CD45 (LCA) is also known as leukocyte common antigen (LCA). It is a sensitive marker for lymphoid cells. In the most general form it is often used as part of a panel for undifferentiated tumors or so-called “small round blue cell tumors.” Such a screening panel usually includes:
Loss of CD45 expression in Hodgkin cells in a case of nodular sclerosing classical Hodgkin lymphoma (CHL).Strong diffuse expression of CD45 in a non-Hodgkin lymphoma.
References
Wick, MR. “Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumor.”Annals of Diagnostic Pathology12(2008):72-84.
CD56 (NCAM – neural-cell adhesion molecule) is expressed on the surface of neuroendocrine epithelial cells, some Schwann cells, and some neuroendocrine tumors. In undifferentiated tumors, CD56 can be used as a screening marker for neuroendocrine differentiation. It appears to be more sensitive than synaptophysin or chromogranin A in most situations, but Ishida, et. al found CD56 to be the least sensitive of the three in neuroendocrine carcinomas of the stomach (47% compared to 94% and 86% for synaptophysin and chromogranin A, respectively).
CD56 also marks a subset of hematopoeitic and gonadal-stromal cells. Expression of CD56 alone should does not have significant specificity.
CD56 Sensitivity for high grade neuroendocrine tumors
Stomach – 47% (Ishida, et. al)
Esophagus – 93% (Huang, et. al)
Lung – >90% (Travis, et. al)
Hematopathology
Marks approximately ~20-50% of cases of leukemia cutis.
Plasma cell myeloma – Abnormal plasma cells will often express CD56 in addition to CD138, and can be very helpful when flow cytometry and kappa/lambda studies fail to identify an abnormal plasma cell population.
Basal cell carcinomas (BCC) show strong membrane and less intense cytoplasmic staining with CD56. Important not to use with the differential diagnosis of merkel cell carcinoma. Squamous cell carcinomas (SCC) do not express CD56, and in the BCC vs. SCC differential CD56 may be helpful.
CD56 Expression Pattern – Other
BM Osteoblasts
Neuroendocrine Neoplasms
Basal cell carcinoma
Photomicrographs
CD56 expression in a NK-cell lymphoma.CD56 expression in small cell carcinoma.CD56 expression in Merkel cell carcinomaCD56 expression in a subset basal cell carcinoma tumor cells.
References
Cronin DMP, George TI, Sundram UN. An updated approach to the diagnosis of myeloid leukemia cutis. Am J Clin Pathol. 2009;132: 101–110. doi:10.1309/AJCP6GR8BDEXPKHR
Wick MR. Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumors. Annals of Diagnostic Pathology. 2008;12: 72–84. doi:10.1016/j.anndiagpath.2007.10.003
Ishida M, Sekine S, Fukagawa T, Ohashi M, Morita S, Taniguchi H, et al. Neuroendocrine carcinoma of the stomach: morphologic and immunohistochemical characteristics and prognosis. Am J Surg Pathol. 2013;37: 949–959. doi:10.1097/PAS.0b013e31828ff59d
Huang Q, Wu H, Nie L, Shi J, Lebenthal A, Chen J, et al. Primary high-grade neuroendocrine carcinoma of the esophagus: a clinicopathologic and immunohistochemical study of 42 resection cases. Am J Surg Pathol. 2013;37: 467–483. doi:10.1097/PAS.0b013e31826d2639
Cronin DMP, George TI, Reichard KK, Sundram UN. Immunophenotypic analysis of myeloperoxidase-negative leukemia cutis and blastic plasmacytoid dendritic cell neoplasm. Am J Clin Pathol. 2012;137: 367–376. doi:10.1309/AJCP9IS9KFSVWKGH
Bénet C, Gomez A, Aguilar C, Delattre C, Vergier B, Beylot-Barry M, et al. Histologic and immunohistologic characterization of skin localization of myeloid disorders: a study of 173 cases. Am J Clin Pathol. 2011;135: 278–290. doi:10.1309/AJCPFMNYCVPDEND0
Joshi R, Horncastle D, Elderfield K, Lampert I, Rahemtulla A, Naresh KN. Bone marrow trephine combined with immunohistochemistry is superior to bone marrow aspirate in follow-up of myeloma patients. J Clin Pathol. 2008;61: 213–216. doi:10.1136/jcp.2007.049130
Seegmiller AC, Xu Y, McKenna RW, Karandikar NJ. Immunophenotypic differentiation between neoplastic plasma cells in mature B-cell lymphoma vs plasma cell myeloma. Am J Clin Pathol. 2007;127: 176–181. doi:10.1309/5EL22BH45PHUPM8P
BELJAARDS RC, KIRTSCHIG G, BOORSMA DM. Expression of neural cell adhesion molecule (CD56) in basal and squamous cell carcinoma. Dermatol Surg. 2008;34: 1577–1579. doi:10.1111/j.1524-4725.2008.34327.x
Herling M, Jones D. CD4+/CD56+ hematodermic tumor: the features of an evolving entity and its relationship to dendritic cells. Am J Clin Pathol. 2007;127: 687–700. doi:10.1309/FY6PK436NBK0RYD4
Travis WD. Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas. Mod Pathol. Nature Publishing Group; 2012;25: S18–S30. doi:10.1038/modpathol.2011.150
CD68 (gp110) is a glycosylated lysosomal transmembrane glycoprotein, which is normally expressed on monocytes, macrophages, dendritic cells, neutrophils, basophils, myeloid progenitor cells, mast cells, activated T-cells, and a subset of blasts. The staining pattern is generally cytoplasmic. Almost all MPO+ bone marrow cells will express CD68.
In the setting of leukemia cutis, CD68 was expressed in >95% of cases (Benet, et. al). Typically, CD68 is used to identify histiocytes. Unfortunately, CD68 lacks specificity and the morphologic differential diagnosis overlaps in many situations, and use as part of a larger panel yields more specific results.
CD68R (PGM-1) is one of the epitopes of CD68, and appears to be the most monocyte specific marker of the CD68 family. Expression in monocytic differentiated AMLs is reported to be 92-94% (Rollins-Raval, et. al)
Photomicrographs
H&E section of ovary showing histiocytes.CD68 staining histiocytes in ovarian parenchyma with physiologic type changes.High power view of ovary parenchyma with histiocytes (physiologic changes).CD68 highlighting scattered macrophages in benign tonsil.
Bénet C, Gomez A, Aguilar C, Delattre C, Vergier B, Beylot-Barry M, et al. Histologic and immunohistologic characterization of skin localization of myeloid disorders: a study of 173 cases. Am J Clin Pathol. 2011;135: 278–290. doi:10.1309/AJCPFMNYCVPDEND0
Cronin DMP, George TI, Sundram UN. An updated approach to the diagnosis of myeloid leukemia cutis. Am J Clin Pathol. 2009;132: 101–110. doi:10.1309/AJCP6GR8BDEXPKHR
Rollins-Raval MA, Roth CG. The value of immunohistochemistry for CD14, CD123, CD33, myeloperoxidase and CD68R in the diagnosis of acute and chronic myelomonocytic leukaemias. Histopathology. 2012;60: 933–942. doi:10.1111/j.1365-2559.2012.04175.x
CD71 is one of the most useful, but least used antibodies in hematopathology. CD71 is an integral membrane protein, which is involved in the uptake of the transferrin-iron complex. Immunoreactivity is restricted to erythroid precursors with a membranous and cytoplasmic stain pattern.
Previously there have been other erythroid markers, but they have been difficult to interpret because they stain all RBCs and precursors. CD71 stains immature erythroid precursors, which are nucleated, and is not significantly expressed in mature RBCs. The utility of CD71 is to help differentiate between normoblasts and myeloblasts in bone marrow specimens. This is especially powerful when combined with CD34 (sensitive/not specific myeloblast marker) on a dual staining IHC platform (red and DAB chromogens).
CD71 can be a particularly useful tool to help accurately characterize immature cellular elements in bone marrow specimens, and decrease misidentification of normoblasts for myeloblasts and/or ALIP. E-Cadherin will also stain immature erythroid precursors (usually in a dimmer pattern compared to CD71).
Utilization of CD71 in gestational pathology has found it to be helpful to identify nucleated red blood cells (NRBCs) in partial molar pregnancies and spontaneous abortions in contrast to complete moles (absence of NRBCs).
Dim staining is expected in lymphoid cells (significantly different from nucleated red cell precursors), which can serve as a nice control (e.g. tonsil tissue).
Photomicrographs
Lymphoid aggregate with dim CD71 expression (erythroid precursors at the periphery). Can be useful as a control (e.g. tonsil).CD34 (red) and CD71 (brown) double stain in a case of acute myelogenous leukemia (AML).CD71 highlighting erythroid precursors in a normal bone marrow sample.
References
Marsee, D. K., Pinkus, G. S., & Yu, H. (2010). CD71 (transferrin receptor): an effective marker for erythroid precursors in bone marrow biopsy specimens. American Journal of Clinical Pathology, 134(3), 429–435. doi:10.1309/AJCPCRK3MOAOJ6AT
Dong, H. Y., Wilkes, S., & Yang, H. (2011). CD71 is Selectively and Ubiquitously Expressed at High Levels in Erythroid Precursors of All Maturation Stages: A Comparative Immunochemical Study With Glycophorin A and Hemoglobin A. The American journal of surgical pathology, 35(5), 723–732. doi:10.1097/PAS.0b013e31821247a8
Luchini C, Parcesepe P, Nottegar A, Parolini C, Mafficini A, Remo A, et al. CD71 in Gestational Pathology: A Versatile Immunohistochemical Marker With New Possible Applications. Appl Immunohistochem Mol Morphol. 2016;24: 215–220. doi:10.1097/PAI.0000000000000175
Acs G, LiVolsi VA. Loss of membrane expression of E-cadherin in leukemic erythroblasts. Arch Pathol Lab Med. 2001;125: 198–201. doi:10.1043/0003-9985(2001)125<0198:LOMEOE>2.0.CO;2
Sadahira Y, Kanzaki A, Wada H, Yawata Y. Immunohistochemical identification of erythroid precursors in paraffin embedded bone marrow sections: spectrin is a superior marker to glycophorin. J Clin Pathol. 1999;52: 919–921.
CD79a (MB1) is a B-cell marker with a wider range of positivity in the B-cell development spectrum compared to CD20 (mature B-cell phenotype). CD79a may be expressed on malignant precursor B-cells and terminally differentiated B-cells (PAX-5 is not expressed in terminally differentiated B-cells). Please note that in the setting of ALL, CD79a is not lineage specific, and up to 50% of T-ALL cases express CD79a. AML cases with t(8;21) may also show CD79a expression (along with CD19, CD20, and TdT).
CD99 (MIC-2 or p30/32) has an unknown function, but has been found to be expressed in vitally all cases of primitive neuroectodermal tumors (PNETs) and Ewing sarcoma. The specificity is more limited and may be seen in alveolar rhabdomyosarcomas (15%), ALLs (90%), neuroendocrine carcinomas (20%), melanomas, etc. Therefore, CD99 should not be interpreted alone, and is best used as part of a panel (e.g. AE1/AE3, desmin, S-100, and CD45 in an undifferentiated small round blue cell tumor situation).
Note: CD99 was originally described as being sensitive and “specific” for PNETs. However, expression in a variety of other tumors (including tumors with similar morphologies to PNETs) were also found to have expression (at least in a subset of cases). Sensitivity of “new” IHC markers can be determined with a fair degree of accuracy using tissue arrays and large tumor libraries, but it usually takes time with efforts from many different laboratories to fully characterize the “specificity” of a marker. This should always be taken into consideration when relying heavily on a “new” marker for diagnostic significance.
Rao, N., Colby, T. V., Falconieri, G., Cohen, H., Moran, C. A., & Suster, S. (2013). Intrapulmonary solitary fibrous tumors: clinicopathologic and immunohistochemical study of 24 cases. The American Journal of Surgical Pathology, 37(2), 155–166. doi:10.1097/PAS.0b013e31826a92f5
CD117 (c-kit) is a member of the type III tyrosine kinase receptor family, and is a transmembrane protein. Immunohistochemical expression of CD117 can be seen in many different normal tissue components (e.g. mast cells) and neoplastic tissues. Therefore, CD117 should be used in a careful targeted manner; usually as part of a larger panel. Limitations of specificity should always be kept in mind.
Renal Tumors: Chromophobe RCC (83-100%, Oncocytoma (71-100%), negative in other subtypes of RCC
Hematopoietic
CD117 is most often used as a myeloblast marker in bone marrow biopsies, and to identify GISTs. It is important to understand what else may stain with CD117 (bright staining of mast cells in BM bxs., compared to dim staining of blasts), so one does not misinterpret the expression pattern. Erythroid precursor cell may also express CD117, which may cause confusion when evaluating for myeloblast percentage. Ohgami recommends using CD117, E-cadherin, and CD34 in combination in this situation. CD71 (erythroid precursor marker) may also be helpful.
Renal Tumors
CD117 has been found to be expressed in 71-100% of oncocytomas and 83-100% of chromophobe renal cell carcinomas with other subtypes of renal cell carcinoma being non-reactive. Therefore, CD117 may be a useful part of a larger panel (e.g. RCCMa, CD10, Vimentin, and cytokeratin) to diagnosis and subtype renal tumors (especially granular cell variant of RCC vs. chromophobe RCC or oncocytoma).
GIST
Approximately 95% of gastrointestinal stromal tumors (GIST) will react with CD117 by immunohistochemistry. It is important to emphasize that CD117 expression does not necessarily correlate with response to imatinib therapy (tyrosine kinase inhibitor). Lack of reactivity with CD117 should not exclude a patient from imatinib therapy. CD117 negative (kit-negative) GIST often contain PDGFRA mutations, which may be sensitive to imatinib. Sometimes weak expression of CD117 may be seen in non-GIST tumors, and this marker should be used as part of a larger panel incorporating the differential diagnosis (e.g. S-100, Desmin, CD34). DOG-1 antibody may be expressed in CD117 negative GIST cases, which may serve as an alternative marker.
Photomicrographs
CD117 expression in a gastrointestinal stromal tumor (GIST).CD117 highlighting scattered mast cells in a bone marrow biopsy.CD117 highlighting areas of blasts in CMML.CD117 expression in myeloblasts in a case of AML M6b.
References:
Wick, MR. “Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumor.”Annals of Diagnostic Pathology12(2008):72-84.
Leidy, J., Khan, A., & Kandil, D. (2014). Basal-like breast cancer: update on clinicopathologic, immunohistochemical, and molecular features. Archives of Pathology & Laboratory Medicine, 138(1), 37–43. doi:10.5858/arpa.2012-0439-RA
Huang, Q., Wu, H., Nie, L., Shi, J., Lebenthal, A., Chen, J., et al. (2013). Primary high-grade neuroendocrine carcinoma of the esophagus: a clinicopathologic and immunohistochemical study of 42 resection cases. The American Journal of Surgical Pathology, 37(4), 467–483. doi:10.1097/PAS.0b013e31826d2639
Dunphy, C. H., O’Malley, D. P., Perkins, S. L., & Chang, C.-C. (2007). Analysis of immunohistochemical markers in bone marrow sections to evaluate for myelodysplastic syndromes and acute myeloid leukemias. Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry, 15(2), 154–159. doi:10.1097/PAI.0b013e318030dec7
Patil, D. T., & Rubin, B. P. (2011). Gastrointestinal stromal tumor: advances in diagnosis and management. Archives of Pathology & Laboratory Medicine, 135(10), 1298–1310. doi:10.5858/arpa.2011-0022-RA
Bénet, C., Gomez, A., Aguilar, C., Delattre, C., Vergier, B., Beylot-Barry, M., et al. (2011). Histologic and immunohistologic characterization of skin localization of myeloid disorders: a study of 173 cases. American Journal of Clinical Pathology, 135(2), 278–290. doi:10.1309/AJCPFMNYCVPDEND0
Al-Ghawi, H., Asojo, O. A., Truong, L. D., Ro, J. Y., Ayala, A. G., & Zhai, Q. J. (2010). Application of Immunohistochemistry to the Diagnosis of Kidney Tumors. Pathology Case Reviews, 15(1), 25–34. doi:10.1097/PCR.0b013e3181d51c70
Liegl-Atzwanger, B., Fletcher, J. A., & Fletcher, C. D. M. (2010). Gastrointestinal stromal tumors. Virchows Archiv : an International Journal of Pathology. doi:10.1007/s00428-010-0891-y
Siegert, S. I., Diebold, J., Ludolph-Hauser, D., & Löhrs, U. (2004). Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis? American Journal of Clinical Pathology, 122(4), 560–565. doi:10.1309/2880-LF7Q-6XK3-HA3Q
Antonescu, C. R. (2008). Targeted therapy of cancer: new roles for pathologists in identifying GISTs and other sarcomas. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 21 Suppl 2, S31–6. doi:10.1038/modpathol.2008.9
Medeiros, F., Corless, C. L., Duensing, A., Hornick, J. L., Oliveira, A. M., Heinrich, M. C., et al. (2004). KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. The American Journal of Surgical Pathology, 28(7), 889–894.
Wang, H.-Y., & Mills, S. E. (2005). KIT and RCC are useful in distinguishing chromophobe renal cell carcinoma from the granular variant of clear cell renal cell carcinoma. The American Journal of Surgical Pathology, 29(5), 640–646.
Ohgami, R. S., Chisholm, K. M., Ma, L., & Arber, D. A. (2014). E-Cadherin Is a Specific Marker for Erythroid Differentiation and Has Utility, in Combination With CD117 and CD34, for Enumerating Myeloblasts in Hematopoietic Neoplasms. American Journal of Clinical Pathology, 141(5), 656–664. doi:10.1309/AJCP8M4QQTAZPGRP
CD138 (Syndecan-1) is expressed in mesenchymal and epithelial cells. In the bone marrow hematopoietic cells, CD138 is a specific (and sensitive) marker for plasma cells (e.g. multiple myeloma). The biggest pitfall in utilization of CD138 is plasmacytoid neoplasms showing expression of CD138 without consideration of a non-hematopoietic neoplasm expressing CD138!! Always consider a metastatic process in the bone marrow, and utilize additional markers (AE1/AE3, kappa/lambda) to exclude/prove plasma cells origin.
The majority of epithelial neoplasms express CD138, and even a significant number of osteosarcomas, osteoid osteomas, and osteoblastomas react with CD138. Recent literature suggests CD138 to be an adverse prognostic indicator in advanced and nonluminal subtype breast carcinomas.
Photomicrographs
CD138 highlighting plasma cells in a bone marrow with multiple myeloma.Combined CD138-Ki67 stain in a case of multiple myeloma.CD138 highlighting plasma cell in a bone marrow biopsy.CD138 highlighting benign plasma cells with a perivascular cuffing pattern.
Nunez, A. L., Siegal, G. P., Reddy, V. V. B., & Wei, S. (2012). CD138 (syndecan-1) expression in bone-forming tumors. American Journal of Clinical Pathology, 137(3), 423–428. doi:10.1309/AJCP6V4YPFBOCYXG
Nguyen, T. L., Grizzle, W. E., Zhang, K., Hameed, O., Siegal, G. P., & Wei, S. (2013). Syndecan-1 overexpression is associated with nonluminal subtypes and poor prognosis in advanced breast cancer. American Journal of Clinical Pathology, 140(4), 468–474. doi:10.1309/AJCPZ1D8CALHDXCJ
Joshi, R., Horncastle, D., Elderfield, K., Lampert, I., Rahemtulla, A., & Naresh, K. N. (2008). Bone marrow trephine combined with immunohistochemistry is superior to bone marrow aspirate in follow-up of myeloma patients. Journal of Clinical Pathology, 61(2), 213–216. doi:10.1136/jcp.2007.049130
CD34 (human hematopoietic progenitor cell antigen) is expressed by endothelial cells and embryonic cells of the hematopoetic system. CD34 is used in a wide variety of ways in diagnostic pathology. It can generally be divided into hematopathology and non-hematopathology uses. As with most situations in diagnostic immunohistochemistry, CD34 is often best used as part of a targeted panel considering the differential diagnosis at hand.
Hematopathology– CD34 will mark myeloblasts and a subset of lymphoblasts. It is therefore not specific for myeloid differentiation (although fairy sensitive). Normal myeloblasts will express CD34, and in cases of AML approximately 70% of cases will be positive. Approximately 1/3rd of cases of ALL may express CD34. It is also important to understand that not all blasts within a specific case may all express CD34, and correlation with flow cytometry data and aspirate count is critical. CD34 also stains vascular endothelium, which makes for a nice internal control in bone marrow biopsies. Granulocytic sarcomas (a.k.a. chloroma, soft tissue AML, or leukemia cutis) often have monocytic differentiation, and only ~5% of case demonstrate CD34 expression.
Non-Hematopathology– CD34 is expressed in cases of dermatofibrosarcoma protuberant (DFSP), hemangiopericytoma, solitary fibrous tumor, angiosarcoma & Kaposi’s sarcoma (>85%), epithelioid sarcoma (often), lymphocyte rich T cell lymphoma, gastrointestinal stromal tumors, and spindle cell lipomas. CD34 is not expressed in dermatofibromas, desmoplastic mesothelioma, & endometrial stromal sarcoma. CD34 is also an excellent vascular marker, which is helpful in identifying lymph-vascular invasion and tumors of vascular origin.
In hepatocellular carcinoma, CD34 highlights increased vascular structures associated with tumorigenesis. Normal liver only shows CD34 expression in portal vasculature and sinusoids immediate adjacent to portal tracts.
Lymphatic & Vascular Invasion – CD34 is sometimes utilized to evaluate for “lymphovascular invasion” (LVI) in different tumors (e.g. breast more commonly). CD34 and CD31 will stain both (blood) vascular endothelium (strong & sensitive) and also lymphatic endothelium (variable & less sensitive). Sometimes CD34 will stain stromal cells, which can mimic endothelium (false positive).
To determine the true nature of LVI (i.e. lymphatic vs. blood vascular invasion) additional markers specific for lymphatic endothelium (podoplanin or D2-40) need to be performed, and comparison made to CD31/CD34 for determination of invasion type:
Gastrointestinal Stromal Tumor (~70%, some smooth muscle neoplasms can express CD34 – up to 10%)
Spindle Cell Lipoma
Epithelioid Sarcoma
Subset of numerous other entities
Photomicrographs
CD34 expression in a case of acute lymphoblastic leukemia/lymphoma (ALL).CD34 expression in a spindle cell lipoma.CD34 expression in a gastrointestinal stromal tumor.CD34 expression in a case of DFSP.CD34 (red) – CD71 (brown) double stain in a case of AML.CD34 highlighting lymphovascular invasion of breast carcinoma.
References
Mohammed RAA, Martin SG, Gill MS, Green AR, Paish EC, Ellis IO. Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences. Am J Surg Pathol. 2007;31: 1825–1833. doi:10.1097/PAS.0b013e31806841f6
Yang H, Yu L. Cutaneous and Superficial Soft Tissue CD34(+) Spindle Cell Proliferation. Arch Pathol Lab Med. 2017;141: 1092–1100. doi:10.5858/arpa.2016-0598-RA
Rao N, Colby TV, Falconieri G, Cohen H, Moran CA, Suster S. Intrapulmonary solitary fibrous tumors: clinicopathologic and immunohistochemical study of 24 cases. Am J Surg Pathol. 2013;37: 155–166. doi:10.1097/PAS.0b013e31826a92f5
de Smet D, Trullemans F, Jochmans K, Renmans W, Smet L, Heylen O, et al. Diagnostic Potential of CD34+ Cell Antigen Expression in Myelodysplastic Syndromes. Am J Clin Pathol. 2012;138: 732–743. doi:10.1309/AJCPAGVO27RPTOTV
Rosado FGN, Itani DM, Coffin CM, Cates JM. Utility of immunohistochemical staining with FLI1, D2-40, CD31, and CD34 in the diagnosis of acquired immunodeficiency syndrome-related and non-acquired immunodeficiency syndrome-related Kaposi sarcoma. Arch Pathol Lab Med. 2012;136: 301–304. doi:10.5858/arpa.2011-0213-OA
Patil DT, Rubin BP. Gastrointestinal stromal tumor: advances in diagnosis and management. Arch Pathol Lab Med. 2011;135: 1298–1310. doi:10.5858/arpa.2011-0022-RA
Bénet C, Gomez A, Aguilar C, Delattre C, Vergier B, Beylot-Barry M, et al. Histologic and immunohistologic characterization of skin localization of myeloid disorders: a study of 173 cases. Am J Clin Pathol. 2011;135: 278–290. doi:10.1309/AJCPFMNYCVPDEND0
Dunphy CH, O’Malley DP, Perkins SL, Chang C-C. Analysis of immunohistochemical markers in bone marrow sections to evaluate for myelodysplastic syndromes and acute myeloid leukemias. Appl Immunohistochem Mol Morphol. 2007;15: 154–159. doi:10.1097/PAI.0b013e318030dec7
Dunphy CH, Polski JM, Evans HL, Gardner LJ. Evaluation of bone marrow specimens with acute myelogenous leukemia for CD34, CD15, CD117, and myeloperoxidase. Arch Pathol Lab Med. 2001;125: 1063–1069.
Wang HL, Kim CJ, Koo J, Zhou W, Choi EK, Arcega R, et al. Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas. Arch Pathol Lab Med. 2017;141: 1155–1180. doi:10.5858/arpa.2016-0489-RA
Wick, MR. “Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumor.”Annals of Diagnostic Pathology12(2008):72-84.
CD31 (PECAM-1) is thought of as a highly sensitive and specific marker for vascular endothelium. It is helpful to identify tumors of vascular origin, and also to identify lympho-vascular invasion by tumors. CD31 may also stain monocytes, megakaryocytic, and granulocytes in addition to endothelial cells. Plasma cells may variably express CD31 (reactive PCs more common). CD31 (like CD34) is more sensitive (and stronger staining) for blood vascular endothelium compared to lymphatic endothelium (less sensitive and variable staining).
Lymphatic & Vascular Invasion
CD31 is sometimes utilized to evaluate for “lymphovascular invasion” (LVI) in different tumors (e.g. breast more commonly). CD34 and CD31 will stain both (blood) vascular endothelium (strong & sensitive) and also lymphatic endothelium (variable & less sensitive). To determine the true nature of LVI (i.e. lymphatic vs. blood vascular invasion) additional markers specific for lymphatic endothelium (podoplanin or D2-40) need to be performed, and comparison made to CD31/CD34 for determination of invasion type:
Kaposi sarcoma is a vascular neoplasm associated with immunodeficiency (usually HIV/AIDS) and is caused by human herpesvirus 8 (HHV-8). Vascular markers (CD31, CD34, D2-40, and FLI1) are helpful (in combination with HHV-8) for diagnosis. CD31 is expressed in 58-75% of cases (strong and diffuse staining). CD34 is considered more sensitive (92%).
Photomicrographs
CD31 highlighting vasculature in a normal section of kidney.
References
Wick, MR. “Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumor.”Annals of Diagnostic Pathology12(2008):72-84.
Vanchinathan V, Mirzamani N, Mizramani N, Kantipudi R, Schwartz EJ, Sundram UN. The vascular marker CD31 also highlights histiocytes and histiocyte-like cells within cutaneous tumors. Am J Clin Pathol. 2015;143: 177–85– quiz 305. doi:10.1309/AJCPRHM8CZH5EMFD
Rosado FGN, Itani DM, Coffin CM, Cates JM. Utility of immunohistochemical staining with FLI1, D2-40, CD31, and CD34 in the diagnosis of acquired immunodeficiency syndrome-related and non-acquired immunodeficiency syndrome-related Kaposi sarcoma. Arch Pathol Lab Med. 2012;136: 301–304. doi:10.5858/arpa.2011-0213-OA
Morgado JMT, Sánchez-Muñoz L, Teodósio CG, Jara-Acevedo M, Álvarez-Twose I, Matito A, et al. Immunophenotyping in systemic mastocytosis diagnosis: ‘CD25 positive’ alone is more informative than the “CD25 and/or CD2” WHO criterion. Mod Pathol. 2012;25: 516–521. doi:10.1038/modpathol.2011.192
Mohammed RAA, Martin SG, Gill MS, Green AR, Paish EC, Ellis IO. Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences. Am J Surg Pathol. 2007;31: 1825–1833. doi:10.1097/PAS.0b013e31806841f6
