OVARIAN GRANULOSA-CELL TUMORS WITH BIZARRE NUCLEI - AN IMMUNOHISTOCHEMICAL ANALYSIS

Granulosa cell tumors with bizarre nuclei (GCT-BN) are rare lesions wi th a prognosis apparently similar to that of conventional granulosa ce ll tumors (GCT-NOS). The immunohistochemical features of GCT-BN have n ot been described, and the exact nature of the bizarre nuclei (BN) is unclear, Thirteen GCT-BN were studied with antibodies to cytokeratin, vimentin, epithelial membrane antigen, muscle-specific actin, alpha sm ooth muscle actin, desmin, and S-100 protein. Six cases were also exam ined by fluorescence in situ hybridization for trisomy 12, a nonrandom chromosomal aberration found in a proportion of ovarian sex-cord stro mal tumors. Histologically, 12 tumors (86%) contained BN areas intersp ersed with large areas of OCT-NOS. The remaining tumor contained only microscopic foci of GCT-NOS. Immunohistochemically, the tumors stained for vimentin (13 tumors), S-100 protein (11 tumors), muscle-specific actin (10 tumors), cytokeratin (eight tumors), alpha smooth muscle act in (eight tumors), and desmin (one tumor), but none stained for epithe lial membrane antigen. Immunostaining results for the BN and OCT-NOS a reas were concordant in eight (73%) of the 11 tumors in which both are as could be independently assessed. The remaining three tumors (27%) s howed discordant results for only one of the eight markers used. In fi ve patients, trisomy 12 was detected by fluorescence in situ hybridiza tion in areas of BN but not in areas of GCT-NOS present in the same tu mor. Trisomy 12 was also present in another BN tumor in which the foci of GCT-NOS were too small to be evaluated. We conclude that within GC T-BN, areas with BN are immunohistochemically similar to areas of OCT- NOS present in the same tumor. The finding of trisomy 12 in areas with BN but not GCT-NOS in the same tumor, however, suggests that cells wi th BN represent a genetically distinct clone of tumor cells arising wi thin OCT-NOS.