Comparative Immunohistochemical Analysis of Granulosa and Sertoli Components in Ovarian Sex Cord-Stromal Tumors with Mixed Differentiation: Potential Implications for Derivation of Sertoli Differentiation in Ovarian Tumors

Abstract

Granulosa cell tumors of the ovary occasionally show admixed Sertoli components, just as tumors that are predominantly Sertoli or Sertoli-Leydig cell tumors can contain minor granulosa elements. Although the immunoprofiles of pure granulosa cell tumors and pure Sertoli cell tumors have been characterized, little is known regarding what immunophenotypic relationships exist between the granulosa and Sertoli components in ovarian sex cord-stromal tumors that contain both elements. Furthermore, it is not completely understood why sex cord-stromal tumors of the ovary with female-type (granulosa) differentiation can produce male-type (Sertoli) differentiation. To better understand why simultaneous differentiation into female-type and male-type components occurs, eight tumors with mixed differentiation were stained with a panel of antibodies to androgen receptor (AR), calretinin, CD10, CD99, estrogen receptor, inhibin, Ki-67, low molecular weight cytokeratin, pancytokeratin, progesterone receptor, p53, and vimentin. Immunohistochemical composite scores were determined separately for the matched pairs of granulosa and Sertoli components in each case. Differences between both components were statistically analyzed using the Wilcoxon signed rank test. AR and vimentin expression showed a difference at the 10% statistical significance level (p < 0.1), demonstrating higher levels of expression in the granulosa components. The differences between the granulosa and Sertoli components in expression of CD99, inhibin, or pancytokeratin were not statistically significant (p > 0.1, each). Statistical calculations could not be made for calretinin, CD10, estrogen receptor, Ki-67, low molecular weight cytokeratin, progesterone receptor, or p53, although the overall mean levels of expression of CD10 and low molecular weight cytokeratin were substantially higher in the Sertoli components. Not surprisingly, the granulosa and Sertoli components of ovarian sex cord-stromal tumors with mixed differentiation show overlapping immunophenotypic profiles consistent with derivation from a common lineage rather than reflecting a composite tumor. However, because components of a sex cord-stromal tumor simultaneously differentiate along granulosa or Sertoli lines, they seem to show preferential expression of certain antigens. CD10 and low molecular weight cytokeratin are more often associated with Sertoli cell differentiation, whereas AR and vimentin expression seem to reflect granulosa differentiation.

Ovarian sertoliform endometrioid adenocarcinoma: A rare variant which causes diagnostic pitfalls

“…Immunohistochemical markers used for this purpose involve PANCK, LMWCK (CK8/18), CK7, ER, PR, EMA of which positivity were in favour of endometrioid carcinoma and inhibin , calretinin, WT-1 to show sex cord lineage (4,5,15,(17)(18)(19). Inhibin  and calretinin are highly sensitive and specific markers to show sex cord lineage, being expressed in 82% to 98% and 50% to 60% of ovarian pure Sertoli cell tumors (15,20).…”

Malignant Ovarian Granulosa Cell Tumour in a Ewe

“…Vimentin is usually detected in granulosa cell tumours and other ovarian tumours and therefore not a useful marker for differentiation among them (Vang et al 2004;Riccardi et al 2007). Negative immunohistochemical reaction for desmin in this case is in accordance with the results of equal reactions, performed in other cases of granulosa cell tumours (Costa et al 1994).…”

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

“…In general, traditional immunohistochemical markers used for the distinction of epithelial, sex cord-stromal, and neuroendocrine tumors, such as pan-cytokeratin (pan-CK), low molecular weight cytokeratin (CK8/18), epithelial membrane antigen (EMA), inhibin, calretinin, CD99, synaptophysin, and chromogranin, can be useful; however, they may sometimes show overlapping patterns of expression. For example, Sertoli cell tumors can express epithelial markers such as cytokeratin (AE1/AE3 and CK8/18) in 38% to 100% of cases 11,13,21,22,37,49 whereas endometrioid carcinomas can express sex cord markers such as inhibin and calretinin in 0% to 25% and 0% to 36% of cases, respectively. 7,8,10,[14][15][16]19,20,25,[29][30][31][32]35,38,41,47,54 Although sex cord-stromal markers such as inhibin and calretinin have been extensively studied in ovarian sex cord-stromal tumors, most studies are predominantly composed of granulosa cell tumors.…”

“…The number of Sertoli cell tumors that have been analyzed for various immunohistochemical markers in any given study is very small, and the majority of available immunohistochemical data are based on a mixture of pure Sertoli cell tumors, Sertoli-Leydig cell tumors, and mixed granulosa cell-Sertoli cell tumors (''gynandroblastoma'') from ovarian and testicular sites. 3,6,7,[11][12][13]17,19,[20][21][22]25,26,28,30,33,[35][36][37]38,44,47,49,51,53 Thus, a formal immunohistochemical comparison of ovarian pure Sertoli cell tumor, endometrioid tumors, and carcinoid tumor is lacking from the literature. Recently, a clinicopathologic study of 54 ovarian pure Sertoli cell tumors was reported, and immunohistochemical results for various markers were available in 23 cases; however, other tumors in the differential diagnosis were not evaluated because that was not the aim of that study.…”

“…4,10,20,24,25,32,43,[45][46][47]53 Cytokeratin 7 (CK7), estrogen receptor (ER), and progesterone receptor (PR) are often expressed in endometrioid tumors, but these markers have not been thoroughly evaluated in ovarian Sertoli cell tumor or carcinoid tumor. 19,21,22,38,49 CD10 expression has been described in Sertoli cell tumor, but sufficient data on the use of this marker for this differential diagnosis is lacking from the literature. 23,36,39,40,49 CD56 can be expressed in nonovarian neuroendocrine tumors; although, it is not known whether it provides any diagnostic advantage in the setting of an ovarian carcinoid tumor.…”