Lymph nodes: Difference between revisions
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{{Comprehensiveness}} | {{Comprehensiveness}} | ||
==Gross processing== | ==Gross processing== | ||
If suspected '''lymphoma''', before putting tissue in formalin, ensure that tissue is preserved in appropriate media for any special tests (usually cytometry). | 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. | 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= | 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:<br>- {{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=== | ===Gross procedure=== | ||
*'''Measure''' the dimensions. For a lymph node with minimal surrounding fatty tissue, measure the greatest dimension {{Moderate-begin}}or 3 dimensions{{Moderate- | *'''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. | ||
*If you will submit multiple bisected lymph nodes in the same cassette, '''ink''' each lymph node differently | <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'''. | |||
[[File: | </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 mm<sup>3</sup>. 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=== | ===Gross report=== | ||
| Line 73: | Line 35: | ||
;Multiple lymph nodes | ;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 in 10 cassettes. | {{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}}.<br>KEY TO SECTIONS: | ||
<br>KEY TO SECTIONS: | |||
*A1–A3– one lymph node, serially section | *A1–A3– one lymph node, serially section | ||
*A4-A5– one lymph node, serially sectioned | *A4-A5– one lymph node, serially sectioned | ||
| Line 81: | Line 42: | ||
*A8– two lymph nodes, each bisected, differentially inked | *A8– two lymph nodes, each bisected, differentially inked | ||
*A9– one lymph node, bisected | *A9– one lymph node, bisected | ||
*A10– multiple lymph nodes. | *A10– multiple lymph nodes. | ||
|} | |||
;Additional information | ;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 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. | *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== | ==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: | Look for: | ||
*Whatever pathology is '''indicated''' by the referral, or findings in other submitted specimens. | *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=== | ===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: | Look primarily at the overall '''architecture''', with main findings being: | ||
<gallery mode=packed heights=220> | <gallery mode=packed heights=220> | ||
File:Histopathology of reactive follicular hyperplasia.jpg|'''Follicular hyperplasia''': Indicates a | 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> | 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> | </gallery> | ||
*'''Paracortical hyperplasia''': | *'''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, | *'''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}}:<br>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}}:<br>Macrometastatic carcinoma involving one of one (1/1) lymph node.<br>Metastatic carcinoma measures 0.4 cm in greatest dimension.<br>{{Moderate-begin}}Negative for extranodal extension{{Moderate-end}}. | |||
|} | |||
{{Bottom}} | {{Bottom}} | ||