CD138

Synonyms: syndecan-1, heparan sulfate proteoglycan

by Jan Klos

Background

A member of the syndecan family of four transmembrane spanning proteins capable of binding to heparan sulfate and chondroitin sulfate molecules. The main functions of syndecans are control of the cell growth and differentiation as well as maintaining cell adhesion and migration. The syndecans together with other cellular receptors are also involved in regulation of cell signaling by integrating external signals from circulating ligands and extracellular matrix.

Staining in normal cells

mature plasma cells and early preB-cells, while other haematolymphoid cells are negative. Various types of epithelial cells including squamous epithelial cells (except for the mature superficial squamous epithelial cells which are not stained) are positive.  Mature mesenchymal tissues are negative.

Staining in tumors

All cases of plasma cell proliferations including plasma cell malignancies and monoclonal gammopathy of undetermined significance (MGUS) as well as cells with plasmacytoid differentiation in lymphoplasmacytic lymphoma and marginal zone lymphoma. In diffuse large B-cell lymphoma CD138 positivity is associated with a poorer prognosis (as it indicates activated B-cell phenotype – together with positivity for MUM1). A varying percentage of classic Hodgkin lymphoma shows positivity in Hodgkin and Reed-Sternberg cells. Nodular lymphocytic predominant Hodgkin lymphoma is negative. Cases of B-cell acute lymphoblastic leukemia/lymphoma may also show positivity. Various types of epithelial proliferations are positive in majority of cases (squamous cell and basal cell carcinoma of the skin, colorectal adenocarcinoma, cholangiocarcinoma, transitional cell carcinoma, pancreas adenocarcinoma, endometrial adenocarcinoma, ductal and lobular breast carcinoma, hepatocellular carcinoma, renal cell carcinoma, and lung adenocarcinoma). Lower frequency of positive staining is reported among prostate adenocarcinoma, adrenal cortical carcinoma, gastric adenocarcinoma, serous carcinoma of the ovary, medullary and papillary thyroid carcinoma, carcinoid tumor, neuroendocrine carcinoma and Merkel cell carcinoma. Few cases of small cell carcinoma of the lung, thymomas and malignant melanoma are also reported positive. Among mesenchymal tumors, synovial sarcoma shows strong positive membranous staining in epithelioid component and weaker staining in spindle cell areas. Cases of alveolar soft part sarcoma, GIST, leiomyosarcoma, epithelioid MPNST, osteoid osteoma are often reported positive. Other mesenchymal tumors are considered negative.

Staining pattern

Staining pattern is predominantly membranous.

Control tissue

Tonsil.

Application

  • Highly sensitive and relatively specific marker of plasma cells and plasmacytic differentiation in lymphoid tissue.
  • May be a part of immunohistochemical prognostic subtyping of diffuse large B-cell lymphomas.
  • May be useful in differential diagnosis between keratoakantoma (strong staining) and infiltrating squamous cell carcinoma (weaker staining in infiltrating component).
  • Sensitive but not specific marker labelling closely to 100% of squamous cell carcinoma and urothelial carcinoma. Some adenocarcinomas including lung and breast tumors are labelled in >75%. Lower frequency of positive staining is reported in adenocarcinomas of prostate, ovary, stomach, thyroid and neuroendocrine tumors.
  • May be useful also in differential diagnosis of mesothelioma (positive <15%) vs. metastatic carcinoma (rate of positive staining varies depending on origin of carcinoma) where negative staining favors mesothelioma (final subtyping has to be confirmed with other antibodies)
  • Heterogeneous staining in reported among soft tissue tumors including positive membrane staining of epithelioid sarcomas and epithelioid elements of synovial sarcomas. Intracytoplasmic positivity is also reported in GISTs, some cases of malignant epithelioid schwannoma and fibromatosis.
  • CD138 is not a definitive marker for plasmacytic differentiation, unless a hematolymphoid origin is confirmed.
  • Melanoma may sometimes show weak membranous reactivity which with common reactivity of melanoma with MUM1 may lead to erroneous diagnosis of plasma cell tumor.

Selected references

  1. Chu PG, Arber DA, Weiss LM. Expression of T/NK-cell and plasma cell antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases.  Am J Clin Pathol. 2003 Jul;120(1):64-70.
  2. https://www.nordiqc.org/epitope.php?id=37
  3. Mukunyadzi P, Sanderson RD, Fan CY, et al. The level of syndecan-1 expression is a distinguishing feature in behavior between keratoacanthoma and invasive cutaneous squamous cell carcinoma. Mod Pathol. 2002 Jan;15(1):45-9.
  4. O’Connell FP1 Pinkus JL, Pinkus GS. CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms. Am J Clin Pathol. 2004 Feb;121(2):254-63.
  5. Orosz Z, Kopper L. Syndecan-1 expression in different soft tissue tumours.  Anticancer Res. 2001 Jan-Feb;21(1B):733-7.
  6. Saqi A1, Yun SS, Yu GH, et al. Utility of CD138 (syndecan-1) in distinguishing carcinomas from mesotheliomas. Diagn Cytopathol. 2005 Aug;33(2):65-70.