Role of CD200 in the Detection of Nonhematologic Neoplasms by Routine Flow Cytometry Analysis

Abstract

Abstract Objectives While flow cytometry is routinely used in the diagnostic work-up of hematolymphoid malignancies, its role in identifying non-hematolymphoid neoplasms is controversial. While a diagnosis of “non-hematolymphoid process” may be suggested by flow cytometry, typically, CD45-negative entities are not further characterized by their immunophenotypic profile. Some markers, such as CD56, have been well documented in non-hematolymphoid malignancies, such as high-grade neuroendocrine carcinomas (Stacchini, et al, 2018; Bryson et al, 2002). Other cell surface markers that are routinely studied with flow cytometry panels, such as CD200, are less well-described in the literature with regards to their presence/absence in non-hematolymphoid processes. We examined all flow cytometry cases from our institution over a 5-year period to identify trends in the immunophenotypes of non-hematolymphoid malignancies that were known to be CD45-negative and CD56-positive by flow cytometry. Methods We examined 3634 flow cytometry cases (2015-2020) and identified non-hematolymphoid cases based upon lack of CD45 expression. After excluding multiple myeloma cases from the CD45-negative entities, we were left with 19 CD45-negative cases. Chart review of these cases confirmed them as non-hematolymphoid by concurrent surgical pathology/cytopathology studies. Of these 19 cases, 2 were excluded because CD56 was not evaluated. Results Of the 17 CD45-negative/CD56-positive cases, 16 showed CD200 positivity (94%). Of these CD200-positive cases, 10 were ultimately diagnosed as small cell carcinoma (59%), 1 was diagnosed as Merkel cell carcinoma (6%), 1 was diagnosed as melanoma (6%), 1 was diagnosed as poorly-differentiated carcinoma (6%), 1 was diagnosed as Ewing-like sarcoma (6%), and 2 were unclassified further (12%). The single CD200-negative case was diagnosed as poorly-differentiated acinar cell carcinoma (6%). All cases of small cell carcinoma that were evaluated by flow cytometry showed expression of CD200 and CD56. Conclusions Our findings suggest that in CD45-negative/CD56-positive non-hematolymphoid malignancies, particularly small cell carcinoma, CD200 is frequently positive. CD200 was also found to be positive in rare cases of other non-hematolymphoid malignancies within the differential diagnosis of small round blue cell tumors. These findings indicate that CD200 may be a useful marker in suggesting the possibility of small cell carcinoma in non-hematolymphoid specimens that are evaluated by flow cytometry.