 || 14 to 27 || ≥28
|}

From: College of American Pathologists. [https://www.cap.org/wp-content/uploads/2026/06/Breast.Invasive.Bx_1.3.0.0.REL_CAPCP.pdf] (Page 8), in turn citing: Pathology Reporting of Breast Disease, by National Health Service Cancer Screening Programme and The Royal College of Pathologists</ref><noinclude>
{{Bottom}}
</noinclude>

Template:Mitotic count in invasive breast cancer

2026-07-14T16:25:34Z

Mikael Häggström: title

Template:Mitotic count in invasive breast cancer

2026-07-14T16:24:56Z

Mikael Häggström: Updated

Template:Mitotic count in invasive breast cancer

2026-07-14T16:24:23Z

Mikael Häggström: Updated

Michael Hegstrom, M.D.

2026-06-21T19:47:10Z

Mikael Häggström: /* Further information */ updated

[[File:Mikael Häggström at pathology in 2019 (crop).jpg|thumb|260px]]
Also known as Mikael Haeggstroem

= Biography =
Michael Hegstrom is a Swedish-American pathologist and clinical informatician. He is the creator of the WikiJournal of Medicine, as well as the open-access medical resources Patholines and Radlines.

He was born in Gothenburg, Sweden. During a six-month backpacking journey in 2005—traveling on the Trans-Siberian Railway to China and crossing the Himalayas from Tibet to Nepal—he decided to pursue a career in medicine.

Dr. Hegstrom graduated with a Doctor of Medicine degree from Uppsala University, Faculty of Medicine, in 2013. He completed two years of rotational internship and subsequently worked as a physician in obstetrics and gynecology, radiology, and pathology in Sweden. He completed residency training in anatomic and clinical pathology at Danbury Hospital in Connecticut in 2024.

He is currently a Clinical Informatics Fellow at the University of Minnesota, with continued clinical involvement in anatomic pathology. He became a naturalized citizen of the United States in 2026.

Dr. Hegstrom has contributed to Wikipedia since 2006 and has an extensive portfolio of medical illustrations. He founded the [[wikiversity:WikiJournal_of_Medicine|WikiJournal of Medicine]], a Wikipedia-integrated, peer-reviewed, open-access academic journal, serving as Editor-in-Chief from 2014 to 2024. He is also the creator of [https://patholines.org/Main_Page Patholines] and [https://radlines.org/Main Radlines], which provide openly accessible practice-oriented guidelines in pathology and radiology.

= Further information =

* [https://drive.google.com/file/d/1cydov9doCveCB5ssW7FvLrIaKLSLQWT9/view?usp=sharing Curriculum Vitae] - This linked document contains detailed information regarding education, training, licensure, publications, presentations, professional memberships, and technical expertise.
* [https://www.linkedin.com/in/drhaggstrom/ Linkedin page]
* [[wikipedia:User:Mikael_Häggström|Wikipedia presentation]]

Hegstrom

2026-06-21T19:45:49Z

Mikael Häggström: Redirected page to Michael Hegstrom, M.D.

#REDIRECT [[Michael Hegstrom, M.D.]]

Template:Immunohistochemistry evaluation of invasive breast cancer

2026-04-28T17:15:25Z

Mikael Häggström: Colors

===Immunohistochemistry===
Look at '''local protocols''' for what immunohistochemistry tests and other biomarker test need to be tested for each case of invasive breast cancer, or what needs to be retested for subsequent excisions at the primary site or at metastatic sites.<ref group=note>If the previous biopsy was negative for ER and PR receptors, and the patient has undergone '''neoadjuvant chemotherapy''' before excision, then generally retest ER/PR on the excision. Retesting ER/PR on any excision with previously negative ER/PR on biopsy on a patient having received neoadjuvant therapy has no scientific support nor opposition. - {{cite web|url=https://www.uptodate.com/contents/general-principles-of-neoadjuvant-management-of-breast-cancer#H4238568521|title=General principles of neoadjuvant management of breast cancer|author=William M Sikov, MD, FACP, FNCBCJudy C Boughey, MD, FACSZahraa Al-Hilli, MD, FACS, FRCSI|website=UpToDate}}

In breast cancer '''metastases''', generally retest estrogen and progesterone receptors, and HER2 in the following circumstances:
*If the status of the primary tumor is unknown or negative for ER/PR and/or HER2
*If the primary tumor is heterogeneous for ER/PR expression
*If the metastatic progression is unusual for the tumor characteristics
*If the relapse is unexpectedly early or late
*If unusual metastasis location
*If the initial test was performed more than 10 years ago
*If the testing turnaround time are relatively short (to reduce potential delays in patient management by retesting)
- {{cite journal| author=Penault-Llorca F, Coudry RA, Hanna WM, Osamura RY, Rüschoff J, Viale G| title=Experts' opinion: Recommendations for retesting breast cancer metastases for HER2 and hormone receptor status. | journal=Breast | year= 2013 | volume= 22 | issue= 2 | pages= 200-202 | pmid=23352656 | doi=10.1016/j.breast.2012.12.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23352656 }}</ref>
====Ki-67 index====
[[File:Positive immunohistochemistry of KI-67 in invasive breast cancer.jpg|thumb|Ki-67 in an invasive breast cancer: cancer nuclei are stained (brown). There is tumor cell positivity in 70% of the cells (''Ki-67 labelling index'' = 70%).]]
[[File:Counting Ki-67 index in immunohistochemistry.jpg|thumb|To count as Ki-67 positive, a nucleus should:
 - Not be located in stroma.
 - Be at least half within the field of view.
 - Be large enough. Otherwise, even weakly positive nuclei count as positive.]]
Ki-67 index is mainly relevant in those with stage T1-T2, N0-N1, to determine if chemotherapy is needed (if Ki67 is >30% rather than <5%).<ref name="DowsettNielsen2011">{{cite journal|last1=Dowsett|first1=M.|last2=Nielsen|first2=T. O.|last3=A'Hern|first3=R.|last4=Bartlett|first4=J.|last5=Coombes|first5=R. C.|last6=Cuzick|first6=J.|last7=Ellis|first7=M.|last8=Henry|first8=N. L.|last9=Hugh|first9=J. C.|last10=Lively|first10=T.|last11=McShane|first11=L.|last12=Paik|first12=S.|last13=Penault-Llorca|first13=F.|last14=Prudkin|first14=L.|last15=Regan|first15=M.|last16=Salter|first16=J.|last17=Sotiriou|first17=C.|last18=Smith|first18=I. E.|last19=Viale|first19=G.|last20=Zujewski|first20=J. A.|last21=Hayes|first21=D. F.|title=Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group|journal=JNCI Journal of the National Cancer Institute|volume=103|issue=22|year=2011|pages=1656–1664|issn=0027-8874|doi=10.1093/jnci/djr393}}</ref>

Ki-67 index is most feasibly quantified by a '''hot spot''' method,<ref group=note>Besides from a hot spot method of Ki67 counting, there is also a ''IKWG global average'' method which is more comprehensive. However, the inter-observer difference between the hot spot method and the 'IKWG global average'' is not statistically significant, and has not shown any significant difference in clinical outcome (theoretically, the area of highest Ki-67 proliferative index is probably most likely to correlate with malignant transformation and risk of metastasis, making the hot spot both more straightforward and clinically relevant than a global average). - '''Reference and instructions for the ''IKWG global average'' method:''' {{cite journal|last1=Dowsett|first1=M.|last2=Nielsen|first2=T. O.|last3=A'Hern|first3=R.|last4=Bartlett|first4=J.|last5=Coombes|first5=R. C.|last6=Cuzick|first6=J.|last7=Ellis|first7=M.|last8=Henry|first8=N. L.|last9=Hugh|first9=J. C.|last10=Lively|first10=T.|last11=McShane|first11=L.|last12=Paik|first12=S.|last13=Penault-Llorca|first13=F.|last14=Prudkin|first14=L.|last15=Regan|first15=M.|last16=Salter|first16=J.|last17=Sotiriou|first17=C.|last18=Smith|first18=I. E.|last19=Viale|first19=G.|last20=Zujewski|first20=J. A.|last21=Hayes|first21=D. F.|title=Assessment of Ki67 in Breast Cancer: Recommendations from the International Ki67 in Breast Cancer Working Group|journal=JNCI Journal of the National Cancer Institute|volume=103|issue=22|year=2011|pages=1656–1664|issn=0027-8874|doi=10.1093/jnci/djr393}}</ref> Hot spots are areas in which Ki-67 staining is particularly higher relative to the adjacent tumor areas.<ref name="ColemanJang2017">{{cite journal|last1=Coleman|first1=William B.|last2=Jang|first2=Min Hye|last3=Kim|first3=Hyun Jung|last4=Chung|first4=Yul Ri|last5=Lee|first5=Yangkyu|last6=Park|first6=So Yeon|title=A comparison of Ki-67 counting methods in luminal Breast Cancer: The Average Method vs. the Hot Spot Method|journal=PLOS ONE|volume=12|issue=2|year=2017|pages=e0172031|issn=1932-6203|doi=10.1371/journal.pone.0172031}}</ref> Usually, the invasive edge of a tumor is a hot spot.<ref name="ColemanJang2017"/> When a tumor had several hot spots, the “hottest” spot is selected.<ref name="ColemanJang2017"/> Aim to count at least 500 cells in each case, but this is not always possible in cases with low tumor cell density and small tumor size.<ref name="ColemanJang2017"/> Also aim to include at least three high-power (×40 objective) fields. Count a nucleus as “positive” if there is any definite brown staining in the nucleus of an invasive breast cancer cell, above the surrounding background in the cytoplasm and extracellular matrix.<ref>{{cite web|url=https://www.ki67inbreastcancerwg.org/wp-content/uploads/2018/12/Ki67-Phase-3b-WS-protocol-v1.pdf|title=Ki67-QC international working group: whole section scoring protocol (global method)|date=2018-11-29|website=International Ki67 in Breast Cancer Working Group}}</ref> If a comparisons must be made between core biopsies and sections from an excision, evaluation of the latter should be across the whole tumor.<ref name="DowsettNielsen2011"/> Only nuclear staining counts. Staining intensity of a positive nucleus is not relevant.<ref name="DowsettNielsen2011"/>

====HER2 ====
HER2 can initially be evaluated by immunohistochemistry (IHC) or fluorescence ''in situ'' hybridization (FISH). If IHC is performed first and is borderline/equivocal, then FISH is recommended.<ref>{{cite web|url=https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html|title=Breast Cancer HER2 Status|website=American Cancer Society}} Last Revised: August 25, 2022</ref> If FISH is performed first and indicates that further workup is required, then IHC may be the performed as per established algorithms.<ref name=HER2fish group=note/>

======HER2 immunohistochemistry======
Look at different parts of the tumor, and evaluate the area(s) with most staining. When negative of faint staining is seen, evaluate at high magnification.
{|class="wikitable" align="center"
|+Immunohistochemistry
|-
! Score<ref name=Breastcancer>{{cite web|url=https://www.breastcancer.org/symptoms/testing/types/ihc|website=Breastcancer.org|access-date=2019-10-04|title=IHC Tests (ImmunoHistoChemistry)}} Last modified on October 23, 2015</ref><ref name="IqbalIqbal2014">{{cite journal | vauthors = Iqbal N, Iqbal N | title = Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications | journal = Molecular Biology International | volume = 2014 | pages = 852748 | year = 2014 | pmid = 25276427 | pmc = 4170925 | doi = 10.1155/2014/852748 | doi-access = free }}</ref> !! Pattern<ref name=2018ASCO-CAP>2018 ASCO/CAP guidelines: - {{cite web|url=https://documents.cap.org/documents/algorithim-evaluation-her2.pdf|title=Figure 1. Algorithm for evaluation of human epidermal growth factor receptor 2 (HER2) protein expression by immunohistochemistry (IHC) assay of the invasive component of a breast cancer specimen.|website=College of American Pathologists: Homepage|accessdate=2022-09-12}} - {{cite journal| author=Ahn S, Woo JW, Lee K, Park SY| title=HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation. | journal=J Pathol Transl Med | year= 2020 | volume= 54 | issue= 1 | pages= 34-44 | pmid=31693827 | doi=10.4132/jptm.2019.11.03 | pmc=6986968 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31693827 }} </ref> !! Status<ref name=Breastcancer/><ref name="IqbalIqbal2014"/>
|-
| 0
| Either:<ref name=2018ASCO-CAP/>
*No staining observed.
*Incomplete membrane staining that is faint or barely perceptible and within ≤10% of the invasive tumor cells
|rowspan="2" | HER2 negative (not present)
|-
| 1+ || Incomplete membrane staining that is faint or barely perceptible and within >10% of the invasive tumor cells.<ref name=2018ASCO-CAP/>
|-
| 2+ || Weak to moderate complete membrane staining observed in >10% of tumor cells.<ref name=2018ASCO-CAP/>
| Borderline/Equivocal
|-
| 3+ || Circumferential membrane staining that is complete, intense, and in >10% of tumor cells.<ref name=2018ASCO-CAP/> || HER2 positive
|}
Micrographs showing each score:<ref>{{cite journal| author=Nitta H, Kelly BD, Padilla M, Wick N, Brunhoeber P, Bai I | display-authors=etal| title=A gene-protein assay for human epidermal growth factor receptor 2 (HER2): brightfield tricolor visualization of HER2 protein, the HER2 gene, and chromosome 17 centromere (CEN17) in formalin-fixed, paraffin-embedded breast cancer tissue sections. | journal=Diagn Pathol | year= 2012 | volume= 7 | issue= | pages= 60 | pmid=22647525 | doi=10.1186/1746-1596-7-60 | pmc=3487810 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22647525 }} - "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)"</ref>
<gallery mode=packed heights=140>
File:HER2 immunohistochemistry with 0 pattern.png|0
File:HER2 immunohistochemistry with 1 plus pattern.png|1+
File:HER2 immunohistochemistry with 2 plus pattern.png|2+
File:HER2 immunohistochemistry with 3 plus pattern.png|3+
</gallery>

======HER2 FISH======
HER2 FISH usually uses ''chromosome enumeration probe 17'' (CEP17) to count the amount of chromosomes. Hence, the HER2/CEP17 ratio reflects any amplification of HER2 as compared to the number of chromosomes.

To '''prepare''' a slide for HER2 testing, you may need to choose a paraffin-embedded and mark the resulting slide so that you or whoever interprets it knows where to look for the target tumor cells. When there are multiple blocks of the same case, choose the the one with most tumor. {{Moderate-begin}}If a block has undergone sectioning for immunohistochemistry (such as ER, PR and/or Ki67) make sure that you have a new H&E slide at a level next to the one to be used for FISH, so that they will correlate better.{{Moderate-end}} In cases of both invasive and ''in situ'' carcinoma in the same specimen, mark all invasive carcinoma (also for crushed tissue or with other artifacts) but not the ''in situ'' carcinoma. Also mark a small area of normal tissue as an internal control. If possible, it should be a bit away from the tumor, even if only consisting of fatty tissue.

To '''interpret''' a HER2 FISH study, first perform a quality control check of the slide as per manufacturer and/or local protocol (generally including checking for proper signals from a control specimen). In cases of both invasive and ''in situ'' carcinoma in the same specimen, only score the invasive cells. The signals of 20 cells are usually counted. Also focus up and down on each nucleus to find all signals therein.
<gallery mode=packed>
File:Tumor cells and normal tissue of the breast in FISH.jpg|Identify the relevant tumor cells. It can be made easier by comparing to an H&E stained slide.
File:HER2 FISH with 2 HER2 signals and 3 CEP17 signals.png|This cell displays 2 signals of HER2 (red) and 3 signals of CEP17 (green)
File:Counting one or two signals on HER2 FISH.png|thumb|Two signals that are closer to each other than the signal diameter count as one.
File:HER2 FISH with debris.png|One of these signals is too faint, and is presumably debris.
File:HER2 FISH with only one signal type.jpg|Cells with only one type of signal are excluded from the count.
File:HER2 FISH with overlapping cells.png|Overlapping cells are also excluded from the count.
File:HER2 FISH with a yellow signal.png|thumb|A yellow signal cunts as one red and one green (which are overlapping)
</gallery>
If a cytotechnologist has already performed a count, you do not have to recount, but make sure the count is reasonable regarding what you see. In any case, also look around for any obvious tumor heterogeneity in HER2 signals.
<gallery mode=packed heights=180>
File:Counting HER2 versus CEP17 probes in FISH of HER2 amplified cell.png
File:HER2 FISH algorithm.svg|Algorithm for the evaluation of HER2 on fluorescence ''in situ'' hybridization (FISH).<ref name=HER2fish>Diagram and table by Mikael Häggström, MD. Adapted from: {{cite journal| author=Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS | display-authors=etal| title=Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. | journal=J Clin Oncol | year= 2018 | volume= 36 | issue= 20 | pages= 2105-2122 | pmid=29846122 | doi=10.1200/JCO.2018.77.8738 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29846122 }}</ref> See source article in cases where additional workup is indicated.<ref name=HER2fish group=note/>
</gallery>
If the HER2/CEP17 ratio is borderline (1.8-2.2), count an additional 20 nuclei and recalculate a ratio for the total of 40 nuclei.
{| class="wikitable" align=center
|+ Classification of HER2 by fluorescence ''in situ'' hybridization (FISH)<ref name=HER2fish group=note/>
|-
|rowspan=2 colspan=2|
! colspan="2" | HER2/CEP17 ratio
|-
! ≥2.0
! <2.0
|-
! rowspan="2" | Average HER2 copy number per cell
! ≥4.0
| style="background:Pink" | HER2 positive
| style="background:LemonChiffon" | Additional work-up required<ref name=HER2fish group=note>If additional work-up is required by FISH study, see source article for detailed algorithms: {{cite journal| author=Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JMS | display-authors=etal| title=Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. | journal=J Clin Oncol | year= 2018 | volume= 36 | issue= 20 | pages= 2105-2122 | pmid=29846122 | doi=10.1200/JCO.2018.77.8738 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29846122 }}</ref>
|-
! <4.0
| style="background:LemonChiffon" | Additional work-up required<ref name=HER2fish group=note/>
| style="background:LightGreen" | HER2 negative
|}
If the initial HER2 result is negative for a needle biopsy of a primary breast cancer, a new HER2 test may be performed on the subsequent breast excision.<ref name=HER2fish group=note/>

<noinclude>
{{Bottom}}
</noinclude>

Invasive ductal carcinoma

2026-04-08T22:26:00Z

Mikael Häggström: /* Tubule formation */ 2

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
{{Comprehensiveness}}</noinclude>
==Gross examination==
[[File:Breast cancer gross appearance.jpg|thumb|Gross appearance of invasive ductal carcinoma.]]
As per:
*[[Breast biopsy or excision]]
or mastectomy.

==Microscopic evaluation==

===Characteristics===
Low power:<ref name=PathologyOutlines>{{cite web|url=http://www.pathologyoutlines.com/topic/breastmalignantductalNOS.html|title=Breast - Invasive breast carcinoma of no special type and variants - NST (ductal)|website=Pathology Outlines|author=Monika Roychowdhury}} Topic Completed: 1 September 2009. Minor changes: 17 September 2020</ref>
*Sheets, nests, cords or individual cells, but generally ratherplump tumor nests (rather than the single-file linear pattern of [[invasive lobular carcinoma]])
*Prominent tubular formations in well differentiated tumors, but absent when poorly differentiated
*The stroma is usually desmoplastic
High power typically shows tumor cells that are more pleomorphic than in lobular carcinoma.<ref name=PathologyOutlines/>
<gallery mode=packed heights=180>
File:Histopathology of invasive ductal carcinoma, intermediate magnification.jpg|IDC, intermediate magnification. The presence in adipose tissue strongly favors invasiveness.
File:Histopathology of adenocarcinoma.png|High magnification shows non-specific adenocarcinoma features.
File:Invasive ductal carcinoma, with occasional entrapped normal ducts.jpg|IDC, with occasional entrapped normal ducts (arrow).
</gallery>

===Differential diagnosis===
====Invasive versus in situ====
In invasive ductal carcinoma, malignant cells have penetrated the basement membrane, in contrast to [[ductal carcinoma in situ]]. In uncertain cases, use immunohistochemistry stain for '''calponin''' (has the highest sensitivity) and '''p63''' (has the highest specificity).

<gallery mode=packed heights=180px>
File:Invasive ductal carcinoma with tubular features - combined.jpg|'''Invasive ductal carcinoma with tubular features''' can look like benign tubules, but the myoepithelial marker{{Myoepithelial marker note}} calponin and p63 shows no surrounding myoepithelial cells.
File:Immunohistochemistry with calponin in ductal carcinoma in situ.jpg|Immunohistochemistry for calponin in '''[[ductal carcinoma in situ]]''', highlighting myoepithelial cells around all tumor cells.
File:Histopathology of fibroadenoma with small cell clusters.jpg|'''[[Fibroadenoma]]''' may have small cell clusters, but lacks the cellular atypia of invasive ductal carcinoma.
</gallery>
In case of both invasive and in situ carcinoma, separately describe the in situ component. Report as "'''extensive intraductal component'''" (EIC) if DCIS is occupying 25% or more of the area encompassed by the invasive tumor and DCIS present in grossly normal adjacent breast tissue.<ref name=Hurd1997>{{cite journal| author=Hurd TC, Sneige N, Allen PK, Strom EA, McNeese MD, Babiera GV | display-authors=etal| title=Impact of extensive intraductal component on recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy. | journal=Ann Surg Oncol | year= 1997 | volume= 4 | issue= 2 | pages= 119-24 | pmid=9084847 | doi=10.1007/BF02303793 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9084847 }} </ref>

====Ductal versus lobular====
*'''[[Invasive lobular carcinoma]]''' typically has single files of tumor cells rather than duct-forming tumor cells. In uncertain cases, stain for E-cadherin and p120:
<gallery mode=packed heights=180>
File:Classic Invasive Lobular Carcinoma of the Breast (6813147194).jpg|'''[[Invasive lobular carcinoma]], in this case with a targetoid pattern
File:Chromogenic immunohistochemistry for E-cadherin in invasive lobular carcinoma, annotated.jpg|'''E-cadherin''' is '''negative''' in invasive '''lobular''' carcinoma (shown), but has membranous staining in invasive ductal carcinoma
File:Chromogenic immunohistochemistry for p120 in invasive lobular carcinoma.jpg|'''p120''' has '''cytoplasmic''' staining in invasive lobular carcinoma (shown), but has membranous staining in [[invasive ductal carcinoma]]
</gallery>
{{Breast cancer staging}}
{{Evaluation of tumors}}

=== Grading ===
The '''Nottingham system'''<ref>{{cite journal |last1= Elston |first1= CW |last2= Ellis |first2= IO |title= Pathologic prognostic factors in breast cancer. I. The value of histological grades in breast cancer. Experience from a large study with long-term follow-up |journal= Histopathology |year= 1991 |volume= 19 |issue= 5 |pages= 403–10 |pmid= 1757079 |doi=10.1111/j.1365-2559.1991.tb00229.x}} {{cite journal |title= Republished |year= 2002 |doi= 10.1046/j.1365-2559.2002.14892.x | volume=41 |journal=Histopathology |pages=154–161}}</ref> is recommended for breast cancer grading.<ref>{{cite web|title=What is the Nottingham combined histologic grade (modified Scarff-Bloom-Richardson grade) system for breast tumors?|url=https://www.medscape.com/answers/1668113-181367/what-is-the-nottingham-combined-histologic-grade-modified-scarff-bloom-richardson-grade-system-for-breast-tumors|author=Oudai Hassan|website=Medscape}} Updated: Mar 20, 2019</ref> The Nottingham system is also called the Bloom–Richardson–Elston system ('''BRE''')<ref>{{cite journal | last1= Al-Kuraya| first1= Khawla| last2=Schraml | first2=Peter |display-authors=et al | title= Prognostic relevance of gene amplifications and coamplifications in breast cancer | journal=Cancer Research| volume=64 | issue=23 | year=2004| pages= 8534–8540}}</ref>, or the Elston-Ellis modification<ref>Elston CW, Ellis IO. Pathologic prognostic factors in breast cancer. I. The value of histological grades in breast cancer. Experience from a large study with long-term follow-up. Histopathology 1991, 19:403-410.</ref> of the Scarff-Bloom-Richardson grading system.<ref name="BloomRichardson1957">{{Cite journal | last1 = Bloom | first1 = H.J. | last2 = Richardson | first2 = W.W. | title = Histological grading and prognosis in breast cancer; A study of 1409 cases of which 359 have been followed for 15 years | journal = British Journal of Cancer | volume = 11 | issue = 3 | pages = 359–77 | year = 1957 | pmid = 13499785 | pmc = 2073885 | doi=10.1038/bjc.1957.43}}</ref><ref name="Genestie1998">{{Cite journal | last1 = Genestie | first1 = C. | last2 = Zafrani | first2 = B. | last3 = Asselain | first3 = B. | last4 = Fourquet | first4 = A. | last5 = Rozan | first5 = S. | last6 = Validire | first6 = P. | last7 = Vincent-Salomon | first7 = A. | last8 = Sastre-Garau | first8 = X. | title = Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in a series of 825 cases of breast cancer: Major importance of the mitotic count as a component of both grading systems | journal = Anticancer Research | volume = 18 | issue = 1B | pages = 571–6 | year = 1998 | pmid = 9568179}}</ref> It grades breast carcinomas by adding up scores for tubule formation, nuclear pleomorphism, and mitotic count, each of which is given 1 to 3 points. The scores for each of these three criteria are then added together to give an overall final score and corresponding grade as follows.

==== Tubule formation ====
[[File:Nottingham tubular score.jpg|thumb|500px|Tubule formation score in the Nottingham system:   1. A cribriform pattern also counts as tubules   2. Between 10 and 75% of tumor is tubule forming.   3. Almost all clear (white) spaces here are entrapped fat cells which do not count as tubules.{{MH}}]]
The overall appearance of the tumor is considered.<ref name="PujaniSharma2014">{{cite journal|last1=Pujani|first1=Mukta|last2=Sharma|first2=KiranLata|last3=Srivastava|first3=AN|last4=Singh|first4=US|last5=Bansal|first5=Cherry|title=Grading systems in the cytological diagnosis of breast cancer: A review|journal=Journal of Cancer Research and Therapeutics|volume=10|issue=4|year=2014|pages=839|issn=0973-1482|doi=10.4103/0973-1482.140979}}</ref>
* 1 point: tubular formation in more than 75% of the tumor
* 2 points: tubular formation in 10 to 75% of the tumor ("moderate")
* 3 points: tubular formation in less than 10% of the tumor ("little or none")

==== Nuclear pleomorphism ====
[[File:Histopathology of invasive ductal carcinoma with high nuclear pleomorphism (3 points).jpg|thumb|190px|IDC with high nuclear pleomorphism (3 points).]]
Such as nuclei being larger, darker, or irregular/pleomorphic.
Note: The cancer areas having cells with the greatest atypia should be evaluated.
* '''1 point''': Nuclei are small or mildly increased in size compared to normal breast epithelial cells. They have uniform nuclear chromatin and only mild pleomorphism.
* '''2 points''': nuclei with moderate variation in size and shape. Cells are larger than normal (usually 1.5 - 2 times larger)<ref name="pmid34196797">{{cite journal| author=van Dooijeweert C, van Diest PJ, Ellis IO| title=Grading of invasive breast carcinoma: the way forward. | journal=Virchows Arch | year= 2022 | volume= 480 | issue= 1 | pages= 33-43 | pmid=34196797 | doi=10.1007/s00428-021-03141-2 | pmc=8983621 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34196797 }} </ref>, display open vesicular nuclei, have visible nucleoli.
* '''3 points''': nuclei with marked variation in size and shape. Cells display vesicular nuclei, often prominent nucleoli. Often very large and bizarre cells.

==== Mitotic count ====
{{Mitotic count in invasive breast cancer}}
==== Overall grade ====
The scores for each of these three criteria are added together to give a final overall score and a corresponding grade as follows:
* 3-5 '''Grade 1''' tumor ('''well-differentiated'''). Best prognosis.
* 6-7 '''Grade 2''' tumor ('''moderately differentiated'''). Medium prognosis.
* 8-9 '''Grade 3''' tumor ('''poorly differentiated'''). Worst prognosis.
[[File:Histopathology of a calcification in an invasive ductal carcinoma.png|thumb|200px|A conventional calcification in invasive ductal carcinoma.]]
{{Microcalcifications in breast cancer}}
{{Immunohistochemistry evaluation of invasive breast cancer}}
====Estrogen and progesterone receptors====
{{Estrogen and progesterone receptors in breast cancers}}
===Neoadjuvant cases===
[[File:Histopathology of invasive ductal carcinoma with partial response to chemotherapy.jpg|thumb|Invasive ductal carcinoma with partial response to chemotherapy, seen as fibroelastic areas between tumor nests.{{MH}}]]
{{Microscopic evaluation of neoadjuvant invasive cancer}}
{{Evaluation of tumors}}
{{Reporting of invasive breast cancer}}
<noinclude>{{Bottom}}</noinclude>

Invasive ductal carcinoma

2026-04-08T22:09:51Z

Mikael Häggström: /* Tubule formation */ Higher res

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
{{Comprehensiveness}}</noinclude>
==Gross examination==
[[File:Breast cancer gross appearance.jpg|thumb|Gross appearance of invasive ductal carcinoma.]]
As per:
*[[Breast biopsy or excision]]
or mastectomy.

==Microscopic evaluation==

===Characteristics===
Low power:<ref name=PathologyOutlines>{{cite web|url=http://www.pathologyoutlines.com/topic/breastmalignantductalNOS.html|title=Breast - Invasive breast carcinoma of no special type and variants - NST (ductal)|website=Pathology Outlines|author=Monika Roychowdhury}} Topic Completed: 1 September 2009. Minor changes: 17 September 2020</ref>
*Sheets, nests, cords or individual cells, but generally ratherplump tumor nests (rather than the single-file linear pattern of [[invasive lobular carcinoma]])
*Prominent tubular formations in well differentiated tumors, but absent when poorly differentiated
*The stroma is usually desmoplastic
High power typically shows tumor cells that are more pleomorphic than in lobular carcinoma.<ref name=PathologyOutlines/>
<gallery mode=packed heights=180>
File:Histopathology of invasive ductal carcinoma, intermediate magnification.jpg|IDC, intermediate magnification. The presence in adipose tissue strongly favors invasiveness.
File:Histopathology of adenocarcinoma.png|High magnification shows non-specific adenocarcinoma features.
File:Invasive ductal carcinoma, with occasional entrapped normal ducts.jpg|IDC, with occasional entrapped normal ducts (arrow).
</gallery>

===Differential diagnosis===
====Invasive versus in situ====
In invasive ductal carcinoma, malignant cells have penetrated the basement membrane, in contrast to [[ductal carcinoma in situ]]. In uncertain cases, use immunohistochemistry stain for '''calponin''' (has the highest sensitivity) and '''p63''' (has the highest specificity).

<gallery mode=packed heights=180px>
File:Invasive ductal carcinoma with tubular features - combined.jpg|'''Invasive ductal carcinoma with tubular features''' can look like benign tubules, but the myoepithelial marker{{Myoepithelial marker note}} calponin and p63 shows no surrounding myoepithelial cells.
File:Immunohistochemistry with calponin in ductal carcinoma in situ.jpg|Immunohistochemistry for calponin in '''[[ductal carcinoma in situ]]''', highlighting myoepithelial cells around all tumor cells.
File:Histopathology of fibroadenoma with small cell clusters.jpg|'''[[Fibroadenoma]]''' may have small cell clusters, but lacks the cellular atypia of invasive ductal carcinoma.
</gallery>
In case of both invasive and in situ carcinoma, separately describe the in situ component. Report as "'''extensive intraductal component'''" (EIC) if DCIS is occupying 25% or more of the area encompassed by the invasive tumor and DCIS present in grossly normal adjacent breast tissue.<ref name=Hurd1997>{{cite journal| author=Hurd TC, Sneige N, Allen PK, Strom EA, McNeese MD, Babiera GV | display-authors=etal| title=Impact of extensive intraductal component on recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy. | journal=Ann Surg Oncol | year= 1997 | volume= 4 | issue= 2 | pages= 119-24 | pmid=9084847 | doi=10.1007/BF02303793 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9084847 }} </ref>

====Ductal versus lobular====
*'''[[Invasive lobular carcinoma]]''' typically has single files of tumor cells rather than duct-forming tumor cells. In uncertain cases, stain for E-cadherin and p120:
<gallery mode=packed heights=180>
File:Classic Invasive Lobular Carcinoma of the Breast (6813147194).jpg|'''[[Invasive lobular carcinoma]], in this case with a targetoid pattern
File:Chromogenic immunohistochemistry for E-cadherin in invasive lobular carcinoma, annotated.jpg|'''E-cadherin''' is '''negative''' in invasive '''lobular''' carcinoma (shown), but has membranous staining in invasive ductal carcinoma
File:Chromogenic immunohistochemistry for p120 in invasive lobular carcinoma.jpg|'''p120''' has '''cytoplasmic''' staining in invasive lobular carcinoma (shown), but has membranous staining in [[invasive ductal carcinoma]]
</gallery>
{{Breast cancer staging}}
{{Evaluation of tumors}}

=== Grading ===
The '''Nottingham system'''<ref>{{cite journal |last1= Elston |first1= CW |last2= Ellis |first2= IO |title= Pathologic prognostic factors in breast cancer. I. The value of histological grades in breast cancer. Experience from a large study with long-term follow-up |journal= Histopathology |year= 1991 |volume= 19 |issue= 5 |pages= 403–10 |pmid= 1757079 |doi=10.1111/j.1365-2559.1991.tb00229.x}} {{cite journal |title= Republished |year= 2002 |doi= 10.1046/j.1365-2559.2002.14892.x | volume=41 |journal=Histopathology |pages=154–161}}</ref> is recommended for breast cancer grading.<ref>{{cite web|title=What is the Nottingham combined histologic grade (modified Scarff-Bloom-Richardson grade) system for breast tumors?|url=https://www.medscape.com/answers/1668113-181367/what-is-the-nottingham-combined-histologic-grade-modified-scarff-bloom-richardson-grade-system-for-breast-tumors|author=Oudai Hassan|website=Medscape}} Updated: Mar 20, 2019</ref> The Nottingham system is also called the Bloom–Richardson–Elston system ('''BRE''')<ref>{{cite journal | last1= Al-Kuraya| first1= Khawla| last2=Schraml | first2=Peter |display-authors=et al | title= Prognostic relevance of gene amplifications and coamplifications in breast cancer | journal=Cancer Research| volume=64 | issue=23 | year=2004| pages= 8534–8540}}</ref>, or the Elston-Ellis modification<ref>Elston CW, Ellis IO. Pathologic prognostic factors in breast cancer. I. The value of histological grades in breast cancer. Experience from a large study with long-term follow-up. Histopathology 1991, 19:403-410.</ref> of the Scarff-Bloom-Richardson grading system.<ref name="BloomRichardson1957">{{Cite journal | last1 = Bloom | first1 = H.J. | last2 = Richardson | first2 = W.W. | title = Histological grading and prognosis in breast cancer; A study of 1409 cases of which 359 have been followed for 15 years | journal = British Journal of Cancer | volume = 11 | issue = 3 | pages = 359–77 | year = 1957 | pmid = 13499785 | pmc = 2073885 | doi=10.1038/bjc.1957.43}}</ref><ref name="Genestie1998">{{Cite journal | last1 = Genestie | first1 = C. | last2 = Zafrani | first2 = B. | last3 = Asselain | first3 = B. | last4 = Fourquet | first4 = A. | last5 = Rozan | first5 = S. | last6 = Validire | first6 = P. | last7 = Vincent-Salomon | first7 = A. | last8 = Sastre-Garau | first8 = X. | title = Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in a series of 825 cases of breast cancer: Major importance of the mitotic count as a component of both grading systems | journal = Anticancer Research | volume = 18 | issue = 1B | pages = 571–6 | year = 1998 | pmid = 9568179}}</ref> It grades breast carcinomas by adding up scores for tubule formation, nuclear pleomorphism, and mitotic count, each of which is given 1 to 3 points. The scores for each of these three criteria are then added together to give an overall final score and corresponding grade as follows.

==== Tubule formation ====
[[File:Nottingham tubular score.jpg|thumb|500px|Tubule formation score in the Nottingham system:   1. A cribriform pattern also counts as tubules   3. Almost all clear (white) spaces here are entrapped fat cells which do not count as tubules.{{MH}}]]
The overall appearance of the tumor is considered.<ref name="PujaniSharma2014">{{cite journal|last1=Pujani|first1=Mukta|last2=Sharma|first2=KiranLata|last3=Srivastava|first3=AN|last4=Singh|first4=US|last5=Bansal|first5=Cherry|title=Grading systems in the cytological diagnosis of breast cancer: A review|journal=Journal of Cancer Research and Therapeutics|volume=10|issue=4|year=2014|pages=839|issn=0973-1482|doi=10.4103/0973-1482.140979}}</ref>
* 1 point: tubular formation in more than 75% of the tumor
* 2 points: tubular formation in 10 to 75% of the tumor ("moderate")
* 3 points: tubular formation in less than 10% of the tumor ("little or none")

==== Nuclear pleomorphism ====
[[File:Histopathology of invasive ductal carcinoma with high nuclear pleomorphism (3 points).jpg|thumb|190px|IDC with high nuclear pleomorphism (3 points).]]
Such as nuclei being larger, darker, or irregular/pleomorphic.
Note: The cancer areas having cells with the greatest atypia should be evaluated.
* '''1 point''': Nuclei are small or mildly increased in size compared to normal breast epithelial cells. They have uniform nuclear chromatin and only mild pleomorphism.
* '''2 points''': nuclei with moderate variation in size and shape. Cells are larger than normal (usually 1.5 - 2 times larger)<ref name="pmid34196797">{{cite journal| author=van Dooijeweert C, van Diest PJ, Ellis IO| title=Grading of invasive breast carcinoma: the way forward. | journal=Virchows Arch | year= 2022 | volume= 480 | issue= 1 | pages= 33-43 | pmid=34196797 | doi=10.1007/s00428-021-03141-2 | pmc=8983621 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34196797 }} </ref>, display open vesicular nuclei, have visible nucleoli.
* '''3 points''': nuclei with marked variation in size and shape. Cells display vesicular nuclei, often prominent nucleoli. Often very large and bizarre cells.

==== Mitotic count ====
{{Mitotic count in invasive breast cancer}}
==== Overall grade ====
The scores for each of these three criteria are added together to give a final overall score and a corresponding grade as follows:
* 3-5 '''Grade 1''' tumor ('''well-differentiated'''). Best prognosis.
* 6-7 '''Grade 2''' tumor ('''moderately differentiated'''). Medium prognosis.
* 8-9 '''Grade 3''' tumor ('''poorly differentiated'''). Worst prognosis.
[[File:Histopathology of a calcification in an invasive ductal carcinoma.png|thumb|200px|A conventional calcification in invasive ductal carcinoma.]]
{{Microcalcifications in breast cancer}}
{{Immunohistochemistry evaluation of invasive breast cancer}}
====Estrogen and progesterone receptors====
{{Estrogen and progesterone receptors in breast cancers}}
===Neoadjuvant cases===
[[File:Histopathology of invasive ductal carcinoma with partial response to chemotherapy.jpg|thumb|Invasive ductal carcinoma with partial response to chemotherapy, seen as fibroelastic areas between tumor nests.{{MH}}]]
{{Microscopic evaluation of neoadjuvant invasive cancer}}
{{Evaluation of tumors}}
{{Reporting of invasive breast cancer}}
<noinclude>{{Bottom}}</noinclude>

Michael Hegstrom, M.D.

2026-03-20T14:54:42Z

Mikael Häggström: size

[[File:Mikael Häggström at pathology in 2019 (crop).jpg|thumb|260px]]
Also known as Mikael Haeggstroem

= Biography =
Michael Hegstrom is a Swedish-American pathologist and clinical informatician. He is the creator of the WikiJournal of Medicine, as well as the open-access medical resources Patholines and Radlines.

He was born in Gothenburg, Sweden. During a six-month backpacking journey in 2005—traveling on the Trans-Siberian Railway to China and crossing the Himalayas from Tibet to Nepal—he decided to pursue a career in medicine.

Dr. Hegstrom graduated with a Doctor of Medicine degree from Uppsala University, Faculty of Medicine, in 2013. He completed two years of rotational internship and subsequently worked as a physician in obstetrics and gynecology, radiology, and pathology in Sweden. He completed residency training in anatomic and clinical pathology at Danbury Hospital in Connecticut in 2024.

He is currently a Clinical Informatics Fellow at the University of Minnesota, with continued clinical involvement in anatomic pathology. He became a naturalized citizen of the United States in 2026.

Dr. Hegstrom has contributed to Wikipedia since 2006 and has an extensive portfolio of medical illustrations. He founded the [[wikiversity:WikiJournal_of_Medicine|WikiJournal of Medicine]], a Wikipedia-integrated, peer-reviewed, open-access academic journal, serving as Editor-in-Chief from 2014 to 2024. He is also the creator of [https://patholines.org/Main_Page Patholines] and [https://radlines.org/Main Radlines], which provide openly accessible practice-oriented guidelines in pathology and radiology.

= Further information =

* [https://drive.google.com/file/d/1BRO2jBnpl8Kou18gxphMmXuEoGQGG7ja/view?usp=sharing Curriculum Vitae] - This linked document contains detailed information regarding education, training, licensure, publications, presentations, professional memberships, and technical expertise.
* [https://www.linkedin.com/in/drhaggstrom/ Linkedin page]
* [[wikipedia:User:Mikael_Häggström|Wikipedia presentation]]

Michael Hegstrom, M.D.

2026-03-06T21:13:49Z

Mikael Häggström: simplified

[[File:Mikael Häggström at pathology in 2019 (crop).jpg|thumb]]
Also known as Mikael Haeggstroem

= Biography =
Michael Hegstrom is a Swedish-American pathologist and clinical informatician. He is the creator of the WikiJournal of Medicine, as well as the open-access medical resources Patholines and Radlines.

He was born in Gothenburg, Sweden. During a six-month backpacking journey in 2005—traveling on the Trans-Siberian Railway to China and crossing the Himalayas from Tibet to Nepal—he decided to pursue a career in medicine.

Dr. Hegstrom graduated with a Doctor of Medicine degree from Uppsala University, Faculty of Medicine, in 2013. He completed two years of rotational internship and subsequently worked as a physician in obstetrics and gynecology, radiology, and pathology in Sweden. He completed residency training in anatomic and clinical pathology at Danbury Hospital in Connecticut in 2024.

He is currently a Clinical Informatics Fellow at the University of Minnesota, with continued clinical involvement in anatomic pathology. He became a naturalized citizen of the United States in 2026.

Dr. Hegstrom has contributed to Wikipedia since 2006 and has an extensive portfolio of medical illustrations. He founded the [[wikiversity:WikiJournal_of_Medicine|WikiJournal of Medicine]], a Wikipedia-integrated, peer-reviewed, open-access academic journal, serving as Editor-in-Chief from 2014 to 2024. He is also the creator of [https://patholines.org/Main_Page Patholines] and [https://radlines.org/Main Radlines], which provide openly accessible practice-oriented guidelines in pathology and radiology.

= Further information =

* [https://drive.google.com/file/d/1BRO2jBnpl8Kou18gxphMmXuEoGQGG7ja/view?usp=sharing Curriculum Vitae] - This linked document contains detailed information regarding education, training, licensure, publications, presentations, professional memberships, and technical expertise.
* [https://www.linkedin.com/in/drhaggstrom/ Linkedin page]
* [[wikipedia:User:Mikael_Häggström|Wikipedia presentation]]

Michael Hegstrom, M.D.

2026-03-06T21:13:31Z

Mikael Häggström: Image

[[File:Mikael Häggström at pathology in 2019 (crop).jpg|thumb|In 2019]]
Also known as Mikael Haeggstroem

= Biography =
Michael Hegstrom is a Swedish-American pathologist and clinical informatician. He is the creator of the WikiJournal of Medicine, as well as the open-access medical resources Patholines and Radlines.

He was born in Gothenburg, Sweden. During a six-month backpacking journey in 2005—traveling on the Trans-Siberian Railway to China and crossing the Himalayas from Tibet to Nepal—he decided to pursue a career in medicine.

Dr. Hegstrom graduated with a Doctor of Medicine degree from Uppsala University, Faculty of Medicine, in 2013. He completed two years of rotational internship and subsequently worked as a physician in obstetrics and gynecology, radiology, and pathology in Sweden. He completed residency training in anatomic and clinical pathology at Danbury Hospital in Connecticut in 2024.

He is currently a Clinical Informatics Fellow at the University of Minnesota, with continued clinical involvement in anatomic pathology. He became a naturalized citizen of the United States in 2026.

Dr. Hegstrom has contributed to Wikipedia since 2006 and has an extensive portfolio of medical illustrations. He founded the [[wikiversity:WikiJournal_of_Medicine|WikiJournal of Medicine]], a Wikipedia-integrated, peer-reviewed, open-access academic journal, serving as Editor-in-Chief from 2014 to 2024. He is also the creator of [https://patholines.org/Main_Page Patholines] and [https://radlines.org/Main Radlines], which provide openly accessible practice-oriented guidelines in pathology and radiology.

= Further information =

* [https://drive.google.com/file/d/1BRO2jBnpl8Kou18gxphMmXuEoGQGG7ja/view?usp=sharing Curriculum Vitae] - This linked document contains detailed information regarding education, training, licensure, publications, presentations, professional memberships, and technical expertise.
* [https://www.linkedin.com/in/drhaggstrom/ Linkedin page]
* [[wikipedia:User:Mikael_Häggström|Wikipedia presentation]]

Michael Hegstrom, M.D.

2026-03-06T21:13:02Z

Mikael Häggström: Started

Also known as Mikael Haeggstroem

= Biography =
Michael Hegstrom is a Swedish-American pathologist and clinical informatician. He is the creator of the WikiJournal of Medicine, as well as the open-access medical resources Patholines and Radlines.

He was born in Gothenburg, Sweden. During a six-month backpacking journey in 2005—traveling on the Trans-Siberian Railway to China and crossing the Himalayas from Tibet to Nepal—he decided to pursue a career in medicine.

Dr. Hegstrom graduated with a Doctor of Medicine degree from Uppsala University, Faculty of Medicine, in 2013. He completed two years of rotational internship and subsequently worked as a physician in obstetrics and gynecology, radiology, and pathology in Sweden. He completed residency training in anatomic and clinical pathology at Danbury Hospital in Connecticut in 2024.

He is currently a Clinical Informatics Fellow at the University of Minnesota, with continued clinical involvement in anatomic pathology. He became a naturalized citizen of the United States in 2026.

Dr. Hegstrom has contributed to Wikipedia since 2006 and has an extensive portfolio of medical illustrations. He founded the [[wikiversity:WikiJournal_of_Medicine|WikiJournal of Medicine]], a Wikipedia-integrated, peer-reviewed, open-access academic journal, serving as Editor-in-Chief from 2014 to 2024. He is also the creator of [https://patholines.org/Main_Page Patholines] and [https://radlines.org/Main Radlines], which provide openly accessible practice-oriented guidelines in pathology and radiology.

= Further information =

* [https://drive.google.com/file/d/1BRO2jBnpl8Kou18gxphMmXuEoGQGG7ja/view?usp=sharing Curriculum Vitae] - This linked document contains detailed information regarding education, training, licensure, publications, presentations, professional memberships, and technical expertise.
* [https://www.linkedin.com/in/drhaggstrom/ Linkedin page]
* [[wikipedia:User:Mikael_Häggström|Wikipedia presentation]]

Learning pathology

2026-01-30T19:33:44Z

Mikael Häggström: /* Using AI "chatbots" */ Expanded

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
</noinclude>The goal of this resource is to make a new pathology trainee able to properly handle at least 70% of cases that are expected at an average general pathology department, including the exclusion of the most pertinent differential diagnoses thereof. Its aim is to present you at least '''one way''' of doing things that is at least adequate for a particular situation. Still, there may be various routines at various locations, but adherence to these methods should not result in a worse reprimand from a senior than ''"although that was adequate, that is not how we do it here"''. Still '''ask for help''' whenever needed, such as first time you are doing something, or whenever you are not sure about what to do, especially when doing something potentially irreversible. When confronted with a question, until you are certain what to answer, rather say something in the line of "I'm not sure, but I'll find out and get back to you".

==What a pathologist needs to memorize==
The best method for memorization is generally through repeated exposure in everyday practice, and the scope thereof will depend on your eventual location and subspecialty, and you will eventually forget everything else, more or less. Yet, the following things are most important for a pathologist trainee to focus on memorizing:

* '''[[Emergency pathology]]''', mostly relating to intraoperative or frozen section consultations. This includes information that usually cannot be timely looked up on the Internet when needed.
* Main '''[[pitfalls]]''': The most common and dangerous situations where a pathologist may not recognize the need to look something up further or [[ask a senior colleague]], or where a significant risk of diagnosis error remains after doing so.
* '''Interpretation of non-written results''', including patterns and signs which can be seen grossly or under the microscope. It confers the ability to translate visuals and other more or less non-verbalizable information into words that can be looked up if needed, and conceive the most likely diagnoses based on both describable and more abstract appearances.
* Proficiency in diagnosing '''equivocal or borderline cases''' where readily available sources and evidence usually deal with discrete and specific disease entities and subcategories thereof. Unusual or equivocal presentations of very common diseases and conditions are still generally more common than rare diseases, and constitutes a major workload in everyday pathology practice. However, most textbooks still give disproportionately large room for rare diseases compared to such presentations. Nevertheless, strive to '''master the common''' conditions (including the most common pitfalls) first, and skip the uncommon in the meantime. After all, you will get by with effectively handling the regular cases wherever you work, so that when unfamiliar cases appear, you will have time to study or ask others for how to handle them, as long as you know your pitfalls, and have an idea about your unknowns:
* Having an idea of one’s '''unknowns'''; being aware of a lack of knowledge in unfamiliar fields. For example, a pathologist generally does not need in depth knowledge about diseases that are generally sent out to specialized centers (such as pediatric musculoskeletal oncology), but just enough to be able to suspect such diseases. In the same manner, a pathologist needs to have an idea of the optimal '''limits of practice''', between what should optimally be handled personally by the pathologist and what is better handled by others, including senior colleagues, technicians, pathology assistants, junior colleagues and artificial intelligence.
* '''Where to find information''' for various situations. It includes which person or which '''search engine''' is most useful for various clinical situations. See the ''Using resources'' section below for further information. Similarly, a pathologist often needs to be efficient at finding what is relevant among a large amount of information, and be able to '''integrate''' it into a decision or a relatively short report. Experience in looking up information will eventually give you an idea of where to locate specifics that you haven't even seen before. For questions where a look-up does not readily give the answer, a new trainee usually gets satisfactory replies even from senior trainees, but the more experienced you get, the more you need to '''establish contacts''' with particular people, such as certain subspecialties, who are most likely to be able to answer your questions when needed.
[[File:Field of pathology.png|thumb|290px|right|The areas of these figures are not exact, but aim to give a rough overview of all information relating to pathology. This resource aims to cover the most important things you need to memorize as a first year pathology trainee.]]
*How to distinguish '''memorization-worthy''' versus '''look-up''' versus '''practically useless''' information. With the ease of access to pathology information on the Internet through smartphones and computers, those studying for the everyday practice as '''a pathologist should not waste time memorizing what can essentially always be conveniently and timely looked up when needed'''. This includes most of the content of books and web pages that are sorted by names of diseases and conditions, because if the name of a disease is already known, then it can relatively quickly be looked up when needed in such sources. When finding relevant look-up information on the Internet or local repositories, it is generally enough to remember enough of its related words in order to find it again. After all, other doctors and even laypersons can look up diseases and conditions themselves, without the need for a pathologist consultation, so the expertise of memorizing such readily available information is expendable. Similarly, electronic systems are better suited than the human brain for the storage and rapid retrieval of databases of for example immunohistochemistry and genetics results of various diseases. The topics listed in this section are already immense enough to cover a lifetime of learning. Learning pathology therefore optimally involves the memorization of where and how to find look-up information, rather than directly memorizing such information. Therefore, if you need to choose a textbook to study, then choose one that you will always be able to quickly reach through your smartphone whenever you need its look-up information. Accordingly, the final '''aim''' of this resource is to help pathology trainees to give accurate and clinically useful reports to clinicians, in '''synergy''' with the resources that are available in everyday pathology practice, and to establish routines to continue such practices. The intended end result is to help clinicians to improve the lives as much as possible to as many people as possible, even if it means forgoing the prestige of becoming a walking encyclopedia. After all, life is not a ''Trivial Pursuit'' game; Don't fill your brain with random facts, even pathology-related ones. Rather, use '''high-yield''' learning sources, for even if they may take longer time to find, you will be better prepared for real life than when you study ''low-yield'' knowledge. For instance, the optimal studying is generally not of diseases individually, but rather of patterns of signs and other findings and the likelihoods of each differential diagnosis thereof. Arguably the best method of acquiring such knowledge is to be involved in many real cases at a pathology department, making your own diagnostic thinking of them, and correcting your thinking based on how you differed from a senior's decision on the case. Real life experience also gives you a better idea of what is memorization-worthy versus look-up information in various resources. After real life experience, the next best resource is arguably to solve virtual cases such as found in pathology qbanks. As a general rule, the following factors makes a piece of information a look-up one:
[[File:Histopathology of fibromatosis-like metaplastic carcinoma.png|thumb|A potential pitfall: Fibromatosis-like metaplastic carcinoma of the breast (pictured) may look like benign fibromatosis. The gland-like components are a clue that it's in fact metaplastic carcinoma.]]
:*The probability of '''realizing''' that you don't know it in situations where it makes a difference. For example, when being presented with a numerical test result and you do not know the normal reference range for it, you at least realize that there are reference ranges out there that you can look up to help you. Thus, reference ranges are generally look-up information. It is generally the opposite for pitfalls. For example, if a person thinks a breast nodule looks like benign fibromatosis but does not know (or does not consider) that fibromatosis-like metaplastic carcinoma (FLMBC) looks similar, the probability is relatively low that the person will look that up.<ref group=note>As a metaphor, pathologists should not waste time memorizing '''"elephants in the room"''', which will most definitely be spotted, and if you don't know which subtype, you will most definitely look it up or ask an expert if needed. Rather, pathologists should memorize how to spot '''"chameleons in the corner"''', which may not be spotted if not knowing what to look for.</ref>
:*The '''ease and speed''' of looking it up in reliable sources. Decisions with higher patient impact require more reliable sources. For example, the first forum answer from an anonymous user can be sufficient for an inconsequential decision, whereas information that may make a diagnosis benign versus malignant generally needs to be found on credible and peer reviewed sites.
*How to efficiently '''study for exams''' that contain questions that require direct memorization of look-up (or even practically useless) information, as long as such exams are in the way of practicing pathology. The best approach is arguably to spend enough time and effort on memorizing what is memorization-worthy, to the point where you will pass an exam even if you will fail multiple questions that require memorization of look-up or practically useless information. However, when starting pathology training, do not focus on studying for any final exams that are years away, because the content on such exams is systematically very different from what you need to know initially. For instance, you initially need to know how to handle the common types of cases, but exam makers on the other hand, in their effort to distinguish those who have studied more extensively than others, will systematically choose presentations that are not commonly encountered. {{further|Secrets}}<includeonly> ''Further exam advice is found in the '''[[Secrets]]''' chapter at patholines.org.''</includeonly>
{|class=wikitable
! Type of information !! Examples (usually) !! Learning approach
|-
! Memorization-worthy
|
*'''Emergent''' matters
*'''Pitfalls'''
*Interpretation of '''non-written''' results
| Directly '''memorizing''' it.
|-
! Look-up
|
*'''Textbooks and websites''' organized by names of diseases and conditions
*'''Immunohistochemistry''' results
*Associations between '''genetic''' mutations and diseases, and related molecular biology.
*'''Classifications''' such as cancer staging
*'''Large tables and diagrams'''
*'''Long lists'''
| Knowing '''where to find it''' when needed, and how to use it.
|-
! Low-yield
|
*'''Diseases individually'''
| Instead studying '''patterns''' of findings and signs, and how they support various differential diagnoses.
|-
! Practically useless
|
* '''History'''
* Most of scholarly '''articles'''
* Most '''clinical management'''
| '''Avoiding''', or '''skipping''' to potentially useful parts.
|}
[[File:Cover to cover reading versus problem or project based learning.png|thumb|560px|Example of problem/project based learning versus reading cover to cover. The problem/project based learner may memorize a smaller amount of total information due to spending time searching for the optimal material across various sources, but will likely learn more useful items for real world scenarios, and will likely be better at knowing where to find information when needed.<ref>Image by Mikael Häggström, MD, using source images by various authors. Source for useful context in problem-based learning: {{cite web|title=Understanding Medical Education - Problem-based learning|author=Mark A Albanese, Laura C Dast|date=2013-10-22|url=https://doi.org/10.1002/9781118472361.ch5|website=Wiley Online Library}}</ref>]]
Whether any piece of information is useful versus useless depend mainly on:
*The '''likelihood''' of a situation where the information is useful.
*The '''benefit versus detriment''' of having versus not having the information at hand in such a situation.

The '''clinical management''' aspects that can be useful for pathologists to learn are the thresholds for pathologic findings that substantially change the clinical management, such as a cancer stage that determines whether clinicians will try to completely remove all tumors versus treat palliatively. With such knowledge, pathologists can put relatively more effort on the cases and parts thereof that make the most difference to the patient. Otherwise, clinical management knowledge is generally useless to a pathologist.

'''Lectures''' may be memorization-worthy depending on the content, but a lecture of look-up-information is practically useless unless you maintain a system to quickly retrieve the information when needed. Thus, sometimes, it is better to study something more memorization-worthy while pretending to listen to a lecturer.

Also keep in mind that pathology in our look-up era is mainly a '''processing''' work rather than a memorization one, since your most important skills are to interpret findings, and sometimes involve a vast amount of information in order to suggest the most likely diagnoses. Again, arguably the best method fur such purposes is solving real or virtual cases.

==Using resources==
This resource is written with the intention to teach you what to do in the most common situations you are expected to encounter during your first years of pathology training, at least until the point that you are usually fairly confident about what disease or condition you have at hand, because then you know what words to use to look it up in the vast literature out there. At that point, the fastest way to get more information is generally by '''[https://www.google.com/ Googling]''' the disease or condition name, followed by '''pathology outlines''' (which is generally the most likely to quickly give you the information you need), since Internet will always be readily available in pathology.<ref group=note>If you worry about Internet outages, then it is still much more worthwhile to purchase satellite Internet as a backup (which costs $50 to $100 per month) than to try to memorize the Internet.</ref> The most efficient method of studying to solve a case at hand is to not read articles in their entirety, but to scroll directly to the parts that are most likely to give you the information you need (generally past the first half of Pathology Outlines articles). A major skill of a pathologist is to have a good idea of what pages and texts can be skipped by only a quick glance.

Specific search methods for some specific purposes include the following (and the author has no financial or other conflicts of interests in mentioning any of these):
*[https://www.google.com/ Google], and then clicking the '''Images''' tab, if you just want to see more micrographs of the disease or condition. Even when you don't have a clue what condition you are looking at, you may find something that looks similar to your case by entering words you would use for the microscopic findings that you see.
:*Adding '''cancer.net staging''' in Google searches for definitions of cancer stages, for example Googling ''prostate cancer cancer.net staging''. The first search will then generally be the one from the American Society of Clinical Oncology.
*Googling "'''CAP synoptics'''" for guidelines for the most common cancer locations and types [https://www.cap.org/protocols-and-guidelines/cancer-reporting-tools/cancer-protocol-templates]. Don't google individual protocols, bypassing the overview list of protocols, as it may cause you to click on an outdated protocol.
*Considering a subscription for '''ImmunoQuery'''{{ImmunoQuery COI declaration}} (or equivalent database if you find one) in order to generate the most pertinent immunohistochemistry stains when you have two or more differential diagnoses for a case at hand. It is not sufficient to just memorize a few usually positive or negative immunostains for each disease and condition, because what you need in reality is to figure out what immunostains to order so that you can pinpoint one diagnosis among your multiple differentials. To master that, you will need to memorize a vast amount of immunostains and at what percentages they are positive for a vast amount of diseases and conditions, or you can have an online service like ImmunoQuery do that work for you. After all, in pathology there is essentially no immunohistochemistry that is so emergent that you do not have the time to use a computer or smartphone to look it up.
*'''[https://www.ncbi.nlm.nih.gov/clinvar/ ClinVar]''' to look up the pathogenicity of specific genetic variants/mutations.

If the above resources do not provide a sufficient answer, more general search tools are mainly:
*'''[https://www.google.com/ Googling]''' what you are looking for. You may add the word '''pathology''' or equivalent if results are too clinical or layman-oriented. Before even reading the title of results, first look at the URL. If it is from a reputable organization then you may proceed to check if the title is pertinent to what you are looking for, but if it is from an unfamiliar site then you should only proceed if you don't find a better source among your search results. On such unfamiliar sites, you will need to look for additional proof of reliability such as authorship of the content in order to use it as part of any diagnostic decisions.
*'''[https://openai.com/blog/chatgpt/ ChatGPT]''' is useful in answering specific questions, or generating texts with particular content or format. However, don't make significant diagnostic decisions based on its answers without first verifying it with reliable sources, as it might give a false answer despite appearing confident.
You can generally rely on online articles for presumably '''well-established''' topics (such as anatomy, and relatively common diseases). However, for potentially controversial and experimental topics, you generally need to ask yourself if the author has a conflict of interest before using its information for important decisions. In such cases, seek highly reliable sources, such as peer reviewed review articles, or professional organizations and societies. In contrast, beware of sites with flashy images, as it indicates a financial interest.

'''[[Ask a colleague]]''' at least whenever your own memory or a resource search is not enough, and there is a significant risk that you may do something irreversible that will negatively affect a patient.

Regarding '''lectures''' and knowledge your colleagues will tell you, make a judgment for each piece of information if it fits a criterion for memorization, or if it merits being written down somewhere you can find it so that you can look it up when needed.

'''Wikipedia''' often shows up among top Google results, and is generally accurate.<ref>{{cite journal|last1=Kräenbring|first1=Jona|last2=Monzon Penza|first2=Tika|last3=Gutmann|first3=Joanna|last4=Muehlich|first4=Susanne|last5=Zolk|first5=Oliver|last6=Wojnowski|first6=Leszek|last7=Maas|first7=Renke|last8=Engelhardt|first8=Stefan|last9=Sarikas|first9=Antonio|last10=Lovis|first10=Christian|title=Accuracy and Completeness of Drug Information in Wikipedia: A Comparison with Standard Textbooks of Pharmacology|journal=PLOS ONE|date=September 24, 2014|volume=9|issue=9|pages=e106930|doi=10.1371/journal.pone.0106930|pmid=25250889|pmc=4174509|bibcode=2014PLoSO...9j6930K|doi-access=free}}</ref>

Whenever possible, use '''textbooks''' and other sources that you can quickly access online, because you will likely always be close to the Internet, but not always close to your collections of physical material. Keep in mind that for the vast majority of content, you only need to have a hunch of where to find it again when needed, or what search terms to use. If something may be difficult to find again, you may add it to a personal digital collection to be readily available in times you need it.

Strive for sources that, taken together, are '''comprehensive''' enough for the presentation at hand. For example, if you first look in a resource on only benign conditions that may cause your presentation, you generally need to look for another source that includes malignant conditions as well.

Generally skip any part that tries to explain a microscopic appearance using '''only words''', since a Google image search is generally more useful.

{{Question|title=A 4 year old girl with a renal mass}}
[[File:Histopathology of Wilms' tumor, original.jpg|250px|right]]
[[File:Histopathology of Wilms' tumor, annotated.jpg|250px|right]]
You are a new resident at a community hospital that is closely affiliated with a university hospital. The attending gives you a couple of slides from a case that is not yet signed out to preview and then come back with what you think would be the next steps. You are also told to share them with a med student who rotates at the department. One of the cases is from a kidney of a 4 year old girl. You look up the patient's history and she was admitted for orthopedic care for multiple fractures, and CT incidentally found a kidney tumor where workup was initiated as an inpatient. Microscopy shows the image at right. The med student has a smartphone and by googling "common kidney tumors in children", Wilms' tumor (also known as nephroblastoma) shows up as one of the top choices. You look up the condition on Pathology Outlines and the case seems to fit the microscopic description with its 3 typical components (second image at right).<ref name=PathologyOutlines-Wilms>{{cite web|url=https://www.pathologyoutlines.com/topic/kidneytumorwilmkids.html|author=Ellen D’Hooghe, M.D., Gordan M. Vujanic, M.D., Ph.D.|website=Pathology Outlines|title=Kidney tumor - Childhood tumors - Nephroblastoma}} Topic Completed: 16 September 2020. Minor changes: 6 October 2021</ref> On the same web page you also quickly see the following pieces of look-up information:
*Risk classification systems, where for example "COG intermediate risk" requires favorable histology and no evidence of anaplasia.
*That there are no specific/diagnostic laboratory findings.
*A bunch of associated genetic changes (WT1 (11p13), CTNNB1 (3p22), IGF2 (11p15), TP53 (17p13), MYCN (2p24), and 1q gain).
*A bunch of associated immunohistochemistry results in the tumor, related non-neoplastic tissue, as well as in notable differential diagnoses (WT1, PAX8, vimentin, CD56, CD57, cytokeratins, EMA, desmin, cyclin D1, BCL2, CD34, myogenin, MyoD1, INI1, Glypican 3, AMACR, CK7, melanocytic markers (MelanA, HMB45), BRAF V600E, TFE3, TFEB, BCOR, and FLI1)
Which of the following would be the best next step if you were to decide yourself?
# Diagnosing Wilms' tumor, COG intermediate risk, based on the shown microscopic view alone.
# Look at the complete blood count for diagnostic findings.
# Order genetic testing for WT1 (11p13), CTNNB1 (3p22), IGF2 (11p15), TP53 (17p13), MYCN (2p24), and 1q gain.
# Order immunohistochemistry for WT1, PAX8, vimentin, CD56, CD57, cytokeratins, EMA, desmin, cyclin D1, BCL2, CD34, myogenin, MyoD1, INI1, Glypican 3, AMACR, CK7, MelanA, HMB45, BRAF V600E, TFE3, TFEB, BCOR, and FLI1.
# Say "I don't know" and ask for help.

;'''Correct answer''':
[[File:Say I don't know and ask for help.png|left|220px]] A major skill of a pathologist is having an idea of one’s unknowns. Furthermore, pediatric oncology is generally outside the limits of independent practice of any individual pathologist, generally requiring at least consultation with a colleague before diagnosis, classification and decisions about further workup (which in this case may be made at a pediatric oncology center). Thus, even if you though you knew how to proceed on your own, saying "I don't know" and asking for help is still the most correct as a new resident for a case like this.

;'''Incorrect answers'''
You can skip reading these if you are already agree with the explanation above.
# Although the microscopic view that is shown is enough to diagnose Wilms' tumor, it is not enough to classify it as COG intermediate risk without first having looked at the entirety of the microscopy slides to exclude evidence of anaplasia.
# There are no specific/diagnostic laboratory findings of Wilms' tumor.
# A senior or specialist consultation would be needed in order to find out which genetic tests would actually be worth performing in this case, even after reviewing the history or asking a clinician for any suspected syndrome associated with Wilms' tumor.
# The choice of immunohistochemistry panels should be based on which ones most efficiently distinguish the possible differential diagnoses of the case at hand, and not just which ones are associated with the lead diagnosis. As with genetic testing, a senior or specialist consultation would be needed in order to find out which immunohistochemistry tests would actually be worth performing in this case. {{further|Immunohistochemistry}}
{{Question-end}}

==Using this resource==
In this resource, it is recommended to read attentively until the end of the [[emergent pathology]] section. That part can be regarded as mainly describing '''concepts''', which are relevant to read through and understand or at least consider. The rest will mainly provide guidelines for various situations, such as when you are presented with a biopsy of the gastrointestinal tract. Memorization-worthy information will generally be highlighted by: {{Memorization-worthy}}, otherwise it is recommended to scroll quickly through such situation-based chapters, just to get an idea of what kind of information is available there, and then keeping this resource at a known location for whenever you are in that situation.
*{{Memorization-worthy}} This resource is available open-access and ad-free by googling ''patholines'' and then '''[[Starting pathology]]''' (handbook).

This resource is aimed at presenting the most important knowledge that you will need when starting pathology. For further knowledge that you will need as a pathologist and any subspecialization, the best way is to '''learn from reality''', by solving the cases and problems that get presented to you, and thereby look specifically for the information that you will need among the immense literature and other information that is out there.

Also, this resource assumes that you use additional sources when needed (such as [https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours The WHO Classification of Tumors] or others in the ''Using resources'' above). Therefore, it will not simply repeat such information, but may display external links to further information.

This resource also assumes that you will '''ask''' a colleague for advise if you see an unfamiliar presentation, and any literature lookup thereof still does not explain it. Therefore, this resource will focus on the most common presentations and the main differential diagnoses thereof, which may include rare conditions if the clinical management thereof would be significantly different. On the other hand, this resource omits rare conditions that rarely look similar to common presentations. Therefore, keep in mind that there are many such rare conditions that you do not know about, so keep asking colleagues whenever a presentation remains strange to you, and choose initial workplaces where you have experienced people to ask if needed.

Be tolerant to encountering many '''repetitions''' of the same content in related articles, since for example a [[cervical biopsy]] and a [[cervical cone]] have similar microscopic evaluation.

==Using AI "chatbots"==
For AI "chatbots" (such as ChatGPT, Gemini or Copilot), you can generally trust a simple answer to a simple and presumably common question. More complex answers generally require you to provide more '''details''' together with your question. For example, a question of "what is the risk that this patient has..." would require you to provide a patient summary for a better answer, while avoiding identifiable information.<ref group="notes">See [https://www.hhs.gov/hipaa/for-professionals/special-topics/de-identification/index.html#standard HHS de-identification standards] for what counts as identifiable information</ref> '''Avoid leading''' prompts (such as "these features indicate invasiveness, right?") but rather keep them neutral and open-minded.

==Using question banks==
To test your knowledge on memorization-worthy information, seek questions that present you with a possible real life situation, as well as all pertinent information you can readily look up before needing to answer the question, so to ensure that it tests you on pertinent information as per the items earlier in this chapter. On the other hand, don't waste time on questions whose answer requires memorization of look-up or practically useless information (except if you want to practice looking up the answers online). There are about 5700 questions in PathPrimer, PathDojo, BoardVitals, and the ASCP Question Bank combined,<ref group=note>As of July 2023, PathPrimer has 2270 Multiple Choice Questions (and has the highest quality of its questions despite an overall bad image quality), PathDojo has 1700, BoardVitals has 1050, and the ASCP Question Bank has 675 MCQs. AceMyPath has multiple whole slide images, but is not really a Qbank.</ref> so you can be picky about which questions to take and which ones to skip.

Consider the '''usefulness''' of each question before spending significant time memorizing its answers or explanations, in order to maximize the useful knowledge you will learn overall. Generally, skip questions that test you on look-up information and practically useless information. Whenever you have a question where you can not picture in what real life situation it would be relevant to remember, then you can generally assume that it never will be. For questions that consists of a useful item combined with a more useless one, only learn the the useful part and move on. The typical example of that combination is a memorization-worthy appearance of a disease, but then the question asks about a rather random fact that you can easily look up if you know the disease name. If you can, flag/mark questions on memorization-worthy information that you did not know, and move on fairly quick on those as well, and later revisit those questions specifically if you have the time, as repetition is generally more efficient than lingering.

A common sign that a question will deal with look-up or practically useless information is where it asks which of the alternatives is '''false or correct''' for one particular condition, and the alternatives are relatively heterogenous (such as one dealing with diagnosis and another one dealing with prognosis). The high prevalence of such questions is mainly because they are easy and quick create, because the question creator can simply look up a condition, choose some more or less random facts, and then change small details to create alternatives. It requires no real life experience in everyday pathology practice, and learning from such a question is hence generally not useful for that purpose either.<ref group=note>The highest yield questions are generally those with one teaching point per question. In contrast, for a true/false question to be of decent quality, each alternative should be relevant as per criteria above, but it is more difficult to create than low-quality ones. Since low-quality true/false questions are generated at much higher rate, the vast majority of true/false questions are subsequently low-quality.</ref> The thought processes of real life pathology is generally the opposite of this, because you are generally presented with a specific location, gross appearance and microscopic appearance, and you need to practice on finding the most likely causative condition thereof among many differential diagnoses. Even other kinds of memorization-worthy pieces of information generally have a more limited scope among alternatives (like knowing the optimal staining duration in hematoxylin for a frozen section among alternative durations (see [[Emergent pathology]]). Thus, to practice your knowledge in memorization-worthy pathology, it is generally most efficient to skip false-versus-correct questions, in order to spend your limited time on something more worthwhile. Similarly, questions are in general rather low-yield whenever they deviate from the realistic direction.

Also, prefer '''succinct''' questions, that give you only the most relevant information in order to test the key learning point, without having to spend effort finding the most relevant information in long patient presentations, because you will get enough practice of that in everyday scrolling through patient charts.

If you have gone through all 5000 questions of the main question banks, and still have plenty of time for a '''second round''', then you may work on lower yield questions as well. For example, you may practice on looking up answers for look-up questions, unless the presentation makes it clear that you cannot timely and conveniently do so (such as being in a rush during a frozen section).

{{Question|title=A question on a question|subsection=yes}}
You want to practice your memorization-worthy knowledge in real life pathology and not for exams ({{further|Secrets}}<includeonly>''as per the '''[[Secrets]]''' chapter at patholines.org.''</includeonly>). You find the following multiple choice question: "Which of the following statements for squamous cell carcinoma (SCC) of the skin is false?"
*For staging of SCC of the of the head and neck, pT1 corresponds to a diameter ≥ 2 cm and < 4 cm (this is the false alternative, as this defines pT2, whereas pT1 is defined as ≤ 2 cm)<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/skintumornonmelanocyticscc.html|title=Skin nonmelanocytic tumor, Carcinoma (nonadnexal), Squamous cell carcinoma|author=Shaofeng Yan, M.D., Ph.D.|website=Pathology Outlines}} Topic Completed: 13 January 2020. Minor changes: 8 December 2021</ref>
*Most patients have a favorable outcome after surgical resection.
*It occurs most often in sun exposed areas.
*It often presents as a hyperkeratotic scaly plaque.
*Microscopy typically shows carcinoma of keratinocytes that infiltrates the dermis.
What is the most efficient way of dealing with this question for real-life pathology practice?
#Choosing an answer, then thoroughly reviewing each alternative, as well as the question explanation.
#Like the first alternative, but only if you answered the question wrong.
#Only carefully review the single association you need to answer the question correctly (in this case, that for SCC of the skin, pT1 is defined as ≤ 2 cm).
#Skip this question and move on.
;'''Correct answer''':
[[File:Skip this question and move on.png|250px]]
 The answer alternatives of this question are all over the place (a mix of prognosis, location, staging, gross description and microscopic description), which usually means that it was created by just looking up the condition in a resource and picking information from there, resulting in a collection of what is usually just look-up information.

;'''Incorrect answers'''
You can skip reading these if you are already agree with the explanation above.
:1 and 2. These are waste of time.
:3. If this was a question of memorization-worthy information, or if you were studying for an exam, this would generally be the correct answer. However, staging of cancers can essentially always conveniently and timely be looked up when needed, so this is not memorization-worthy for everyday pathology practice.
{{Question-end}}
Other indications for '''skipping''' a question include:
*'''Unrealistically withholding''' information, such as mentioning what kind of test identified the condition without giving you the test result (such as a case presentation that includes "Serology identified the organism").
*'''Unrealistic chronology''', that is, not following the order of actual processes. It may include giving you the diagnosis and asking you what would be the expected clinical history.
*Showing you a '''molecular structure''' and asking you to identify the substance or its category, which is extremely unlikely to be a task in real life, and which can generally quickly be looked up (such as googling ''search by image'' and clicking the camera icon, followed by uploading the image of the structure, such as a photo or screenshot thereof).
*'''Unpractical statistics''' that is very unlikely to be used diagnostically, mainly because their calculations would be so complex that it is not worth it. For example, in reality you generally have a ''pattern'' of signs and other findings and you want to know the likelihood of each differential diagnosis, and for this purpose you only get limited help by knowing the reverse likelihood of what percentage each individual condition is to display the finding, because it would still be necessary to also know the epidemiology of each disease to calculate its likelihood.

==Learning clinical pathology==
{{Learning hematopathology}}
<noinclude>Still, if you get the task as a trainee to make a draft of a bone marrow, see '''[[Bone marrow]]'''.</noinclude>

For '''molecular pathology''', focus on learning the situations in which molecular workup is needed, rather than the specific derangement. The latter can generally easily be looked up when needed, whereas the former can easily be missed.

'''Microbiology''': {{Learning microbiology}}
<noinclude>
{{General notes}}
{{Bottom}}
</noinclude>

Learning pathology

2026-01-30T19:30:53Z

Mikael Häggström: /* Using question banks */ Started

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
</noinclude>The goal of this resource is to make a new pathology trainee able to properly handle at least 70% of cases that are expected at an average general pathology department, including the exclusion of the most pertinent differential diagnoses thereof. Its aim is to present you at least '''one way''' of doing things that is at least adequate for a particular situation. Still, there may be various routines at various locations, but adherence to these methods should not result in a worse reprimand from a senior than ''"although that was adequate, that is not how we do it here"''. Still '''ask for help''' whenever needed, such as first time you are doing something, or whenever you are not sure about what to do, especially when doing something potentially irreversible. When confronted with a question, until you are certain what to answer, rather say something in the line of "I'm not sure, but I'll find out and get back to you".

==What a pathologist needs to memorize==
The best method for memorization is generally through repeated exposure in everyday practice, and the scope thereof will depend on your eventual location and subspecialty, and you will eventually forget everything else, more or less. Yet, the following things are most important for a pathologist trainee to focus on memorizing:

* '''[[Emergency pathology]]''', mostly relating to intraoperative or frozen section consultations. This includes information that usually cannot be timely looked up on the Internet when needed.
* Main '''[[pitfalls]]''': The most common and dangerous situations where a pathologist may not recognize the need to look something up further or [[ask a senior colleague]], or where a significant risk of diagnosis error remains after doing so.
* '''Interpretation of non-written results''', including patterns and signs which can be seen grossly or under the microscope. It confers the ability to translate visuals and other more or less non-verbalizable information into words that can be looked up if needed, and conceive the most likely diagnoses based on both describable and more abstract appearances.
* Proficiency in diagnosing '''equivocal or borderline cases''' where readily available sources and evidence usually deal with discrete and specific disease entities and subcategories thereof. Unusual or equivocal presentations of very common diseases and conditions are still generally more common than rare diseases, and constitutes a major workload in everyday pathology practice. However, most textbooks still give disproportionately large room for rare diseases compared to such presentations. Nevertheless, strive to '''master the common''' conditions (including the most common pitfalls) first, and skip the uncommon in the meantime. After all, you will get by with effectively handling the regular cases wherever you work, so that when unfamiliar cases appear, you will have time to study or ask others for how to handle them, as long as you know your pitfalls, and have an idea about your unknowns:
* Having an idea of one’s '''unknowns'''; being aware of a lack of knowledge in unfamiliar fields. For example, a pathologist generally does not need in depth knowledge about diseases that are generally sent out to specialized centers (such as pediatric musculoskeletal oncology), but just enough to be able to suspect such diseases. In the same manner, a pathologist needs to have an idea of the optimal '''limits of practice''', between what should optimally be handled personally by the pathologist and what is better handled by others, including senior colleagues, technicians, pathology assistants, junior colleagues and artificial intelligence.
* '''Where to find information''' for various situations. It includes which person or which '''search engine''' is most useful for various clinical situations. See the ''Using resources'' section below for further information. Similarly, a pathologist often needs to be efficient at finding what is relevant among a large amount of information, and be able to '''integrate''' it into a decision or a relatively short report. Experience in looking up information will eventually give you an idea of where to locate specifics that you haven't even seen before. For questions where a look-up does not readily give the answer, a new trainee usually gets satisfactory replies even from senior trainees, but the more experienced you get, the more you need to '''establish contacts''' with particular people, such as certain subspecialties, who are most likely to be able to answer your questions when needed.
[[File:Field of pathology.png|thumb|290px|right|The areas of these figures are not exact, but aim to give a rough overview of all information relating to pathology. This resource aims to cover the most important things you need to memorize as a first year pathology trainee.]]
*How to distinguish '''memorization-worthy''' versus '''look-up''' versus '''practically useless''' information. With the ease of access to pathology information on the Internet through smartphones and computers, those studying for the everyday practice as '''a pathologist should not waste time memorizing what can essentially always be conveniently and timely looked up when needed'''. This includes most of the content of books and web pages that are sorted by names of diseases and conditions, because if the name of a disease is already known, then it can relatively quickly be looked up when needed in such sources. When finding relevant look-up information on the Internet or local repositories, it is generally enough to remember enough of its related words in order to find it again. After all, other doctors and even laypersons can look up diseases and conditions themselves, without the need for a pathologist consultation, so the expertise of memorizing such readily available information is expendable. Similarly, electronic systems are better suited than the human brain for the storage and rapid retrieval of databases of for example immunohistochemistry and genetics results of various diseases. The topics listed in this section are already immense enough to cover a lifetime of learning. Learning pathology therefore optimally involves the memorization of where and how to find look-up information, rather than directly memorizing such information. Therefore, if you need to choose a textbook to study, then choose one that you will always be able to quickly reach through your smartphone whenever you need its look-up information. Accordingly, the final '''aim''' of this resource is to help pathology trainees to give accurate and clinically useful reports to clinicians, in '''synergy''' with the resources that are available in everyday pathology practice, and to establish routines to continue such practices. The intended end result is to help clinicians to improve the lives as much as possible to as many people as possible, even if it means forgoing the prestige of becoming a walking encyclopedia. After all, life is not a ''Trivial Pursuit'' game; Don't fill your brain with random facts, even pathology-related ones. Rather, use '''high-yield''' learning sources, for even if they may take longer time to find, you will be better prepared for real life than when you study ''low-yield'' knowledge. For instance, the optimal studying is generally not of diseases individually, but rather of patterns of signs and other findings and the likelihoods of each differential diagnosis thereof. Arguably the best method of acquiring such knowledge is to be involved in many real cases at a pathology department, making your own diagnostic thinking of them, and correcting your thinking based on how you differed from a senior's decision on the case. Real life experience also gives you a better idea of what is memorization-worthy versus look-up information in various resources. After real life experience, the next best resource is arguably to solve virtual cases such as found in pathology qbanks. As a general rule, the following factors makes a piece of information a look-up one:
[[File:Histopathology of fibromatosis-like metaplastic carcinoma.png|thumb|A potential pitfall: Fibromatosis-like metaplastic carcinoma of the breast (pictured) may look like benign fibromatosis. The gland-like components are a clue that it's in fact metaplastic carcinoma.]]
:*The probability of '''realizing''' that you don't know it in situations where it makes a difference. For example, when being presented with a numerical test result and you do not know the normal reference range for it, you at least realize that there are reference ranges out there that you can look up to help you. Thus, reference ranges are generally look-up information. It is generally the opposite for pitfalls. For example, if a person thinks a breast nodule looks like benign fibromatosis but does not know (or does not consider) that fibromatosis-like metaplastic carcinoma (FLMBC) looks similar, the probability is relatively low that the person will look that up.<ref group=note>As a metaphor, pathologists should not waste time memorizing '''"elephants in the room"''', which will most definitely be spotted, and if you don't know which subtype, you will most definitely look it up or ask an expert if needed. Rather, pathologists should memorize how to spot '''"chameleons in the corner"''', which may not be spotted if not knowing what to look for.</ref>
:*The '''ease and speed''' of looking it up in reliable sources. Decisions with higher patient impact require more reliable sources. For example, the first forum answer from an anonymous user can be sufficient for an inconsequential decision, whereas information that may make a diagnosis benign versus malignant generally needs to be found on credible and peer reviewed sites.
*How to efficiently '''study for exams''' that contain questions that require direct memorization of look-up (or even practically useless) information, as long as such exams are in the way of practicing pathology. The best approach is arguably to spend enough time and effort on memorizing what is memorization-worthy, to the point where you will pass an exam even if you will fail multiple questions that require memorization of look-up or practically useless information. However, when starting pathology training, do not focus on studying for any final exams that are years away, because the content on such exams is systematically very different from what you need to know initially. For instance, you initially need to know how to handle the common types of cases, but exam makers on the other hand, in their effort to distinguish those who have studied more extensively than others, will systematically choose presentations that are not commonly encountered. {{further|Secrets}}<includeonly> ''Further exam advice is found in the '''[[Secrets]]''' chapter at patholines.org.''</includeonly>
{|class=wikitable
! Type of information !! Examples (usually) !! Learning approach
|-
! Memorization-worthy
|
*'''Emergent''' matters
*'''Pitfalls'''
*Interpretation of '''non-written''' results
| Directly '''memorizing''' it.
|-
! Look-up
|
*'''Textbooks and websites''' organized by names of diseases and conditions
*'''Immunohistochemistry''' results
*Associations between '''genetic''' mutations and diseases, and related molecular biology.
*'''Classifications''' such as cancer staging
*'''Large tables and diagrams'''
*'''Long lists'''
| Knowing '''where to find it''' when needed, and how to use it.
|-
! Low-yield
|
*'''Diseases individually'''
| Instead studying '''patterns''' of findings and signs, and how they support various differential diagnoses.
|-
! Practically useless
|
* '''History'''
* Most of scholarly '''articles'''
* Most '''clinical management'''
| '''Avoiding''', or '''skipping''' to potentially useful parts.
|}
[[File:Cover to cover reading versus problem or project based learning.png|thumb|560px|Example of problem/project based learning versus reading cover to cover. The problem/project based learner may memorize a smaller amount of total information due to spending time searching for the optimal material across various sources, but will likely learn more useful items for real world scenarios, and will likely be better at knowing where to find information when needed.<ref>Image by Mikael Häggström, MD, using source images by various authors. Source for useful context in problem-based learning: {{cite web|title=Understanding Medical Education - Problem-based learning|author=Mark A Albanese, Laura C Dast|date=2013-10-22|url=https://doi.org/10.1002/9781118472361.ch5|website=Wiley Online Library}}</ref>]]
Whether any piece of information is useful versus useless depend mainly on:
*The '''likelihood''' of a situation where the information is useful.
*The '''benefit versus detriment''' of having versus not having the information at hand in such a situation.

The '''clinical management''' aspects that can be useful for pathologists to learn are the thresholds for pathologic findings that substantially change the clinical management, such as a cancer stage that determines whether clinicians will try to completely remove all tumors versus treat palliatively. With such knowledge, pathologists can put relatively more effort on the cases and parts thereof that make the most difference to the patient. Otherwise, clinical management knowledge is generally useless to a pathologist.

'''Lectures''' may be memorization-worthy depending on the content, but a lecture of look-up-information is practically useless unless you maintain a system to quickly retrieve the information when needed. Thus, sometimes, it is better to study something more memorization-worthy while pretending to listen to a lecturer.

Also keep in mind that pathology in our look-up era is mainly a '''processing''' work rather than a memorization one, since your most important skills are to interpret findings, and sometimes involve a vast amount of information in order to suggest the most likely diagnoses. Again, arguably the best method fur such purposes is solving real or virtual cases.

==Using resources==
This resource is written with the intention to teach you what to do in the most common situations you are expected to encounter during your first years of pathology training, at least until the point that you are usually fairly confident about what disease or condition you have at hand, because then you know what words to use to look it up in the vast literature out there. At that point, the fastest way to get more information is generally by '''[https://www.google.com/ Googling]''' the disease or condition name, followed by '''pathology outlines''' (which is generally the most likely to quickly give you the information you need), since Internet will always be readily available in pathology.<ref group=note>If you worry about Internet outages, then it is still much more worthwhile to purchase satellite Internet as a backup (which costs $50 to $100 per month) than to try to memorize the Internet.</ref> The most efficient method of studying to solve a case at hand is to not read articles in their entirety, but to scroll directly to the parts that are most likely to give you the information you need (generally past the first half of Pathology Outlines articles). A major skill of a pathologist is to have a good idea of what pages and texts can be skipped by only a quick glance.

Specific search methods for some specific purposes include the following (and the author has no financial or other conflicts of interests in mentioning any of these):
*[https://www.google.com/ Google], and then clicking the '''Images''' tab, if you just want to see more micrographs of the disease or condition. Even when you don't have a clue what condition you are looking at, you may find something that looks similar to your case by entering words you would use for the microscopic findings that you see.
:*Adding '''cancer.net staging''' in Google searches for definitions of cancer stages, for example Googling ''prostate cancer cancer.net staging''. The first search will then generally be the one from the American Society of Clinical Oncology.
*Googling "'''CAP synoptics'''" for guidelines for the most common cancer locations and types [https://www.cap.org/protocols-and-guidelines/cancer-reporting-tools/cancer-protocol-templates]. Don't google individual protocols, bypassing the overview list of protocols, as it may cause you to click on an outdated protocol.
*Considering a subscription for '''ImmunoQuery'''{{ImmunoQuery COI declaration}} (or equivalent database if you find one) in order to generate the most pertinent immunohistochemistry stains when you have two or more differential diagnoses for a case at hand. It is not sufficient to just memorize a few usually positive or negative immunostains for each disease and condition, because what you need in reality is to figure out what immunostains to order so that you can pinpoint one diagnosis among your multiple differentials. To master that, you will need to memorize a vast amount of immunostains and at what percentages they are positive for a vast amount of diseases and conditions, or you can have an online service like ImmunoQuery do that work for you. After all, in pathology there is essentially no immunohistochemistry that is so emergent that you do not have the time to use a computer or smartphone to look it up.
*'''[https://www.ncbi.nlm.nih.gov/clinvar/ ClinVar]''' to look up the pathogenicity of specific genetic variants/mutations.

If the above resources do not provide a sufficient answer, more general search tools are mainly:
*'''[https://www.google.com/ Googling]''' what you are looking for. You may add the word '''pathology''' or equivalent if results are too clinical or layman-oriented. Before even reading the title of results, first look at the URL. If it is from a reputable organization then you may proceed to check if the title is pertinent to what you are looking for, but if it is from an unfamiliar site then you should only proceed if you don't find a better source among your search results. On such unfamiliar sites, you will need to look for additional proof of reliability such as authorship of the content in order to use it as part of any diagnostic decisions.
*'''[https://openai.com/blog/chatgpt/ ChatGPT]''' is useful in answering specific questions, or generating texts with particular content or format. However, don't make significant diagnostic decisions based on its answers without first verifying it with reliable sources, as it might give a false answer despite appearing confident.
You can generally rely on online articles for presumably '''well-established''' topics (such as anatomy, and relatively common diseases). However, for potentially controversial and experimental topics, you generally need to ask yourself if the author has a conflict of interest before using its information for important decisions. In such cases, seek highly reliable sources, such as peer reviewed review articles, or professional organizations and societies. In contrast, beware of sites with flashy images, as it indicates a financial interest.

'''[[Ask a colleague]]''' at least whenever your own memory or a resource search is not enough, and there is a significant risk that you may do something irreversible that will negatively affect a patient.

Regarding '''lectures''' and knowledge your colleagues will tell you, make a judgment for each piece of information if it fits a criterion for memorization, or if it merits being written down somewhere you can find it so that you can look it up when needed.

'''Wikipedia''' often shows up among top Google results, and is generally accurate.<ref>{{cite journal|last1=Kräenbring|first1=Jona|last2=Monzon Penza|first2=Tika|last3=Gutmann|first3=Joanna|last4=Muehlich|first4=Susanne|last5=Zolk|first5=Oliver|last6=Wojnowski|first6=Leszek|last7=Maas|first7=Renke|last8=Engelhardt|first8=Stefan|last9=Sarikas|first9=Antonio|last10=Lovis|first10=Christian|title=Accuracy and Completeness of Drug Information in Wikipedia: A Comparison with Standard Textbooks of Pharmacology|journal=PLOS ONE|date=September 24, 2014|volume=9|issue=9|pages=e106930|doi=10.1371/journal.pone.0106930|pmid=25250889|pmc=4174509|bibcode=2014PLoSO...9j6930K|doi-access=free}}</ref>

Whenever possible, use '''textbooks''' and other sources that you can quickly access online, because you will likely always be close to the Internet, but not always close to your collections of physical material. Keep in mind that for the vast majority of content, you only need to have a hunch of where to find it again when needed, or what search terms to use. If something may be difficult to find again, you may add it to a personal digital collection to be readily available in times you need it.

Strive for sources that, taken together, are '''comprehensive''' enough for the presentation at hand. For example, if you first look in a resource on only benign conditions that may cause your presentation, you generally need to look for another source that includes malignant conditions as well.

Generally skip any part that tries to explain a microscopic appearance using '''only words''', since a Google image search is generally more useful.

{{Question|title=A 4 year old girl with a renal mass}}
[[File:Histopathology of Wilms' tumor, original.jpg|250px|right]]
[[File:Histopathology of Wilms' tumor, annotated.jpg|250px|right]]
You are a new resident at a community hospital that is closely affiliated with a university hospital. The attending gives you a couple of slides from a case that is not yet signed out to preview and then come back with what you think would be the next steps. You are also told to share them with a med student who rotates at the department. One of the cases is from a kidney of a 4 year old girl. You look up the patient's history and she was admitted for orthopedic care for multiple fractures, and CT incidentally found a kidney tumor where workup was initiated as an inpatient. Microscopy shows the image at right. The med student has a smartphone and by googling "common kidney tumors in children", Wilms' tumor (also known as nephroblastoma) shows up as one of the top choices. You look up the condition on Pathology Outlines and the case seems to fit the microscopic description with its 3 typical components (second image at right).<ref name=PathologyOutlines-Wilms>{{cite web|url=https://www.pathologyoutlines.com/topic/kidneytumorwilmkids.html|author=Ellen D’Hooghe, M.D., Gordan M. Vujanic, M.D., Ph.D.|website=Pathology Outlines|title=Kidney tumor - Childhood tumors - Nephroblastoma}} Topic Completed: 16 September 2020. Minor changes: 6 October 2021</ref> On the same web page you also quickly see the following pieces of look-up information:
*Risk classification systems, where for example "COG intermediate risk" requires favorable histology and no evidence of anaplasia.
*That there are no specific/diagnostic laboratory findings.
*A bunch of associated genetic changes (WT1 (11p13), CTNNB1 (3p22), IGF2 (11p15), TP53 (17p13), MYCN (2p24), and 1q gain).
*A bunch of associated immunohistochemistry results in the tumor, related non-neoplastic tissue, as well as in notable differential diagnoses (WT1, PAX8, vimentin, CD56, CD57, cytokeratins, EMA, desmin, cyclin D1, BCL2, CD34, myogenin, MyoD1, INI1, Glypican 3, AMACR, CK7, melanocytic markers (MelanA, HMB45), BRAF V600E, TFE3, TFEB, BCOR, and FLI1)
Which of the following would be the best next step if you were to decide yourself?
# Diagnosing Wilms' tumor, COG intermediate risk, based on the shown microscopic view alone.
# Look at the complete blood count for diagnostic findings.
# Order genetic testing for WT1 (11p13), CTNNB1 (3p22), IGF2 (11p15), TP53 (17p13), MYCN (2p24), and 1q gain.
# Order immunohistochemistry for WT1, PAX8, vimentin, CD56, CD57, cytokeratins, EMA, desmin, cyclin D1, BCL2, CD34, myogenin, MyoD1, INI1, Glypican 3, AMACR, CK7, MelanA, HMB45, BRAF V600E, TFE3, TFEB, BCOR, and FLI1.
# Say "I don't know" and ask for help.

;'''Correct answer''':
[[File:Say I don't know and ask for help.png|left|220px]] A major skill of a pathologist is having an idea of one’s unknowns. Furthermore, pediatric oncology is generally outside the limits of independent practice of any individual pathologist, generally requiring at least consultation with a colleague before diagnosis, classification and decisions about further workup (which in this case may be made at a pediatric oncology center). Thus, even if you though you knew how to proceed on your own, saying "I don't know" and asking for help is still the most correct as a new resident for a case like this.

;'''Incorrect answers'''
You can skip reading these if you are already agree with the explanation above.
# Although the microscopic view that is shown is enough to diagnose Wilms' tumor, it is not enough to classify it as COG intermediate risk without first having looked at the entirety of the microscopy slides to exclude evidence of anaplasia.
# There are no specific/diagnostic laboratory findings of Wilms' tumor.
# A senior or specialist consultation would be needed in order to find out which genetic tests would actually be worth performing in this case, even after reviewing the history or asking a clinician for any suspected syndrome associated with Wilms' tumor.
# The choice of immunohistochemistry panels should be based on which ones most efficiently distinguish the possible differential diagnoses of the case at hand, and not just which ones are associated with the lead diagnosis. As with genetic testing, a senior or specialist consultation would be needed in order to find out which immunohistochemistry tests would actually be worth performing in this case. {{further|Immunohistochemistry}}
{{Question-end}}

==Using this resource==
In this resource, it is recommended to read attentively until the end of the [[emergent pathology]] section. That part can be regarded as mainly describing '''concepts''', which are relevant to read through and understand or at least consider. The rest will mainly provide guidelines for various situations, such as when you are presented with a biopsy of the gastrointestinal tract. Memorization-worthy information will generally be highlighted by: {{Memorization-worthy}}, otherwise it is recommended to scroll quickly through such situation-based chapters, just to get an idea of what kind of information is available there, and then keeping this resource at a known location for whenever you are in that situation.
*{{Memorization-worthy}} This resource is available open-access and ad-free by googling ''patholines'' and then '''[[Starting pathology]]''' (handbook).

This resource is aimed at presenting the most important knowledge that you will need when starting pathology. For further knowledge that you will need as a pathologist and any subspecialization, the best way is to '''learn from reality''', by solving the cases and problems that get presented to you, and thereby look specifically for the information that you will need among the immense literature and other information that is out there.

Also, this resource assumes that you use additional sources when needed (such as [https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours The WHO Classification of Tumors] or others in the ''Using resources'' above). Therefore, it will not simply repeat such information, but may display external links to further information.

This resource also assumes that you will '''ask''' a colleague for advise if you see an unfamiliar presentation, and any literature lookup thereof still does not explain it. Therefore, this resource will focus on the most common presentations and the main differential diagnoses thereof, which may include rare conditions if the clinical management thereof would be significantly different. On the other hand, this resource omits rare conditions that rarely look similar to common presentations. Therefore, keep in mind that there are many such rare conditions that you do not know about, so keep asking colleagues whenever a presentation remains strange to you, and choose initial workplaces where you have experienced people to ask if needed.

Be tolerant to encountering many '''repetitions''' of the same content in related articles, since for example a [[cervical biopsy]] and a [[cervical cone]] have similar microscopic evaluation.

==Using AI "chatbots"==
For AI "chatbots" (such as ChatGPT, Gemini or Copilot), you can generally trust a simple answer to a simple and presumably common question. More complex answers generally require you to provide more details together with your question. For example, a question of "what is the risk that this patient has..." would require you to provide a patient summary for a better answer, while avoiding identifiable information.<ref group=notes">See [https://www.hhs.gov/hipaa/for-professionals/special-topics/de-identification/index.html#standard HHS de-identification standards] for what counts as identifiable information</ref>

==Using question banks==
To test your knowledge on memorization-worthy information, seek questions that present you with a possible real life situation, as well as all pertinent information you can readily look up before needing to answer the question, so to ensure that it tests you on pertinent information as per the items earlier in this chapter. On the other hand, don't waste time on questions whose answer requires memorization of look-up or practically useless information (except if you want to practice looking up the answers online). There are about 5700 questions in PathPrimer, PathDojo, BoardVitals, and the ASCP Question Bank combined,<ref group=note>As of July 2023, PathPrimer has 2270 Multiple Choice Questions (and has the highest quality of its questions despite an overall bad image quality), PathDojo has 1700, BoardVitals has 1050, and the ASCP Question Bank has 675 MCQs. AceMyPath has multiple whole slide images, but is not really a Qbank.</ref> so you can be picky about which questions to take and which ones to skip.

Consider the '''usefulness''' of each question before spending significant time memorizing its answers or explanations, in order to maximize the useful knowledge you will learn overall. Generally, skip questions that test you on look-up information and practically useless information. Whenever you have a question where you can not picture in what real life situation it would be relevant to remember, then you can generally assume that it never will be. For questions that consists of a useful item combined with a more useless one, only learn the the useful part and move on. The typical example of that combination is a memorization-worthy appearance of a disease, but then the question asks about a rather random fact that you can easily look up if you know the disease name. If you can, flag/mark questions on memorization-worthy information that you did not know, and move on fairly quick on those as well, and later revisit those questions specifically if you have the time, as repetition is generally more efficient than lingering.

A common sign that a question will deal with look-up or practically useless information is where it asks which of the alternatives is '''false or correct''' for one particular condition, and the alternatives are relatively heterogenous (such as one dealing with diagnosis and another one dealing with prognosis). The high prevalence of such questions is mainly because they are easy and quick create, because the question creator can simply look up a condition, choose some more or less random facts, and then change small details to create alternatives. It requires no real life experience in everyday pathology practice, and learning from such a question is hence generally not useful for that purpose either.<ref group=note>The highest yield questions are generally those with one teaching point per question. In contrast, for a true/false question to be of decent quality, each alternative should be relevant as per criteria above, but it is more difficult to create than low-quality ones. Since low-quality true/false questions are generated at much higher rate, the vast majority of true/false questions are subsequently low-quality.</ref> The thought processes of real life pathology is generally the opposite of this, because you are generally presented with a specific location, gross appearance and microscopic appearance, and you need to practice on finding the most likely causative condition thereof among many differential diagnoses. Even other kinds of memorization-worthy pieces of information generally have a more limited scope among alternatives (like knowing the optimal staining duration in hematoxylin for a frozen section among alternative durations (see [[Emergent pathology]]). Thus, to practice your knowledge in memorization-worthy pathology, it is generally most efficient to skip false-versus-correct questions, in order to spend your limited time on something more worthwhile. Similarly, questions are in general rather low-yield whenever they deviate from the realistic direction.

Also, prefer '''succinct''' questions, that give you only the most relevant information in order to test the key learning point, without having to spend effort finding the most relevant information in long patient presentations, because you will get enough practice of that in everyday scrolling through patient charts.

If you have gone through all 5000 questions of the main question banks, and still have plenty of time for a '''second round''', then you may work on lower yield questions as well. For example, you may practice on looking up answers for look-up questions, unless the presentation makes it clear that you cannot timely and conveniently do so (such as being in a rush during a frozen section).

{{Question|title=A question on a question|subsection=yes}}
You want to practice your memorization-worthy knowledge in real life pathology and not for exams ({{further|Secrets}}<includeonly>''as per the '''[[Secrets]]''' chapter at patholines.org.''</includeonly>). You find the following multiple choice question: "Which of the following statements for squamous cell carcinoma (SCC) of the skin is false?"
*For staging of SCC of the of the head and neck, pT1 corresponds to a diameter ≥ 2 cm and < 4 cm (this is the false alternative, as this defines pT2, whereas pT1 is defined as ≤ 2 cm)<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/skintumornonmelanocyticscc.html|title=Skin nonmelanocytic tumor, Carcinoma (nonadnexal), Squamous cell carcinoma|author=Shaofeng Yan, M.D., Ph.D.|website=Pathology Outlines}} Topic Completed: 13 January 2020. Minor changes: 8 December 2021</ref>
*Most patients have a favorable outcome after surgical resection.
*It occurs most often in sun exposed areas.
*It often presents as a hyperkeratotic scaly plaque.
*Microscopy typically shows carcinoma of keratinocytes that infiltrates the dermis.
What is the most efficient way of dealing with this question for real-life pathology practice?
#Choosing an answer, then thoroughly reviewing each alternative, as well as the question explanation.
#Like the first alternative, but only if you answered the question wrong.
#Only carefully review the single association you need to answer the question correctly (in this case, that for SCC of the skin, pT1 is defined as ≤ 2 cm).
#Skip this question and move on.
;'''Correct answer''':
[[File:Skip this question and move on.png|250px]]
 The answer alternatives of this question are all over the place (a mix of prognosis, location, staging, gross description and microscopic description), which usually means that it was created by just looking up the condition in a resource and picking information from there, resulting in a collection of what is usually just look-up information.

;'''Incorrect answers'''
You can skip reading these if you are already agree with the explanation above.
:1 and 2. These are waste of time.
:3. If this was a question of memorization-worthy information, or if you were studying for an exam, this would generally be the correct answer. However, staging of cancers can essentially always conveniently and timely be looked up when needed, so this is not memorization-worthy for everyday pathology practice.
{{Question-end}}
Other indications for '''skipping''' a question include:
*'''Unrealistically withholding''' information, such as mentioning what kind of test identified the condition without giving you the test result (such as a case presentation that includes "Serology identified the organism").
*'''Unrealistic chronology''', that is, not following the order of actual processes. It may include giving you the diagnosis and asking you what would be the expected clinical history.
*Showing you a '''molecular structure''' and asking you to identify the substance or its category, which is extremely unlikely to be a task in real life, and which can generally quickly be looked up (such as googling ''search by image'' and clicking the camera icon, followed by uploading the image of the structure, such as a photo or screenshot thereof).
*'''Unpractical statistics''' that is very unlikely to be used diagnostically, mainly because their calculations would be so complex that it is not worth it. For example, in reality you generally have a ''pattern'' of signs and other findings and you want to know the likelihood of each differential diagnosis, and for this purpose you only get limited help by knowing the reverse likelihood of what percentage each individual condition is to display the finding, because it would still be necessary to also know the epidemiology of each disease to calculate its likelihood.

==Learning clinical pathology==
{{Learning hematopathology}}
<noinclude>Still, if you get the task as a trainee to make a draft of a bone marrow, see '''[[Bone marrow]]'''.</noinclude>

For '''molecular pathology''', focus on learning the situations in which molecular workup is needed, rather than the specific derangement. The latter can generally easily be looked up when needed, whereas the former can easily be missed.

'''Microbiology''': {{Learning microbiology}}
<noinclude>
{{General notes}}
{{Bottom}}
</noinclude>

Evaluation

2026-01-28T18:37:37Z

Mikael Häggström: /* Marking slides */ Intro

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}</noinclude>
First, confirm that the '''identity''' of the sample evaluated is the same as that of the requisition form and/or other medical history.
==Microscopy settings==
[[File:Parts of a light microscope (english) - larger text.png|thumb|300px|Usual parts of a microscope.]]
If only one eye piece has adjustable '''focus''', you generally raise or lower the stage until you are in focus on the non-adjustable eyepiece, and then adjust the other eyepiece. {{Memorization-worthy}} With objectives that are close to the microscope slide, start focusing from what you know is a lower stage level, and slowly raise it from there, to avoid colliding with the objective and potentially damaging the slide.

<noinclude>Low magnification has a greater span of focus compared to high magnification, so it is normal to need to re-focus if you're switching to a higher magnification objective. However, if you find that you need to '''change focus''' even if going from high to low magnification, try the following (if you can adjust the eye piece):
#Use high magnification and focus on a specimen using the main focus knob.
#Switch to low magnification, and focus using the eye piece adjustment.</noinclude>
===Condenser===
Generally the '''condenser''' is placed in its highest position or just slightly lower. At low magnification objectives (mainly 4x and 10x objectives), the opening of the condenser (or iris) diaphragm should be wide open. This corresponds to turning away or "lowering" the condenser on microscopes where the condenser apparatus can be turned to the side (and is shown as "without condenser" in images below). For high-dry (40x) and oil-immersion objectives (100x), the diaphragm should be closed slowly while looking at a sharply focused section until the level of illumination is just slightly reduced, in order to attain optimal contrast and resolution (and corresponds to "with condenser" in images below).<ref>{{cite web|url=https://histologylab.ctl.columbia.edu/HistologyLabManual.pdf|title=Histology Laboratory Manual, Vagelos College of Physicians & Surgeons Columbia University|author=Patrice F Spitalnik|accessdate=2021-09-20}}</ref>
<gallery mode=packed heights=200>
File:Light microscopy with and without condenser.jpg|Light microscopy with and without condenser. At low magnification, using a condenser may limit the field of view, and in such cases it is preferable to not use it. At high magnification, a condenser makes borders less marked, and is generally preferable in such cases.
File:Calcium pyrophosphate dihydrate crystals without and with condenser, annotated.jpg|An example of a situation where microscopy without condenser is preferable at high magnification is the evaluation of '''crystals''' (calcium pyrophosphate dihydrate crystal deposition disease pictured).
File:Sclerosing adenosis with and without condenser.jpg|Looking without a condenser may also enhance '''basement membranes''', such as negating an invasive carcinoma in this case.
</gallery>

If there's a '''constant visual artifact''', even after you've cleaned the eye piece and objective lenses with lens tissue, try raising or lowering the condenser if you can, and the artifact may disappear out of focus.
</noinclude>

==Priority==
Whenever you have more than one case, generally have an '''initial look''' at the requisition form and/or in the microscope at the most likely relevant area of each case, and prioritize the case(s) that likely need to be done first. Indications to prioritize case(s) are mainly:
* '''Clinical management''' of the patient highly benefits from a fast diagnosis.
* Being '''marked''' as a rush case.
* There's a significant probability that it will require '''further workup''' such as [[immunohistochemistry]], especially when there is an impending deadline for ordering it.
* The optimal person to ask for '''advice''' may not be available later. {{Further|Consultation}}
As part of initial triaging, also determine what tasks can be '''delegated'' to juniors or pathologist assistants.

For a pile of many cases of relatively low risk of a need to prioritize any one over another, such as [[gastrointestinal biopsies]], a very quick glance at the forms and/or a naked eye look at the glass slides is generally sufficient.

==Main steps==
*Preferably, look up past '''medical history''' of the patient, mainly past cancers that could possibly appear in the current specimen.
*Try to pick up glass slides '''without touching''' the tissue area, as fingerprints may interfere with the evaluation.
*Look at each microscopy slide by plain '''eye''', to plan the microscopy scanning so as to not miss peripheral fragments.
*Have a '''systematic direction''' of scanning through microscopy slides, such as from top left to bottom right as seen in the microscope. When the microscope makes what you see two-way mirrored, the starting position is with the objective pointing at the bottom right of the glass slide. You may center on findings on interest and evaluate them at higher magnification, and then resume the scanning.
<gallery mode=packed heights=140px>
File:Position of objective (edited).jpg|Example starting position of objective.
File:Microscopy slide scanning.jpg|Example slide scanning movement.
</gallery>
<gallery mode=packed heights=170px>
File:Screening method 1.jpg|Starting at top left in the view, aim to scan a strip that trajects a circular field of view approximately at the clock positions shown...
File:Screening method 2.jpg|...When reaching the end of relevant material, set your eyes on any object at the edge of the strip that you just scanned...
File:Screening method 3.jpg|...Move the field of view over so that the object is seen on the opposite side. The new strip to be scanned will now be juxtaposed to the one you previously scanned.
</gallery>
This scanning technique above makes sure that you don't miss any area, and also minimizes redundant scanning. The width or clock position that you scan in each field of view is not exact, as you may scan up to the entire width in cases where you think relevant findings will clearly present themselves even if only partially showing in the periphery of your view.
*Look in particular for whatever is '''requested''' or '''suspected''' on the requisition form or equivalent. For each type of condition, initially you will generally focus relatively more on high magnification features with high specificity, but you should still have a habit of looking at '''low magnification''' as well to get an idea of its pattern. In time, you will increasingly correlate diseases and conditions with their overall low magnification patterns - patterns that may require 1000 words to describe and thus cannot conveniently be part of written criteria, but will nevertheless allow you to make quicker and more accurate diagnoses, or at least clues thereof.
*When you find something suspicious, it is helpful at least in the beginning to evaluate them systematically by a '''low-to-high magnification approach''' (example below showing a [[basal-cell carcinoma]]):
<gallery mode=packed heights=180px>>
File:Systematic microscopy 2 - Orientation.jpg|'''Orientation''' (lowest magnification): In this case oriented by the skin surface (green). A lesion is seen (red) and its demarcation can be discerned (diffuse in this case)
File:Systematic microscopy 3 - Architectural pattern.jpg|'''Architectural pattern''' of any suspicious cells, in this case nests of cells (an overview of patterns will be given later in this chapter), as well as components of the intervening stroma.
File:Systematic microscopy 4 - Cellular arrangement.jpg|'''Cellular arrangement''', including crowding and polarity (common tendencies among cells at the border, such as positions of nuclei within cells, cell elongation or "palisading" in this case). Amount of mitoses can also be appreciated at this level.
File:Systematic microscopy 5 - Subcellular features.jpg|'''Subcellular features''' (may need highest magnification)
</gallery>
*'''Complete''' the scanning even if you encounter a finding, as there may be additional findings as well. It is usually helpful to Google multiple images of the normal histology of the location you are looking at, and compare those to what you see, and focus on whatever features may deviate from the normal.

==General patterns==
Following are major patterns that often help in making a diagnosis.
===Architectural patterns===
<gallery mode=packed heights=190>
File:High-magnification micrograph of basal-cell carcinoma.jpg|'''Nests''': islands of cells of similar type.
File:Prostate adenocarcinoma - acinar pattern.jpg|'''Acinar''' or '''tubular''': Each acinus consists of cells that surround a lumen.
File:Typical carcinoid tumor of the lung, trabecular pattern.jpg|'''Trabecular''', elongated (rod-shaped) groups of cells.
File:Encapsulated Papillary Carcinoma of the Breast, H&E (15768688957).jpg|'''Papillary''': Protuberances of epithelioid cells around fibrovascular cores.
File:Micropapillary urothelial carcinoma, very high mag.jpg|'''Micropapillary''': Papillary tufts without fibrovascular cores
File:Histopathology of fascicular growth in a leiomyoma.jpg|thumb|'''Fascicular''': Generally the same cell type throughout, but some form band-like groups that are aligned in the same direction.
File:Histopathology of woven or storiform pattern.jpg|'''Woven''' or '''storiform''': Elongated cells or nuclei wherein small bundles are aligned in an otherwise haphazard pattern.
File:Micrograph of prostate cancer with Gleason score 10 (5+5) with solid sheets of cells (crop).jpg|'''Solid''' or "'''sheets'''": More or less the same cell type throughout, with no spaces between, and no other particular pattern.
File:Papillary urothelial carcinoma with cribriform morphology, very high mag.jpg|'''Cribriform''': Solid with multiple clear spaces.
File:Bovine Bone Sample and 430 times Magnification.jpg|'''Whorled''': Multiple concentric objects, or spiral-shaped
File:Histopathology of cartwheel pattern in dermatofibrosarcoma protuberans, annotated.jpg|'''Cartwheel pattern''': Center points that radiate cells or connective tissue outward
</gallery>

===Cellular patterns===
<gallery mode=packed heights=170>
File:Eosinophilic, basophilic, chromophobic and amphophilic staining.png|Main staining types of the cytoplasm when using hematoxylin and eosin (H&E).
File:Histopathology of ovarian serous borderline tumor with hobnailing.jpg|'''Hobnailing''': smooth projections from an epithelial surface.
</gallery>

===Nuclear patterns===
When feasible, classify nuclei as follows:
<gallery mode=packed heights=180>
File:Histopathology of clear cell renal cell carcinoma, grade 1, high magnification.jpg|'''Monomorphic''' when having relatively similar sizes and shapes.
File:Pleomorphic nuclei.jpg|'''Pleomorphic''' when having different sizes and shapes. This often correlates with an increased '''nucleus to cytoplasm ratio'''. These features generally favor malignancy in the '''[[evaluation of suspected malignancies]]'''.
File:Fine versus coarse chromatin.jpg|'''Fine chromatin''' when inconspicuous (essentially only nucleoli seen in the nuclei), versus '''coarse''' chromatin.
File:Heterochromatic versus euchromatic nuclei.jpg|Sometimes "heterochromatic" versus "euchromatic" nuclei are used, but this strictly refers to the molecular structure of DNA, so you may simply use fine versus coarse.
File:Well-differentiated neuroendocrine tumor with salt-and-pepper chromatin.png|Granular "salt-and-pepper" chromatin.
</gallery>
;Patterns of nuclear disintegration:
<gallery mode=packed heights=250>
File:Nuclear changes.jpg
</gallery>

===Other patterns===
<gallery mode=packed heights=180>
File:Histology of deep zone of articular cartilage.jpg|'''Hyaline''' usually refers to extracellular material that stains homogeneously pink on H&E stain (like the matrix of hyaline cartilage, pictured).
File:Histopathology of hyaline membranes in diffuse alveolar damage.jpg|Example of hyaline material (in alveoli of lungs, indicating diffuse alveolar damage)
File:Glass for pathologist.png|This is what pathologists also refer to as "glassy" (because hyaline cartilage looks like glass grossly).
</gallery>

==Inflammation==
<gallery mode=packed heights=180px>
File:Histopathology of acute cholecystitis with neutrophils.jpg|'''Neutrophils''' generally confers a diagnosis of '''acute inflammation'''.
File:Histopathology of mucosal plasma cell infiltrate in chronic gastritis.jpg|'''Plasma cells''' and '''lymphocytes''' generally confers a diagnosis of '''chronic inflammation''' if present in increased amount for the location.
File:Histopathology of intravascular neutrophils.jpg|However, disregard intravascular white blood cells.
</gallery>

==Marking slides==
The main indications for marking slides are hard-to-see findings on a slide, and/or to distinguish one slide out of many. Just make a figure rather than a word if you are not sure what it is, as it might be confusing for reviewers if the pathology report ends up being something different.
<gallery mode=packed heights=140>
File:Photograph of marking a microscopy slide.jpg|To mark a microscopy slide, use an objective that gives you enough space underneath. Rest a finger on the stage, while holding the marker pen relatively close to its tip. Move the tip of the marker pen into the field of view but at least a few millimeters from the slide...
File:Micrograph of marking a microscopy slide.jpg|...Then slowly approach the slide while making sure that the tip remains in the location you want to mark. Be careful not to obscure findings of interest with the mark. If the slide is likely to undergo whole slide imaging, make the mark on the back and not on the coverslip (as it reduces the risk of erroneous focusing of the cameras).
File:Wiping a slide.png|You can generally remove marks from a microscopy slide by using alcohol. Hold the cover slip in place with two fingers while wiping from side to side, to avoid the risk of moving the coverslip. Don't press hard against the glass, as it may disrupt the tissue.
</gallery>

==Measuring distances==
<gallery mode=packed heights=220>
File:Measurement using transparent ruler in microscopy.jpg|You can use a regular transparent ruler for most purposes, since it is rarely necessary to specify distances as more exact than millimeters. It works best on low magnification.
File:Measurement of tumor size on two microscopy slides.jpg|Alternatively, mark the limits under microscopy, and then use a regular ruler to measure the dimensions. This works even if the distance exceeds the field of view, or spans more than one slide.
File:Calibration slide with rulers and grids.jpg|Rarely, sub-millimeter measurement is needed, in which case you may use a calibration slide, which is basically a translucent ruler with 0.1 mm line resolution or smaller, which may cost about $15 if none of your colleagues has one to lend, or the department can't provide one for you.
File:Measuring distance on a microscopy slide using a calibration slide.jpg|To measure distance with a calibration slide, put it on top of the tissue slide and switch focus between the two.
</gallery>
There are also eye pieces that show a ruler in the field of view, but make sure you match it with the correct objective and other settings to make the measurement valid. A calibration slide is more robust because of such sources of error.

==Counts per mm2==
There are multiple situations where a finding will be quantified in terms of amount per mm2. To make such calculations, you need to know the size of the area you see in the microscope. It is usually possible to look up what theoretically would be the area, but the most reliable way of knowing is to use a calibration slide to measure the diameter of your view. The area is then calculated as:
*Area in mm2 ≈ (diameter in mm2) x 0.79

<gallery mode=packed heights=220>
File:Micrograph of a calibration slide, showing the diameter of the field of view.jpg|Micrograph of a calibration slide, showing the diameter of the field of view.
</gallery>
On the imaged example, each square is 0.05 mm wide, and each line represents 0.01 mm, making the diameter of the field of view 0.55 mm in this case. Thus, you can calculate the area in mm2 by Googling:
:0.55 x 0.55 x 0.79
:(equals approximately 0.24 mm2).

Generally count at least 10 fields of a high power view (or more if specifically instructed). You can keep the count in your head by repeating the total count and the order of the area you are looking at, such as:
*"Zero (instances) of one (field of view)"
*"One of two (as you see one instance as you've moved to the second field of view)"
*"Two of two" etc.
Subsequently, the '''count per mm2''' is calculated as follows:
{|
|rowspan=2| Count per mm2 = ||align=center| Total count
|-
| Number of fields x Area per field (in mm2)
|}

For example, if you reached "15 of 10", and the area of your field is 0.2 mm2, the count per mm2 can be calculated by Googling:
:15/10/0.2
:= 7.5

Sometimes '''"high power field"''' (HPF) is used for area, but it has a substantially different area for different microscopes, for example:
{|class="wikitable"
! Microscope type !! Area per HPF
|-
|
*Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece
*Olympus BX43 with 10x eyepiece
| 0.096 mm2 <ref name=stanford-idc>{{cite web|url=http://surgpathcriteria.stanford.edu/breast/infductcabr/grading.html|title=Infiltrating Ductal Carcinoma of the Breast (Carcinoma of No Special Type)|website=Stanford University School of Medicine|accessdate=2019-10-02}}</ref>
|-
| AO with 10x eyepiece || 0.12 mm2 <ref name=stanford-idc/>
|-
| Nikon Eclipse E400 with 10x eyepiece and 40x objective || 0.25 mm2
|-
| Leitz Ortholux || 0.27 mm2 <ref name=stanford-idc/>
|-
| Leitz Diaplan || 0.31 mm2 <ref name=stanford-idc/>
|}

When your instructions are to '''count a specific number of HPFs''', one HPF can be assumed to be 0.2 mm2.<ref name="KlimstraModlin2010">{{cite journal|last1=Klimstra|first1=David S.|last2=Modlin|first2=Irvin R.|last3=Coppola|first3=Domenico|last4=Lloyd|first4=Ricardo V.|last5=Suster|first5=Saul|title=The Pathologic Classification of Neuroendocrine Tumors|journal=Pancreas|volume=39|issue=6|year=2010|pages=707–712|issn=0885-3177|doi=10.1097/MPA.0b013e3181ec124e}}</ref> If the view area in your microscope significantly differs from this area, calculate how many views you need to count as:
{|class=
|rowspan=2| Views = HPFs required x ||align=center| 0.2
|-
| Your microscope area (in mm2)
|}

For example, if your instruction is to count 10 HPFs and each view in your microscope shows 0.096 mm2, you should count in this many views:
{|
|rowspan=2| 10 x ||align=center|0.2 ||rowspan=2| ≈ 21
|-
| 0.096
|}

Subsequently, if your microscope area is significantly different from 0.2 mm2 and you need to '''state your result in terms of count/HPF''', use:

{|
|rowspan=2| Count/HPF = Average count in your view x ||align=center| 0.2
|-
| Area of your view in mm2
|}

For example, if you have counted an average of 10 cells (or other object of interest) in each of your views, and the area of your view is 0.096 mm2, then your count/HPF is:
{|
|rowspan=2| 10 x ||align=center| 0.2 ||rowspan=2| ≈ 21
|-
| 0.096
|}

==Artifacts==
In microscopy, an artifact is an apparent structural detail that is caused by the processing of the specimen and is thus not a legitimate feature of the specimen. Major artifacts to account for include:
<gallery mode=packed>
File:Cellulose contamination in H&E and polarized light.jpg|Cellulose '''contamination''', here seen on H&E stain and polarized light, respectively. In contrast to foreign bodies that were truly in the specimen, contamination overlaps with or disrupts tissue more unnaturally.
File:Histopathology of cardiac muscle with contamination from thyroid tissue.jpg|Cardiac muscle (bottom) with '''contamination''' from thyroid tissue (center).
File:Crush artifact from forceps.jpg|'''Crush''' artifact from compression by forceps on the tissue sample.
File:Skin with folds and crush artifact by needle.jpg|'''Folding''' artifacts (white arrows) and a crush artifact (black arrow, with dark cytoplasmic staining and nuclear pleomorphism) from a needle.
File:Tearing artifacts in histopathology.jpg|'''Tearing''' artifacts, such as can be caused by: - Microtomy with a nick or blemish in the knife edge.<ref name="TaqiSami2018">{{cite journal|last1=Taqi|first1=SyedAhmed|last2=Sami|first2=SyedAbdus|last3=Sami|first3=LateefBegum|last4=Zaki|first4=SyedAhmed|title=A review of artifacts in histopathology|journal=Journal of Oral and Maxillofacial Pathology|volume=22|issue=2|year=2018|pages=279|issn=0973-029X|doi=10.4103/jomfp.JOMFP_125_15}}</ref> - Traction of the sections. - Too much or too little alcohol dehydration.<ref name="TaqiSami2018"/> - Sectioning calcified parts, which can be decalcified or removed.<ref name="TaqiSami2018"/>
File:Microscopy of liver parenchyma with tearing artifacts.jpg|More '''tearing''' artifacts, showing that they may be more circular than fusiform.
File:Formalin pigment artifacts.jpg|''''Formalin pigment''' artifacts
File:Air bubble entrapment artifacts.jpg|'''Air bubble entrapment''' artifacts
File:Staining artifacts by residual wax.jpg|'''Staining''' artifacts by residual wax, resulting in pale areas where cellular structures are not discernible.
File:Histopathology of radically excised basal-cell carcinoma with separation artifact (horizontal layout).jpg|A '''separation''' artifact in top image makes the tumor look incompletely excised, but the next microtomy level (bottom image) shows a surgical margin of connective tissue.
</gallery>
Differential diagnoses of artifacts are mainly:
*'''Foreign bodies'''. In contrast to contamination, these conform more naturally to the surrounding tissue.
*'''Organisms''', to be particularly considered when there are multiple objects of the same size.

Order '''recuts''' from the same paraffin-embedded tissue if artifacts significantly impairs your diagnostic evaluation of the glass slide. However, artifacts caused by gross processing may affect recuts as well.

==Micrography and telepathology==
Unless you have more specific equipment for taking microscopic images and showing cases to remote colleagues, you can perform these tasks as follows:
*With a '''stationary computer''', you can connect to a microscopy camera. For telepathology, you can start a videoconferencing session with your senior, then share the screen while showing a micrograph, or the live view so that you can move around.
*With a '''mobile phone''':
<gallery mode=packed heights=240>
File:Micrography with a smartphone 1.jpg|To perform '''micrography''' with a smartphone, stabilize the smartphone over the eyepiece (preferably using both hands), about 3-5 cm away from it, and direct it on the bright circle on your phone display...
File:Micrography with a smartphone 2.jpg|...and then slowly move the smartphone closer to the eyepiece, while adjusting both direction and location so as to keep the bright circle in the center of the display, until the camera is able to focus and you have a visible field that is large enough for evaluation, and then take your photos.
</gallery>
:You can send micrographs to your senior, but it is technically difficult to keep the focus while moving the glass slide.
<noinclude>
==Cytology==
In cytology samples, or any sample with scattered cells rather than coherent tissue, also evaluate the following:
*Adequacy of specimen. Cells may be too few or too obscured by other material to make a proper diagnosis.
*Background, mainly if it is clear or dirty
*Overall cellularity
{{further|Cytology}}</noinclude>
==Consideration==
Consider the '''adequacy''' of the specimen. Have a somewhat lower threshold to make a report of "inadequate" or "insufficient" if it is easy to resample from the patient, such as remaining diagnostic tissue at a superficial location.

First, generally suspect the '''common conditions''' for the location at hand. A less common variant of a common condition is often still more likely than a rare condition, so generally call the latter only if it really fits the picture.

Whenever you consider a certain diagnosis, also consider whether it is one step '''better or worse'''. For example, when you consider a non-invasive but high-grade dysplasia, also consider both low-grade dysplasia and invasiveness.
</noinclude>
{{General notes}}
{{Bottom}}
</noinclude>

Talk:Lymph nodes

2026-01-06T21:53:35Z

Mikael Häggström: Moved from main

==Definition of an enlarged lymph node==
Moved to here since it's not that relevant.
[[File:Long and short axis.png|120px|right]]
*By size, where lymphadenopathy in adults is often defined as a short axis of one or more lymph nodes is greater than 10mm.<ref name="GaneshalingamKoh2009"/><ref name="Schmidt JúniorRodrigues2007"/> However, there is regional variation as detailed in this table:
{|class="wikitable"
|+Upper limit of lymph node sizes in adults
|-
| Generally || 10 mm<ref name="GaneshalingamKoh2009">{{cite journal|last1=Ganeshalingam|first1=Skandadas|last2=Koh|first2=Dow-Mu|title=Nodal staging|journal=Cancer Imaging|volume=9|issue=1|pages=104–111|year=2009|issn=1470-7330|doi=10.1102/1470-7330.2009.0017|pmid=20080453|pmc=2821588}}</ref><ref name="Schmidt JúniorRodrigues2007">{{cite journal|last1=Schmidt Júnior|first1=Aurelino Fernandes|last2=Rodrigues|first2=Olavo Ribeiro|last3=Matheus|first3=Roberto Storte|last4=Kim|first4=Jorge Du Ub|last5=Jatene|first5=Fábio Biscegli|title=Distribuição, tamanho e número dos linfonodos mediastinais: definições por meio de estudo anatômico|journal=Jornal Brasileiro de Pneumologia|volume=33|issue=2|year=2007|pages=134–140|issn=1806-3713|doi=10.1590/S1806-37132007000200006|pmid=17724531|doi-access=free}}</ref>
|-
| Inguinal || 10<ref name=Torabi2004>{{cite journal | vauthors = Torabi M, Aquino SL, Harisinghani MG | title = Current concepts in lymph node imaging | journal = Journal of Nuclear Medicine | volume = 45 | issue = 9 | pages = 1509–18 | date = September 2004 | pmid = 15347718 }}</ref> – 20 mm<ref>{{cite web|url=http://bestpractice.bmj.com/best-practice/monograph/838/diagnosis/step-by-step.html|title=Assessment of lymphadenopathy|website=[[BMJ Best Practice]]|accessdate=2017-03-04}} Last updated: Last updated: Feb 16, 2017</ref>
|-
| Pelvis || 10 mm for ovoid lymph nodes, 8 mm for rounded<ref name=Torabi2004/>
|-
!colspan=2|Neck
|-
| Generally (non-retropharyngeal) || 10 mm<ref name=Torabi2004/><ref name=Saba2016>[https://books.google.com/books?id=q7v1CwAAQBAJ&pg=PA432 Page 432] in: {{cite book|title=Image Principles, Neck, and the Brain|author=Luca Saba|publisher=CRC Press|year=2016|isbn=9781482216202}}</ref>
|-
| Jugulodigastric lymph nodes || 11mm<ref name=Torabi2004/> or 15 mm<ref name=Saba2016/>
|-
| Retropharyngeal || 8 mm<ref name=Saba2016/>
*Lateral retropharyngeal: 5 mm<ref name=Torabi2004/>
|-
!colspan=2|Mediastinum
|-
| [[Mediastinum]], generally || 10 mm<ref name=Torabi2004/>
|-
| Superior mediastinum and high paratracheal || 7mm<ref name="SharmaFidias2004"/>
|-
| Low paratracheal and subcarinal || 11 mm<ref name="SharmaFidias2004">{{cite journal|last1=Sharma|first1=Amita|last2=Fidias|first2=Panos|last3=Hayman|first3=L. Anne|last4=Loomis|first4=Susanne L.|last5=Taber|first5=Katherine H.|last6=Aquino|first6=Suzanne L.|title=Patterns of Lymphadenopathy in Thoracic Malignancies|journal=RadioGraphics|volume=24|issue=2|year=2004|pages=419–434|issn=0271-5333|doi=10.1148/rg.242035075|pmid=15026591|url=https://semanticscholar.org/paper/145256a2605c552c77534f2a509227902440bf7b}}</ref>
|-
!colspan=2| Upper abdominal
|-
| Retrocrural space || 6 mm<ref name="DorfmanAlpern1991">{{cite journal|last1=Dorfman|first1=R E|last2=Alpern|first2=M B|last3=Gross|first3=B H|last4=Sandler|first4=M A|title=Upper abdominal lymph nodes: criteria for normal size determined with CT.|journal=Radiology|volume=180|issue=2|year=1991|pages=319–322|issn=0033-8419|doi=10.1148/radiology.180.2.2068292|pmid=2068292}}</ref>
|-
| Paracardiac || 8 mm<ref name="DorfmanAlpern1991"/>
|-
| Gastrohepatic ligament || 8 mm<ref name="DorfmanAlpern1991"/>
|-
| Upper paraaortic region || 9 mm<ref name="DorfmanAlpern1991"/>
|-
| Portacaval space || 10 mm<ref name="DorfmanAlpern1991"/>
|-
| Porta hepatis || 7 mm<ref name="DorfmanAlpern1991"/>
|-
| Lower paraaortic region || 11 mm<ref name="DorfmanAlpern1991"/>
|}

Lymphadenopathy of the '''axillary''' lymph nodes can be defined as solid nodes measuring more than 15 mm without fatty hilum.<ref name=dahnert2011>[https://books.google.com/books?id=uYREa2bKNW8C&pg=PA559 Page 559] in: {{cite book|title=Radiology Review Manual|author=Wolfgang Dähnert|publisher=Lippincott Williams & Wilkins|year=2011|isbn=9781609139438}}</ref> Axillary lymph nodes may be normal up to 30 mm if consisting largely of fat.<ref name=dahnert2011/>

In '''children''', a short axis of 8 mm can be used.<ref>[https://books.google.com/books?id=nmpI1bLGCV4C&pg=PA942 Page 942] in: {{cite book|title=High Yield Imaging Gastrointestinal HIGH YIELD in Radiology|author=Richard M. Gore, Marc S. Levine|publisher=Elsevier Health Sciences|year=2010|isbn=9781455711444}}</ref> However, inguinal lymph nodes of up to 15 mm and cervical lymph nodes of up to 20 mm are generally normal in children up to age 8–12.<ref>{{cite web|website=[[Patient UK]]|url=http://patient.info/doctor/generalised-lymphadenopathy|title=Generalised Lymphadenopathy|author=Laurence Knott|accessdate=2017-03-04}} Last checked: 24 March 2014</ref>

Lymphadenopathy of more than 1.5 cm - 2 cm increases the risk of cancer or granulomatous disease as the cause rather than only inflammation or infection.<ref name="pmid12484692">{{cite journal | vauthors = Bazemore AW, Smucker DR | title = Lymphadenopathy and malignancy | journal = American Family Physician | volume = 66 | issue = 11 | pages = 2103–10 | date = December 2002 | pmid = 12484692 }}</ref>

Lymph nodes

2026-01-06T21:53:01Z

Mikael Häggström: Moved to talk page

{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
{{Comprehensiveness}}
==Gross processing==
If suspected '''[[lymphoma]]''', before putting tissue in formalin, ensure that tissue is preserved in appropriate media for any special tests (usually flow cytometry). {{further|Lymphoma}}

In samples with '''tumors''', slice through all included fat while palpating and looking for lymph nodes, and submit all that are found.

For lymph nodes taken for potential '''breast cancer''' metastasis, find out and report the procurement time and the time when put in formalin.<ref group=note>The duration that a specimen has been without formalin affects mainly the reliability of estreogen and progesteron receptor testing: - {{cite journal|last1=Pekmezci|first1=Melike|last2=Szpaderska|first2=Anna|last3=Osipo|first3=Clodia|last4=Erşahin|first4=Çağatay|title=The Effect of Cold Ischemia Time and/or Formalin Fixation on Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor-2 Results in Breast Carcinoma|journal=Pathology Research International|volume=2012|year=2012|pages=1–7|issn=2090-8091|doi=10.1155/2012/947041}}</ref>

===Gross procedure===
*'''Measure''' the dimensions. For a lymph node with minimal surrounding fatty tissue, measure the greatest dimension {{Moderate-begin}}or 3 dimensions{{Moderate-end}}. For specimens with substantial amount of fatty tissue, measure the specimen in 3 dimensions, and measure the greatest dimension seen for individual lymph nodes therein after serial sectioning.
*'''Find''' as many lymph nodes as you can in a specimen. Good locations to start include the presumed lymphatic drainage directions from a tumor, as well as when following the lymphatic directions from the vascular margins of a specimen. Serially section fatty tissue into slices that are thin enough to be palpated for small ovoid resistances. If you still have trouble finding enough lymph nodes, put fatty tissue in a vinegar and acetic acid solution made for the purpose of turning lymph nodes pale/white as well as making them more firm for palpation. [[Colon tumor]]s are sometimes tattooed during endoscopy, and in such cases the tatoo ink often stains lymph nodes as well.
<gallery mode=packed heights=200>
File:Gross pathology of a mesenteric lymph node.jpg|Gross pathology of a mesenteric lymph node.
File:Gross pathology of mesorectal lymph node after acetic acid.jpg|Lymph node in partially inked mesorectal fat after a night in '''acetic acid'''.
</gallery>
*'''Section''' lymph nodes if needed. Lymph nodes less than 5 mm may be submitted whole, while larger lymph nodes may be sectioned at 2-3 mm intervals.<ref>{{cite web|url=https://documents.cap.org/protocols/cp-skin-melanoma-biopsy-19-4100.pdf|title=Protocol for the Examination of Biopsy Specimens From Patients With Melanoma of the Skin|website=College of American Pathologists}} Version: Melanoma Biopsy 4.1.0.0 Protocol Posting Date: August 2019</ref>
*Generally do not submit multiple sectioned lymph nodes in the same '''cassette''', to allow exact counting of the number of involved lymph nodes on microscopy. If you will nevertheless submit multiple bisected lymph nodes in the same cassette, '''[[ink]]''' each lymph node differently.
[[File:Touch prep on a lymph node.jpg|thumb|220px|Making a "touch prep": Press a glass slide against the cut surface of the lymph node, apply cytologic fixative solution immediately and stain with H&E.]]
*If suspected '''[[lymphoma]]''', such as an enlarged lymph node without any adjacent tumor or another almost certain cause, make a touch prep. Also, take a small fresh sample for flow cytometry:
:*For '''flow cytometry''', aim for a tissue size of approximately 5 mm3. Put it in specific flow cytometry preservative medium (such as RPMI), and ensure it gets to the flow cytometry lab. If it is after normal hours and there is no one to ask to find such medium, you can put the specimen in normal sterile saline (enough to cover the tissue) in a fridge (2-8°C) until the next morning.<ref>{{cite web|url=https://lifelabs.azureedge.net/lifelabs-wp-cdn/wp-content/uploads/2018/08/SPECIMEN-INFORMATION-AND-REQUIREMENTS-FOR-FLOW-CYTOMETRY-TESTING.pdf|title=Specimen Information and Requirements for Flow Cytometry Testing|website=Lifelabs}} Doc #8218 Ver: 7.0 Current Issued: 13-Apr-2018</ref> If you receive multiple lymph nodes for flow cytometry, still only sample one (unless the referral asks for separate flow cytometry studies, or there is a given history of one lymph node having high uptake and another having low uptake on PET scanning).

===Urgency===
The processing of lymph nodes is preferably rushed when the H&E stain will determine whether immunohistochemistry will be performed, especially when a lymph node is submitted together with a separate specimen that may be solved without immunostains. This rushing allows you to have the immunostained slides by a similar time as the rest of the case.<ref name="pmid12610108">{{cite journal| author=Chandler IP, Oommen R, Lawson CW| title=Invasive lobular carcinoma and cytokeratin immunohistochemistry: an audit. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 240 | pmid=12610108 | doi=10.1136/jcp.56.3.240 | pmc=1769908 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610108 }} </ref> Examples of cases that are preferably rushed for such reasons include those that may be stained by CK AE1/AE3 in order to visualize otherwise occult lymph node involvement if you don't see any involvement on the H&E stain, mainly in cases when one or more sentinel lymph nodes are submitted together with any of the following:
*A [[breast biopsy or excision]] of a suspected or previously confirmed [[invasive lobular carcinoma]] (but not necessarily invasive carcinoma with lobular features)
*A [[uterus]] specimen of a suspected or previously confirmed [[endometrial cancer]].
Rushing is not necessary for non-sentinel lymph nodes.

===Gross report===
;Individual lymph node, example:
{{Report-begin}} __ fragment(s) of soft pink-tan tissue, measuring __ cm in greatest dimension {{Moderate-begin}}or __ x __ x __{{Moderate-begin}}.{{Report-end}}

;Multiple lymph nodes
{{Report-begin|fresh=yes}} 2 irregular fragments of yellow-tan fatty and fibrous soft tissue measuring __ and ___ cm in greatest dimension. Within the adipose tissue are multiple tan-brown lymph nodes measuring up to __ cm in greatest dimension. The cut surfaces display no gross lesions. The lymph nodes are entirely submitted for microscopic examination {{Moderate-begin}}in 10 cassettes{{Moderate-end}}. KEY TO SECTIONS:
*A1–A3– one lymph node, serially section
*A4-A5– one lymph node, serially sectioned
*A6– one lymph node, bisected
*A7– one lymph node, bisected
*A8– two lymph nodes, each bisected, differentially inked
*A9– one lymph node, bisected
*A10– multiple lymph nodes.
|}

;Additional information
*If potential breast cancer metastasis: The specimen was procured at __ AM/PM on (date), 2020. The specimen was placed in formalin at __ AM/PM on (date), 2020.
*If '''[[lymphoma]]''' workup: A touch prep is made, and a minor part of the specimen is submitted for flow cytometry. The remainder of the specimen is submitted for microscopic examination in one cassette.

==Microscopic examination==
===Defining a lymph node===
For counting lymph nodes, each should have a discernible capsule around lymphoid cells. Also count larger free-standing lymphoid aggregates. However, the definition of what constitutes a lymph node is largely subjective.<ref>{{cite journal| author=Parkash V, Bifulco C, Feinn R, Concato J, Jain D| title=To count and how to count, that is the question: interobserver and intraobserver variability among pathologists in lymph node counting. | journal=Am J Clin Pathol | year= 2010 | volume= 134 | issue= 1 | pages= 42-9 | pmid=20551265 | doi=10.1309/AJCPO92DZMUCGEUF | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20551265 }}</ref> Also strive to keep a consistency with the gross description. In addition, any cancer involvement is in itself a relative indication of being a lymph node.

===General screening===
Look for:
*Whatever pathology is '''indicated''' by the referral, or findings in other submitted specimens.
:*'''Enlargement''', as preferably measured during grossing, but can possibly be made on the microscopy slide. If present, see separate section below.
<gallery mode=packed heights=200>
File:Microscopic lymph node screening.jpg|'''Metastases''': generally first look around the edges with intermediate magnification, and low mag in the middle, since cancer metastases usually occur at edges (as in this case). For suspected urothelial cancers, however, look closely throughout the node, as they have a tendency to show up anywhere in lymph nodes.
File:Lymph node metastasis from neuroendocrine tumor.jpg|Lymph node '''metastasis''' from a [[neuroendocrine tumor of the midgut]]. Metastates generally look similar to its primary tumor.
File:Granuloma 20x.jpg|'''Granulomas''' (non-necrotizing granuloma pictured). If seen generally perform staining for acid-fast bacilli, and GMS stain for fungi.
</gallery>

===Microscopy of enlarged lymph nodes===
Look at any '''other slides''' for the same case first, in order to find any pathology that may be reflected in in the lymph nodes as well, mainly cancer metastasis or '''[[reactive lymph node]]s''' from inflammation.

Look primarily at the overall '''architecture''', with main findings being:
<gallery mode=packed heights=220>
File:Histopathology of reactive follicular hyperplasia.jpg|'''Follicular hyperplasia''': Indicates mainly ''follicular hyperplasia of a '''[[reactive lymph node]]''''' (pictured) or ''follicular lymphoma''. {{Further|Follicular hyperplasia|linebreak=no}}
File:Sinus histiocytosis (intermediate magnification).jpg|'''Dilated sinuses'''. The most cellular expansion is '''sinus histiocytosis''' (pictured). If it appears as such, look for a ''signet ring appearance'', which may be a [[signet ring carcinoma]] or [[melanoma]]. If unsure, use immunostains for CD68, cytokeratin, S100 and mucin.<ref name="EganJaffe2018">{{cite journal|last1=Egan|first1=Caoimhe|last2=Jaffe|first2=Elaine S.|title=Non-neoplastic histiocytic and dendritic cell disorders in lymph nodes|journal=Seminars in Diagnostic Pathology|volume=35|issue=1|year=2018|pages=20–33|issn=07402570|doi=10.1053/j.semdp.2017.11.002}}</ref>
</gallery>
*'''Paracortical hyperplasia''': Paracortical hyperplasia of a '''[[reactive lymph node]]''' shows expansion of paracortical areas by a mixed infiltrate, often having a mottled appearance, and it usually has a concomitant reactive follicular hyperplasia.<ref name="WeissO'Malley2013">{{cite journal|last1=Weiss|first1=Lawrence M|last2=O'Malley|first2=Dennis|title=Benign lymphadenopathies|journal=Modern Pathology|volume=26|issue=S1|year=2013|pages=S88–S96|issn=0893-3952|doi=10.1038/modpathol.2012.176}}</ref> A [[T-cell lymphoma]] should be suspected if there is obliteration or marked diminution of the B-cell cortical region, or highly irregular or hyperchromatic nuclei.<ref name="WeissO'Malley2013"/>
*'''Unspecific hyperplasia''': An unspecific pattern of lymph node enlargement, without atypical cells, in the lymphatic drainage direction from an inflamed area, may simply be diagnosed as "benign '''[[reactive lymph node]]'''".

===Workup of cancerous lymph nodes===
If cancer is detected in a lymph node:
*Attempt to specify a specific cancer ''diagnosis'''. If the patient has a known carcinoma or sarcoma etc, it is generally enough to confirm that it is consistent with a metastasis thereof.
*Measure the '''size''' of involvement.
*Look for '''extranodal extension'''.

==Reporting==
A non-involved lymph node in a patient with cancer can be reported for example as:
{|class=wikitable
| Sentinel lymph node #1, left axilla, {{Moderate-begin}}excision{{Moderate-end}}: One benign lymph node{{Comprehensive-begin}}, negative for malignancy (0/1){{Comprehensive-end}}.
|}

Cancerous lymph nodes with patients with known consistent cancer primary can be reported as metastatic,, such as:
{|class=wikitable
| Sentinel lymph node #2, left axilla, {{Moderate-begin}}excision{{Moderate-end}}: Macrometastatic carcinoma involving one of one (1/1) lymph node. Metastatic carcinoma measures 0.4 cm in greatest dimension. {{Moderate-begin}}Negative for extranodal extension{{Moderate-end}}.
|}
{{Bottom}}

General guidelines

2025-12-17T19:53:06Z

Mikael Häggström: /* General advice */ Update

<noinclude>{{Top
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}}</noinclude>
==General advice==
*When making a mistake, '''admit''' that you did it and '''learn''' from it so as to focus on not repeating it. Also learn from the mistakes of others.
*Say '''"I don't know"''' instead of making up answers for what you do not know.
*'''Ask for help''' whenever needed, such as first time you are doing something, or whenever you are not sure about what to do, especially when doing something potentially irreversible. Also ask for help in moments whenever there is a high risk that you will not achieve what you need to do within a clinically acceptable time. Still, before asking, '''try''' to do as much as you can, as long as you do not do anything potentially irreversible, so that you can evaluate how you did it compared to the standard, and thereby know better how you will do it next time.
*Try to '''fit''' findings with the clinical picture so that the report makes sense, but '''do not make up''' findings that you do not see, especially in cases where you copy-paste words from a previous report or template. At the same time, do not '''omit''' relevant features just to fit an expected story.
*'''Do not wait for the whole pile'''. Whenever you can, do not be idle or do less urgent work while there is a pile of more urgent work gathering for you elsewhere. Instead, be familiar with where such piles are forming, and go there and grab whatever you may start working on right away.
*For larger specimens that need fixation before final grossing, you can still '''start writing''' a report of measurements and other externally visible findings to save time for later.
*'''Save''' your digital reports frequently.
*Focus on '''learning''' pitfalls and the interpretation of visual patterns and other non-written results, and do not waste much time memorizing information that can essentially always be conveniently and timely looked up when needed (but have an idea of where to find it). {{further|Learning pathology}}
<noinclude>
*Whenever you '''update''' something in a report, consider if it needs updating at other locations as well, such as in an attached synoptic report.
*Always at least have a '''look''' at your cases, for even if the order implies that someone else is more suitable for it, it may turn out to have a very simple answer.
*When ordering '''additional tests on an older sample''', such as when wanting to compare it to a more current one, it is a courtesy to notify whoever reported on the older sample.

==Topics==
{{List of general notes}}
{{List of more general notes}}
{{Bottom}}
</noinclude>

Evaluation

2025-06-03T20:48:09Z

Mikael Häggström: /* Microscopy settings */ Expanded

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
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First, confirm that the '''identity''' of the sample evaluated is the same as that of the requisition form and/or other medical history.
==Microscopy settings==
[[File:Parts of a light microscope (english) - larger text.png|thumb|300px|Usual parts of a microscope.]]
If only one eye piece has adjustable '''focus''', you generally raise or lower the stage until you are in focus on the non-adjustable eyepiece, and then adjust the other eyepiece. {{Memorization-worthy}} With objectives that are close to the microscope slide, start focusing from what you know is a lower stage level, and slowly raise it from there, to avoid colliding with the objective and potentially damaging the slide.

<noinclude>Low magnification has a greater span of focus compared to high magnification, so it is normal to need to re-focus if you're switching to a higher magnification objective. However, if you find that you need to '''change focus''' even if going from high to low magnification, try the following (if you can adjust the eye piece):
#Use high magnification and focus on a specimen using the main focus knob.
#Switch to low magnification, and focus using the eye piece adjustment.</noinclude>
===Condenser===
Generally the '''condenser''' is placed in its highest position or just slightly lower. At low magnification objectives (mainly 4x and 10x objectives), the opening of the condenser (or iris) diaphragm should be wide open. This corresponds to turning away or "lowering" the condenser on microscopes where the condenser apparatus can be turned to the side (and is shown as "without condenser" in images below). For high-dry (40x) and oil-immersion objectives (100x), the diaphragm should be closed slowly while looking at a sharply focused section until the level of illumination is just slightly reduced, in order to attain optimal contrast and resolution (and corresponds to "with condenser" in images below).<ref>{{cite web|url=https://histologylab.ctl.columbia.edu/HistologyLabManual.pdf|title=Histology Laboratory Manual, Vagelos College of Physicians & Surgeons Columbia University|author=Patrice F Spitalnik|accessdate=2021-09-20}}</ref>
<gallery mode=packed heights=200>
File:Light microscopy with and without condenser.jpg|Light microscopy with and without condenser. At low magnification, using a condenser may limit the field of view, and in such cases it is preferable to not use it. At high magnification, a condenser makes borders less marked, and is generally preferable in such cases.
File:Calcium pyrophosphate dihydrate crystals without and with condenser, annotated.jpg|An example of a situation where microscopy without condenser is preferable at high magnification is the evaluation of '''crystals''' (calcium pyrophosphate dihydrate crystal deposition disease pictured).
File:Sclerosing adenosis with and without condenser.jpg|Looking without a condenser may also enhance '''basement membranes''', such as negating an invasive carcinoma in this case.
</gallery>

If there's a '''constant visual artifact''', even after you've cleaned the eye piece and objective lenses with lens tissue, try raising or lowering the condenser if you can, and the artifact may disappear out of focus.
</noinclude>

==Priority==
Whenever you have more than one case, generally have an '''initial look''' at the requisition form and/or in the microscope at the most likely relevant area of each case, and prioritize the case(s) that likely need to be done first. Indications to prioritize case(s) are mainly:
* '''Clinical management''' of the patient highly benefits from a fast diagnosis.
* Being '''marked''' as a rush case.
* There's a significant probability that it will require '''further workup''' such as [[immunohistochemistry]], especially when there is an impending deadline for ordering it.
* The optimal person to ask for '''advice''' may not be available later. {{Further|Consultation}}
As part of initial triaging, also determine what tasks can be '''delegated'' to juniors or pathologist assistants.

For a pile of many cases of relatively low risk of a need to prioritize any one over another, such as [[gastrointestinal biopsies]], a very quick glance at the forms and/or a naked eye look at the glass slides is generally sufficient.

==Main steps==
*Preferably, look up past '''medical history''' of the patient, mainly past cancers that could possibly appear in the current specimen.
*Try to pick up glass slides '''without touching''' the tissue area, as fingerprints may interfere with the evaluation.
*Look at each microscopy slide by plain '''eye''', to plan the microscopy scanning so as to not miss peripheral fragments.
*Have a '''systematic direction''' of scanning through microscopy slides, such as from top left to bottom right as seen in the microscope. When the microscope makes what you see two-way mirrored, the starting position is with the objective pointing at the bottom right of the glass slide. You may center on findings on interest and evaluate them at higher magnification, and then resume the scanning.
<gallery mode=packed heights=140px>
File:Position of objective (edited).jpg|Example starting position of objective.
File:Microscopy slide scanning.jpg|Example slide scanning movement.
</gallery>
<gallery mode=packed heights=170px>
File:Screening method 1.jpg|Starting at top left in the view, aim to scan a strip that trajects a circular field of view approximately at the clock positions shown...
File:Screening method 2.jpg|...When reaching the end of relevant material, set your eyes on any object at the edge of the strip that you just scanned...
File:Screening method 3.jpg|...Move the field of view over so that the object is seen on the opposite side. The new strip to be scanned will now be juxtaposed to the one you previously scanned.
</gallery>
This scanning technique above makes sure that you don't miss any area, and also minimizes redundant scanning. The width or clock position that you scan in each field of view is not exact, as you may scan up to the entire width in cases where you think relevant findings will clearly present themselves even if only partially showing in the periphery of your view.
*Look in particular for whatever is '''requested''' or '''suspected''' on the requisition form or equivalent. For each type of condition, initially you will generally focus relatively more on high magnification features with high specificity, but you should still have a habit of looking at '''low magnification''' as well to get an idea of its pattern. In time, you will increasingly correlate diseases and conditions with their overall low magnification patterns - patterns that may require 1000 words to describe and thus cannot conveniently be part of written criteria, but will nevertheless allow you to make quicker and more accurate diagnoses, or at least clues thereof.
*When you find something suspicious, it is helpful at least in the beginning to evaluate them systematically by a '''low-to-high magnification approach''' (example below showing a [[basal-cell carcinoma]]):
<gallery mode=packed heights=180px>>
File:Systematic microscopy 2 - Orientation.jpg|'''Orientation''' (lowest magnification): In this case oriented by the skin surface (green). A lesion is seen (red) and its demarcation can be discerned (diffuse in this case)
File:Systematic microscopy 3 - Architectural pattern.jpg|'''Architectural pattern''' of any suspicious cells, in this case nests of cells (an overview of patterns will be given later in this chapter), as well as components of the intervening stroma.
File:Systematic microscopy 4 - Cellular arrangement.jpg|'''Cellular arrangement''', including crowding and polarity (common tendencies among cells at the border, such as positions of nuclei within cells, cell elongation or "palisading" in this case). Amount of mitoses can also be appreciated at this level.
File:Systematic microscopy 5 - Subcellular features.jpg|'''Subcellular features''' (may need highest magnification)
</gallery>
*'''Complete''' the scanning even if you encounter a finding, as there may be additional findings as well. It is usually helpful to Google multiple images of the normal histology of the location you are looking at, and compare those to what you see, and focus on whatever features may deviate from the normal.

==General patterns==
Following are major patterns that often help in making a diagnosis.
===Architectural patterns===
<gallery mode=packed heights=190>
File:High-magnification micrograph of basal-cell carcinoma.jpg|'''Nests''': islands of cells of similar type.
File:Prostate adenocarcinoma - acinar pattern.jpg|'''Acinar''' or '''tubular''': Each acinus consists of cells that surround a lumen.
File:Typical carcinoid tumor of the lung, trabecular pattern.jpg|'''Trabecular''', elongated (rod-shaped) groups of cells.
File:Encapsulated Papillary Carcinoma of the Breast, H&E (15768688957).jpg|'''Papillary''': Protuberances of epithelioid cells around fibrovascular cores.
File:Micropapillary urothelial carcinoma, very high mag.jpg|'''Micropapillary''': Papillary tufts without fibrovascular cores
File:Histopathology of fascicular growth in a leiomyoma.jpg|thumb|'''Fascicular''': Generally the same cell type throughout, but some form band-like groups that are aligned in the same direction.
File:Histopathology of woven or storiform pattern.jpg|'''Woven''' or '''storiform''': Elongated cells or nuclei wherein small bundles are aligned in an otherwise haphazard pattern.
File:Micrograph of prostate cancer with Gleason score 10 (5+5) with solid sheets of cells (crop).jpg|'''Solid''' or "'''sheets'''": More or less the same cell type throughout, with no spaces between, and no other particular pattern.
File:Papillary urothelial carcinoma with cribriform morphology, very high mag.jpg|'''Cribriform''': Solid with multiple clear spaces.
File:Bovine Bone Sample and 430 times Magnification.jpg|'''Whorled''': Multiple concentric objects, or spiral-shaped
File:Histopathology of cartwheel pattern in dermatofibrosarcoma protuberans, annotated.jpg|'''Cartwheel pattern''': Center points that radiate cells or connective tissue outward
</gallery>

===Cellular patterns===
<gallery mode=packed heights=170>
File:Eosinophilic, basophilic, chromophobic and amphophilic staining.png|Main staining types of the cytoplasm when using hematoxylin and eosin (H&E).
File:Histopathology of ovarian serous borderline tumor with hobnailing.jpg|'''Hobnailing''': smooth projections from an epithelial surface.
</gallery>

===Nuclear patterns===
When feasible, classify nuclei as follows:
<gallery mode=packed heights=180>
File:Histopathology of clear cell renal cell carcinoma, grade 1, high magnification.jpg|'''Monomorphic''' when having relatively similar sizes and shapes.
File:Pleomorphic nuclei.jpg|'''Pleomorphic''' when having different sizes and shapes. This often correlates with an increased '''nucleus to cytoplasm ratio'''. These features generally favor malignancy in the '''[[evaluation of suspected malignancies]]'''.
File:Fine versus coarse chromatin.jpg|'''Fine chromatin''' when inconspicuous (essentially only nucleoli seen in the nuclei), versus '''coarse''' chromatin.
File:Heterochromatic versus euchromatic nuclei.jpg|Sometimes "heterochromatic" versus "euchromatic" nuclei are used, but this strictly refers to the molecular structure of DNA, so you may simply use fine versus coarse.
File:Well-differentiated neuroendocrine tumor with salt-and-pepper chromatin.png|Granular "salt-and-pepper" chromatin.
</gallery>
;Patterns of nuclear disintegration:
<gallery mode=packed heights=250>
File:Nuclear changes.jpg
</gallery>

===Other patterns===
<gallery mode=packed heights=180>
File:Histology of deep zone of articular cartilage.jpg|'''Hyaline''' usually refers to extracellular material that stains homogeneously pink on H&E stain (like the matrix of hyaline cartilage, pictured).
File:Histopathology of hyaline membranes in diffuse alveolar damage.jpg|Example of hyaline material (in alveoli of lungs, indicating diffuse alveolar damage)
File:Glass for pathologist.png|This is what pathologists also refer to as "glassy" (because hyaline cartilage looks like glass grossly).
</gallery>

==Inflammation==
<gallery mode=packed heights=180px>
File:Histopathology of acute cholecystitis with neutrophils.jpg|'''Neutrophils''' generally confers a diagnosis of '''acute inflammation'''.
File:Histopathology of mucosal plasma cell infiltrate in chronic gastritis.jpg|'''Plasma cells''' and '''lymphocytes''' generally confers a diagnosis of '''chronic inflammation''' if present in increased amount for the location.
File:Histopathology of intravascular neutrophils.jpg|However, disregard intravascular white blood cells.
</gallery>

==Marking slides==
<gallery mode=packed heights=140>
File:Photograph of marking a microscopy slide.jpg|To mark a microscopy slide, use an objective that gives you enough space underneath. Rest a finger on the stage, while holding the marker pen relatively close to its tip. Move the tip of the marker pen into the field of view but at least a few millimeters from the slide...
File:Micrograph of marking a microscopy slide.jpg|...Then slowly approach the slide while making sure that the tip remains in the location you want to mark. Be careful not to obscure findings of interest with the mark. If the slide is likely to undergo whole slide imaging, make the mark on the back and not on the coverslip (as it reduces the risk of erroneous focusing of the cameras).
File:Wiping a slide.png|You can generally remove marks from a microscopy slide by using alcohol. Hold the cover slip in place with two fingers while wiping from side to side, to avoid the risk of moving the coverslip. Don't press hard against the glass, as it may disrupt the tissue.
</gallery>

==Measuring distances==
<gallery mode=packed heights=220>
File:Measurement using transparent ruler in microscopy.jpg|You can use a regular transparent ruler for most purposes, since it is rarely necessary to specify distances as more exact than millimeters. It works best on low magnification.
File:Measurement of tumor size on two microscopy slides.jpg|Alternatively, mark the limits under microscopy, and then use a regular ruler to measure the dimensions. This works even if the distance exceeds the field of view, or spans more than one slide.
File:Calibration slide with rulers and grids.jpg|Rarely, sub-millimeter measurement is needed, in which case you may use a calibration slide, which is basically a translucent ruler with 0.1 mm line resolution or smaller, which may cost about $15 if none of your colleagues has one to lend, or the department can't provide one for you.
File:Measuring distance on a microscopy slide using a calibration slide.jpg|To measure distance with a calibration slide, put it on top of the tissue slide and switch focus between the two.
</gallery>
There are also eye pieces that show a ruler in the field of view, but make sure you match it with the correct objective and other settings to make the measurement valid. A calibration slide is more robust because of such sources of error.

==Counts per mm2==
There are multiple situations where a finding will be quantified in terms of amount per mm2. To make such calculations, you need to know the size of the area you see in the microscope. It is usually possible to look up what theoretically would be the area, but the most reliable way of knowing is to use a calibration slide to measure the diameter of your view. The area is then calculated as:
*Area in mm2 ≈ (diameter in mm2) x 0.79

<gallery mode=packed heights=220>
File:Micrograph of a calibration slide, showing the diameter of the field of view.jpg|Micrograph of a calibration slide, showing the diameter of the field of view.
</gallery>
On the imaged example, each square is 0.05 mm wide, and each line represents 0.01 mm, making the diameter of the field of view 0.55 mm in this case. Thus, you can calculate the area in mm2 by Googling:
:0.55 x 0.55 x 0.79
:(equals approximately 0.24 mm2).

Generally count at least 10 fields of a high power view (or more if specifically instructed). You can keep the count in your head by repeating the total count and the order of the area you are looking at, such as:
*"Zero (instances) of one (field of view)"
*"One of two (as you see one instance as you've moved to the second field of view)"
*"Two of two" etc.
Subsequently, the '''count per mm2''' is calculated as follows:
{|
|rowspan=2| Count per mm2 = ||align=center| Total count
|-
| Number of fields x Area per field (in mm2)
|}

For example, if you reached "15 of 10", and the area of your field is 0.2 mm2, the count per mm2 can be calculated by Googling:
:15/10/0.2
:= 7.5

Sometimes '''"high power field"''' (HPF) is used for area, but it has a substantially different area for different microscopes, for example:
{|class="wikitable"
! Microscope type !! Area per HPF
|-
|
*Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece
*Olympus BX43 with 10x eyepiece
| 0.096 mm2 <ref name=stanford-idc>{{cite web|url=http://surgpathcriteria.stanford.edu/breast/infductcabr/grading.html|title=Infiltrating Ductal Carcinoma of the Breast (Carcinoma of No Special Type)|website=Stanford University School of Medicine|accessdate=2019-10-02}}</ref>
|-
| AO with 10x eyepiece || 0.12 mm2 <ref name=stanford-idc/>
|-
| Nikon Eclipse E400 with 10x eyepiece and 40x objective || 0.25 mm2
|-
| Leitz Ortholux || 0.27 mm2 <ref name=stanford-idc/>
|-
| Leitz Diaplan || 0.31 mm2 <ref name=stanford-idc/>
|}

When your instructions are to '''count a specific number of HPFs''', one HPF can be assumed to be 0.2 mm2.<ref name="KlimstraModlin2010">{{cite journal|last1=Klimstra|first1=David S.|last2=Modlin|first2=Irvin R.|last3=Coppola|first3=Domenico|last4=Lloyd|first4=Ricardo V.|last5=Suster|first5=Saul|title=The Pathologic Classification of Neuroendocrine Tumors|journal=Pancreas|volume=39|issue=6|year=2010|pages=707–712|issn=0885-3177|doi=10.1097/MPA.0b013e3181ec124e}}</ref> If the view area in your microscope significantly differs from this area, calculate how many views you need to count as:
{|class=
|rowspan=2| Views = HPFs required x ||align=center| 0.2
|-
| Your microscope area (in mm2)
|}

For example, if your instruction is to count 10 HPFs and each view in your microscope shows 0.096 mm2, you should count in this many views:
{|
|rowspan=2| 10 x ||align=center|0.2 ||rowspan=2| ≈ 21
|-
| 0.096
|}

Subsequently, if your microscope area is significantly different from 0.2 mm2 and you need to '''state your result in terms of count/HPF''', use:

{|
|rowspan=2| Count/HPF = Average count in your view x ||align=center| 0.2
|-
| Area of your view in mm2
|}

For example, if you have counted an average of 10 cells (or other object of interest) in each of your views, and the area of your view is 0.096 mm2, then your count/HPF is:
{|
|rowspan=2| 10 x ||align=center| 0.2 ||rowspan=2| ≈ 21
|-
| 0.096
|}

==Artifacts==
In microscopy, an artifact is an apparent structural detail that is caused by the processing of the specimen and is thus not a legitimate feature of the specimen. Major artifacts to account for include:
<gallery mode=packed>
File:Cellulose contamination in H&E and polarized light.jpg|Cellulose '''contamination''', here seen on H&E stain and polarized light, respectively. In contrast to foreign bodies that were truly in the specimen, contamination overlaps with or disrupts tissue more unnaturally.
File:Histopathology of cardiac muscle with contamination from thyroid tissue.jpg|Cardiac muscle (bottom) with '''contamination''' from thyroid tissue (center).
File:Crush artifact from forceps.jpg|'''Crush''' artifact from compression by forceps on the tissue sample.
File:Skin with folds and crush artifact by needle.jpg|'''Folding''' artifacts (white arrows) and a crush artifact (black arrow, with dark cytoplasmic staining and nuclear pleomorphism) from a needle.
File:Tearing artifacts in histopathology.jpg|'''Tearing''' artifacts, such as can be caused by: - Microtomy with a nick or blemish in the knife edge.<ref name="TaqiSami2018">{{cite journal|last1=Taqi|first1=SyedAhmed|last2=Sami|first2=SyedAbdus|last3=Sami|first3=LateefBegum|last4=Zaki|first4=SyedAhmed|title=A review of artifacts in histopathology|journal=Journal of Oral and Maxillofacial Pathology|volume=22|issue=2|year=2018|pages=279|issn=0973-029X|doi=10.4103/jomfp.JOMFP_125_15}}</ref> - Traction of the sections. - Too much or too little alcohol dehydration.<ref name="TaqiSami2018"/> - Sectioning calcified parts, which can be decalcified or removed.<ref name="TaqiSami2018"/>
File:Microscopy of liver parenchyma with tearing artifacts.jpg|More '''tearing''' artifacts, showing that they may be more circular than fusiform.
File:Formalin pigment artifacts.jpg|''''Formalin pigment''' artifacts
File:Air bubble entrapment artifacts.jpg|'''Air bubble entrapment''' artifacts
File:Staining artifacts by residual wax.jpg|'''Staining''' artifacts by residual wax, resulting in pale areas where cellular structures are not discernible.
File:Histopathology of radically excised basal-cell carcinoma with separation artifact (horizontal layout).jpg|A '''separation''' artifact in top image makes the tumor look incompletely excised, but the next microtomy level (bottom image) shows a surgical margin of connective tissue.
</gallery>
Differential diagnoses of artifacts are mainly:
*'''Foreign bodies'''. In contrast to contamination, these conform more naturally to the surrounding tissue.
*'''Organisms''', to be particularly considered when there are multiple objects of the same size.

Order '''recuts''' from the same paraffin-embedded tissue if artifacts significantly impairs your diagnostic evaluation of the glass slide. However, artifacts caused by gross processing may affect recuts as well.

==Micrography and telepathology==
Unless you have more specific equipment for taking microscopic images and showing cases to remote colleagues, you can perform these tasks as follows:
*With a '''stationary computer''', you can connect to a microscopy camera. For telepathology, you can start a videoconferencing session with your senior, then share the screen while showing a micrograph, or the live view so that you can move around.
*With a '''mobile phone''':
<gallery mode=packed heights=240>
File:Micrography with a smartphone 1.jpg|To perform '''micrography''' with a smartphone, stabilize the smartphone over the eyepiece (preferably using both hands), about 3-5 cm away from it, and direct it on the bright circle on your phone display...
File:Micrography with a smartphone 2.jpg|...and then slowly move the smartphone closer to the eyepiece, while adjusting both direction and location so as to keep the bright circle in the center of the display, until the camera is able to focus and you have a visible field that is large enough for evaluation, and then take your photos.
</gallery>
:You can send micrographs to your senior, but it is technically difficult to keep the focus while moving the glass slide.
<noinclude>
==Cytology==
In cytology samples, or any sample with scattered cells rather than coherent tissue, also evaluate the following:
*Adequacy of specimen. Cells may be too few or too obscured by other material to make a proper diagnosis.
*Background, mainly if it is clear or dirty
*Overall cellularity
{{further|Cytology}}</noinclude>
==Consideration==
Consider the '''adequacy''' of the specimen. Have a somewhat lower threshold to make a report of "inadequate" or "insufficient" if it is easy to resample from the patient, such as remaining diagnostic tissue at a superficial location.

First, generally suspect the '''common conditions''' for the location at hand. A less common variant of a common condition is often still more likely than a rare condition, so generally call the latter only if it really fits the picture.

Whenever you consider a certain diagnosis, also consider whether it is one step '''better or worse'''. For example, when you consider a non-invasive but high-grade dysplasia, also consider both low-grade dysplasia and invasiveness.
</noinclude>
{{General notes}}
{{Bottom}}
</noinclude>

Evaluation

2025-06-03T20:35:32Z

Mikael Häggström: /* Main steps */ .

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}</noinclude>
First, confirm that the '''identity''' of the sample evaluated is the same as that of the requisition form and/or other medical history.
==Microscopy settings==
[[File:Parts of a light microscope (english) - larger text.png|thumb|300px|Usual parts of a microscope.]]
Generally the '''condenser''' is placed in its highest position or just slightly lower. At low magnification objectives (mainly 4x and 10x objectives), the opening of the condenser (or iris) diaphragm should be wide open. This corresponds to turning away or "lowering" the condenser on microscopes where the condenser apparatus can be turned to the side (and is shown as "without condenser" in images below). For high-dry (40x) and oil-immersion objectives (100x), the diaphragm should be closed slowly while looking at a sharply focused section until the level of illumination is just slightly reduced, in order to attain optimal contrast and resolution (and corresponds to "with condenser" in images below).<ref>{{cite web|url=https://histologylab.ctl.columbia.edu/HistologyLabManual.pdf|title=Histology Laboratory Manual, Vagelos College of Physicians & Surgeons Columbia University|author=Patrice F Spitalnik|accessdate=2021-09-20}}</ref>
<gallery mode=packed heights=200>
File:Light microscopy with and without condenser.jpg|Light microscopy with and without condenser. At low magnification, using a condenser may limit the field of view, and in such cases it is preferable to not use it. At high magnification, a condenser makes borders less marked, and is generally preferable in such cases.
File:Calcium pyrophosphate dihydrate crystals without and with condenser, annotated.jpg|An example of a situation where microscopy without condenser is preferable at high magnification is the evaluation of '''crystals''' (calcium pyrophosphate dihydrate crystal deposition disease pictured).
File:Sclerosing adenosis with and without condenser.jpg|Looking without a condenser may also enhance '''basement membranes''', such as negating an invasive carcinoma in this case.
</gallery>

Low magnification has a greater span of focus compared to high magnification, so it is normal to need to focus if you're increasing magnification.<noinclude> However, if you find that you need to '''change focus''' even if going from high to low magnification, try the following (if you can adjust the eye piece):
#Use high magnification and focus on a specimen using the main focus knob.
#Switch to low magnification, and focus using the eye piece adjustment.</noinclude>
If there's a '''constant visual artifact''', even after you've cleaned the eye piece and objective lenses with lens tissue, try raising or lowering the condenser if you can, and the artifact may disappear out of focus.

==Priority==
Whenever you have more than one case, generally have an '''initial look''' at the requisition form and/or in the microscope at the most likely relevant area of each case, and prioritize the case(s) that likely need to be done first. Indications to prioritize case(s) are mainly:
* '''Clinical management''' of the patient highly benefits from a fast diagnosis.
* Being '''marked''' as a rush case.
* There's a significant probability that it will require '''further workup''' such as [[immunohistochemistry]], especially when there is an impending deadline for ordering it.
* The optimal person to ask for '''advice''' may not be available later. {{Further|Consultation}}
As part of initial triaging, also determine what tasks can be '''delegated'' to juniors or pathologist assistants.

For a pile of many cases of relatively low risk of a need to prioritize any one over another, such as [[gastrointestinal biopsies]], a very quick glance at the forms and/or a naked eye look at the glass slides is generally sufficient.

==Main steps==
*Preferably, look up past '''medical history''' of the patient, mainly past cancers that could possibly appear in the current specimen.
*Try to pick up glass slides '''without touching''' the tissue area, as fingerprints may interfere with the evaluation.
*Look at each microscopy slide by plain '''eye''', to plan the microscopy scanning so as to not miss peripheral fragments.
*Have a '''systematic direction''' of scanning through microscopy slides, such as from top left to bottom right as seen in the microscope. When the microscope makes what you see two-way mirrored, the starting position is with the objective pointing at the bottom right of the glass slide. You may center on findings on interest and evaluate them at higher magnification, and then resume the scanning.
<gallery mode=packed heights=140px>
File:Position of objective (edited).jpg|Example starting position of objective.
File:Microscopy slide scanning.jpg|Example slide scanning movement.
</gallery>
<gallery mode=packed heights=170px>
File:Screening method 1.jpg|Starting at top left in the view, aim to scan a strip that trajects a circular field of view approximately at the clock positions shown...
File:Screening method 2.jpg|...When reaching the end of relevant material, set your eyes on any object at the edge of the strip that you just scanned...
File:Screening method 3.jpg|...Move the field of view over so that the object is seen on the opposite side. The new strip to be scanned will now be juxtaposed to the one you previously scanned.
</gallery>
This scanning technique above makes sure that you don't miss any area, and also minimizes redundant scanning. The width or clock position that you scan in each field of view is not exact, as you may scan up to the entire width in cases where you think relevant findings will clearly present themselves even if only partially showing in the periphery of your view.
*Look in particular for whatever is '''requested''' or '''suspected''' on the requisition form or equivalent. For each type of condition, initially you will generally focus relatively more on high magnification features with high specificity, but you should still have a habit of looking at '''low magnification''' as well to get an idea of its pattern. In time, you will increasingly correlate diseases and conditions with their overall low magnification patterns - patterns that may require 1000 words to describe and thus cannot conveniently be part of written criteria, but will nevertheless allow you to make quicker and more accurate diagnoses, or at least clues thereof.
*When you find something suspicious, it is helpful at least in the beginning to evaluate them systematically by a '''low-to-high magnification approach''' (example below showing a [[basal-cell carcinoma]]):
<gallery mode=packed heights=180px>>
File:Systematic microscopy 2 - Orientation.jpg|'''Orientation''' (lowest magnification): In this case oriented by the skin surface (green). A lesion is seen (red) and its demarcation can be discerned (diffuse in this case)
File:Systematic microscopy 3 - Architectural pattern.jpg|'''Architectural pattern''' of any suspicious cells, in this case nests of cells (an overview of patterns will be given later in this chapter), as well as components of the intervening stroma.
File:Systematic microscopy 4 - Cellular arrangement.jpg|'''Cellular arrangement''', including crowding and polarity (common tendencies among cells at the border, such as positions of nuclei within cells, cell elongation or "palisading" in this case). Amount of mitoses can also be appreciated at this level.
File:Systematic microscopy 5 - Subcellular features.jpg|'''Subcellular features''' (may need highest magnification)
</gallery>
*'''Complete''' the scanning even if you encounter a finding, as there may be additional findings as well. It is usually helpful to Google multiple images of the normal histology of the location you are looking at, and compare those to what you see, and focus on whatever features may deviate from the normal.

==General patterns==
Following are major patterns that often help in making a diagnosis.
===Architectural patterns===
<gallery mode=packed heights=190>
File:High-magnification micrograph of basal-cell carcinoma.jpg|'''Nests''': islands of cells of similar type.
File:Prostate adenocarcinoma - acinar pattern.jpg|'''Acinar''' or '''tubular''': Each acinus consists of cells that surround a lumen.
File:Typical carcinoid tumor of the lung, trabecular pattern.jpg|'''Trabecular''', elongated (rod-shaped) groups of cells.
File:Encapsulated Papillary Carcinoma of the Breast, H&E (15768688957).jpg|'''Papillary''': Protuberances of epithelioid cells around fibrovascular cores.
File:Micropapillary urothelial carcinoma, very high mag.jpg|'''Micropapillary''': Papillary tufts without fibrovascular cores
File:Histopathology of fascicular growth in a leiomyoma.jpg|thumb|'''Fascicular''': Generally the same cell type throughout, but some form band-like groups that are aligned in the same direction.
File:Histopathology of woven or storiform pattern.jpg|'''Woven''' or '''storiform''': Elongated cells or nuclei wherein small bundles are aligned in an otherwise haphazard pattern.
File:Micrograph of prostate cancer with Gleason score 10 (5+5) with solid sheets of cells (crop).jpg|'''Solid''' or "'''sheets'''": More or less the same cell type throughout, with no spaces between, and no other particular pattern.
File:Papillary urothelial carcinoma with cribriform morphology, very high mag.jpg|'''Cribriform''': Solid with multiple clear spaces.
File:Bovine Bone Sample and 430 times Magnification.jpg|'''Whorled''': Multiple concentric objects, or spiral-shaped
File:Histopathology of cartwheel pattern in dermatofibrosarcoma protuberans, annotated.jpg|'''Cartwheel pattern''': Center points that radiate cells or connective tissue outward
</gallery>

===Cellular patterns===
<gallery mode=packed heights=170>
File:Eosinophilic, basophilic, chromophobic and amphophilic staining.png|Main staining types of the cytoplasm when using hematoxylin and eosin (H&E).
File:Histopathology of ovarian serous borderline tumor with hobnailing.jpg|'''Hobnailing''': smooth projections from an epithelial surface.
</gallery>

===Nuclear patterns===
When feasible, classify nuclei as follows:
<gallery mode=packed heights=180>
File:Histopathology of clear cell renal cell carcinoma, grade 1, high magnification.jpg|'''Monomorphic''' when having relatively similar sizes and shapes.
File:Pleomorphic nuclei.jpg|'''Pleomorphic''' when having different sizes and shapes. This often correlates with an increased '''nucleus to cytoplasm ratio'''. These features generally favor malignancy in the '''[[evaluation of suspected malignancies]]'''.
File:Fine versus coarse chromatin.jpg|'''Fine chromatin''' when inconspicuous (essentially only nucleoli seen in the nuclei), versus '''coarse''' chromatin.
File:Heterochromatic versus euchromatic nuclei.jpg|Sometimes "heterochromatic" versus "euchromatic" nuclei are used, but this strictly refers to the molecular structure of DNA, so you may simply use fine versus coarse.
File:Well-differentiated neuroendocrine tumor with salt-and-pepper chromatin.png|Granular "salt-and-pepper" chromatin.
</gallery>
;Patterns of nuclear disintegration:
<gallery mode=packed heights=250>
File:Nuclear changes.jpg
</gallery>

===Other patterns===
<gallery mode=packed heights=180>
File:Histology of deep zone of articular cartilage.jpg|'''Hyaline''' usually refers to extracellular material that stains homogeneously pink on H&E stain (like the matrix of hyaline cartilage, pictured).
File:Histopathology of hyaline membranes in diffuse alveolar damage.jpg|Example of hyaline material (in alveoli of lungs, indicating diffuse alveolar damage)
File:Glass for pathologist.png|This is what pathologists also refer to as "glassy" (because hyaline cartilage looks like glass grossly).
</gallery>

==Inflammation==
<gallery mode=packed heights=180px>
File:Histopathology of acute cholecystitis with neutrophils.jpg|'''Neutrophils''' generally confers a diagnosis of '''acute inflammation'''.
File:Histopathology of mucosal plasma cell infiltrate in chronic gastritis.jpg|'''Plasma cells''' and '''lymphocytes''' generally confers a diagnosis of '''chronic inflammation''' if present in increased amount for the location.
File:Histopathology of intravascular neutrophils.jpg|However, disregard intravascular white blood cells.
</gallery>

==Marking slides==
<gallery mode=packed heights=140>
File:Photograph of marking a microscopy slide.jpg|To mark a microscopy slide, use an objective that gives you enough space underneath. Rest a finger on the stage, while holding the marker pen relatively close to its tip. Move the tip of the marker pen into the field of view but at least a few millimeters from the slide...
File:Micrograph of marking a microscopy slide.jpg|...Then slowly approach the slide while making sure that the tip remains in the location you want to mark. Be careful not to obscure findings of interest with the mark. If the slide is likely to undergo whole slide imaging, make the mark on the back and not on the coverslip (as it reduces the risk of erroneous focusing of the cameras).
File:Wiping a slide.png|You can generally remove marks from a microscopy slide by using alcohol. Hold the cover slip in place with two fingers while wiping from side to side, to avoid the risk of moving the coverslip. Don't press hard against the glass, as it may disrupt the tissue.
</gallery>

==Measuring distances==
<gallery mode=packed heights=220>
File:Measurement using transparent ruler in microscopy.jpg|You can use a regular transparent ruler for most purposes, since it is rarely necessary to specify distances as more exact than millimeters. It works best on low magnification.
File:Measurement of tumor size on two microscopy slides.jpg|Alternatively, mark the limits under microscopy, and then use a regular ruler to measure the dimensions. This works even if the distance exceeds the field of view, or spans more than one slide.
File:Calibration slide with rulers and grids.jpg|Rarely, sub-millimeter measurement is needed, in which case you may use a calibration slide, which is basically a translucent ruler with 0.1 mm line resolution or smaller, which may cost about $15 if none of your colleagues has one to lend, or the department can't provide one for you.
File:Measuring distance on a microscopy slide using a calibration slide.jpg|To measure distance with a calibration slide, put it on top of the tissue slide and switch focus between the two.
</gallery>
There are also eye pieces that show a ruler in the field of view, but make sure you match it with the correct objective and other settings to make the measurement valid. A calibration slide is more robust because of such sources of error.

==Counts per mm2==
There are multiple situations where a finding will be quantified in terms of amount per mm2. To make such calculations, you need to know the size of the area you see in the microscope. It is usually possible to look up what theoretically would be the area, but the most reliable way of knowing is to use a calibration slide to measure the diameter of your view. The area is then calculated as:
*Area in mm2 ≈ (diameter in mm2) x 0.79

<gallery mode=packed heights=220>
File:Micrograph of a calibration slide, showing the diameter of the field of view.jpg|Micrograph of a calibration slide, showing the diameter of the field of view.
</gallery>
On the imaged example, each square is 0.05 mm wide, and each line represents 0.01 mm, making the diameter of the field of view 0.55 mm in this case. Thus, you can calculate the area in mm2 by Googling:
:0.55 x 0.55 x 0.79
:(equals approximately 0.24 mm2).

Generally count at least 10 fields of a high power view (or more if specifically instructed). You can keep the count in your head by repeating the total count and the order of the area you are looking at, such as:
*"Zero (instances) of one (field of view)"
*"One of two (as you see one instance as you've moved to the second field of view)"
*"Two of two" etc.
Subsequently, the '''count per mm2''' is calculated as follows:
{|
|rowspan=2| Count per mm2 = ||align=center| Total count
|-
| Number of fields x Area per field (in mm2)
|}

For example, if you reached "15 of 10", and the area of your field is 0.2 mm2, the count per mm2 can be calculated by Googling:
:15/10/0.2
:= 7.5

Sometimes '''"high power field"''' (HPF) is used for area, but it has a substantially different area for different microscopes, for example:
{|class="wikitable"
! Microscope type !! Area per HPF
|-
|
*Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece
*Olympus BX43 with 10x eyepiece
| 0.096 mm2 <ref name=stanford-idc>{{cite web|url=http://surgpathcriteria.stanford.edu/breast/infductcabr/grading.html|title=Infiltrating Ductal Carcinoma of the Breast (Carcinoma of No Special Type)|website=Stanford University School of Medicine|accessdate=2019-10-02}}</ref>
|-
| AO with 10x eyepiece || 0.12 mm2 <ref name=stanford-idc/>
|-
| Nikon Eclipse E400 with 10x eyepiece and 40x objective || 0.25 mm2
|-
| Leitz Ortholux || 0.27 mm2 <ref name=stanford-idc/>
|-
| Leitz Diaplan || 0.31 mm2 <ref name=stanford-idc/>
|}

When your instructions are to '''count a specific number of HPFs''', one HPF can be assumed to be 0.2 mm2.<ref name="KlimstraModlin2010">{{cite journal|last1=Klimstra|first1=David S.|last2=Modlin|first2=Irvin R.|last3=Coppola|first3=Domenico|last4=Lloyd|first4=Ricardo V.|last5=Suster|first5=Saul|title=The Pathologic Classification of Neuroendocrine Tumors|journal=Pancreas|volume=39|issue=6|year=2010|pages=707–712|issn=0885-3177|doi=10.1097/MPA.0b013e3181ec124e}}</ref> If the view area in your microscope significantly differs from this area, calculate how many views you need to count as:
{|class=
|rowspan=2| Views = HPFs required x ||align=center| 0.2
|-
| Your microscope area (in mm2)
|}

For example, if your instruction is to count 10 HPFs and each view in your microscope shows 0.096 mm2, you should count in this many views:
{|
|rowspan=2| 10 x ||align=center|0.2 ||rowspan=2| ≈ 21
|-
| 0.096
|}

Subsequently, if your microscope area is significantly different from 0.2 mm2 and you need to '''state your result in terms of count/HPF''', use:

{|
|rowspan=2| Count/HPF = Average count in your view x ||align=center| 0.2
|-
| Area of your view in mm2
|}

For example, if you have counted an average of 10 cells (or other object of interest) in each of your views, and the area of your view is 0.096 mm2, then your count/HPF is:
{|
|rowspan=2| 10 x ||align=center| 0.2 ||rowspan=2| ≈ 21
|-
| 0.096
|}

==Artifacts==
In microscopy, an artifact is an apparent structural detail that is caused by the processing of the specimen and is thus not a legitimate feature of the specimen. Major artifacts to account for include:
<gallery mode=packed>
File:Cellulose contamination in H&E and polarized light.jpg|Cellulose '''contamination''', here seen on H&E stain and polarized light, respectively. In contrast to foreign bodies that were truly in the specimen, contamination overlaps with or disrupts tissue more unnaturally.
File:Histopathology of cardiac muscle with contamination from thyroid tissue.jpg|Cardiac muscle (bottom) with '''contamination''' from thyroid tissue (center).
File:Crush artifact from forceps.jpg|'''Crush''' artifact from compression by forceps on the tissue sample.
File:Skin with folds and crush artifact by needle.jpg|'''Folding''' artifacts (white arrows) and a crush artifact (black arrow, with dark cytoplasmic staining and nuclear pleomorphism) from a needle.
File:Tearing artifacts in histopathology.jpg|'''Tearing''' artifacts, such as can be caused by: - Microtomy with a nick or blemish in the knife edge.<ref name="TaqiSami2018">{{cite journal|last1=Taqi|first1=SyedAhmed|last2=Sami|first2=SyedAbdus|last3=Sami|first3=LateefBegum|last4=Zaki|first4=SyedAhmed|title=A review of artifacts in histopathology|journal=Journal of Oral and Maxillofacial Pathology|volume=22|issue=2|year=2018|pages=279|issn=0973-029X|doi=10.4103/jomfp.JOMFP_125_15}}</ref> - Traction of the sections. - Too much or too little alcohol dehydration.<ref name="TaqiSami2018"/> - Sectioning calcified parts, which can be decalcified or removed.<ref name="TaqiSami2018"/>
File:Microscopy of liver parenchyma with tearing artifacts.jpg|More '''tearing''' artifacts, showing that they may be more circular than fusiform.
File:Formalin pigment artifacts.jpg|''''Formalin pigment''' artifacts
File:Air bubble entrapment artifacts.jpg|'''Air bubble entrapment''' artifacts
File:Staining artifacts by residual wax.jpg|'''Staining''' artifacts by residual wax, resulting in pale areas where cellular structures are not discernible.
File:Histopathology of radically excised basal-cell carcinoma with separation artifact (horizontal layout).jpg|A '''separation''' artifact in top image makes the tumor look incompletely excised, but the next microtomy level (bottom image) shows a surgical margin of connective tissue.
</gallery>
Differential diagnoses of artifacts are mainly:
*'''Foreign bodies'''. In contrast to contamination, these conform more naturally to the surrounding tissue.
*'''Organisms''', to be particularly considered when there are multiple objects of the same size.

Order '''recuts''' from the same paraffin-embedded tissue if artifacts significantly impairs your diagnostic evaluation of the glass slide. However, artifacts caused by gross processing may affect recuts as well.

==Micrography and telepathology==
Unless you have more specific equipment for taking microscopic images and showing cases to remote colleagues, you can perform these tasks as follows:
*With a '''stationary computer''', you can connect to a microscopy camera. For telepathology, you can start a videoconferencing session with your senior, then share the screen while showing a micrograph, or the live view so that you can move around.
*With a '''mobile phone''':
<gallery mode=packed heights=240>
File:Micrography with a smartphone 1.jpg|To perform '''micrography''' with a smartphone, stabilize the smartphone over the eyepiece (preferably using both hands), about 3-5 cm away from it, and direct it on the bright circle on your phone display...
File:Micrography with a smartphone 2.jpg|...and then slowly move the smartphone closer to the eyepiece, while adjusting both direction and location so as to keep the bright circle in the center of the display, until the camera is able to focus and you have a visible field that is large enough for evaluation, and then take your photos.
</gallery>
:You can send micrographs to your senior, but it is technically difficult to keep the focus while moving the glass slide.
<noinclude>
==Cytology==
In cytology samples, or any sample with scattered cells rather than coherent tissue, also evaluate the following:
*Adequacy of specimen. Cells may be too few or too obscured by other material to make a proper diagnosis.
*Background, mainly if it is clear or dirty
*Overall cellularity
{{further|Cytology}}</noinclude>
==Consideration==
Consider the '''adequacy''' of the specimen. Have a somewhat lower threshold to make a report of "inadequate" or "insufficient" if it is easy to resample from the patient, such as remaining diagnostic tissue at a superficial location.

First, generally suspect the '''common conditions''' for the location at hand. A less common variant of a common condition is often still more likely than a rare condition, so generally call the latter only if it really fits the picture.

Whenever you consider a certain diagnosis, also consider whether it is one step '''better or worse'''. For example, when you consider a non-invasive but high-grade dysplasia, also consider both low-grade dysplasia and invasiveness.
</noinclude>
{{General notes}}
{{Bottom}}
</noinclude>

Ductal carcinoma in situ

2025-06-02T18:34:45Z

Mikael Häggström: Templated

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
Ductal carcinoma in situ (DCIS):
{{Comprehensiveness}}</noinclude>
==Gross examination==
As per:
*[[Breast biopsy or excision]]
or mastectomy.

==Microscopic evaluation==
[[File:DCIS - Intraductal carcinoma of the breast.jpg|thumb|DCIS.]]
Malignant epithelial cells confined to the ductal system of the breast.<ref name="Siziopikou2013">{{cite journal|last1=Siziopikou|first1=Kalliopi P.|title=Ductal Carcinoma In Situ of the Breast: Current Concepts and Future Directions|journal=Archives of Pathology & Laboratory Medicine|volume=137|issue=4|year=2013|pages=462–466|issn=0003-9985|doi=10.5858/arpa.2012-0078-RA}}</ref> The cells are cohesive and have high grade atypia.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/breastmalignantlcis.html|title=Breast - Noninvasive lobular neoplasia - LCIS classic (Differential diagnosis section)|author=Sucheta Srivastava, M.D.}} Topic Completed: 1 September 2017. Minor changes: 17 May 2021</ref>

===Differential diagnoses===
;[[Invasive ductal carcinoma]]: Has invasion through the basement membrane of over 1 mm in size.<ref>{{cite web|url=https://documents.cap.org/protocols/Breast.DCIS_4.4.0.0.REL_CAPCP.pdf|title=Protocol for the Examination of Resection Specimens from Patients with Ductal Carcinoma In Situ (DCIS) of the Breast, Version: 4.4.0.0. Protocol Posting Date: June 2021|website=College of American Pathologists}}</ref>
<gallery mode=packed heights=200>
File:Histopathology of microinvasive ductal carcinoma in situ.png|'''DCIS with microinvasion''', defined as DCIS with focus of invasive cancer measuring up to 1.0 mm in size.<ref>Image annotation by Mikael Häggström, MD, using source image from: {{cite journal| author=Moatasim A, Mamoon N| title=Primary Breast Mucinous Cystadenocarcinoma and Review of Literature. | journal=Cureus | year= 2022 | volume= 14 | issue= 3 | pages= e23098 | pmid=35464581 | doi=10.7759/cureus.23098 | pmc=8997314 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35464581 }} - "This is an open access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0." '''Source for microinvasion''': {{cite web|url=https://documents.cap.org/protocols/Breast.DCIS_4.4.0.0.REL_CAPCP.pdf|title=Protocol for the Examination of Resection Specimens from Patients with Ductal Carcinoma In Situ (DCIS) of the Breast, Version: 4.4.0.0. Protocol Posting Date: June 2021|website=College of American Pathologists}}</ref>
</gallery>
In uncertain cases, use immunohistochemistry stain for myoepithelial markers{{Myoepithelial marker note}}.
<gallery mode=packed heights=220>
File:Immunohistochemistry with calponin in ductal carcinoma in situ.jpg|Immunohistochemistry for the myoepithelial marker{{Myoepithelial marker note}} calponin in '''ductal carcinoma in situ''', highlighting myoepithelial cells around all tumor cells, thereby ruling out [[invasive ductal carcinoma]].
File:Invasive ductal carcinoma with tubular features - combined.jpg|'''[[Invasive ductal carcinoma]] with tubular features''' can look like benign tubules, but calponin and p63 shows no surrounding myoepithelial cells.
</gallery>

;[[Atypical ductal hyperplasia]]
There is no single definite cutoff, but the following are suggested cutoffs defining a ductal carcinoma in situ:<ref name="TozbikianBrogi2016">{{cite journal|last1=Tozbikian|first1=Gary|last2=Brogi|first2=Edi|last3=Vallejo|first3=Christina E.|last4=Giri|first4=Dilip|last5=Murray|first5=Melissa|last6=Catalano|first6=Jeffrey|last7=Olcese|first7=Cristina|last8=Van Zee|first8=Kimberly J.|last9=Wen|first9=Hannah Yong|title=Atypical Ductal Hyperplasia Bordering on Ductal Carcinoma In Situ|journal=International Journal of Surgical Pathology|volume=25|issue=2|year=2016|pages=100–107|issn=1066-8969|doi=10.1177/1066896916662154}}</ref>
*Size over 2 mm.
*Involving more than one duct.

;[[Lobular carcinoma in situ]] (LCIS)
<gallery mode=packed heights=220>
File:Histopathology of lobular carcinoma in situ.jpg|Lobular carcinoma in situ (LCIS) displays discohesive cells, often a feathery clear space between cells, solid growth pattern, intracytoplasmic vacuoles, and lack of polarization around luminal spaces.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/breastmalignantDCIS.html|title=Breast - Ductal carcinoma in situ - DCIS|author=Gary Tozbikian, M.D.|website=pathologyOutlines}} Topic Completed: 20 May 2020. Minor changes: 6 May 2021</ref>
File:Histopathology of DCIS with lobular cancerization.jpg|LCIS typically fills smaller lobules rather than ducts, but '''DCIS can display lobular cancerization''' as shown at bottom of image.{{MH}}
</gallery>
When unsure, perform immunohistochemistry for E-cadherin and p120. Both E-cadherin (left image below) and p120 (right) have a '''membranous''' staining pattern in ductal carcinoma in situ:
<gallery mode=packed heights=200>
Immunohistochemistry for E-cadherin in ductal carcinoma in situ.jpg
Immunohistochemistry for p120 in ductal carcinoma in situ.jpg
</gallery>
In contrast:
<gallery mode=packed heights=200>>
File:Immunohistochemistry for E-cadherin in lobular carcinoma in situ.jpg|thumb|'''E-cadherin''' is '''negative''' in '''lobular''' carcinoma in situ.
File:Immunohistochemistry for p120 in lobular carcinoma in situ.jpg|'''p120''' has a '''cytoplasmic''' staining in '''lobular''' carcinoma in situ.
</gallery>

===Grading===
At least a '''low/intermediate/high''' grading (by Van Nuys criteria) as follows:<ref>{{cite web|url=http://surgpathcriteria.stanford.edu/breast/dcis/grading.html|title=Ductal Carcinoma in Situ of the Breast|website=Stanford Medical School|date=2020-08-27}}</ref>
;Low grade DCIS
*Nuclei 10-15 microns (2-3 times the size of a red blood cell)
*Nuclei oval, round, regular, evenly dispersed chromatin up to mildly irregular and minimally pleomorphic
*Nucleoi, if present, are small and indistinct
;Intermediate grade DCIS
*Same nuclear features as low grade
[[File:Histopathology of ductal carcinoma in situ with comedo necrosis.jpg|thumb|220px|Ductal carcinoma in situ with '''comedo necrosis''' spanning 30% of its diameter, which is generally regarded as the minimal size to classify it as comedo.<ref name="pmid30980039">Image by Mikael Häggström, MD. - Reference for most common definition of comedo necrosis by size: - {{cite journal| author=Harrison BT, Hwang ES, Partridge AH, Thompson AM, Schnitt SJ| title=Variability in diagnostic threshold for comedo necrosis among breast pathologists: implications for patient eligibility for active surveillance trials of ductal carcinoma in situ. | journal=Mod Pathol | year= 2019 | volume= 32 | issue= 9 | pages= 1257-1262 | pmid=30980039 | doi=10.1038/s41379-019-0262-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30980039 }}</ref>]]
*Substantial tumor cell (comedo) necrosis is present
[[File:Histopathology of high-grade DCIS.png|thumb||220px|High-grade DCIS. H&E stain. RBC = red blood cell.<ref>Image by Mikael Häggström, MD. References for features: - {{cite web|url=http://surgpathcriteria.stanford.edu/breast/dcis/grading.html|title=Ductal Carcinoma in Situ of the Breast|website=Stanford Medical School|date=2020-08-27}} - {{cite journal| author=Hayward MK, Louise Jones J, Hall A, King L, Ironside AJ, Nelson AC | display-authors=etal| title=Derivation of a nuclear heterogeneity image index to grade DCIS. | journal=Comput Struct Biotechnol J | year= 2020 | volume= 18 | issue= | pages= 4063-4070 | pmid=33363702 | doi=10.1016/j.csbj.2020.11.040 | pmc=7744935 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33363702 }}</ref>]]
;High grade DCIS
*Nuclei >15 microns (over 2.5<ref name=Hayward2020>{{cite journal| author=Hayward MK, Louise Jones J, Hall A, King L, Ironside AJ, Nelson AC | display-authors=etal| title=Derivation of a nuclear heterogeneity image index to grade DCIS. | journal=Comput Struct Biotechnol J | year= 2020 | volume= 18 | issue= | pages= 4063-4070 | pmid=33363702 | doi=10.1016/j.csbj.2020.11.040 | pmc=7744935 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33363702 }} </ref> times the size of a red blood cell)
*Nuclei are pleomorphic with clumped chromatin
*Nucleoli are prominent, enlarged
*Necrosis is almost universal and lumenal

{{Moderate-begin}}'''Numerical grading'''

Use the low/intermediate/high grade to give a '''numerical grading''' as follows:<ref name="Allred2010">{{cite journal|last1=Allred|first1=D. C.|title=Ductal Carcinoma In Situ: Terminology, Classification, and Natural History|journal=JNCI Monographs|volume=2010|issue=41|year=2010|pages=134–138|issn=1052-6773|doi=10.1093/jncimonographs/lgq035}}</ref>
{|class=wikitable
!rowspan=2| Feature !!colspan=3| Points
|-
! 1 !! 2 !! 3
|-
! Nuclear grade
| Low || Intermediate || High
|-
! Glands/papillae
| >75% || 10% - 75% || <10%
|-
! Mitotic rate (per 10 HPF)
| <1 || 1 - 2 || >2
|-
! Central necrosis
| <10% || 10% - 50% || >50%
|}
The points for each feature are added together, giving the following result:<ref name="Allred2010"/>
*4 - 7 points: '''Grade 1'''
*8 - 9 points: '''Grade 2'''
*10 - 12 points: '''Grade 3'''
{{Moderate-end}}

===Extent===
*In '''biopsies''', do not state the extent of DCIS.
*In '''excisions''', state the distance to the closest margin. {{Moderate-begin}}Additional extent specification is optional. If there is invasive tumor in addition to DCIS, you may give the DCIS extent in terms of the number of blocks containing DCIS. If an excision has DCIS without any invasive component, consider stating the total size in terms of the greatest distance between any DCIS foci.{{Moderate-end}}
[[File:Histopathology of dystrophic microcalcifications in ductal carcinoma in situ.jpg|thumb|170px|Histopathology of dystrophic microcalcifications in DCIS.]]
{{Microcalcifications in breast cancer}}

===Estrogen and progesterone receptors===
[[File:Immunohistochemistry of ductal carcinoma in situ (DCIS) with necrosis.jpg|thumb|200px|In DCIS with necrosis, only use the areas of viable DCIS for the calculation of hormone receptors on immunohistochemistry.]]
{{Estrogen and progesterone receptors in breast cancers}}

===HER2===
{{Comprehensive-begin}}HER2 testing is not necessary, but can be done for prognostic profiling.<ref>{{cite web|url=https://www.uptodate.com/contents/ductal-carcinoma-in-situ-treatment-and-prognosis|title=Ductal carcinoma in situ: Treatment and prognosis|website=UpToDate|author=Laura C Collins, MD, Christine Laronga, MD, FACS, Julia S Wong, MD}} Literature review current through: Sep 2022. | This topic last updated: Aug 19, 2022.</ref>{{Comprehensive-end}} See '''[[invasive ductal carcinoma]]''' for how to evaluate HER2.

==Reporting==
[[File:Histopathologic architectural patterns of DCIS.png|thumb|Architectural patterns of DCIS.<ref>Top and bottom left images by Mikael Häggström, MD. Bottom right image from: {{cite journal| author=Kulka J, Madaras L, Floris G, Lax SF| title=Papillary lesions of the breast. | journal=Virchows Arch | year= 2022 | volume= 480 | issue= 1 | pages= 65-84 | pmid=34734332 | doi=10.1007/s00428-021-03182-7 | pmc=8983543 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34734332 }} - "This article is licensed under a Creative Commons Attribution 4.0 International License"</ref>]]
Example:
{|class=wikitable
| Left breast mass, 2:00, 1 cm from nipple, ultrasound-guided vacuum assisted core needle biopsy: Ductal carcinoma in situ. Negative for invasive carcinoma.
|}
{{CAP}}
{{Reporting}}
<noinclude>{{Bottom}}
</noinclude>

Template:Myoepithelial marker note

2025-06-02T18:34:24Z

Mikael Häggström: Expanded

<ref group=note>For myoepithelial markers, a combination of '''p63''' (higher specificity) with either '''SMM''' or '''calponin''' (both have higher sensitivity) is generally recommended for breast lesions. D2-40 is useful for highlighting lymphatics for invasion.</ref><noinclude>{{Bottom}}</noinclude>

Template:Myoepithelial marker note

2025-06-02T18:31:00Z

Mikael Häggström: Or

<ref group=note>For myoepithelial markers, a combination of p63 with either SMM or calponin is generally recommended for breast lesions. D2-40 is useful for highlighting lymphatics for invasion.</ref><noinclude>{{Bottom}}</noinclude>

Template:Undifferentiated malignancy

2025-05-06T21:59:23Z

Mikael Häggström: mh

===Undifferentiated malignancy===
[[File:Histopathology of undifferentiated tumor cells.jpg|thumb|220px|Histopathology of a biopsy of a lymph node with cancer of unknown primary origin, showing undifferentiated high-grade tumor cells.]]
An initial panel of '''cytokeratin''' (CK, such as by CK AE1/AE3 cocktail), '''S100''', '''vimentin''' and '''LCA (CD45)''' can be used (see source article for subsequent work-up).<ref name="pmid25427040">{{cite journal| author=Lin F, Liu H| title=Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 12 | pages= 1583-610 | pmid=25427040 | doi=10.5858/arpa.2014-0061-RA | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25427040 }} </ref>

Alternatively, a more comprehensive panel can be performed upfront, with the most pertinent panel suggested below (with main associated primary origins in parentheses), but it should be tailored to additional clues from each individual case:<ref>Partly inspired by: {{cite journal| author=Beauchamp K, Moran B, O'Brien T, Brennan D, Crown J, Sheahan K | display-authors=etal| title=Carcinoma of unknown primary (CUP): an update for histopathologists. | journal=Cancer Metastasis Rev | year= 2023 | volume= | issue= | pages= | pmid=37394540 | doi=10.1007/s10555-023-10101-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=37394540 }} </ref>
[[File:Histopathology of signet ring cell carcinoma of urinary bladder on mucicarmine stain.jpg|thumb|220px|Mucicarmine stain showing signet ring cell carcinoma, with the mucin within tumor cells colored pink/red.]]
*'''Mucicarmine''' or '''Cytokeratin CAM 5.2''' ([[adenocarcinoma]])
:*'''CK7 and CK20''' can give a broad indication of the primary site. Still use more specific immunohistochemistry stains instead or in addition where applicable. See image below for main patterns.
:*'''NKX3.1''' in males ([[prostate adenocarcinoma]]), or '''PAX-8''' or '''estrogen and progesterone receptor''' in females ([[Female reproductive system|female reproductive tract]]).
:*'''TTF-1''' ([[thyroid]] or [[lung tumor]])
:*'''GATA3''' ([[urothelial carcinoma]], [[Breast pathology|breast tumor]])
:*'''CDX2''' (gastro[[Intestine with tumor|intestinal tumor]])
:*'''p63''' ([[squamous cell carcinoma]])
*'''S100''' (neural, [[invasive melanoma]])
*'''LCA (CD45)''' (hematopoietic)
*'''Synaptophysin''' (neuroendocrine)
[[File:CK7 and CK20 by body location.svg|thumb|center|500px|CK7 and CK20 expression by various body locations.{{MH}}]]
<noinclude>
{{Bottom}}
</noinclude>

Template:Undifferentiated malignancy

2025-05-06T21:57:12Z

Mikael Häggström: /* Undifferentiated malignancy */ 500px

Template:Undifferentiated malignancy

2025-05-06T21:56:46Z

Mikael Häggström: /* Undifferentiated malignancy */ ]]

===Undifferentiated malignancy===
[[File:Histopathology of undifferentiated tumor cells.jpg|thumb|220px|Histopathology of a biopsy of a lymph node with cancer of unknown primary origin, showing undifferentiated high-grade tumor cells.]]
An initial panel of '''cytokeratin''' (CK, such as by CK AE1/AE3 cocktail), '''S100''', '''vimentin''' and '''LCA (CD45)''' can be used (see source article for subsequent work-up).<ref name="pmid25427040">{{cite journal| author=Lin F, Liu H| title=Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 12 | pages= 1583-610 | pmid=25427040 | doi=10.5858/arpa.2014-0061-RA | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25427040 }} </ref>

Alternatively, a more comprehensive panel can be performed upfront, with the most pertinent panel suggested below (with main associated primary origins in parentheses), but it should be tailored to additional clues from each individual case:<ref>Partly inspired by: {{cite journal| author=Beauchamp K, Moran B, O'Brien T, Brennan D, Crown J, Sheahan K | display-authors=etal| title=Carcinoma of unknown primary (CUP): an update for histopathologists. | journal=Cancer Metastasis Rev | year= 2023 | volume= | issue= | pages= | pmid=37394540 | doi=10.1007/s10555-023-10101-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=37394540 }} </ref>
[[File:Histopathology of signet ring cell carcinoma of urinary bladder on mucicarmine stain.jpg|thumb|220px|Mucicarmine stain showing signet ring cell carcinoma, with the mucin within tumor cells colored pink/red.]]
*'''Mucicarmine''' or '''Cytokeratin CAM 5.2''' ([[adenocarcinoma]])
:*'''CK7 and CK20''' can give a broad indication of the primary site. Still use more specific immunohistochemistry stains instead or in addition where applicable. See image below for main patterns.
:*'''NKX3.1''' in males ([[prostate adenocarcinoma]]), or '''PAX-8''' or '''estrogen and progesterone receptor''' in females ([[Female reproductive system|female reproductive tract]]).
:*'''TTF-1''' ([[thyroid]] or [[lung tumor]])
:*'''GATA3''' ([[urothelial carcinoma]], [[Breast pathology|breast tumor]])
:*'''CDX2''' (gastro[[Intestine with tumor|intestinal tumor]])
:*'''p63''' ([[squamous cell carcinoma]])
*'''S100''' (neural, [[invasive melanoma]])
*'''LCA (CD45)''' (hematopoietic)
*'''Synaptophysin''' (neuroendocrine)
[[File:CK7 and CK20 by body location.svg|thumb|center|300px|CK7 and CK20 expression by various body locations.<ref>{{MH}}</ref>]]
<noinclude>
{{Bottom}}
</noinclude>

Template:Undifferentiated malignancy

2025-05-06T21:56:22Z

Mikael Häggström: /* Undifferentiated malignancy */ Image

===Undifferentiated malignancy===
[[File:Histopathology of undifferentiated tumor cells.jpg|thumb|220px|Histopathology of a biopsy of a lymph node with cancer of unknown primary origin, showing undifferentiated high-grade tumor cells.]]
An initial panel of '''cytokeratin''' (CK, such as by CK AE1/AE3 cocktail), '''S100''', '''vimentin''' and '''LCA (CD45)''' can be used (see source article for subsequent work-up).<ref name="pmid25427040">{{cite journal| author=Lin F, Liu H| title=Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. | journal=Arch Pathol Lab Med | year= 2014 | volume= 138 | issue= 12 | pages= 1583-610 | pmid=25427040 | doi=10.5858/arpa.2014-0061-RA | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25427040 }} </ref>

Alternatively, a more comprehensive panel can be performed upfront, with the most pertinent panel suggested below (with main associated primary origins in parentheses), but it should be tailored to additional clues from each individual case:<ref>Partly inspired by: {{cite journal| author=Beauchamp K, Moran B, O'Brien T, Brennan D, Crown J, Sheahan K | display-authors=etal| title=Carcinoma of unknown primary (CUP): an update for histopathologists. | journal=Cancer Metastasis Rev | year= 2023 | volume= | issue= | pages= | pmid=37394540 | doi=10.1007/s10555-023-10101-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=37394540 }} </ref>
[[File:Histopathology of signet ring cell carcinoma of urinary bladder on mucicarmine stain.jpg|thumb|220px|Mucicarmine stain showing signet ring cell carcinoma, with the mucin within tumor cells colored pink/red.]]
*'''Mucicarmine''' or '''Cytokeratin CAM 5.2''' ([[adenocarcinoma]])
:*'''CK7 and CK20''' can give a broad indication of the primary site. Still use more specific immunohistochemistry stains instead or in addition where applicable. See image below for main patterns.
:*'''NKX3.1''' in males ([[prostate adenocarcinoma]]), or '''PAX-8''' or '''estrogen and progesterone receptor''' in females ([[Female reproductive system|female reproductive tract]]).
:*'''TTF-1''' ([[thyroid]] or [[lung tumor]])
:*'''GATA3''' ([[urothelial carcinoma]], [[Breast pathology|breast tumor]])
:*'''CDX2''' (gastro[[Intestine with tumor|intestinal tumor]])
:*'''p63''' ([[squamous cell carcinoma]])
*'''S100''' (neural, [[invasive melanoma]])
*'''LCA (CD45)''' (hematopoietic)
*'''Synaptophysin''' (neuroendocrine)
[[File:CK7 and CK20 by body location.svg|thumb|center|300px|CK7 and CK20 expression by various body locations.<ref>{{MH}}</ref>
<noinclude>
{{Bottom}}
</noinclude>

Template:Learning hematopathology

2025-04-30T01:47:01Z

Mikael Häggström: wording

{{Edit|Template:Learning hematopathology}} 
For '''[[learning pathology|learning]] hematopathology''', unless you plan on specializing in that field: focus on the aspects of it that you may be expected to handle rather independently, mainly including '''[[peripheral blood smear]]s''' and general screening of '''[[lymph node]]s'''. Also learn how to suspect an incidental hematopathologic disease for specimens submitted for other reasons. Otherwise, a hematopathology workup is generally a very complex matter that should be performed by subspecialists thereof. In the unlikely event that you will end up at a workplace without an internal arrangement for how to consult a hematopathologist, make such arrangement yourself, since it will save you a lot of time compared to even trying to learn yourself how to perform a modern hematology workup.

Template:Learning hematopathology

2025-04-30T01:38:47Z

Mikael Häggström:

{{Edit|Template:Learning hematopathology}} 
For '''[[learning pathology|learning]] hematopathology''', unless you plan on specializing in that field: focus on the aspects of it that you may be expected to handle rather independently, mainly including '''[[peripheral blood smear]]s''' and general screening of '''[[lymph node]]s'''. Also learn how to suspect an incidental hematopathologic disease even when it wasn't initially suspected. Otherwise, a hematopathology workup is generally a very complex matter that should be performed by subspecialists thereof. In the unlikely event that you will end up at a workplace without an internal arrangement for how to consult a hematopathologist, make such arrangement yourself, since it will save you a lot of time compared to even trying to learn yourself how to perform a modern hematology workup.

Gastroesophageal junction

2025-03-20T15:49:13Z

Mikael Häggström: </noinclude>

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
{{Endoscopic biopsies}}
{{Comprehensiveness}}</noinclude>
==Microscopic examination==
The main findings to look for are:
*'''[[Barrett's esophagus|Intestinalized mucosa]]''' ([[Barrett's esophagus]])
*(Reflux) '''esophagitis'''.
*'''Gastritis'''. {{Further|Stomach|linebreak=no}}
*'''[[Esophageal adenocarcinoma]]'''

===Barrett's esophagus===
The main diagnostic sign of Barrett's esophagus is the presence of '''goblet cells'''. A true goblet cell should have rounded shape, clear to bluish cytoplasmic mucin, and be randomly scattered.<ref name=PathologyOutlines-Barrett>{{cite web|url=http://www.pathologyoutlines.com/topic/esophagusBarrettsgeneral.html|title=Esophagus - Premalignant - Barrett esophagus|author=Dipti M. Karamchandani}} Topic Completed: 19 March 2020, Minor changes: 29 June 2020</ref> The mucin usually indents the nucleus.<ref name=PathologyOutlines-Barrett/>
<gallery mode=packed heights=220>
File:Histopathology of Barrett's esophagus, annotated.jpg|Histopathology of '''[[Barrett's esophagus]]''', showing intestinalized epithelium with goblet cells, as opposed to normal stratified squamous epithelium of the esophagus, and pseudostratified columnar epithelium of the fundus of the stomach. H&E stain.
File:Histopathology of goblet cells (annotated) and foveolar cells in incomplete Barrett's esophagus.jpg|In '''incomplete''' intestinal metaplasia, there are both foveolar cells and goblet cells, the latter (indicated by arrows) usually having a slightly bluish color compared to the apical cytoplasm of foveolar cells. An occasional but specific sign of goblet cells is crescent shaped nuclei (seen in middle one).
</gallery>

{{further|Barrett's esophagus}}

{{Esophagitis}}

===Report===
{{Moderate-begin}}Document the '''type of mucosa''':
*If both gastric and squamous mucosa is present in the same fragment, report as "'''Gastroesophageal junctional mucosa with...'''"
*If not, report the presence of '''squamous''' and/or '''gastric mucosa'''.{{Moderate-end}}

Examples:
{|class=wikitable
| {{Moderate-begin}}GE junction, biopsy:{{Moderate-end}} Squamous mucosa without significant histopathologic changes. {{Moderate-begin}}Negative for gastric mucosa or intestinalized (Barrett's) mucosa.{{Moderate-end}}
|}

{|class=wikitable
| {{Moderate-begin}}GE junction, biopsy:{{Moderate-end}} Gastroesophageal junctional mucosa with '''chronic inflammation''' and reactive changes{{Moderate-begin}}, non-specific. Negative for intestinalized (Barrett's) mucosa.{{Moderate-end}}
|}

In case of multiple signs of reflux esophagitis:
{|class=wikitable
| {{Moderate-begin}}GE junction, biopsy:{{Moderate-end}} Gastroesophageal junctional mucosa with changes consistent with '''reflux esophagitis'''. {{Moderate-begin}}Negative for intestinalized (Barrett's) mucosa.{{Moderate-end}}
|}
<noinclude>{{Bottom}}</noinclude>

Gastrointestinal pathology

2025-03-20T15:20:53Z

Mikael Häggström: Carcinomas

<noinclude>{{Top
|author1={{MH top}}
|author2=
}}</noinclude>
=Appendix=
{{Appendix - entire article}}

=Appendicitis=
{{Appendicitis - entire article}}

=Gallbladder=
{{Gallbladder - entire article}}

=Cholecystitis=
{{Cholecystitis - entire article}}

=Gallbladder polyp=
{{Gallbladder polyp - entire article}}

=Endoscopic gastrointestinal biopsies=
{{Endoscopic gastrointestinal biopsies - entire article}}

=Esophagus=
{{Esophagus - entire article}}

=Eosinophilic esophagitis=
{{Eosinophilic esophagitis - entire article}}

=Gastroesophageal junction=
{{Gastroesophageal junction - entire article}}

=Barrett's esophagus=
{{Barrett's esophagus - entire article}}

=Esophageal adenocarcinoma=
{{Esophageal adenocarcinoma - entire article}}

=Stomach=
{{Stomach - entire article}}

=Gastric polyp=
{{Gastric polyp - entire article}}

=Fundic gland polyp=
{{Fundic gland polyp - entire article}}

=Gastritis=
{{Gastritis - entire article}}

=Stomach biopsy for Helicobacter pylori=
{{Stomach biopsy for Helicobacter pylori - entire article}}

=Stomach tumor=
{{Stomach tumor - entire article}}

=Gastric sleeve=
{{Gastric sleeve - entire article}}

=Duodenum=
{{Duodenum - entire article}}

=Small intestine in celiac disease=
{{Small intestine in celiac disease - entire article}}

=Colorectal polyp=
{{Colorectal polyp - entire article}}

=Hyperplastic polyp=
{{Hyperplastic polyp - entire article}}

=Tubular and ⁄or villous adenoma=
{{Tubular and ⁄or villous adenoma - entire article}}

=Sessile serrated adenoma=
{{Sessile serrated adenoma - entire article}}

=Traditional serrated adenoma=
{{Traditional serrated adenoma - entire article}}

=Colitis=
{{Colitis - entire article}}

==Intestine with tumor==
{{Intestine with tumor - entire article}}

==Colorectal carcinoma==
{{Colorectal carcinoma - entire article}}
<noinclude>
{{Bottom}}</noinclude>

Gastrointestinal pathology

2025-03-20T15:15:37Z

Mikael Häggström: /* Colitis */ Update

<noinclude>{{Top
|author1={{MH top}}
|author2=
}}</noinclude>
=Appendix=
{{Appendix - entire article}}

=Appendicitis=
{{Appendicitis - entire article}}

=Gallbladder=
{{Gallbladder - entire article}}

=Cholecystitis=
{{Cholecystitis - entire article}}

=Gallbladder polyp=
{{Gallbladder polyp - entire article}}

=Endoscopic gastrointestinal biopsies=
{{Endoscopic gastrointestinal biopsies - entire article}}

=Esophagus=
{{Esophagus - entire article}}

=Eosinophilic esophagitis=
{{Eosinophilic esophagitis - entire article}}

=Gastroesophageal junction=
{{Gastroesophageal junction - entire article}}

=Barrett's esophagus=
{{Barrett's esophagus - entire article}}

=Esophageal adenocarcinoma=
{{Esophageal adenocarcinoma - entire article}}

=Stomach=
{{Stomach - entire article}}

=Gastric polyp=
{{Gastric polyp - entire article}}

=Fundic gland polyp=
{{Fundic gland polyp - entire article}}

=Gastritis=
{{Gastritis - entire article}}

=Stomach biopsy for Helicobacter pylori=
{{Stomach biopsy for Helicobacter pylori - entire article}}

=Stomach tumor=
{{Stomach tumor - entire article}}

=Gastric sleeve=
{{Gastric sleeve - entire article}}

=Duodenum=
{{Duodenum - entire article}}

=Small intestine in celiac disease=
{{Small intestine in celiac disease - entire article}}

=Colorectal polyp=
{{Colorectal polyp - entire article}}

=Hyperplastic polyp=
{{Hyperplastic polyp - entire article}}

=Tubular and ⁄or villous adenoma=
{{Tubular and ⁄or villous adenoma - entire article}}

=Sessile serrated adenoma=
{{Sessile serrated adenoma - entire article}}

=Traditional serrated adenoma=
{{Traditional serrated adenoma - entire article}}

=Colitis=
{{Colitis - entire article}}

'''[[Intestine with tumor]]''' and '''[[colorectal carcinoma]]''' are given later in this handbook. If you suspect a colorectal carcinoma at this time, and you are not familiar with the condition, refer the case to a senior.<noinclude>
{{Bottom}}</noinclude>

Template:Colitis - entire article

2025-03-20T15:14:44Z

Mikael Häggström: Redirected page to Colitis

#REDIRECT [[Colitis]]

Gastrointestinal pathology

2025-03-20T15:11:47Z

Mikael Häggström: Colitis

<noinclude>{{Top
|author1={{MH top}}
|author2=
}}</noinclude>
=Appendix=
{{Appendix - entire article}}

=Appendicitis=
{{Appendicitis - entire article}}

=Gallbladder=
{{Gallbladder - entire article}}

=Cholecystitis=
{{Cholecystitis - entire article}}

=Gallbladder polyp=
{{Gallbladder polyp - entire article}}

=Endoscopic gastrointestinal biopsies=
{{Endoscopic gastrointestinal biopsies - entire article}}

=Esophagus=
{{Esophagus - entire article}}

=Eosinophilic esophagitis=
{{Eosinophilic esophagitis - entire article}}

=Gastroesophageal junction=
{{Gastroesophageal junction - entire article}}

=Barrett's esophagus=
{{Barrett's esophagus - entire article}}

=Esophageal adenocarcinoma=
{{Esophageal adenocarcinoma - entire article}}

=Stomach=
{{Stomach - entire article}}

=Gastric polyp=
{{Gastric polyp - entire article}}

=Fundic gland polyp=
{{Fundic gland polyp - entire article}}

=Gastritis=
{{Gastritis - entire article}}

=Stomach biopsy for Helicobacter pylori=
{{Stomach biopsy for Helicobacter pylori - entire article}}

=Stomach tumor=
{{Stomach tumor - entire article}}

=Gastric sleeve=
{{Gastric sleeve - entire article}}

=Duodenum=
{{Duodenum - entire article}}

=Small intestine in celiac disease=
{{Small intestine in celiac disease - entire article}}

=Colorectal polyp=
{{Colorectal polyp - entire article}}

=Hyperplastic polyp=
{{Hyperplastic polyp - entire article}}

=Tubular and ⁄or villous adenoma=
{{Tubular and ⁄or villous adenoma - entire article}}

=Sessile serrated adenoma=
{{Sessile serrated adenoma - entire article}}

=Traditional serrated adenoma=
{{Traditional serrated adenoma - entire article}}

=Colitis=
{{Colitis - entire article}}
'''[[Intestine with tumor]]''' and '''[[colorectal carcinoma]]''' are given later in this handbook. If you suspect a colorectal carcinoma at this time, and you are not familiar with the condition, refer the case to a senior.<noinclude>
{{Bottom}}</noinclude>

Colitis

2025-03-20T15:10:44Z

Mikael Häggström: /* Microscopic evaluation */ generally

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
Most commonly found by [[endoscopic gastrointestinal biopsies]].
{{Comprehensiveness}}</noinclude>
==Microscopic evaluation==
*Look for signs of '''active''' (or acute) and/or '''chronic''' colitis:

Signs of '''active''' (or acute) colitis:<ref name=Kellermann2021/>
<gallery mode=packed heights=170>
File:Histopathology of neutrophilic cryptitis in active colitis, annotated.jpg|Neutrophilic cryptitis (neutrophils within crypt epithelium)
File:Histopathology of a crypt abscess.jpg|Crypt abscesses (luminal neutrophilic aggregates)
File:Histopathology of small crypt abscess.jpg|In fact, one neutrophil is enough for the feature
File:Histopathology of a mucosal fold.jpg|Normal mucosal fold for comparison
File:Histopathology of gland destruction in active colitis.jpg|Gland destruction
File:Histopathology of colonic ulceration.jpg|Ulceration (seen here as absence of epithelium, and granulation tissue with many fibroblasts)
</gallery>
Active colitis may also cause ischemic changes (including superficial necrosis, hemorrhage, crypt shrinkage/dropout, fibrin thrombi)

Signs of '''chronic''' colitis:<ref name=Kellermann2021/>
<gallery mode=packed heights=170>
File:Histopathology of a degenerated crypt of chronic inactive colitis.jpg|Crypt degeneration
File:Histopathology of crypt branching of colon.jpg|Crypt branching and other architectural distortions
File:Histopathology Paneth cell metaplasia.jpg|Paneth cell (pictured) or gastric metaplasia (only applies in the left colon and rectum)
</gallery>
Chronic colitis may also cause elevation of crypts relative to the muscularis mucosa. Other findings include basal plasmacytosis and mucin depletion.<ref name=Kellermann2021/>

Have a high threshold for chronic colitis in the '''rectum''', as it often shows chronic changes even without any disease.

===Special types===
In addition, look for the following types of colitis:
<gallery mode=packed heights=170>
File:Histopathology of lymphocytic colitis, high magnification.png|'''Lymphocytic colitis''', characterized by > 20 intraepithelial lymphocytes per 100 epithelial cells, away from lymphoid aggregates.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/colonlymphocytic.html|title=Lymphocytic colitis|author=Martha M. Yearsley, M.D.|website=Pathology Outlines}} Last author update: 28 July 2020</ref>
File:Histopathology of lymphocytic colitis, low magnification.png|'''Lymphocytic colitis''' generally also shows increased lymphocytes, plasma cells, eosinophils, and occasional neutrophils in lamina propria, but with preserved architecture
File:Histopathology of collagenous colitis.jpg|'''Collagenous colitis''', with a thickened subepithelial collagen band that is typically more than 10 μm in thickness.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/coloncollagenous.html|website=Pathology Outlines|title=Collagenous colitis|author=Benjamin J. Van Treeck, M.D., Catherine E. Hagen, M.D.}} Topic Completed: 3 August 2020. Minor changes: 29 September 2020</ref>
File:Histology of a normal colonic mucosal epithelium.jpg|Compare to normal colonic mucosa, which can have a band of basal epithelial cytoplasm.
</gallery>
{{Moderate-begin}}Consider the clinical and/or endoscopic findings in the evaluation.{{Moderate-end}}

===Further workup of colitis===
Distinguish:
*{{Moderate-begin}}'''Severity''': Mild, moderate or severe.{{Moderate-end}}
*Presence of '''crypt regeneration''', '''granuloma''', inflammatory '''pseudomembranes''', '''parasites''' or '''viral inclusions'''.
*Presence of '''epithelial dysplasia''' or even '''cancer'''. If unsure of the latter, consider [[immunohistochemistry]] for cytokeratins such as CK AE1/AE3. {{further|Evaluation of suspected malignancies}}
*{{Comprehensive-begin}}Distribution: '''Patchy''' versus '''diffuse'''{{Comprehensive-end}}
<gallery mode=packed heights=170>
File:Histopathology of granuloma of colonic mucosa.jpg|A non-necrotizing '''granuloma'''. It is seen as an aggregate of histiocytes in the center of the image, having ample eosinophilic cytoplasm.
File:Non-proliferative versus proliferative colonic crypts.jpg|'''Dysplastic''' crypt at right. In such case, consider '''[[tubular and ⁄or villous adenoma]]'''.
File:Histopathology of signet ring cell carcinoma of ileum.jpg|Look particularly in ulcers for '''signet ring cells'''.
</gallery>
Apart from histologically defined diagnoses (collagenous colitis, lymphocytic colitis), there is no need to speculate about the exact underlying diagnosis (such as Crohn's disease, ulcerative colitis etc.).

===Microscopy report===
A biopsy report generally does not state the diagnosis, but should state any presence of chronic colitis, give an indication of disease activity, as well as state the presence of any epithelial damage (erosions and ulcerations).<ref name=Kellermann2021>{{cite journal|author=Kellermann L, Riis LB.|title=A close view on histopathological changes in inflammatory bowel disease, a narrative review.|journal=Dig Med Res|year=2021|volume=4|issue=3|url=https://dmr.amegroups.org/article/view/7171/html}}</ref>

Example of a normal sample, when colitis was suspected in the referral:
{|class=wikitable
| {{Moderate-begin}}Colonic/Rectal mucosa without significant histopathologic changes.{{Moderate-end}} Negative for {{Moderate-begin}}acute and chronic{{Moderate-end}} colitis.
|}

Example of findings of both active and chronic colitis:
{|class=wikitable
| {{Moderate-begin}}Ascending, transverse, descending, and sigmoid colon, biopsies:{{Moderate-end}} {{Comprehensive-begin}}Patchy{{Comprehensive-end}} {{Moderate-begin}}mild{{Moderate-end}} chronic active colitis{{Comprehensive-begin}}, with associated cryptitis and crypt abscesses.{{Comprehensive-end}} {{Moderate-begin}}Negative for ulceration, granulomata and dysplasia.{{Moderate-end}}
|}<noinclude>
{{Bottom}}</noinclude>

Colitis

2025-03-20T15:07:54Z

Mikael Häggström: /* Microscopic evaluation */ Rectum

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
Most commonly found by [[endoscopic gastrointestinal biopsies]].
{{Comprehensiveness}}</noinclude>
==Microscopic evaluation==
*Look for signs of '''active''' (or acute) and/or '''chronic''' colitis:

Signs of '''active''' (or acute) colitis:<ref name=Kellermann2021/>
<gallery mode=packed heights=170>
File:Histopathology of neutrophilic cryptitis in active colitis, annotated.jpg|Neutrophilic cryptitis (neutrophils within crypt epithelium)
File:Histopathology of a crypt abscess.jpg|Crypt abscesses (luminal neutrophilic aggregates)
File:Histopathology of small crypt abscess.jpg|In fact, one neutrophil is enough for the feature
File:Histopathology of a mucosal fold.jpg|Normal mucosal fold for comparison
File:Histopathology of gland destruction in active colitis.jpg|Gland destruction
File:Histopathology of colonic ulceration.jpg|Ulceration (seen here as absence of epithelium, and granulation tissue with many fibroblasts)
</gallery>
Active colitis may also cause ischemic changes (including superficial necrosis, hemorrhage, crypt shrinkage/dropout, fibrin thrombi)

Signs of '''chronic''' colitis:<ref name=Kellermann2021/>
<gallery mode=packed heights=170>
File:Histopathology of a degenerated crypt of chronic inactive colitis.jpg|Crypt degeneration
File:Histopathology of crypt branching of colon.jpg|Crypt branching and other architectural distortions
File:Histopathology Paneth cell metaplasia.jpg|Paneth cell (pictured) or gastric metaplasia (only applies in the left colon and rectum)
</gallery>
Chronic colitis may also cause elevation of crypts relative to the muscularis mucosa. Other findings include basal plasmacytosis and mucin depletion.<ref name=Kellermann2021/>

Have a high threshold for chronic colitis in the '''rectum''', as it often shows chronic changes even without any disease.

In addition, look for the following types of colitis:
<gallery mode=packed heights=170>
File:Histopathology of lymphocytic colitis, high magnification.png|'''Lymphocytic colitis''', characterized by > 20 intraepithelial lymphocytes per 100 epithelial cells, away from lymphoid aggregates.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/colonlymphocytic.html|title=Lymphocytic colitis|author=Martha M. Yearsley, M.D.|website=Pathology Outlines}} Last author update: 28 July 2020</ref>
File:Histopathology of lymphocytic colitis, low magnification.png|'''Lymphocytic colitis''' also shows increased lymphocytes, plasma cells, eosinophils, and occasional neutrophils in lamina propria, but with preserved architecture
File:Histopathology of collagenous colitis.jpg|'''Collagenous colitis''', with a thickened subepithelial collagen band that is typically more than 10 μm in thickness.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/coloncollagenous.html|website=Pathology Outlines|title=Collagenous colitis|author=Benjamin J. Van Treeck, M.D., Catherine E. Hagen, M.D.}} Topic Completed: 3 August 2020. Minor changes: 29 September 2020</ref>
File:Histology of a normal colonic mucosal epithelium.jpg|Compare to normal colonic mucosa, which can have a band of basal epithelial cytoplasm.
</gallery>
{{Moderate-begin}}Consider the clinical and/or endoscopic findings in the evaluation.{{Moderate-end}}

===Further workup of colitis===
Distinguish:
*{{Moderate-begin}}'''Severity''': Mild, moderate or severe.{{Moderate-end}}
*Presence of '''crypt regeneration''', '''granuloma''', inflammatory '''pseudomembranes''', '''parasites''' or '''viral inclusions'''.
*Presence of '''epithelial dysplasia''' or even '''cancer'''. If unsure of the latter, consider [[immunohistochemistry]] for cytokeratins such as CK AE1/AE3. {{further|Evaluation of suspected malignancies}}
*{{Comprehensive-begin}}Distribution: '''Patchy''' versus '''diffuse'''{{Comprehensive-end}}
<gallery mode=packed heights=170>
File:Histopathology of granuloma of colonic mucosa.jpg|A non-necrotizing '''granuloma'''. It is seen as an aggregate of histiocytes in the center of the image, having ample eosinophilic cytoplasm.
File:Non-proliferative versus proliferative colonic crypts.jpg|'''Dysplastic''' crypt at right. In such case, consider '''[[tubular and ⁄or villous adenoma]]'''.
File:Histopathology of signet ring cell carcinoma of ileum.jpg|Look particularly in ulcers for '''signet ring cells'''.
</gallery>
Apart from histologically defined diagnoses (collagenous colitis, lymphocytic colitis), there is no need to speculate about the exact underlying diagnosis (such as Crohn's disease, ulcerative colitis etc.).

===Microscopy report===
A biopsy report generally does not state the diagnosis, but should state any presence of chronic colitis, give an indication of disease activity, as well as state the presence of any epithelial damage (erosions and ulcerations).<ref name=Kellermann2021>{{cite journal|author=Kellermann L, Riis LB.|title=A close view on histopathological changes in inflammatory bowel disease, a narrative review.|journal=Dig Med Res|year=2021|volume=4|issue=3|url=https://dmr.amegroups.org/article/view/7171/html}}</ref>

Example of a normal sample, when colitis was suspected in the referral:
{|class=wikitable
| {{Moderate-begin}}Colonic/Rectal mucosa without significant histopathologic changes.{{Moderate-end}} Negative for {{Moderate-begin}}acute and chronic{{Moderate-end}} colitis.
|}

Example of findings of both active and chronic colitis:
{|class=wikitable
| {{Moderate-begin}}Ascending, transverse, descending, and sigmoid colon, biopsies:{{Moderate-end}} {{Comprehensive-begin}}Patchy{{Comprehensive-end}} {{Moderate-begin}}mild{{Moderate-end}} chronic active colitis{{Comprehensive-begin}}, with associated cryptitis and crypt abscesses.{{Comprehensive-end}} {{Moderate-begin}}Negative for ulceration, granulomata and dysplasia.{{Moderate-end}}
|}<noinclude>
{{Bottom}}</noinclude>

Colitis

2025-03-20T15:03:50Z

Mikael Häggström: linked

<noinclude>{{Top
|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=
}}
Most commonly found by [[endoscopic gastrointestinal biopsies]].
{{Comprehensiveness}}</noinclude>
==Microscopic evaluation==
*Look for signs of '''active''' (or acute) and/or '''chronic''' colitis:

Signs of '''active''' (or acute) colitis:<ref name=Kellermann2021/>
<gallery mode=packed heights=170>
File:Histopathology of neutrophilic cryptitis in active colitis, annotated.jpg|Neutrophilic cryptitis (neutrophils within crypt epithelium)
File:Histopathology of a crypt abscess.jpg|Crypt abscesses (luminal neutrophilic aggregates)
File:Histopathology of small crypt abscess.jpg|In fact, one neutrophil is enough for the feature
File:Histopathology of a mucosal fold.jpg|Normal mucosal fold for comparison
File:Histopathology of gland destruction in active colitis.jpg|Gland destruction
File:Histopathology of colonic ulceration.jpg|Ulceration (seen here as absence of epithelium, and granulation tissue with many fibroblasts)
</gallery>
Active colitis may also cause ischemic changes (including superficial necrosis, hemorrhage, crypt shrinkage/dropout, fibrin thrombi)

Signs of '''chronic''' colitis:<ref name=Kellermann2021/>
<gallery mode=packed heights=170>
File:Histopathology of a degenerated crypt of chronic inactive colitis.jpg|Crypt degeneration
File:Histopathology of crypt branching of colon.jpg|Crypt branching and other architectural distortions
File:Histopathology Paneth cell metaplasia.jpg|[[Paneth cell]] (pictured) or gastric metaplasia (only applies in the left colon and rectum)
</gallery>
Chronic colitis may also cause elevation of crypts relative to the muscularis mucosa. Other findings include basal plasmacytosis and mucin depletion.<ref name=Kellermann2021/>

In addition, look for the following types of colitis:
<gallery mode=packed heights=170>
File:Histopathology of lymphocytic colitis, high magnification.png|'''Lymphocytic colitis''', characterized by > 20 intraepithelial lymphocytes per 100 epithelial cells, away from lymphoid aggregates.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/colonlymphocytic.html|title=Lymphocytic colitis|author=Martha M. Yearsley, M.D.|website=Pathology Outlines}} Last author update: 28 July 2020</ref>
File:Histopathology of lymphocytic colitis, low magnification.png|'''Lymphocytic colitis''' also shows increased lymphocytes, plasma cells, eosinophils, and occasional neutrophils in lamina propria, but with preserved architecture
File:Histopathology of collagenous colitis.jpg|'''Collagenous colitis''', with a thickened subepithelial collagen band that is typically more than 10 μm in thickness.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/coloncollagenous.html|website=Pathology Outlines|title=Collagenous colitis|author=Benjamin J. Van Treeck, M.D., Catherine E. Hagen, M.D.}} Topic Completed: 3 August 2020. Minor changes: 29 September 2020</ref>
File:Histology of a normal colonic mucosal epithelium.jpg|Compare to normal colonic mucosa, which can have a band of basal epithelial cytoplasm.
</gallery>
{{Moderate-begin}}Consider the clinical and/or endoscopic findings in the evaluation.{{Moderate-end}}

===Further workup of colitis===
Distinguish:
*{{Moderate-begin}}'''Severity''': Mild, moderate or severe.{{Moderate-end}}
*Presence of '''crypt regeneration''', '''granuloma''', inflammatory '''pseudomembranes''', '''parasites''' or '''viral inclusions'''.
*Presence of '''epithelial dysplasia''' or even '''cancer'''. If unsure of the latter, consider [[immunohistochemistry]] for cytokeratins such as CK AE1/AE3. {{further|Evaluation of suspected malignancies}}
*{{Comprehensive-begin}}Distribution: '''Patchy''' versus '''diffuse'''{{Comprehensive-end}}
<gallery mode=packed heights=170>
File:Histopathology of granuloma of colonic mucosa.jpg|A non-necrotizing '''granuloma'''. It is seen as an aggregate of histiocytes in the center of the image, having ample eosinophilic cytoplasm.
File:Non-proliferative versus proliferative colonic crypts.jpg|'''Dysplastic''' crypt at right. In such case, consider '''[[tubular and ⁄or villous adenoma]]'''.
File:Histopathology of signet ring cell carcinoma of ileum.jpg|Look particularly in ulcers for '''signet ring cells'''.
</gallery>
Apart from histologically defined diagnoses (collagenous colitis, lymphocytic colitis), there is no need to speculate about the exact underlying diagnosis (such as Crohn's disease, ulcerative colitis etc.).

===Microscopy report===
A biopsy report generally does not state the diagnosis, but should state any presence of chronic colitis, give an indication of disease activity, as well as state the presence of any epithelial damage (erosions and ulcerations).<ref name=Kellermann2021>{{cite journal|author=Kellermann L, Riis LB.|title=A close view on histopathological changes in inflammatory bowel disease, a narrative review.|journal=Dig Med Res|year=2021|volume=4|issue=3|url=https://dmr.amegroups.org/article/view/7171/html}}</ref>

Example of a normal sample, when colitis was suspected in the referral:
{|class=wikitable
| {{Moderate-begin}}Colonic/Rectal mucosa without significant histopathologic changes.{{Moderate-end}} Negative for {{Moderate-begin}}acute and chronic{{Moderate-end}} colitis.
|}

Example of findings of both active and chronic colitis:
{|class=wikitable
| {{Moderate-begin}}Ascending, transverse, descending, and sigmoid colon, biopsies:{{Moderate-end}} {{Comprehensive-begin}}Patchy{{Comprehensive-end}} {{Moderate-begin}}mild{{Moderate-end}} chronic active colitis{{Comprehensive-begin}}, with associated cryptitis and crypt abscesses.{{Comprehensive-end}} {{Moderate-begin}}Negative for ulceration, granulomata and dysplasia.{{Moderate-end}}
|}<noinclude>
{{Bottom}}</noinclude>