Extraovarian granulosa cell tumor.

Granulosa cell tumor (GCT) of the ovary is a rare tumor representing 2-5% of all ovarian neoplasms.[] It can recur or metastasize many years after initial treatment. Rarely, GCT can develop at an extraovarian site, even in an oophorectomized patient. One such rare case of extraovarian GCT in a 58-year-old patient who had undergone oophorectomy 20 years ago is being reported. Until 2001, only eight cases of such tumors have been reported in the English literature.[] CASE REPORT A 58-year-old woman presented with pain in the right side of the abdomen for 9 months. On clinical examination, a lump was identified involving the right lumbar region, measuring 8cm × 9cm, with ill-defined margins. The patient had undergone hysterectomy with bilateral salpingooophorectomy 20 years ago because of uterine leiomyoma. The ovaries were reported as normal on histopathology. No hormone replacement therapy was prescribed as per clinical records. A computerized tomography scan of the abdomen revealed a well-defined heterogenous mass measuring 15cm × 16cm with areas of necrosis, displacing aorta, inferior vena cava and right kidney as well as pushing the pancreas anteriorly. There was another mesenteric mass of heterogenous echotexture measuring 8cm × 5cm. Ultrasonography-guided fine needle aspiration cytology smears from both masses revealed high cellularity composed of uniform-looking round to oval cells present as aggregates as well as singly. In some foci, the tumor cells formed glandular structures containing central globular amorphous material stained magenta on May Grunwald-Giemsa stain [Figure 1] and green-blue on papanicolaou stain. The cells had scanty cytoplasm and finely granular nuclear chromatin. Based on cytomorphology, the lesion was diagnosed as GCT. The patient underwent laparotomy and excision of mesenteric and retroperitoneal masses was performed. Grossly, the mesenteric mass was encapsulated, grayish-brown, measuring 8cm × 4.5cm × 5cm. The cut surface was predominantly solid, homogenous and grayish with some hemorrhagic areas along with small cystic foci. The retroperitoneal mass comprised of multiple grayish-brown fleshy pieces of tissue, partly encapsulated, collectively measuring 13cm × 15cm × 8cm. There were extensive areas of hemorrhage and necrosis. Microscopic examination of both lesions showed a tumor having cells with scanty cytoplasm and pale, round to oval nuclei. Nuclear grooves were identified in many of the cells [Figure 2]. The cells were arranged in microfollicular, trabecular and diffuse patterns. Mitotic figures were rare. There were large areas of necrosis. The tumor cells stained positive with antibodies to α-inhibin of BioGenix, Hyderabad, India, source mouse, clone R1 [Figure 3] and were negative for epithelial membrane antigen (EMA), also of BioGenex (Hyderabad, India), source mouse, clone E29 and Mc-5. Considering the location, typical cytological and histological morphology, positive inhibin immunostain and absence of past history of granulosa cell tumor, the lesion was diagnosed as extraovarian GCT, adult type.

GCT, an uncommon ovarian cancer,[] can be of adult or juvenile type based on different clinical and histological features. The more common adult type of GCT usually presents during the perimenopausal or the early menopausal period, the median age being 50-54 years.[] Patients with GCT require long-term follow-up with history, physical examination and tumor marker studies because 17% of relapses occur more than 10 years after diagnosis.[] The most common site of recurrence is in the pelvis. Rarely, extraovarian GCT can develop. Eight such cases have so far been reported in the English literature till 2001[] of which one was reported from India.[] Four cases originated from the broad ligament, three from the retroperitoneum and one case from the adrenal.[] Recently, one case of GCT arising in a müllerian cyst of the broad ligament has been reported.[] The histogenetic origin of extraovarian sex-cord stromal tumors is thought to be from the ectopic gonadal stromal tissue, with the sex-cord originating from the mesonephros. A possible dual origin from both coelomic epithelium and mesonephros has also been proposed.[] Mesonephros or its influence seems to be necessary for creating the sex-cord. This may explain the sites of extraovarian sex-cord stromal tumors being limited to the broad ligament, the retroperitoneum and the adrenal gland, all of which differentiate close to the mesonephros and the mesonephric duct.[] The cytological smears of a GCT are usually cellular, the cells being present in loose aggregates, follicular groupings and some in a dispersed fashion. The cells have scanty to moderate pale cytoplasm and monomorphic round to oval nuclei having longitudinal grooves and granular chromatin. The characteristic amorphous globular structures called Call-Exner bodies are present in some GCTs.[] The present case had identical cytological features. Typical histological findings of a GCT include small, pale, round to oval granulosa cells with characteristic 'Coffee-bean' nuclei. Call-Exner bodies are present in 30-60% of the cases. A variety of histological patterns, e.g. microfollicular, trabecular, insular, diffuse or mixture of these patterns are often found.[] Similar histologic findings were noted in the present case - with a predominantly diffuse and microfollicular pattern. The morphological differential diagnosis of GCT includes undifferentiated carcinoma, small cell carcinoma and endometrial stromal sarcoma.[] However, characteristic histological findings and immunostains are helpful in definitive diagnosis. A number of tumor markers are used for confirmation of histologic diagnosis of GCT, an important one being inhibin.[] The ovary is the only source in non-pregnant woman whereas in pregnancy, the placenta secretes inhibin. It has been found to be a more reliable marker for GCT than estradiol.[] Although an elevated inhibin level may be observed in some epithelial ovarian cancers, these may be confirmed by their EMA positivity, which is negative in GCT.[] In the present case, strong positivity for inhibin with a negative EMA stain confirmed the diagnosis of GCT. Recently, Activin B has been introduced as a new marker for post-operative follow-up of patients suffering from GCT.[] The patient presented with two separate intraabdominal masses, which is apparently unusual for a primary tumor. Because GCT can recur or metastasize years after initial diagnosis and treatment, there is a strong possibility of metastatic deposit in intraabdominal sites. As slides of the excised ovaries are not available for thorough review, the possibility of late metastasis of a low-grade GCT cannot be entirely excluded. However, as there was no evidence of GCT of the ovary in the previous histopathology report, the diagnosis of extraovarian GCT was considered to be the most appropriate. In conclusion, GCT can arise in locations other than the ovary and is said to be derived from the mesenchyme of the genital ridge. Thus, women who have undergone oophorectomy may develop GCT from an extraovarian location. A diagnosis of extraovarian GCT can be made by excluding any previous history of GCT of the ovary. Immunostains help in differentiating GCT from other neoplasms. Source of Support: Nil Conflict of Interest: None declared.

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