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Adult Granulosa Cell Tumor of the Testis Masquerading As Hydrocele ______ CHALLENGING CLINICAL CASES Vol. 41 (6): 1226-1231, November . December, 2015 doi: 10.1590/S1677-5538.IBJU.2014.0187 Adult granulosa cell tumor of the testis masquerading as hydrocele _______________________________________________ Archana George Vallonthaiel 1, Aanchal Kakkar 1, Animesh Singh 2, Prem N Dogra 2, Ruma Ray 1 1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India; 2 Departments of Urology, All India Institute of Medical Sciences, New Delhi, India ABSTRACT ARTICLE INFO ______________________________________________________________ ______________________ Adult testicular granulosa cell tumor is a rare, potentially malignant sex cord-stromal Key words: tumor, of which 30 cases have been described to date. We report the case of a 43-year- Granulosa Cell Tumor; Sex -old male who complained of a left testicular swelling. Scrotal ultrasound showed a Cord-Gonadal Stromal Tumors; cystic lesion, suggestive of hydrocele. However, due to a clinical suspicion of a solid- Testis; Immunohistochemistry; -cystic neoplasm, a high inguinal orchidectomy was performed, which, on pathological Neoplasms, Germ Cell and examination, was diagnosed as adult granulosa cell tumor. Embryonal Adult testicular granulosa cell tumors have aggressive behaviour as compared to their ovarian counterparts. They may rarely be predominantly cystic and present as hydroce- Int Braz J Urol. 2015; 41: 1226-31 le. 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 the- Submitted for publication: rapeutic point of view. March 15, 2014 _____________________ Accepted after revision: June 04, 2014 INTRODUCTION Case Report This 43 years old male, under follow-up in While granulosa cell tumor represents the the Urology clinic for stone disease, complained most common sex cord-stromal tumor arising in of painless, progressively increasing left testicular the ovary (1), and juvenile testicular granulosa cell swelling for two months. On physical examina- tumor (TGCT) is the commonest sex cord-stromal tion, vitals were stable. No abdominal distension tumor seen in male children, adult TGCT remains or mass was noted. Peripheral lymphadenopathy an enigmatic entity. Due to its rarity, not much is was absent. Left testicular enlargement was iden- known about its natural course; however, literature tified, caused by a cystic scrotal swelling. Scrotal suggests that adult TGCTs are slow-growing neo- ultrasound (Figure-1a) showed an anechoic cystic plasms with potential for lymph node metastasis, lesion measuring 5.5cm x 3.4cm, with nodular soft even many years after initial diagnosis. We report tissue shadows at the periphery and only a thin a case of this rare tumor which was predominantly rim of testicular tissue. Based on ultrasonography, cystic, causing a diagnostic dilemma clinically, and differential diagnoses included intra-testicular ultimately diagnosed on histopathology. cystic neoplasm and a cystic lesion compressing 1226 IBJU | ADULT TESTICULAR GRANULOSA CELL TUMOR the testis. On investigation, routine haematologi- x 4.5cm, with attached spermatic cord measuring cal and biochemical parameters, as well as serum 6cm. A predominantly cystic tumor (Figure-2a) alpha-fetoprotein (AFP), lactate dehydrogenase measuring 6cm x 3.5cm x 2.5cm was identified, and human chorionic gonadotropin levels were almost completely replacing the testis, with a thin within normal limits. The patient was counselled rim of compressed normal testicular parenchyma for and submitted to a high-inguinal orchidec- at the lower pole. Cysts varied from 0.5cm to 5cm tomy. Post-operative period was uneventful. The in diameter, were smooth-walled, and contained patient is doing well one year after surgery. CT clear fluid. Few solid nodules, 0.4cm to 1cm in abdomen revealed no retroperitoneal lymphade- maximum dimension, were seen within the cyst nopathy (Figure-1b). walls (Figure-2b). The tumor did not appear to in- filtrate the tunica albuginea. No areas of hemor- Pathological examination rhage or necrosis were identified. Left high inguinal orchidectomy speci- On microscopic examination (Figure-3), men comprised of testis measuring 8cm x 5.5cm the tumor was well-circumscribed, unencapsu- Figure 1 - Scrotal ultrasound showing a cystic lesion with nodular soft tissue shadows at the periphery (a). CT abdomen one year post-surgery shows no lymphadenopathy (b). A B Figure 2 - Orchidectomy specimen showing a solid cystic tumor (a); multiple cysts with few small nodules (arrows) are seen, along with a rim of normal testicular parenchyma (N) at the periphery (b). A B 1227 IBJU | ADULT TESTICULAR GRANULOSA CELL TUMOR Figure 3 - Photomicrographs showing solid areas of tumor along with compressed seminiferous tubules at the periphery (a; HE, x40); tumor cells were arranged in trabeculae and microfollicles, had scant cytoplasm and ovoid nuclei with grooves (b; HE, x400); frequent mitotic figures seen (c; HE, x400). Tumor cells were positive for inhibin (d), MIC2 (e), calretinin (f) and vimentin (g), MIB1-LI was high (h); EMA (i), AFP (j), synaptophysin (k) and CD117 (l) were negative (IHC, x400) A B C D E F G H I J K L 1228 IBJU | ADULT TESTICULAR GRANULOSA CELL TUMOR lated, and was composed of monomorphic cells non-Hodgkin lymphoma and neuroendocrine tu- arranged in sheets and trabeculae. Focally, mi- mors difficult. Microfollicular, macrofollicular, tra- crofollicular structures (Call-Exner bodies) were becular, and insular growth patterns are common- seen. Tumor cells had scant cytoplasm, ill-defined ly observed (3). Typical Call-Exner bodies may or cytoplasmic borders, and ovoid medium-sized nu- may not be present. These tumors are immunopo- clei with fine chromatin and inconspicuous nu- sitive for vimentin, inhibin, MIC2, calretinin, and cleoli. Longitudinal nuclear grooves were seen smooth muscle actin (3), and are usually negative at places. Frequent mitotic figures (8-10/10 high for CK, EMA, LCA, synaptophysin, chromogranin, power fields) were identified. No necrosis, lym- PLAP, and AFP (9). Morphological features along phovascular invasion or pseudosarcomatous areas with immunohistochemistry help in clinching the were present. On immunohistochemistry, tumor correct diagnosis (Table-1). A recent review by Ra- cells were diffusely immunopositive for vimentin, bban et al. succinctly summarizes the immunohis- inhibin, MIC2, and calretinin. They were negati- tochemical differential diagnosis between sex cord ve for pancytokeratin (CK), epithelial membrane stromal tumors and germ cell tumors using newer antigen (EMA), leukocyte common antigen (LCA), IHC markers (16). While PLAP is a fairly reliable AFP, placental alkaline phosphatise (PLAP), CD117 marker for germ cell tumors like dysgerminoma, and synaptophysin. MIB-1 labelling index (LI) was yolk sac tumor, choriocarcinoma, and embryonal high (18% in highest proliferating areas). Based carcinoma, SALL4 is a novel marker that has hi- on histomorphological and immunohistochemical gher sensitivity for the above-mentioned tumors features, a diagnosis of adult granulosa cell tumor with the exception of choriocarcinoma. OCT4 is a of the testis was made. Section from resected end transcription factor which is expressed in dysger- of spermatic cord was free of tumor. minoma and gonadoblastoma. Sex cord-stromal tumours including adult granulosa cell tumours DISCUSSION are, however, negative for PLAP, OCT4 and SALL4. Glypican-3 is another new marker with high spe- Adult testicular granulosa cell tumor cificity for yolk sac tumors, and is not expressed (TGCT) is a rare sex cord-stromal neoplasm arising in sex cord stromal tumors. Newer markers for the in the testes, of which thirty cases have been re- sex cord stromal family of tumors include SF-1 ported until now (2-15). Majority of patients pre- and FOXL2, which are highly specific and are not sent with testicular enlargement which is painless expressed by germ cell tumors. and of variable duration (3). Some may present In contrast to their more common juveni- with features of hormonal dysregulation, like gy- le counterparts that have a benign course and are naecomastia (4, 5). In some instances, however, cured by simple orchidectomy, adult TGCTs are be- this tumor may be detected incidentally, as in our lieved to be potentially malignant tumors, which case (6). The age range at presentation is wide, behave more aggressively than their namesakes in varying from 16 to 77 years (2). the ovary (2, 3). Reports of metastases to lymph no- Adult TGCTs occur as solid, circumscri- des as well as distant sites, even as late as ten years bed tumors, in contrast to the multicystic juvenile after initial surgery, have served to consolidate this TGCTs. While it is not unusual to identify small opinion (10). Definitive criteria for malignancy are cystic foci within adult TGCTs (1), predominantly lacking, and identification of aggressive cases re- cystic tumors are rarely encountered, contributing mains difficult. Few features have been proposed by to lack of suspicion of this diagnosis preoperative- Jimenez-Quintero et al. (10), including size greater ly, as in the case under discussion. Only two cases than 7cm, lymphovascular invasion, necrosis, and have been previously documented as presenting hemorrhage, while Hanson et al. have suggested with hydrocele on the same side of
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