Testicular Tumours: Large Cell Calcifying Sertoli Cell Tumour

Large Cell Calcifying Sertoli Cell Tumour:

This subtype of Sertoli cell tumour is associated in almost half of the reported cases with other endocrine lesions, such as pituitary adenomas, bilateral primary adrenocortical hyperplasia, and testicular Leydig cell tumours.
Cardiac myxomas and spotty mucotaneous pigmentation have also been reported.
The clinical associations have included acromegaly, gigantism, hypercortisolemia, sexual precocity, sudden death, and the Peutz-Jeghers syndrome.
The large cell calcifying Sertoli cell tumour is usually 4 cm or less in diameter and is multifocal or bilateral in almost half of the cases.
Sectioning discloses firm yellow to tan tissue in which granular calcific foci may be detectable. The tumours appear grossly well circumscribed in most cases.
Microscopic examination reveals that the neoplastic cells are arranged in sheets, nests, trabeculae, cords, small clusters, or solid tubules. The characteristic feature is the presence of calcification, which is usually conspicuous and sometimes massive, with the formation of large, wavy, laminated nodules. The neoplastic cells are typically large and rounded, but occasionally are cuboidal or columnar, and rarely are spindle shaped. In most of the cases, the cytoplasm is abundant, eosinophilic, and finely granular. The nuclei are round or oval without conspicuous nucleoli. Mitotic figures are generally rare.
Features of malignant and benign large cell calcifying Sertoli cell tumours have also been studied. It showed that the malignant tumours were unilateral and solitary and occurred at a mean age of 39 years, whereas the benign neoplasms were more often bilateral and multifocal in some of the cases and occurred at a mean age of 17 years.
There were strong associations of a malignant behavior with size larger than 4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and a mitotic rate of more than 3 mitoses per 10 high-power fields. All of the malignant cases exhibited at least 2 of these features, whereas all of the benign cases lacked any of them. The presence of any 1 of these features in a solitary large cell calcifying Sertoli cell tumour, especially in a patient older than 25 years, should be considered suspicious for a malignant behavior, whereas 2 or more of these indicate a strong probability of a malignant course.

Abstract:
Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature. Am J Surg Pathol. 1997 Nov;21(11):1271-80.
We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. "Low" percentages (< or ="35%)">

Abstracts:
Utility of immunostaining for S-100 protein subunits in gonadal sex cord-stromal tumors, with emphasis on the large-cell calcifying Sertoli cell tumor of the testis. Hum Pathol.2002 Mar;33(3):285-9.
This study concerns the immunohistochemical localization of S-100 alpha, S-100 beta, and whole brain S-100 (wbS-100) in testicular large-cell calcifying Sertoli cell tumor (LCCSCT). We examined 8 LCCSCTs (7 benign and 1 malignant), 6 Sertoli cell tumors not otherwise specified (SCTs-NOS), 6 Leydig cell tumors (LCTs), 5 ovarian Sertoli-Leydig cell tumors (SLCTs), and 7 gonadoblastomas (GBLs). The 8 LCCSCTs showed immunoreactivity for S-100 alpha, S-100 beta, and wbS-100. Five of the 6 LCTs and the Leydig cell components in the ovarian SLCTs stained positively for S-100 alpha and wbS-100 but were negative for S-100 beta. SCTs-NOS and the Sertoli cell components in the SLCTs occasionally showed focal and weak/moderate positivity for S-100 alpha, S-100 beta, and wbS-100. Sex cord cells of the GBLs were positive for S-100 beta and wbS-100 and negative for S-100 alpha. Germ cell elements of the GBLs were negative for S-100 alpha, S-100 beta, and wbS-100. In nonneoplastic testicular parenchyma adjacent to the above-mentioned tumors, there was S-100 alpha reactivity in Leydig cells, rete testis, and a few Sertoli cells. S-100 beta reactivity was seen in a few Sertoli cells, Schwann cells, and some endothelial cells. WbS-100 reactivity was present in Leydig cells, a few Sertoli cells, rete testis, Schwann cells, and some endothelial cells. The results indicate that S-100 alpha and S-100 beta can potentially be used as immunohistochemical markers for LCCSCT, especially when differentiating it from LCT, which may mimic LCCSCT on routine histopathology. Although the biological significance of both S-100 subunits expression in LCCSCT remains unknown, these notable calcium-binding proteins may be associated with the characteristic calcification in LCCSCT through regulation of calcium levels in the tumor cells.

Abstract:
Large cell calcifying Sertoli cell tumor of the testis. A clinicopathologic, immunohistochemical, and ultrastructural study of two cases. Am J Clin Pathol. 1991 Dec;96(6):717-22.
The clinicopathologic, immunohistochemical, and electron microscopic study of two patients with large cell calcifying Sertoli cell tumors (LCCSCT) of the testis is reported to elucidate the histogenesis of this rare tumor. Both tumors occurred in young individuals (16 and 32 years); case 1 was found incidentally, and the patient in case 2 presented with a 3-4-week history of testicular pain. Evidence of testosterone production was demonstrated in one case. In the same case, at the ultrastructural level Charcot-Böttcher crystalloids were observed. These data support previous reports that LCCSCT shows Sertoli cell differentiation.