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CD Markers

CD56


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 24 November 2011, last major update November 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

Definition
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● Homophilic binding glycoprotein with role in cell–cell adhesion (Wikipedia)

Terminology
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● Also called N-CAM (neural cell adhesion molecule)

Pathophysiology
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Nerves: regulates homophilic (like-like) interactions between neurons and between neurons and muscle; associates with fibroblast growth factor receptor and stimulates tyrosine kinase activity of receptor to induce neurite outgrowth; when neural crest cells stop making N-CAM and N-cadherin and start displaying integrin receptors, cells separate and migrate (J Cell Sci 2002;115:283)
Hematopoiesis: prototypic marker of Natural Killer (NK) cells; it also presents on subset of CD4+ and CD8+ T cells; NK cells include a less mature (CD56(bright)/CD16-) subset that is more common in lymph nodes and a more mature (CD56(dim)/CD16+) subset that is more numerous in peripheral blood (Hum Pathol 2011;42:679)
Adhesion: contributes to cell-cell or cell-matrix adhesion during development

Prognostic factors
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● CD56 negative myeloma has poor prognosis (Leuk Lymphoma 2004;45:61)
● Preliminary study suggests CD56+ lymphocytes may be associated with regression of melanoma (Hum Pathol 2011;42:1960)

Case reports
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● 6 year old girl with B-ALL and CD56 and CD57 coexpression (Pediatr Hematol Oncol 2004;21:677)
● 56 year old woman with CD56+ plasma cell leukemia (University of Pittsburgh)

Uses by Pathologists
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● (1) Marker of NK cells and NK lymphomas
● (2) Detect residual myeloma (Am J Clin Pathol 2009;132:60) and residual AML in bone marrow (Am J Clin Pathol 2008;129:934)
● (3) Differentiate plasma cells in myeloma (CD56+) from reactive plasmacytosis or MGUS (CD56-, Am J Pathol 2002;160:1293, Am J Clin Pathol 2009;132:728)
● (4) Detect neuroendocrine disorders (J Clin Pathol 2002;55:535), particularly if extensive crush artifact (J Clin Pathol 2005;58:978); other neuroendocrine markers are synaptophysin and chromogranin
● (5) Predicts poor prognosis for cutaneous lymphoproliferative disorders other than cutaneous T cell lymphoma (J Clin Pathol 2007;60:981)

Micro images
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Osteoblasts (normal)


Aggressive NK cell leukemia

   
Alveolar rhabdomyosarcoma (left and right - figure C)

   
Blastic NK lymphoma: left-figure 3, right-figure 5


Blastic plasmacytoid dendritic cell neoplasm (left: CD56, right: CD4)


Malignant peripheral nerve sheath tumor


Merkel cell carcinoma (figure b)


NK-like T cell lymphoma of ileum (figure 4)

               
NK lymphoma-nasal type (left to right): nasal cavity (3 images), testes (figure 3C), bone marrow (figure E)


Plasma cells in various disorders


Renal carcinoid (primary)


Small cell carcinoma of nasal cavity (figure 1E)

   
Solid pseudopapillary neoplasms of the pancreas

Flow cytometry images
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Extranodal nasal NK/T-Cell Lymphoma


Plasma cell leukemia - coexpression of CD56 and CD138 (not typical)


Primary intestinal intraepithelial NK–like T-Cell lymphoma


Small cell carcinoma of nasal cavity

Positive staining - normal
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● NK cells (80-90%), large granular lymphocytes, activated T cells, osteoblasts
● Cerebellum and cortex at neuromuscular junctions, neuroendocrine tissue, neurons (membranous pattern), glia
● Ovarian stromal cells
● Rete testis cells (clusters of sloughed cells in hydrocele and spermatocele specimens may mimic small cell carcinoma, Hum Pathol 2010;41:88)
● Skeletal muscle

Positive staining - disease
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Hematopoietic disorders:
● Acute myeloid leukemia (variable, Am J Clin Pathol 2007;128:550, Am J Clin Pathol 2009;132:101), blastic plasmacytoid dendritic cell neoplasm (Arch Pathol Lab Med 2007;131:149), chronic myelomonocytic leukemia (occasionally), cutaneous lymphoproliferative disorders, enteropathy associated T cell lymphoma (Am J Clin Pathol 2007;127:701, Am J Surg Pathol 2011;35:1557), myeloid sarcoma (variable, Am J Clin Pathol 2000;114:807), myelofibrosis (Am J Clin Pathol 2010;133:314), myeloma, NK/T cell lymphoma (Am J Clin Pathol 2008;130:343, Am J Surg Pathol 2011;35:1195), pediatric anaplastic large cell lymphoma (some, Arch Pathol Lab Med 2006;130:1859), primary cutaneous gamma-delta T-cell lymphoma

Other:
● Alveolar rhabdomyosarcoma (Hum Pathol 2009;40:341, Mod Pathol 2008;21:795)
● Cardiac ischemic damage (Verh Dtsch Ges Pathol 2004;88:246)
● Extrahepatic biliary atresia (Am J Surg Pathol 2003;27:1454)
● Meningiomas and pulmonary meningothelial-like nodules (Am J Surg Pathol 2009;33:487)
● Intrahepatic clear cell cholangiocarcinoma (Am J Surg Pathol 2007;31:902)
● Merkel cell carcinoma (J Dermatol Sci 2003;31:219)
● Mesotheliomas (some)
● Neuroblastoma (adult)
● Merkel cell carcinoma (Mod Pathol 2007;20:1113)
● Neuroendocrine carcinomas (Am J Surg Pathol 2006;30:684, Am J Clin Pathol 2010;133:618)
● Ossifying fibromyxoid tumor of soft parts (43%, Am J Surg Pathol 2011;35:1615)
● Ovarian fibroma, fibrothecoma, leiomyoma (Am J Surg Pathol 2008;32:884)
● Pancreatic neuroendocrine tumor and solid pseudopapillary tumor (usually, Mod Pathol 2006;19:1409)
● Pheochromocytoma
● Small cell carcinomas of cervix (Int J Gynecol Pathol 2005;24:113), lung and prostate (Am J Surg Pathol 2006;30:705)
● Sustentacular cell tumor (Am J Surg Pathol 2006;30:268)
● Synovial sarcoma (usually, Mod Pathol 2006;19:659)
● Thyroid tumors (various, Am J Clin Pathol 2003;120:64, Am J Surg Pathol 2010;34:1582)
● Uterine plexiform tumor / tumorlet
● Wilm’s tumor (Am J Surg Pathol 2009;33:454)

Negative staining
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● Normal: B cells, granulocytes, monocytes, plasma cells
● ALL, large granular NK cell lymphocytosis (some cases, Am J Pathol 2004;165:1117), peirpheral T cell lymphoma, plasma cell leukemia, PNET/Ewing’s sarcoma, subcutaneous panniculitis-like T-cell lymphoma (Arch Pathol Lab Med 2009;133:303)

Additional references
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OMIM 116930

End of CD Markers > CD56


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