Adult granulosa cell tumor of the testis masquerading as hydrocele

ABSTRACT Adult testicular granulosa cell tumor is a rare, potentially malignant sex cord-stromal tumor, of which 30 cases have been described to date. We report the case of a 43-year-old male who complained of a left testicular swelling. Scrotal ultrasound showed a cystic lesion, suggestive of hydrocele. However, due to a clinical suspicion of a solid-cystic neoplasm, a high inguinal orchidectomy was performed, which, on pathological examination, was diagnosed as adult granulosa cell tumor. Adult testicular granulosa cell tumors have aggressive behaviour as compared to their ovarian counterparts. They may rarely be predominantly cystic and present as hydrocele. Lymph node and distant metastases have been reported in few cases. Role of MIB-1 labelling index in prognostication is not well defined. Therefore, their recognition and documentation of their behaviour is important from a diagnostic, prognostic and therapeutic point of view.


InTRODuCTIOn
While granulosa cell tumor represents the most common sex cord-stromal tumor arising in the ovary (1), and juvenile testicular granulosa cell tumor (TGCT) is the commonest sex cord-stromal tumor seen in male children, adult TGCT remains an enigmatic entity. Due to its rarity, not much is known about its natural course; however, literature suggests that adult TGCTs are slow-growing neoplasms with potential for lymph node metastasis, even many years after initial diagnosis. We report a case of this rare tumor which was predominantly cystic, causing a diagnostic dilemma clinically, and ultimately diagnosed on histopathology.

Case Report
This 43 years old male, under follow-up in the Urology clinic for stone disease, complained of painless, progressively increasing left testicular swelling for two months. On physical examination, vitals were stable. No abdominal distension or mass was noted. Peripheral lymphadenopathy was absent. Left testicular enlargement was identified, caused by a cystic scrotal swelling. Scrotal ultrasound ( Figure-1a) showed an anechoic cystic lesion measuring 5.5cm x 3.4cm, with nodular soft tissue shadows at the periphery and only a thin rim of testicular tissue. Based on ultrasonography, differential diagnoses included intra-testicular cystic neoplasm and a cystic lesion compressing the testis. On investigation, routine haematological and biochemical parameters, as well as serum alpha-fetoprotein (AFP), lactate dehydrogenase and human chorionic gonadotropin levels were within normal limits. The patient was counselled for and submitted to a high-inguinal orchidectomy. Post-operative period was uneventful. The patient is doing well one year after surgery. CT abdomen revealed no retroperitoneal lymphadenopathy ( Figure-1b).

Pathological examination
Left high inguinal orchidectomy specimen comprised of testis measuring 8cm x 5.5cm x 4.5cm, with attached spermatic cord measuring 6cm. A predominantly cystic tumor (Figure-2a) measuring 6cm x 3.5cm x 2.5cm was identified, almost completely replacing the testis, with a thin rim of compressed normal testicular parenchyma at the lower pole. Cysts varied from 0.5cm to 5cm in diameter, were smooth-walled, and contained clear fluid. Few solid nodules, 0.4cm to 1cm in maximum dimension, were seen within the cyst walls ( Figure-2b). The tumor did not appear to infiltrate the tunica albuginea. No areas of hemorrhage or necrosis were identified.
Adult TGCTs occur as solid, circumscribed tumors, in contrast to the multicystic juvenile TGCTs. While it is not unusual to identify small cystic foci within adult TGCTs (1), predominantly cystic tumors are rarely encountered, contributing to lack of suspicion of this diagnosis preoperatively, as in the case under discussion. Only two cases have been previously documented as presenting with hydrocele on the same side of tumor (7,8).
A variety of microscopic patterns may occur in adult TGCTs, making differential diagnosis from Sertoli-Leydig cell tumor, germ cell tumors, non-Hodgkin lymphoma and neuroendocrine tumors difficult. Microfollicular, macrofollicular, trabecular, and insular growth patterns are commonly observed (3). Typical Call-Exner bodies may or may not be present. These tumors are immunopositive for vimentin, inhibin, MIC2, calretinin, and smooth muscle actin (3), and are usually negative for CK, EMA, LCA, synaptophysin, chromogranin, PLAP, and AFP (9). Morphological features along with immunohistochemistry help in clinching the correct diagnosis (Table-1). A recent review by Rabban et al. succinctly summarizes the immunohistochemical differential diagnosis between sex cord stromal tumors and germ cell tumors using newer IHC markers (16). While PLAP is a fairly reliable marker for germ cell tumors like dysgerminoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma, SALL4 is a novel marker that has higher sensitivity for the above-mentioned tumors with the exception of choriocarcinoma. OCT4 is a transcription factor which is expressed in dysgerminoma and gonadoblastoma. Sex cord-stromal tumours including adult granulosa cell tumours are, however, negative for PLAP, OCT4 and SALL4. Glypican-3 is another new marker with high specificity for yolk sac tumors, and is not expressed in sex cord stromal tumors. Newer markers for the sex cord stromal family of tumors include SF-1 and FOXL2, which are highly specific and are not expressed by germ cell tumors.
In contrast to their more common juvenile counterparts that have a benign course and are cured by simple orchidectomy, adult TGCTs are believed to be potentially malignant tumors, which behave more aggressively than their namesakes in the ovary (2,3). Reports of metastases to lymph nodes as well as distant sites, even as late as ten years after initial surgery, have served to consolidate this opinion (10). Definitive criteria for malignancy are lacking, and identification of aggressive cases remains difficult. Few features have been proposed by Jimenez-Quintero et al. (10), including size greater than 7cm, lymphovascular invasion, necrosis, and hemorrhage, while Hanson et al. have suggested that tumors greater than 5cm may behave aggressively (3). However, it is not clear whether size of the entire tumor should be taken into consideration in tumors that are solid-cystic, or only the solid  areas. The role of MIB-1 LI (proliferation marker) in predicting malignant behavior is not clear and needs to be ascertained. As our case showed high MIB-1 LI, the patient was followed-up closely, but has remained free of disease one year post-surgery.
In conclusion, adult TGCTs are potentially malignant tumors that may have unusual clinical presentation occasionally. Recognition of these rare neoplasms and documentation of their behaviour is important from diagnostic, prognostic and therapeutic points of view. As delayed lymph nodal and distant metastases have been reported, patients need to be followed-up over a prolonged period after orchidectomy. Utility of MIB-1 LI in identification of tumors that may behave aggressively needs further evaluation.