MIC2 gene expression in cutaneous neuroendocrine carcinoma (Merkel cell carcinoma)

The distinction between small round-cell tumors in the skin is difficult and is dependent on clinical characteristics, morphology, immunophenotype, and genotype. We attempted to characterize further the immunophenotype of cutaneous neuroendocrine carcinomas (CNCs; Merkel cell tumors) by using CD99, which recognizes the product of the pseudoautosomal gene, MIC2. We studied the staining pattern of 12E7, a CD99 monoclonal antibody, in 21 examples of CNCs and O13, another CD99 monoclonal antibody, in a subset of cases for which formalin-fixed, paraffin-embedded tissue was available in our archives. An additional neuroendocrine carcinoma from the endometrium also was studied. Nineteen cutaneous cases did not display any staining, whereas two cases demonstrated convincing cytoplasmic reactivity (two of 21). The endometrial neuroendocrine carcinoma was also CD99(+). Regardless of these rare positive cases, the results contrast with the almost uniformly positive staining pattern reported in a subset of other small round-cell tumors, including Ewing's sarcoma, primitive neuroectodermal tumors, and many acute lymphoblastic leukemias and lymphoblastic lymphomas. Despite the rare CNC that may express CD99, a negative reaction with 12E7 or O13 or both favors the diagnosis of CNC over other small round-cell tumors, given the appropriate clinical, morphologic, and immunologic findings.