CD200 Expression in Neuroendocrine Neoplasms

Jason E. Love, MD; Kimberly Thompson, HT(ASCP), QIHC; Mark R. Kilgore, MD; Maria Westerhoff, MD; Claire E. Murphy, MD; Antonios Papanicolau Sengos, MD, MS; Kinsey A. McCormick, MD; Veena Shankaran, MD, MS; Natalie Vandeven; Faith Miller, CLS (ASCP); Astrid Blom, MD; Paul T. Nghiem, MD, PhD; Steven J. Kussick, MD, PhD


Am J Clin Pathol. 2017;148(3):236-242. 

In This Article

Abstract and Introduction


Objectives. CD200 expression has been well studied in hematopoietic malignancies; however, CD200 expression has not been well-characterized in neuroendocrine neoplasms. We examined CD200 expression in 391 neuroendocrine neoplasms from various anatomic sites.

Methods. Tissue blocks containing pulmonary small cell carcinoma, pulmonary carcinoid, large cell neuroendocrine carcinoma, pancreatic neuroendocrine tumor, gastrointestinal carcinoid, and Merkel cell carcinoma were evaluated for CD200 expression by immunohistochemistry. A set of nonneuroendocrine carcinomas was stained for comparison.

Results. CD200 was expressed in 87% of the neuroendocrine neoplasms studied, including 60 of 72 (83%) pulmonary small cell carcinomas, 15 of 22 (68%) pulmonary carcinoids, three of four (75%) pulmonary large cell neuroendocrine carcinomas, 125 of 146 (86%) Merkel cell carcinomas, 79 of 83 (95%) gastrointestinal luminal carcinoids, and 56 of 60 (93%) pancreatic neuroendocrine tumors. Thirty-two of 157 (20%) nonneuroendocrine carcinomas expressed CD200. In gastrointestinal carcinoid and pancreatic neuroendocrine neoplasms, CD200 negativity correlated with higher grade.

Conclusions. CD200 is a relatively sensitive marker of neuroendocrine neoplasms and represents a potential therapeutic target in these difficult-to-treat malignancies.


CD200 is a membrane-bound glycoprotein normally expressed by neurons, endothelial cells, follicular dendritic cells, lymphocytes, macrophages, and granulocytes.[1–3] CD200 expression may promote tumor formation and metastasis by helping malignant cells evade the immune system.[4] CD200 has been well studied in hematopoietic malignancies including lymphoma, plasma cell myeloma, and acute leukemia, among others.[5–12] Although less well-studied in nonhematopoietic neoplasms, CD200 expression has been reported in renal cell carcinoma, ovarian carcinoma, neuroblastoma, melanoma, cutaneous squamous carcinoma, and basal cell carcinoma, and studied but not identified in prostate carcinoma, breast carcinoma, and non–small cell lung carcinoma.[13,14] Early studies reported no expression of CD200 in astrocytoma or glioblastoma, but recent studies show expression.[13,15] While we have previously characterized CD200 expression in small cell lung carcinoma by both flow cytometry and immunohistochemistry, to the best of our knowledge, CD200 expression has not been characterized by immunohistochemistry in a large series of neuroendocrine neoplasms; such characterization is the primary objective of this study.[16]