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Sertoli cell (SC) and sertoliform tumors of the testis are very uncommon; for this reason their differential diagnosis and classification can be challenging. We applied an extensive immunophenotypic panel that included androgenic hormones, enzymes and receptors, neuroendocrine, lineage and genitourinary markers to a series of these lesions to determine if and which immunostains can aid in their diagnostic workup. Study cases included: 2 androgen insensitivity syndrome-associated SC adenomas, 3 SC tumors (SCT) not otherwise specified (SCT-NOS), 3 sclerosing SCT, 2 large cell calcifying SCT, 1 SCT with heterologous sarcomatous elements, 1 malignant SCT, and 1 sertoliform rete testis adenoma (sertoliform RTA). We found that SCT-NOS and variants with sclerosis showed a phenotype akin to atrophic seminiferous tubules characterized by gain of expression of pankeratin, calretinin, CD56, which are negative in normal SC. Distinctive phenotypes were identified in: sclerosing SCT: androgen receptors (AR) + (strong)/PAX2/PAX8+ (subset)/S100+/inhibin-; large cell calcifying SCT: calretinin+ (strong)/S100+/AR-; sertoliform RTA: PAX2/PAX8+/pankeratin+/inhibin-. Androgenic hormones and enzymes did not show diagnostic utility. A panel of calretinin, inhibin, pankeratin, S100, PAX2/PAX8, and AR consistently allowed distinction between variants of Sertoli and sertoliform tumors., (Published by Elsevier Inc.)

The recent availability of monoclonal antibodies raised against cell cycle nuclear antigens makes possible, by means of immunohistochemical techniques, an easy and quick method of evaluating tumour kinetic activity, in addition to older methods such as measurement of the mitotic index. Some of these antibodies can be used on formalin-fixed paraffin wax-embedded samples, thus allowing the use of archival material. In the present study the proliferative activity of testicular tumours of the dog (seminomas and Sertoli and Leydig cell tumours) was investigated with two monoclonal antibodies to proliferating cell nuclear antigen (PCNA) clone PC10, and Ki67 clone MIB1. The former recognizes a formalin-resistant epitope of PCNA, and MIB1 the same antigen as Ki67 in formalin-fixed, paraffin wax-embedded sections after incubation in a microwave oven. Three parameters of proliferative activity were considered: PCNA and Ki67 indices (percentage of nuclear area positive to PCNA and to Ki67), and mitotic index (number of mitoses per 1000 cells). The PCNA index and Ki67 index revealed a good correlation in linear regression analysis (P < 0.001) as did the mitotic index (P < 0.01). None of the parameters considered revealed a significant difference in proliferative activity of the three types of tumour (P > 0.05-Spearman test), but in both seminomas and Sertoli cell tumours the progression from tubular to diffuse pattern paralleled an increase in growth fraction. It is interesting that some seminomas of the diffuse type, often considered on histological grounds to be the most malignant, showed the highest values of the above-mentioned parameters.

Poorly differentiated Sertoli-stromal cell tumors and carcinosarcomas of the ovary both show biphasic epithelial and stromal patterns and may both show heterologous stromal elements, presenting a difficult diagnosis. We studied the immunohistochemical profile of Sertoli cell differentiation in human testes and applied these findings to the ovarian tumors. Eleven Sertoli-stromal cell tumors, six carcinosarcomas of the ovary, and 11 testes (six fetal, one infant, and four adult) were studied using antibodies to cytokeratin AE1:AE3 (AE1:3), cytokeratin CAM 5.2 (CAM), epithelial membrane antigen (EMA), vimentin, desmin, muscle-specific actin (MSA), S-100 protein (S-100), CA 19-9, CA 125, carcinoembryonic antigen monoclonal (CEA-M), carcinoembryonic antigen polyclonal (CEA-P), and placental alkaline phosphatase (PLAP). In the fetal testes, immature gonadal stroma and sex cord areas stained with vimentin (six of six cases), AE1:3 (five of six cases), and CAM (six of six cases). Sertoli cells in immature gonadal stroma areas, sex cords, and seminiferous tubules of normal fetal, infant, or adult testes never showed immunoreactivity for EMA, S-100, CA 19-9, CA 125, CEA-M, CEA-P, or PLAP. All Sertoli-stromal cell tumors stained with AE1:3 and CAM in areas of Sertoli cell differentiation (11 of 11 cases) but did not stain with EMA, PLAP, CEA-P, CEA-M, CA 19-9, CA 125, or S-100 (none of 11 cases). Carcinosarcomas expressed AE1:3 and CAM in all epithelial areas (six of six cases) and most stromal areas (five of six cases). Carcinomatous areas of carcinosarcoma also showed immunoreactivity for EMA (six of six cases), CA 125 (two of six cases), PLAP (two of six cases), CEA-P (two of six cases), and CEA-M (one of six cases), while stromal areas of carcinosarcoma expressed EMA (four of six cases) and S-100 (four of six cases). Heterologous stromal elements were present in three of 11 Sertoli-stromal cell tumors (two showed skeletal muscle and one showed both skeletal muscle and cartilage differentiation) and in four of six carcinosarcomas (one skeletal muscle, one cartilage, and two cartilage and skeletal muscle). All skeletal muscle heterologous elements expressed desmin, vimentin, and MSA. The heterologous cartilage in carcinosarcoma stained with S-100 (three of three), while the one case of heterologous cartilage in Sertoli-stromal cell tumor did not. These results suggest that ovarian Sertoli-stromal cell tumor can be distinguished from carcinosarcoma by the absence of staining for EMA, PLAP, CEA, CA 125, or CA 19-9 in epithelial areas of Sertoli-stromal cell tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Seventy ovarian sex-cord-stromal and germ-cell tumors were immunohistochemically studied for the presence of intermediate-filament proteins of different types used as markers for cellular differentiation. Cells of ovarian granulosa-cell tumors constantly expressed vimentin and appeared to lack cytokeratin. Two tumors previously classified as granulosa-cell tumors were reclassified as poorly differentiated "common" epithelial tumors based on their cytokeratin positivity, vimentin negativity, and morphologic features. Dysgerminomas and Leydig-cell tumors showed only vimentin positivity. Tubular structures in androblastomas, which are considered to represent Sertoli-cell differentiation, were cytokeratin positive, and thus differed from the majority of normal Sertoli cells that are known to express vimentin and not cytokeratin. Embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors showed cytokeratin positivity in the neoplastic cells whereas vimentin was observed in the stromal cells. In immature teratomas, epithelial differentiation was demonstrated with cytokeratin antibodies, and neural and glial differentiation was also frequently demonstrated by immunostaining with antibodies to neurofilaments and glial fibrillary acidic protein. The results show that antibodies to intermediate filaments can be used in the differential diagnosis between ovarian epithelial and nonepithelial tumors, and they provide a very accurate additional method to characterize the cellular differentiation of ovarian neoplasms.