Difference between revisions of "Breast biopsy or excision"

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{{Fixation - standard}}
 
{{Fixation - standard}}
Fresh breast specimens should be put in formalin within one hour.<ref group=notes name=time>An increased cold ischemia time (time from procurement to time in formalin) negatively effects the utility of immunohistochemistry.<br>- {{cite journal|last1=Khoury|first1=Thaer|title=Delay to Formalin Fixation (Cold Ischemia Time) Effect on Breast Cancer Molecules|journal=American Journal of Clinical Pathology|volume=149|issue=4|year=2018|pages=275–292|issn=0002-9173|doi=10.1093/ajcp/aqx164}}</ref> Breast specimens should be immersed in formalin for 6-72 hours.<ref>{{cite web|url=https://webapps.cap.org/apps/docs/committees/immunohistochemistry/her2_faqs.pdf|title=Recommendations for HER2 Testing in Breast Cancer: ASCO – CAP Clinical Practice Guideline Update|date=2013-10-17|website=College of American Pathologists}}</ref>
+
Fresh breast specimens should be put in formalin within one hour.<ref group=note name=time>An increased cold ischemia time (time from procurement to time in formalin) negatively effects the utility of immunohistochemistry.<br>- {{cite journal|last1=Khoury|first1=Thaer|title=Delay to Formalin Fixation (Cold Ischemia Time) Effect on Breast Cancer Molecules|journal=American Journal of Clinical Pathology|volume=149|issue=4|year=2018|pages=275–292|issn=0002-9173|doi=10.1093/ajcp/aqx164}}</ref> Breast specimens should be immersed in formalin for 6-72 hours.<ref>{{cite web|url=https://webapps.cap.org/apps/docs/committees/immunohistochemistry/her2_faqs.pdf|title=Recommendations for HER2 Testing in Breast Cancer: ASCO – CAP Clinical Practice Guideline Update|date=2013-10-17|website=College of American Pathologists}}</ref>
  
 
{{Comprehensiveness|otherlegend=yes}}
 
{{Comprehensiveness|otherlegend=yes}}
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*Determine total specimen '''size'''. {{Comprehensive-begin}}Weight the specimen<ref name=Roychowdhury>{{cite web|url=https://www.pathologyoutlines.com/topic/breastmalignantgrossing.html|title=Grossing (histologic sampling) of breast lesions|author=Monika Roychowdhury|website=Pathologyoutlines.com}} Topic Completed: 1 August 2012. Revised: 19 September 2019</ref>{{Comprehensive-end}}
 
*Determine total specimen '''size'''. {{Comprehensive-begin}}Weight the specimen<ref name=Roychowdhury>{{cite web|url=https://www.pathologyoutlines.com/topic/breastmalignantgrossing.html|title=Grossing (histologic sampling) of breast lesions|author=Monika Roychowdhury|website=Pathologyoutlines.com}} Topic Completed: 1 August 2012. Revised: 19 September 2019</ref>{{Comprehensive-end}}
 
*'''[[Ink]]''' margins. If sample orientations are marked, use different colors for different directions.<ref name=Roychowdhury/>
 
*'''[[Ink]]''' margins. If sample orientations are marked, use different colors for different directions.<ref name=Roychowdhury/>
*'''Palpate''' the specimen for masses. Compare with radiography if available.<ref name=Roychowdhury/> Confirm the presence of any known biopsy clips, either visibly or by post-operative radiography (in order to confirm that the specimen includes the region of interest).
+
*'''Palpate''' the specimen for masses. If felt, estimate the greatest dimension.<ref group=note>A palpated greatest dimension before cutting is still superior to trying to align cut pieces together or mathematically adding the thicknesses of involved slices.</ref> Compare with radiography if available.<ref name=Roychowdhury/> Confirm the presence of any known biopsy clips, either visibly or by post-operative radiography (in order to confirm that the specimen includes the region of interest).
[[File:Cutting of uneven lumpectomy.jpg|thumb|Cut a lumpectomy in the direction that gives the shortest distance from margin to margin. If a lumpectomy is uneven as shown, cut so that the first and last slice become wedge shaped (because these will later be cut further, perpendicularly to the margin), avoiding a wedge-shape for remaining slices.]]
+
[[File:Cutting of uneven lumpectomy.jpg|thumb|240px|Cut a lumpectomy in the direction that gives the shortest distance from margin to margin. If a lumpectomy is uneven as shown, cut so that the first and last slice become wedge shaped (because these will later be cut further, perpendicularly to the margin), avoiding a wedge-shape for remaining slices.]]
 
*'''Serially section''' the specimen.
 
*'''Serially section''' the specimen.
:*When performing '''triage''' of fresh lumpectomies, generally make slices 1.1 to 1.5 cm thick. When laid down and flattened, this is generally thin enough to allow for fixation over at least 6 hours, and thick enough to be further cut into 2 or 3 slices after fixation. Slices with solid tumors are cut somewhat thinner since they won't flatten as much when laid down.
+
:*When performing '''triage''' of fresh lumpectomies, generally make slices 1.1 to 1.5 cm thick. When laid down and flattened, this is generally thin enough to allow for fixation over at least 6 hours, and thick enough to be further cut into 2 or 3 slices after fixation; Note the direction of up/down on each such thick slice so that the relative orientation of the thinner slices thereof is maintained. Slices with solid tumors are cut somewhat thinner since they won't flatten as much when laid down.
 
:*When selecting tissue for submission after fixation, make 3-4 mm thick '''slices'''.<ref name=Roychowdhury/>
 
:*When selecting tissue for submission after fixation, make 3-4 mm thick '''slices'''.<ref name=Roychowdhury/>
*'''Inspect''' for any grossly visible lesions. If found, measure at least the greatest dimension, including stacking slices or mathematically adding the thicknesses of involved slices. {{Moderate-begin}}Also compare it to the measurement of previous imaging, and note if it confers a staging discrepancy between imaging and gross dimensions, with cutoffs at 0.1 cm, 0.5 cm, 1.0 cm, 2.0 cm, and 5 cm.{{Moderate-end}}
+
*'''Inspect''' for any grossly visible lesions. If found, measure at least the greatest dimension of the lesion on the slice where it appears largest. {{Moderate-begin}}Also compare the greatest gross measurement (including any palpated one) with the greatest measurement at previous imaging, and note if it confers a staging discrepancy between imaging and gross dimensions, with cutoffs at 0.1 cm, 0.5 cm, 1.0 cm, 2.0 cm, and 5 cm.{{Moderate-end}}
*Submit:<ref name=Roychowdhury/>
+
<gallery mode=packed heights=180>
 +
File:Histopathology of invasive ductal carcinoma and a radioactive seed.jpg|'''[[Invasive ductal carcinomas]]''' generally appear grossly as tan-white firm areas, here seen (white arrow) on a slice with inked margins. A radioactive seed (black arrow) was inserted by radiology to locate the tumor.
 +
</gallery>
 +
;'''Re-excisions''':
 +
<gallery mode=packed heights=180>
 +
File:Gross pathology of breast re-excision.jpg|For breast '''re-excisions''', ink the new margin (in this case marked with a suture).
 +
File:Gross pathology cutting of breast re-excision.jpg|Re-excisions are subsequently serially sectioned perpendicularly to the new margin (to be able to measure distance from any tumor to the new margin). For large specimens, every other section may be submitted.
 +
</gallery>
 +
 
 +
===Tissue selection===
 +
[[File:Selective sections of perpendicular margins of lumpectomy.jpg|thumb|Further serially section each of the two '''end sections''' into perpendicular sections, so that the distance between the surgical margin and any tumor involvement can be measured. If they are visibly involved as pictured, sections can be selectively taken from there. If end sections are not grossly involved, submit one perpendicular section, {{Moderate-begin}}every other perpendicular section{{Moderate-end}}, {{Comprehensive-begin}}or the entire end sections{{Comprehensive-end}}.]]
 +
*For lumpectomies, '''submit''':<ref name=Roychowdhury/>
 
:*Entire specimen if it can fit in 3-5 slices.
 
:*Entire specimen if it can fit in 3-5 slices.
:*If larger, 1 slice per cm of tumor (minimum of 3 slices of tumor), including both center and periphery of tumor, including closest distance to the surgical margin if possible.
+
:*If larger:
 +
::*For relatively '''well demarcated tumors''': 1 slice per cm of tumor (minimum of 3 slices of tumor), including both center and periphery of tumor, including closest distance to the surgical margin if possible.
 +
::*For '''diffuse''' or even invisible tumors such as often is the case for DCIS and ILC, either still submit whole, or use X-ray to guide  what tissue to submit.
 
:*Additional suspicious areas, including those indicated by radiography.
 
:*Additional suspicious areas, including those indicated by radiography.
 +
:*{{Comprehensive-begin}}Representative sections of margins in each direction.{{Comprehensive-end}}
 
Breast specimens where breast cancer is possible should generally not be decalcified even when containing small calcifications, to preserve the ability to perform immunohistochemistry.
 
Breast specimens where breast cancer is possible should generally not be decalcified even when containing small calcifications, to preserve the ability to perform immunohistochemistry.
 +
 
{{Gross processing}}
 
{{Gross processing}}
  
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:*Consistency<ref name=Roychowdhury/>
 
:*Consistency<ref name=Roychowdhury/>
 
*{{Moderate-begin}}Description of sectioning and submissions.{{Moderate-end}}
 
*{{Moderate-begin}}Description of sectioning and submissions.{{Moderate-end}}
*{{Comprehensive-begin}}Time of procurement and time of placement in formalin.<ref group=notes name=time/>{{Comprehensive-end}}
+
*{{Comprehensive-begin}}Time of procurement and time of placement in formalin.<ref group=note name=time/>{{Comprehensive-end}}
  
 
Example:
 
Example:
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| {{Moderate-begin}}The specimen is received fresh and consists of{{Moderate-end}} an irregular fragment of yellow tan fibrofatty tissue measuring 4.0 x 2.8 x 2.0 cm. {{Moderate-begin}}The specimen is oriented with two sutures and{{Moderate-end}} the surgical margins are inked as follows: superior-blue, inferior-green, medial-red, lateral-yellow, anterior-orange, and posterior-black. {{Finding-begin}}A radioactive seed is embedded in the tissue.{{Finding-end}} The tissue is serially sectioned {{Finding-begin}}to reveal a tan-gray, spiculated, indurated mass measuring _cm in greatest dimension. The mass is located _cm from the nearest (<<superior, inferior etc>>) margin. {{Moderate-begin}}The specimen is entirely submitted in sequential sections from medial to lateral in 10 cassettes. The medial and lateral margins are submitted as perpendicular sections.{{Moderate-end}} The specimen was procured at _AM/PM on _/_/2020.  The specimen was placed in formalin at _AM/PM on _/_/2020.
 
| {{Moderate-begin}}The specimen is received fresh and consists of{{Moderate-end}} an irregular fragment of yellow tan fibrofatty tissue measuring 4.0 x 2.8 x 2.0 cm. {{Moderate-begin}}The specimen is oriented with two sutures and{{Moderate-end}} the surgical margins are inked as follows: superior-blue, inferior-green, medial-red, lateral-yellow, anterior-orange, and posterior-black. {{Finding-begin}}A radioactive seed is embedded in the tissue.{{Finding-end}} The tissue is serially sectioned {{Finding-begin}}to reveal a tan-gray, spiculated, indurated mass measuring _cm in greatest dimension. The mass is located _cm from the nearest (<<superior, inferior etc>>) margin. {{Moderate-begin}}The specimen is entirely submitted in sequential sections from medial to lateral in 10 cassettes. The medial and lateral margins are submitted as perpendicular sections.{{Moderate-end}} The specimen was procured at _AM/PM on _/_/2020.  The specimen was placed in formalin at _AM/PM on _/_/2020.
 
|}
 
|}
 +
 +
===Lymph nodes===
 +
When lymph nodes are submitted together with a biopsy or excision of a suspected or previously confirmed [[invasive lobular carcinoma]] (but not necessarily invasive carcinoma with lobular features), generally put the lymph node specimen through H&E processing at a relative rush. If you don't see any involvement on the H&E stain, order immunostain for CK AE1/AE3 in order to visualize otherwise occult lymph node involvement. The rushing of the lymph node samples 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>
 +
{{further|Lymph node|linebreak=yes}}
  
 
==Staining==
 
==Staining==
 
{{Routine staining}}
 
{{Routine staining}}
 
Routine immunohistochemistry usually include estrogen and progesterone receptors (ER, PR) and HER2.<ref>{{cite journal |vauthors=Williams SL, Birdsong GG, Cohen C, Siddiqui MT |title=Immunohistochemical detection of estrogen and progesterone receptor and HER2 expression in breast carcinomas: comparison of cell block and tissue block preparations |journal=Int J Clin Exp Pathol |volume=2 |issue=5 |pages=476–80 |date=2009 |pmid=19294006 |pmc=2655151 |doi= |url=}}</ref>
 
  
 
==Microscopic evaluation==
 
==Microscopic evaluation==
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! Image
 
! Image
 
|-  
 
|-  
|rowspan=2| '''[[Fibrocystic breast changes]]''' ||rowspan=2| 40% || '''[[Sclerosing adenosis]]''' (pictured), with an increase in glandular elements in addition to stromal proliferation that distorts and compresses glands.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/breastsclerosingadenosis.html|title=Breast - Fibrocystic changes - Sclerosing adenosis|author=Jaya Ruth Asirvatham, M.B.B.S., Julie M. Jorns, M.D.|website=Pathology Outlines}} Topic Completed: 1 January 2015. Minor changes: 31 December 2020</ref> || [[File:Histopathology of sclerosing adenosis of the breast.jpg|180px]]
+
|rowspan=3| '''[[Fibrocystic breast changes]]''' ||rowspan=3| 40% || '''[[Sclerosing adenosis]]''' (pictured), with an increase in glandular elements in addition to stromal proliferation that distorts and compresses glands.<ref>{{cite web|url=https://www.pathologyoutlines.com/topic/breastsclerosingadenosis.html|title=Breast - Fibrocystic changes - Sclerosing adenosis|author=Jaya Ruth Asirvatham, M.B.B.S., Julie M. Jorns, M.D.|website=Pathology Outlines}} Topic Completed: 1 January 2015. Minor changes: 31 December 2020</ref> || [[File:Histopathology of sclerosing adenosis of the breast.jpg|180px]]
 
|-
 
|-
| '''Radial scar''', seen as a fibroelastic stroma and entrapped glands radiating outward. Measure the size of these.<ref group=notes>Size is a major factor in whether to fully excise radial scars, at an approximate cutoff at around 1 cm.</ref>
+
| '''Radial scar''', seen as a fibroelastic stroma and entrapped glands radiating outward. Measure the size of these.<ref group=note>Size is a major factor in whether to fully excise radial scars, at an approximate cutoff at around 1 cm.</ref>
 
| [[File:Histopathology of a radial scar of the breast.jpg|180px]]
 
| [[File:Histopathology of a radial scar of the breast.jpg|180px]]
 +
|-
 +
| '''[[Usual ductal hyperplasia]]''': Cohesive proliferation with haphazard, jumbled cell arrangement or streaming growth pattern. Cells have mild variation in cellular and nuclear size and shape.<ref name=PathologyOutlinesUDH>{{cite web|url=https://www.pathologyoutlines.com/topic/breastepithelialductalhyperplasia.html|title=Usual ductal hyperplasia|author= Sofia Lérias, M.D., Melinda Lerwill, M.D.|website=Pathology Outlines}} Last author update: 11 February 2021. Last staff update: 25 April 2022</ref>
 +
| [[File:Histopathology of usual ductal hyperplasia.jpg|180px]]
 
|-  
 
|-  
 
| No disease || 30% ||  ||
 
| No disease || 30% ||  ||
 
|-  
 
|-  
| [[Fibroadenoma]] || 7% || Proliferation of both stromal and epithelial components,<ref group="notes">The proliferation of two histological components is called "biplasia", from ''Latin'' bis (“twice”) and -plasia (“formation”), or "biphasic proliferation"</ref> arranged into either a pericanalicular pattern (stromal proliferation around epithelial structures), or an intracanalicular pattern (stromal proliferation compressing the epithelial structures into clefts). Fibroadenomas characteristically display hypovascular stroma compared to malignant tumors.<ref name="WHO">{{cite book |editor=Tavassoli, F.A. |editor2=Devilee, P. |title=World Health Organization Classification of Tumours: Pathology & Genetics: Tumours of the breast and female genital organs |publisher=IARC Press |location=Lyon |year=2003 |isbn=978-92-832-2412-9 |url=}}</ref><ref name="POW">{{cite web|title=Breast nonmalignant, Fibroepithelial neoplasms, Fibroadenoma|url=http://www.pathologyoutlines.com/topic/breastfibroadenoma.html|accessdate=2019-11-04|author=Jaya Ruth Asirvatham, M.B.B.S., Carlos C. Diez Freire, M.D., Cansu Karakas, M.D., Belinda Lategan, M.D., Nat Pernick, M.D., Emily S. Reisenbichler, M.D., Monika Roychowdhury, M.D., Mary Ann Gimenez Sanders, M.D, Ph.D., Gary Tozbikian, M.D., Hind Warzecha, M.D. Senior Authors: Julie M. Jorns, M.D., Shahla Masood}} Revised: 31 October 2019</ref><ref name="Rosen">{{cite book |author=Rosen, PP. |title=Rosen's Breast Pathology |isbn=978-0-7817-7137-5 |edition=3rd|year=2009 }}</ref> Furthermore, the epithelial proliferation appears in a single terminal ductal unit and has duct-like spaces surrounded by a fibroblastic stroma. The basement membrane is intact.<ref name="titleFibroadenoma of the breast">{{cite web |url=http://www.pathologyatlas.ro/fibroadenoma-breast-pathology.php |title=Fibroadenoma of the breast |access-date=2007-12-15 }}</ref>
+
| [[Fibroepithelial tumor]] || 7% || Proliferation of both stromal and epithelial components.<ref group=note>The proliferation of two histological components is called "biplasia", from ''Latin'' bis (“twice”) and -plasia (“formation”), or "biphasic proliferation"</ref> The tumor group mainly includes fibroadenoma and phyllodes tumor.
 
| [[File:Micrograph of a fibroadenoma.jpg|180px]]
 
| [[File:Micrograph of a fibroadenoma.jpg|180px]]
 
|-  
 
|-  
 
| [[Atypical ductal hyperplasia]] || 7%<ref name=Statpearls-atypical>{{cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK470258/|title=Atypical Breast Hyperplasia|author=David J. Myers; Andrew L. Walls.|website=StatPearls, National Center for Biotechnology Information}} Last Update: February 15, 2019.</ref> || Epithelial proliferations which are not qualitatively or quantitatively abnormal enough to be classified as ductal carcinoma in situ.<ref name=Statpearls-atypical/> || [[File:Micrograph of atypical ductal hyperplasia.jpg|180px]]
 
| [[Atypical ductal hyperplasia]] || 7%<ref name=Statpearls-atypical>{{cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK470258/|title=Atypical Breast Hyperplasia|author=David J. Myers; Andrew L. Walls.|website=StatPearls, National Center for Biotechnology Information}} Last Update: February 15, 2019.</ref> || Epithelial proliferations which are not qualitatively or quantitatively abnormal enough to be classified as ductal carcinoma in situ.<ref name=Statpearls-atypical/> || [[File:Micrograph of atypical ductal hyperplasia.jpg|180px]]
 
|-
 
|-
| Other benign mammary dysplasias and neoplasms || 5% || Including:
+
|rowspan=3| Other benign mammary dysplasias and neoplasms ||rowspan=3| 5% || Including:
 
*'''Flat epithelial atypia''': variably dilated acini lined by one to several layers of epithelial cells with low-grade cytologic atypia, usually columnar.<ref name="Schnitt2003">{{cite journal|last1=Schnitt|first1=Stuart J|title=The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance|journal=Breast Cancer Research|volume=5|issue=5|year=2003|issn=1465-542X|doi=10.1186/bcr625}}</ref>
 
*'''Flat epithelial atypia''': variably dilated acini lined by one to several layers of epithelial cells with low-grade cytologic atypia, usually columnar.<ref name="Schnitt2003">{{cite journal|last1=Schnitt|first1=Stuart J|title=The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance|journal=Breast Cancer Research|volume=5|issue=5|year=2003|issn=1465-542X|doi=10.1186/bcr625}}</ref>
 
*'''Columnar cell change''': Terminal duct lobular unit with epithelium exhibiting tall cells with oval or elongated nuclei orientated perpendicularly to the basement membrane.<ref name="LogulloNimir2019">{{cite journal|last1=Logullo|first1=Angela Flavia|last2=Nimir|first2=Cristiane|title=Columnar cell lesions of the breast: a practical review for the pathologist|journal=Surgical and Experimental Pathology|volume=2|issue=1|year=2019|issn=2520-8454|doi=10.1186/s42047-018-0027-2}}</ref>  
 
*'''Columnar cell change''': Terminal duct lobular unit with epithelium exhibiting tall cells with oval or elongated nuclei orientated perpendicularly to the basement membrane.<ref name="LogulloNimir2019">{{cite journal|last1=Logullo|first1=Angela Flavia|last2=Nimir|first2=Cristiane|title=Columnar cell lesions of the breast: a practical review for the pathologist|journal=Surgical and Experimental Pathology|volume=2|issue=1|year=2019|issn=2520-8454|doi=10.1186/s42047-018-0027-2}}</ref>  
 
| [[File:Histopathology of flat epithelial atypia and columnar cell change.jpg|180px]]
 
| [[File:Histopathology of flat epithelial atypia and columnar cell change.jpg|180px]]
 +
|-
 +
| '''Intraductal papilloma''': unremarkable epithelial cells lining fibrovascular cores.
 +
| [[File:Histopathology of intraductal papilloma.jpg|180px]]
 +
|-
 +
| '''Pseudoangiomatous stromal hyperplasia (PASH)''': Complex interanastomosing vessel-like spaces in dense collagenous, keloid-like stroma.
 +
| [[File:Histopathology of pseudoangiomatous stromal hyperplasia (PASH).jpg|180px]]
 
|-
 
|-
 
| Breast cancer (in situ or invasive) || 10% || See next section. ||
 
| Breast cancer (in situ or invasive) || 10% || See next section. ||
 
 
|}
 
|}
  
 
{{Breast cancer types}}
 
{{Breast cancer types}}
 
{{Evaluation of tumors}}
 
{{Evaluation of tumors}}
 +
 +
===Previous biopsy site===
 +
{{Moderate-begin}}For excisions or larger, look up past biopsies, and if in the same area, look for biopsy sites in order to confirm that the previous biopsy represents the same pathologies.{{Moderate-end}}
 +
<gallery mode=packed heights=180>
 +
File:Biopsy site at 11 days, low magnification.jpg|Biopsy site at 11 days, low magnification, showing involved area consistent with a needle size
 +
File:Histopathology of biopsy site at 11 days, high magnification.jpg|High magnification shows granulation tissue (fibroblasts, red blood cells and lymphocytes). Multinucleated giant cells may be present.
 +
File:Histopathology of one month old biopsy site of the breast, annotated.jpg|One month after biopsy, typically showing fibrosis. Foreign material is also present.
 +
</gallery>
  
 
===If tumor is not found===
 
===If tumor is not found===
[[File:Histopathology of stromal fibrosis of the breast.jpg|thumb|210px|'''Dense stromal fibrosis''', in this case with entrapped fat cells and involuted entrapped ducts (arrows). In contrast, normal breast parenchyma has loose collagenous mammary stroma.<ref name="NassarBaassiri2019">{{cite journal|last1=Nassar|first1=Lara|last2=Baassiri|first2=Amro|last3=Salah|first3=Fatima|last4=Barakat|first4=Andrew|last5=Najem|first5=Elie|last6=Boulos|first6=Fouad|last7=Berjawi|first7=Ghina|title=Stromal Fibrosis of the Breast: A Spectrum of Benign to Malignant Imaging Appearances|journal=Radiology Research and Practice|volume=2019|year=2019|pages=1–6|issn=2090-1941|doi=10.1155/2019/5045908}}</ref>]]
+
Check the imaging indication, and look for abnormalities that may explain the diagnostic findings:
 +
*'''Dense stromal fibrosis''' for radiodense areas.
 +
*'''Calcifications''' if found on X-ray.
 +
If still not found, note their absence, since it indicates that the biopsy may have missed the target of interest.
  
Look for other abnormalities that may explain any diagnostic findings, mainly '''dense stromal fibrosis'''.
+
<gallery mode=packed heights=180>
 +
File:Histopathology of stromal fibrosis of the breast.jpg|'''Dense stromal fibrosis''', in this case with entrapped fat cells and involuted entrapped ducts (arrows). In contrast, normal breast parenchyma has loose collagenous mammary stroma.<ref name="NassarBaassiri2019">{{cite journal|last1=Nassar|first1=Lara|last2=Baassiri|first2=Amro|last3=Salah|first3=Fatima|last4=Barakat|first4=Andrew|last5=Najem|first5=Elie|last6=Boulos|first6=Fouad|last7=Berjawi|first7=Ghina|title=Stromal Fibrosis of the Breast: A Spectrum of Benign to Malignant Imaging Appearances|journal=Radiology Research and Practice|volume=2019|year=2019|pages=1–6|issn=2090-1941|doi=10.1155/2019/5045908}}</ref>
 +
File:Micrograph of stacked cells.jpg|'''Stacking''' of cells on top of each may mimic microcalcifications, but will be revealed by focusing at different levels.
 +
</gallery>
  
 
===Microscopy report===
 
===Microscopy report===

Latest revision as of 15:41, 19 June 2022

Author: Mikael Häggström [note 1]

Fixation

Generally 10% neutral buffered formalin. Fresh breast specimens should be put in formalin within one hour.[note 2] Breast specimens should be immersed in formalin for 6-72 hours.[1]

Comprehensiveness

On this resource, the following formatting is used for comprehensiveness:

  • Minimal depth
  • (Moderate depth)
  • ((Comprehensive))
Other legend

<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
[[Comments]]
Link to another page

Gross processing

Selection and trimming

For excision (also called lumpectomy):

  • Determine total specimen size. ((Weight the specimen[2]))
  • Ink margins. If sample orientations are marked, use different colors for different directions.[2]
  • Palpate the specimen for masses. If felt, estimate the greatest dimension.[note 3] Compare with radiography if available.[2] Confirm the presence of any known biopsy clips, either visibly or by post-operative radiography (in order to confirm that the specimen includes the region of interest).
Cut a lumpectomy in the direction that gives the shortest distance from margin to margin. If a lumpectomy is uneven as shown, cut so that the first and last slice become wedge shaped (because these will later be cut further, perpendicularly to the margin), avoiding a wedge-shape for remaining slices.
  • Serially section the specimen.
  • When performing triage of fresh lumpectomies, generally make slices 1.1 to 1.5 cm thick. When laid down and flattened, this is generally thin enough to allow for fixation over at least 6 hours, and thick enough to be further cut into 2 or 3 slices after fixation; Note the direction of up/down on each such thick slice so that the relative orientation of the thinner slices thereof is maintained. Slices with solid tumors are cut somewhat thinner since they won't flatten as much when laid down.
  • When selecting tissue for submission after fixation, make 3-4 mm thick slices.[2]
  • Inspect for any grossly visible lesions. If found, measure at least the greatest dimension of the lesion on the slice where it appears largest. (Also compare the greatest gross measurement (including any palpated one) with the greatest measurement at previous imaging, and note if it confers a staging discrepancy between imaging and gross dimensions, with cutoffs at 0.1 cm, 0.5 cm, 1.0 cm, 2.0 cm, and 5 cm.)
Re-excisions

Tissue selection

Further serially section each of the two end sections into perpendicular sections, so that the distance between the surgical margin and any tumor involvement can be measured. If they are visibly involved as pictured, sections can be selectively taken from there. If end sections are not grossly involved, submit one perpendicular section, (every other perpendicular section), ((or the entire end sections)).
  • For lumpectomies, submit:[2]
  • Entire specimen if it can fit in 3-5 slices.
  • If larger:
  • For relatively well demarcated tumors: 1 slice per cm of tumor (minimum of 3 slices of tumor), including both center and periphery of tumor, including closest distance to the surgical margin if possible.
  • For diffuse or even invisible tumors such as often is the case for DCIS and ILC, either still submit whole, or use X-ray to guide what tissue to submit.
  • Additional suspicious areas, including those indicated by radiography.
  • ((Representative sections of margins in each direction.))

Breast specimens where breast cancer is possible should generally not be decalcified even when containing small calcifications, to preserve the ability to perform immunohistochemistry.

  See also: General notes on gross processing


Gross report

  • Size of original tissue sample, preferably in 3 dimensions.
  • Description of inking
  • Tumor properties, at least:
  • Size in 3 dimensions.[2]
  • Distance from margins[2]
  • Consistency[2]
  • (Description of sectioning and submissions.)
  • ((Time of procurement and time of placement in formalin.[note 2]))

Example:

(The specimen is received fresh and consists of) an irregular fragment of yellow tan fibrofatty tissue measuring 4.0 x 2.8 x 2.0 cm. (The specimen is oriented with two sutures and) the surgical margins are inked as follows: superior-blue, inferior-green, medial-red, lateral-yellow, anterior-orange, and posterior-black. {{A radioactive seed is embedded in the tissue.}} The tissue is serially sectioned {{to reveal a tan-gray, spiculated, indurated mass measuring _cm in greatest dimension. The mass is located _cm from the nearest (<<superior, inferior etc>>) margin. (The specimen is entirely submitted in sequential sections from medial to lateral in 10 cassettes. The medial and lateral margins are submitted as perpendicular sections.) The specimen was procured at _AM/PM on _/_/2020. The specimen was placed in formalin at _AM/PM on _/_/2020.

Lymph nodes

When lymph nodes are submitted together with a biopsy or excision of a suspected or previously confirmed invasive lobular carcinoma (but not necessarily invasive carcinoma with lobular features), generally put the lymph node specimen through H&E processing at a relative rush. If you don't see any involvement on the H&E stain, order immunostain for CK AE1/AE3 in order to visualize otherwise occult lymph node involvement. The rushing of the lymph node samples allows you to have the immunostained slides by a similar time as the rest of the case.[3]

Further information: Lymph node

Staining

Usually H&E staining.

Microscopic evaluation

If tumor is found, determine:

  • Tumor size
  • Malignancy
  • Distance from excision margin

Malignancy

The most important is to classify a sample as either of the following:

  • Benign
  • Carcinoma in situ
  • Invasive cancer

Most common types

Women seeking evaluation of a breast lump[4]
Finding Relative
incidence
Histopathology Image
Fibrocystic breast changes 40% Sclerosing adenosis (pictured), with an increase in glandular elements in addition to stromal proliferation that distorts and compresses glands.[5] Histopathology of sclerosing adenosis of the breast.jpg
Radial scar, seen as a fibroelastic stroma and entrapped glands radiating outward. Measure the size of these.[note 4] Histopathology of a radial scar of the breast.jpg
Usual ductal hyperplasia: Cohesive proliferation with haphazard, jumbled cell arrangement or streaming growth pattern. Cells have mild variation in cellular and nuclear size and shape.[6] Histopathology of usual ductal hyperplasia.jpg
No disease 30%
Fibroepithelial tumor 7% Proliferation of both stromal and epithelial components.[note 5] The tumor group mainly includes fibroadenoma and phyllodes tumor. Micrograph of a fibroadenoma.jpg
Atypical ductal hyperplasia 7%[7] Epithelial proliferations which are not qualitatively or quantitatively abnormal enough to be classified as ductal carcinoma in situ.[7] Micrograph of atypical ductal hyperplasia.jpg
Other benign mammary dysplasias and neoplasms 5% Including:
  • Flat epithelial atypia: variably dilated acini lined by one to several layers of epithelial cells with low-grade cytologic atypia, usually columnar.[8]
  • Columnar cell change: Terminal duct lobular unit with epithelium exhibiting tall cells with oval or elongated nuclei orientated perpendicularly to the basement membrane.[9]
Histopathology of flat epithelial atypia and columnar cell change.jpg
Intraductal papilloma: unremarkable epithelial cells lining fibrovascular cores. Histopathology of intraductal papilloma.jpg
Pseudoangiomatous stromal hyperplasia (PASH): Complex interanastomosing vessel-like spaces in dense collagenous, keloid-like stroma. Histopathology of pseudoangiomatous stromal hyperplasia (PASH).jpg
Breast cancer (in situ or invasive) 10% See next section.

Breast cancer types

Breast cancer types, with relative incidences and prognoses.
Cancer type Histopathology Image
Invasive ductal carcinoma (IDC) Carcinomatous cells are seen below the basement membrane of lactiferous ducts. Otherwise, there are no specific histologic characteristics, essentially making it a diagnosis of exclusion.[10] Invasive ductal carcinoma, with occasional entrapped normal ducts.jpg
Ductal carcinoma in situ (DCIS) Malignant epithelial cells confined to the ductal system of the breast, without invasion through the basement membrane.[11] DCIS - Intraductal carcinoma of the breast.jpg
Invasive lobular carcinoma (ILC) The "classic" pattern is round or ovoid cells with little cytoplasm in a single-file infiltrating pattern, sometimes concentrically giving a targetoid pattern. Classic Invasive Lobular Carcinoma of the Breast (6813147194).jpg
Lobular carcinoma in situ (LCIS)
  • Monomorphic, loosely cohesive, slightly enlarged and evenly spaced cells that fill acini.[12]

Cells have indistinct cell borders, pale cytoplasm, and uniform small nuclei with evenly distributed chromatin and inconspicuous nucleoli.[12]

Histopathology of lobular carcinoma in situ.jpg
Mucinous carcinoma Extracellular mucin areas around tumor cells. Histopathology of mucinous invasive ductal carcinoma of the breast.jpg
Medullary carcinoma Seemingly fused tumor cells (syncytial pattern), and a prominent lymphoid infiltrate. Histopathology of medullary breast carcinoma.jpg
Further information: Evaluation of tumors

Previous biopsy site

(For excisions or larger, look up past biopsies, and if in the same area, look for biopsy sites in order to confirm that the previous biopsy represents the same pathologies.)

If tumor is not found

Check the imaging indication, and look for abnormalities that may explain the diagnostic findings:

  • Dense stromal fibrosis for radiodense areas.
  • Calcifications if found on X-ray.

If still not found, note their absence, since it indicates that the biopsy may have missed the target of interest.

Microscopy report

A normal biopsy may be reported as follows

(Fibrofatty tissue with benign ducts and lobules.) Negative for (atypia and) malignancy.

More detailed reports are given at the disease-related articles.

  See also: General notes on reporting


Notes

  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
  2. 2.0 2.1 An increased cold ischemia time (time from procurement to time in formalin) negatively effects the utility of immunohistochemistry.
    - Khoury, Thaer (2018). "Delay to Formalin Fixation (Cold Ischemia Time) Effect on Breast Cancer Molecules ". American Journal of Clinical Pathology 149 (4): 275–292. doi:10.1093/ajcp/aqx164. ISSN 0002-9173. 
  3. A palpated greatest dimension before cutting is still superior to trying to align cut pieces together or mathematically adding the thicknesses of involved slices.
  4. Size is a major factor in whether to fully excise radial scars, at an approximate cutoff at around 1 cm.
  5. The proliferation of two histological components is called "biplasia", from Latin bis (“twice”) and -plasia (“formation”), or "biphasic proliferation"

Main page

References

  1. . Recommendations for HER2 Testing in Breast Cancer: ASCO – CAP Clinical Practice Guideline Update. College of American Pathologists (2013-10-17).
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Monika Roychowdhury. Grossing (histologic sampling) of breast lesions. Pathologyoutlines.com. Topic Completed: 1 August 2012. Revised: 19 September 2019
  3. Chandler IP, Oommen R, Lawson CW (2003). "Invasive lobular carcinoma and cytokeratin immunohistochemistry: an audit. ". J Clin Pathol 56 (3): 240. doi:10.1136/jcp.56.3.240. PMID 12610108. PMC: 1769908. Archived from the original. . 
  4. Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. p. 739. ISBN 978-1-4160-2973-1. 
  5. Jaya Ruth Asirvatham, M.B.B.S., Julie M. Jorns, M.D.. Breast - Fibrocystic changes - Sclerosing adenosis. Pathology Outlines. Topic Completed: 1 January 2015. Minor changes: 31 December 2020
  6. Sofia Lérias, M.D., Melinda Lerwill, M.D.. Usual ductal hyperplasia. Pathology Outlines. Last author update: 11 February 2021. Last staff update: 25 April 2022
  7. 7.0 7.1 David J. Myers; Andrew L. Walls.. Atypical Breast Hyperplasia. StatPearls, National Center for Biotechnology Information. Last Update: February 15, 2019.
  8. Schnitt, Stuart J (2003). "The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance ". Breast Cancer Research 5 (5). doi:10.1186/bcr625. ISSN 1465-542X. 
  9. Logullo, Angela Flavia; Nimir, Cristiane (2019). "Columnar cell lesions of the breast: a practical review for the pathologist ". Surgical and Experimental Pathology 2 (1). doi:10.1186/s42047-018-0027-2. ISSN 2520-8454. 
  10. Peter Abdelmessieh. Breast Cancer Histology. Medscape. Retrieved on 2019-10-04. Updated: May 24, 2018
  11. Siziopikou, Kalliopi P. (2013). "Ductal Carcinoma In Situ of the Breast: Current Concepts and Future Directions ". Archives of Pathology & Laboratory Medicine 137 (4): 462–466. doi:10.5858/arpa.2012-0078-RA. ISSN 0003-9985. 
  12. 12.0 12.1 Sucheta Srivastava. Breast - Noninvasive lobular neoplasia - LCIS classic. Topic Completed: 1 September 2017. Minor changes: 21 June 2020
  13. Nassar, Lara; Baassiri, Amro; Salah, Fatima; Barakat, Andrew; Najem, Elie; Boulos, Fouad; Berjawi, Ghina (2019). "Stromal Fibrosis of the Breast: A Spectrum of Benign to Malignant Imaging Appearances ". Radiology Research and Practice 2019: 1–6. doi:10.1155/2019/5045908. ISSN 2090-1941. 

Image sources