Stains & CD Markers
CD38


Last author update: 16 June 2023
Last staff update: 21 May 2024

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PubMed Search: CD38

Frido Bruehl, M.D.
Christian M. Schürch, M.D., Ph.D.
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Cite this page: Bruehl F, Schürch CM. CD38. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd38.html. Accessed July 13th, 2024.
Definition / general
  • Marker of cellular activation expressed by plasma cells, T cells, NK cells and other hematopoietic cell types during various stages of maturation
Essential features
  • Marker of activation that is present on many hematopoietic cells, especially plasma cells
  • Used clinically as a prognostic marker in chronic lymphocytic leukemia (CLL) as evaluated by flow cytometry
  • CD38 expression in lymphoid neoplasms is not specific for any discrete disease entity
  • Can be aberrantly expressed in carcinoma and melanoma
  • Absence of CD38 (in conjunction with CD34 positivity) is used as a marker for bone marrow hematopoietic stem cells
Terminology
Pathophysiology
Clinical features
Interpretation
  • CD38 expression is considered positive when the cell membrane shows strong and diffuse staining; the cytoplasm and nucleus should not stain with CD38 (Blood 2008;111:5173)
  • Few studies have reported on the use and interpretation of anti-CD38 antibodies in tissue sections for diagnostic purposes; interpretation is difficult due to the prevalence of CD38 in many cell types and the necessity for quantitative assessment more amenable to flow cytometric studies (Am J Surg Pathol 2006;30:585)
Uses by pathologists
  • Flow cytometry is the primary use of anti-CD38 antibodies in the pathology laboratory
  • There is considerable confusion in the literature regarding CD38 and the unrelated antibody VS38 which targets the p63 antigen and is also used for detection of plasma cells in tissue sections and flow cytometry (Blood Cancer J 2018;8:117)
Prognostic factors
  • Chronic lymphocytic leukemia with CD38 expression is associated with a more aggressive clinical course and shorter overall survival (J Clin Pathol 2002;55:180, Br J Haematol 2003;120:1017)
  • Hairy cell leukemia with CD38 expression is associated with a more aggressive clinical course (Cancer Res 2015;75:3902)
  • Acute myeloid leukemia with CD38 expression was shown to be associated with a favorable prognosis and high numbers of immature CD34+ / CD38- blasts in myeloid leukemia are associated with unfavorable prognosis (Leuk Res 2000;24:153, Leukemia 2019;33:1102)
  • CD38 expression on multiple myeloma cells has been correlated to anti-CD38 treatment response (Blood 2016;128:959)
    • In the future, CD38 expression in tissue sections could be used to monitor anti-CD38 therapy with (bispecific) antibodies for early detection of treatment resistance (loss of CD38 expression)
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Frido Bruehl, M.D.
Plasmacytoma

Plasmacytoma

Plasmacytoma, CD38

Plasmacytoma, CD38

Positive staining - normal
Positive staining - disease
Negative staining
  • Absence of CD38 expression does not reliably exclude a given pathologic diagnosis based on currently available data
  • CD38 surface expression may be reduced on multiple myeloma / plasma cells due to CD38 internalization induced by treatment with anti-CD38 antibodies (e.g., daratumumab) (Oncoimmunology 2018;7:e1486948)
  • CD38 has been used in conjunction with CD117 in fluorescence activated cell sorting of mast cells from bone marrow samples (CD117 positive and CD38 negative cells) (Am J Pathol 1996;149:1493)
  • CD4+ CD26- T cells in patients with a diagnosis of Sézary syndrome are typically negative for CD38 (Dis Markers 2022;2022:3424413)
Flow cytometry images

Contributed by Frido Bruehl, M.D.
CD38 positive CLL

CD38 positive CLL

CD38 negative CLL

CD38 negative CLL

Plasma cell neoplasm, CD38 versus CD45

Plasma cell neoplasm, CD38 versus CD45

Plasma cell neoplasm, CD38 versus CD138

Plasma cell neoplasm, CD38 versus CD138

Plasma cell neoplasm, CD38 versus CD19

Plasma cell neoplasm, CD38 versus CD19

Sample pathology report
  • Bone lesion, needle core biopsy:
    • Monotypic kappa expressing plasma cell neoplasm, consistent with plasmacytoma (see comment)
    • Comment: The needle core biopsy demonstrates a dense infiltration by a clonal plasma cell population with kappa light chain restriction. The neoplastic plasma cells are positive for CD38, CD138 and CD79a. Lambda light chains, CD20 and CD43 are not expressed. There are only scattered CD3 positive T cells. There is no amyloid deposition. In summary, the bone lesion represents a plasmacytoma; clinical, serological and imaging correlation is required.
Board review style question #1

Which statement about CD38 is correct?

  1. CD38 is typically downregulated in neoplastic plasma cells
  2. CD38 is brightly expressed on hematogones
  3. CD38 expression is a specific marker for hairy cell leukemia
  4. In chronic lymphocytic leukemia / small lymphocytic lymphoma, CD38 expression is considered a favorable prognosis
Board review style answer #1
B. CD38 is brightly expressed on hematogones. Answer A is incorrect because plasma cells typically downregulate CD38 only after daratumumab therapy. Answer C is incorrect because CD38 expression in hematolymphoid cells is nonspecific but is typically brightly expressed by hematogones. Answer D is incorrect because in chronic lymphocytic leukemia, CD38 expression is a poor prognostic indicator.

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