INHIBIN AND EPITHELIAL MEMBRANE ANTIGEN IMMUNOHISTOCHEMISTRY ASSIST IN THE DIAGNOSIS OF SEX CORD-STROMAL TUMORS AND PROVIDE CLUES TO THE HISTOGENESIS OF HYPERCALCEMIC SMALL-CELL CARCINOMAS

Ovarian sex cord-stromal tumors are a morphologically diverse group of neoplasms that can mimic the appearance of other ovarian tumors. Beca use the treatment and prognosis of sex cord-stromal tumors differs sub stantially from those of other ovarian neoplasms, the development of a n immunohistochemical panel to support the diagnosis of the former gro up of tumors would be useful. In this report, the utility of immunosta ining for inhibin cr, epithelial membrane antigen, MIC2 gene protein p roduct, and keratin in the differential diagnosis of sex cord-stromal tumors was assessed in formalin-fixed, paraffin-embedded sections. In addition, the immunohistochemical staining pattern of ovarian small ce ll carcinomas (SCCs), hypercalcemic type, was analyzed in an attempt t o clarify the histogenesis of these tumors. Thirty-two (97%) of 33, gr anulosa cell tumors (GCTs), 10 (91%) of 11 Sertoli-Leydig cell tumors (SLCTs), and (8%) of 51 carcinomas showed inhibin alpha immunopositivi ty. None of the 3 lymphomas, 5 carcinoids, 6 dysgerminomas, or 12 SCCs showed inhibin a positivity. Eighteen (55%) GCTs, 6 (55%) SLCTs, 6 (1 2%) carcinomas, and 7 (58%) SCCs showed MIC2 gene expression. None of the GCTs and only one SLCT showed epithelial membrane antigen (EMA) po sitivity, although 92% of surface epithelial carcinomas and 75% of SCC s were immunoreactive. These data suggest that detection of inhibin im munoreactivity in an ovarian tumor that is EMA-negative provides both sensitive and specific support for the diagnosis of a sex cord-stromal tumor. Because SCCs generally stain for EMA but not for inhibin, it a ppears that SCCs probably represent a variant of surface epithelial tu mor rather than a type of sex cord-stromal tumor.