Comparative Analysis of Alternative and Traditional Immunohistochemical Markers for the Distinction of Ovarian Sertoli Cell Tumor From Endometrioid Tumors and Carcinoid Tumor

Abstract

The main neoplasms in the differential diagnosis for primary ovarian tumors with a tubule-rich pattern are pure Sertoli cell tumor, endometrioid tumors (including borderline tumor, well-differentiated carcinoma, and the sertoliform variant of endometrioid carcinoma), and carcinoid tumor. Because traditional immunohistochemical markers [pan-cytokeratin (pan-CK), low molecular weight cytokeratin (CK8/18), epithelial membrane antigen (EMA), inhibin, calretinin, CD99, chromogranin, and synaptophysin] can occasionally have diagnostic limitations, the goal of this study was to determine whether or not any alternative markers [cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), CD10, and CD56] have better diagnostic utility when compared with traditional markers for this differential diagnosis. Immunohistochemical stains for alternative, as well as traditional, markers were performed on the following primary ovarian tumors: pure Sertoli cell tumor (n = 40), endometrioid borderline tumor (n = 38), sertoliform endometrioid carcinoma (n = 13), well-differentiated endometrioid carcinoma (n = 27), and carcinoid tumor (n = 42). Extent and intensity of immunostaining were semiquantitatively scored. In addition, immunohistochemical composite scores (ICSs) in positive cases were calculated on the basis of the combination of extent and intensity scores. Cytokeratin 7 (CK7) was positive in 97% of endometrioid tumors, 13% of Sertoli cell tumors, and 24% of carcinoid tumors. The differences in the mean ICSs for endometrioid tumors versus Sertoli cell tumor or carcinoid tumor were statistically significant (P values ranging from <0.001 to 0.018). ER and PR were positive in 87% and 86% of endometrioid tumors, 8% and 13% of Sertoli cell tumors, and 2% each of carcinoid tumors, respectively. The differences in the mean ICSs for endometrioid tumors versus Sertoli cell tumor were statistically significant (P values ranging from <0.001 to 0.012). Among the epithelial markers, EMA seemed to be the most discriminatory but only slightly better than CK7, ER, or PR. Pan-CK and CK8/18 were not helpful. CD10 showed overlapping patterns of expression in all categories of tumors. Among the sex cord markers, CD10 was markedly less useful than inhibin or calretinin; CD99 was not discriminatory. CD56 showed overlapping patterns of expression in all categories of tumors. Among the neuroendocrine markers, CD56 was less useful than chromogranin or synaptophysin. When traditional immunohistochemical markers are problematic for the differential diagnosis of ovarian Sertoli cell tumor versus endometrioid tumors versus carcinoid tumor, adding CK7, ER, and/or PR to a panel of markers can be helpful. Endometrioid tumors more frequently express CK7, ER, and PR and show a greater extent of immunostaining in contrast to Sertoli cell tumor and carcinoid tumor. Compared with traditional epithelial markers, CK7, ER, and PR are nearly as advantageous as EMA. Inhibin is the most discriminatory sex cord marker, and CD10 is not helpful in the differ...

Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation

“…In this setting, a panel of site-specific lineage markers (TTF-1 for pulmonary origin, CDX2 for gastrointestinal tract origin, PAX8/PAX6 for gastropancreatic and duodenal origin, and ER/PR, mammaglobin, GCDFP-15 and GATA3 for mammary origin) may be helpful in distinguishing metastatic neuroendocrine neoplasms (particularly well-differentiated neuroendocrine tumors) from invasive mammary carcinomas with neuroendocrine differentiation. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] In this study, CDX2 was positive in all examined metastatic neuroendocrine neoplasms of small bowel origin, TTF-1 was positive in 70% of examined metastatic neuroendocrine neoplasms of lung origin, and ER and GATA3 were positive in 91 and 100% of invasive mammary carcinomas with neuroendocrine differentiation, respectively. Similarly, in the study by Perry et al 9 (which with the exception of one high-grade neuroendocrine carcinoma consisted entirely of well-differentiated neuroendocrine tumors), all metastatic neuroendocrine neoplasms from the gastrointestinal tract expressed CDX2 and 60% of tumors originating from the lung expressed TTF-1.…”

“…39 Likewise, focal weak to diffuse and strong immunoexpression of ER and PR can be noted in endometrial and cervical high-grade neuroendocrine carcinomas. [44][45][46] Therefore, in the absence of a relevant clinical history, determining whether an invasive carcinoma with neuroendocrine differentiation in the breast is primary or metastatic and suggesting the site of origin of a metastatic neuroendocrine neoplasm in the breast based solely on the results of immunohistochemical studies can be problematic.…”

The Utility of Immunohistochemistry in the Differential Diagnosis of Gynecologic Disorders

“…Diagnostic mimics such as serous carcinoma, carcinoid tumor, endometrial stromal sarcoma, and extraovarian neuroendocrine carcinoma also express CD56. [190][191][192] The Differential Diagnosis of Granulosa Cell Tumor.-EMA, cytokeratin, inhibin, calretinin, FOXL2, and SF-1.…”

“…204 CK7, CAM 5.2, CK8/18, CK(AE1/AE3), and cytokeratin may show variable degrees of reactivity in up to half of the cases of Sertoli stromal tumors. 190,195,215 Their use is limited in excluding adenocarcinoma with certainty. However, EMA is negative in all cases of Sertoli-stromal tumors.…”

“…Sertoli-stromal cell tumors are positive for calretinin, inhibin, SF-1, and WT1. 190,202,203,215,216 The use of FOXL2 is limited, since it is not expressed in approximately half of the cases of Sertoli-stromal tumors, particularly the retiform variant. 204 CK7, CAM 5.2, CK8/18, CK(AE1/AE3), and cytokeratin may show variable degrees of reactivity in up to half of the cases of Sertoli stromal tumors.…”