Expression of transcription factors and nuclear receptors in mixed germ cell-sex cord stromal tumor and related tumors of the gonads

In this study, we compare the expression of OCT4, SALL4, and TSPYL1 in mixed germ cell-sex cord stromal tumor (MGC-SCST) of either gonad to that of normal adult testis, classic and spermatocytic seminoma, intratubular germ cell neoplasia, unclassified, gonadoblastoma, and dysgerminoma to determine the entity or entities that most closely resemble MGC-SCST by immunohistochemistry of germ cells. The most useful transcription factor was OCT4. In addition, to its already described value in distinguishing germinoma and embryonal carcinoma from yolk sac tumor and in differentiating classic from spermatocytic seminoma, we found that OCT4 is useful in confirming or ruling out potential malignancy in MGC-SCST of either gonad. Expression of OCT4 in most ovarian MGC-SCSTs resembles that of dysgerminoma, whereas most testicular examples resemble that of spermatocytic seminoma and normal adult testis. Thus, most MGC-SCSTs of the ovary are potentially malignant, and corresponding tumors of the testis are mostly benign; however, exceptions likely can be detected by the use of OCT4, potentially leading to more appropriate clinical management in some cases. SALL4 is an underutilized transcription factor that is useful in distinguishing testicular MGC-SCST from sex cord stromal tumor, unclassified in those neoplasms where the germ cells are sparse or unevenly distributed. Compared with other transcription factors studied, TSPY and its congener TSPYL1 have little value in the assessment of germ cell tumors because of their relatively wide range of expression in normal adult testis and in germ cell tumors.