Stains & CD markers

Last author update: 18 December 2023
Last staff update: 18 December 2023

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PubMed Search: CD56

Wiebke Solass, M.D.
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Cite this page: Solass W. CD56. website. Accessed February 23rd, 2024.
Definition / general
Essential features
  • Marker of natural killer (NK) cells and NK lymphomas
  • Subsets of T cell lymphomas can show expression of CD56
  • Sensitive marker for neuroendocrine tumors in the majority of small cell carcinoma / carcinoid tumors
  • Not specific for neuroendocrine differentiation; should always be used in conjunction with other markers of neuroendocrine lineage (synaptophysin, chromogranin)
  • CD56 antigen is a 140 kDa isoform of the neural cell adhesion molecule (NCAM)
    • Posttranslational modifications to the polypeptide include N and O glycosylations, acylation, sulphation and phosphorylation
    • Different NCAM isoforms have molecular weights ranging from 135 to 220 kDa
    • CD56 antigen is moderately expressed on a subpopulation of peripheral blood large granular lymphocytes and on all cells with NK activity; it is also expressed by subsets of T lymphocytes
    • CD56 antibodies do not react with granulocytes, monocytes or B cells
  • Reference: Beckman Coulter: CD34 Antibodies [Accessed 19 July 2023]
  • 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 NCAM and N-cadherin and start displaying integrin receptors, cells separate and migrate (J Cell Sci 2002;115:283)
  • Hematopoiesis
    • Prototypic marker of NK cells
    • Also presents on a 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
  • Membranous expression is interpreted as positive staining
Case reports
Uses by pathologists
Prognostic factors
Microscopic (histologic) images

Contributed by Wiebke Solass, M.D., Ankur R. Sangoi, M.D. (Case #101), Julia Braza, M.D. (Case #121)
and Jennifer A. Jeung, M.D. (Case #204)

Alveolar rhabdomyosarcoma Alveolar rhabdomyosarcoma

Alveolar rhabdomyosarcoma

Lung carcinoid Lung carcinoid

Lung carcinoid

extranodal NK / T cell lymphoma extranodal NK / T cell lymphoma

Extranodal NK / T cell lymphoma

Solid pseudopapillary neoplasm, pancreas

Solid pseudopapillary neoplasm, pancreas

Primary renal carcinoid

Primary renal carcinoid

Positive staining - normal
  • 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
Negative staining
Sample pathology report
  • Lower right lung lobe, mucosal biopsies:
    • Atypical carcinoid / neuroendocrine tumor of the lung with associated areas of necrosis and portions of respiratory mucosa (see comment)
    • Comment: In this case, a neuroendocrine tumor of the lung is present, which shows areas of necrosis. Although the mitotic count in this section is low, the presence of necrosis advocates the diagnosis of an atypicial carcinoid.
    • The neoplastic cells are positive for CD56, synaptophysin, chromogranin A and express SSTR2.
Board review style question #1

Which of the following statements is true about CD56?

  1. It can differentiate MGUS from myeloma because MGUS plasma cells are CD56+
  2. It is a marker of B cells
  3. It is a marker of natural killer (NK) cells and NK lymphomas
  4. It is a marker of plasma cells
Board review style answer #1
C. It is a marker of natural killer (NK) cells and NK lymphomas. Answers B and D are incorrect because these cells are typically negative for CD56. Answer A is incorrect because although it can differentiate MGUS from myeloma, MGUS plasma cells are CD56- and myeloma plasma cells are CD56+.

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Reference: CD56
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