Testicular Tumours: Granulosa Cell Tumour : Adult-type Granulosa Cell Tumour

Granulosa cell tumour
This tumour is morphologically similar to the ovarian counterpart. It is exceedingly rare in the testis.
Granulosa cell tumours are divided into 2 types, adult and juvenile, and both types represent a distinct group of the sex cord–stromal tumours of the gonads.


I Adult Granulosa Cell Tumour:

Adult-type granulosa cell tumour is considered a very rare testicular tumour. The tumours are usually non functional and may be associated with gynecomastia.
Age: 20-50 years.
Gross features: The tumour mass is often partially encapsulated and come in direct contact with the tunica albuginea. The cut surface may be homogeneous, beige, firm, and fleshy. There is usually no evidence of necrosis or hemorrhage. In some cases there may be a small area of ossification. A central round nodule with a yellow surface and firm consistency may be present. The mass usually do not infiltrate the adjacent testicular tissue.
Microscopic features: Histologic examination from the tumour reveal a wide variety of patterns which included gyriform, macrofollicular, insular, trabecular, solid, pseudosarcomatous, and microfollicular. The microfollicular pattern is characterized by the presence of numerous cavities simulating Call-Exner bodies. These cavities contain eosinophilic fluid and sometimes hyalinized basement membrane material. The microfollicles are separated by well-differentiated granulosa cells that contained scant cytoplasm and pale, angular, or oval, often grooved nuclei arranged haphazardly in relation to one another and to the follicle. Rare theca cells may be seen scattered in between the neoplastic granulosa cells. Few mitotic figures are seen, but no abnormal forms are noted. Necrosis is usually not present. The yellow nodule consist of interlacing bundles of spindle cells with cigar-shaped nuclei that contain similar grooves (these are not as prominent as other areas) and eosinophilic cytoplasm. Mitotic figures in the spindle cell area are more prominent.
It does have the potential to metastasize, even a long time after the initial presentation, and it is usually associated with a long survival period.
By immunophenotyping, membranous staining with MIC2 (O13) is helpful in differentiating this tumour from other gonadal tumours. Reactions for desmin, epithelial membrane antigen, S100 protein, and leukocyte common antigen are negative.

Abstract:
Anti-Müllerian hormone is a specific marker of sertoli- and granulosa-cell origin in gonadal tumors. Hum Pathol.2000 Oct;31(10):1202-8.
Sex cord stromal tumors are gonadal neoplasms containing Sertoli, granulosa, Leydig, or thecal cells, which originate from cells derived from either the sex cords (Sertoli and granulosa cell tumors) or the specific mesenchymal stroma (Leydig and thecal cell tumors) of the embryonic gonad. Only granulosa and Sertoli cells produce anti-Müllerian hormone (AMH). Our purpose was to investigate whether AMH can be used as a specific marker of human granulosa or Sertoli cell origin in gonadal tumors, to distinguish them from other primary or metastatic neoplasms, using immunohistochemistry. We studied 7 juvenile and 6 adult-type granulosa cell tumors of ovarian localization and 3 extraovarian metastases, 20 other ovarian tumors, 6 testicular Sertoli cell tumors, 2 gonadoblastomas, and 13 extragonadal tumors. Granulosa cell tumors, both juvenile- and adult-type of either ovarian or metastatic localization, showed an heterogeneous pattern of AMH immunoreactivity: Areas containing intensely or weakly AMH-positive cells were intermingled with AMH-negative areas. Although in most cases AMH-positive areas represented a minor proportion of tumor cells, we found a positive reaction in all the cases examined. In testes, although normal prepubertal Sertoli cells were intensely positive, testicular Sertoli cell tumors showed large areas of negative reaction, with few positive cells scattered throughout the tumor. AMH was also reactive in most of the cells of sex-cord origin in gonadoblastomas. No AMH immunoreaction was observed in other gonadal and extragonadal tumors. We conclude that AMH expression is conserved in only a small proportion of tumor cells of granulosa or Sertoli cell origin; however, a positive reaction in a few cells helps to distinguish between granulosa or Sertoli cell tumors or gonadoblastomas and other gonadal tumors of different origin.

Abstract:
Granulosa cell tumor of the adult type: a case report and review of the literature of a very rare testicular tumor. Arch Pathol Lab Med.2000 Oct;124(10):1525-8.
We report a case of testicular granulosa cell tumor of the adult type in a 48-year-old man. Microscopically, the tumor consisted of round to ovoid cells with grooved nuclei that were arranged in several patterns, including microfollicular, macrofollicular, insular, trabecular, gyriform, solid, and pseudosarcomatous. These cells demonstrated strong immunopositivity with MIC2 (O13) antibody, vimentin, and smooth muscle actin and focal positivity with cytokeratin. Although this type of sex cord-stromal tumor is relatively common in the ovaries, it is still extremely unusual in the testis, and it probably represents the rarest type of testicular sex cord-stromal tumor.

Abstract:
Granulosa cell tumor of the adult testis: a clinicopathologic study of seven cases and a review of the literature.Hum Pathol.1993 Oct;24(10):1120-5.
We report a study of seven men, aged 16 to 76 years (average age, 47.4 years) with granulosa cell tumor (GCT) of the testis. Three patients presented with testicular enlargement of several years' duration and a fourth presented with a testicular enlargement of unknown duration. The tumors in three patients were detected during routine physical examination. None of the patients had endocrine-related symptoms. All tumors were well circumscribed and showed the solid, cystic, microfollicular, gyriform, insular, and trabecular patterns typical of GCT of the ovary. Call-Exner bodies were present in three tumors and two tumors had a focal spindle-cell component. In one case the surrounding testicular parenchyma showed Leydig's cell hyperplasia and a Sertoli cell nodule. The tumor cells revealed strong immunoreactivity for vimentin but showed no expression for keratin or epithelial membrane antigen. One patient developed liver and retroperitoneal lymph node metastases 121 months after initial diagnosis and died 13 months later. Another patient initially presented with retroperitoneal lymph node metastasis and developed metastasis to the inguinal lymph nodes 12 months later. Three patients are alive at 1, 4, and 37 months with no evidence of disease. Another patient died of an unrelated condition. Follow-up information was not available for the seventh patient. Twelve cases of GCT of the adult testis have been reported in the literature, with metastases occurring in two: one of these two patients had a tumor for 8 years and died of disease 5 months after diagnosis with multiple metastases and the other had metastasis at the time of diagnosis, but was free of disease for 14 years. Our findings and a review of the literature indicate that GCT of the adult testis is a rare and slow-growing neoplasm with the potential to form distant metastases. Because recurrence or distant metastasis may occur late in the clinical course, long-term follow-up of these patients is recommended.