Cutaneous neuroendocrine (Merkel cell) carcinoma: an immunophenotypic, clinicopathologic, and flow cytometric study

Twenty-one cases of cutaneous neuroendocrine (Merkel cell) carcinoma (CNEC) were examined by the ABC-immunoperoxidase method with a panel of antibodies to 5 intermediate filaments, 6 neuroendocrine-associated antigens, 6 peptide hormones, as well as melanoma-associated cytoplasmic antigen (HMB-45) and leukocyte common antigen. All tumors showed strong cytokeratin staining in characteristic dense, inclusion-like, cytoplasmic globules and in a reticular peripheral cytoplasmic pattern. Cytoplasmic coexpression of inclusions of neurofilament antigen was observed in 9/21 cases. Staining for one or more neuroendocrine markers in formalin-fixed tissue (bombesin, 7/20; chromogranin, 11/21; synaptophysin, 6/21) was weak and focal but present in 17/21 cases. In 3 cases, sections of unfixed, snap-frozen tumor were compared with formalin-fixed tissue, and these showed strong, diffuse staining for multiple neuroendocrine antigens. Immunostaining for peptide hormones was not observed, with the exception of weak, focal staining for insulin (1 case), calcitonin (1 case) and somatostatin (2 cases). In 13 cases DNA indices and S-phase fractions (SPF) were determined by flow cytometry on nuclear suspensions from paraffin blocks. DNA histograms in 12 of 13 cases had normal range DNA content (diploid) and elevated S-phase fractions (mean 15%, range 8 to 22%). Mean SPF was not significantly different in the group of patients who developed recurrent and/or metastatic disease (15.6%, N = 10) compared with patients without recurrence (15.8%, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)