SEX CORD STROMAL TUMOR WITH COMBINED POORLY DIFFERENTIATED JUVENILE GRANULOSA AND SERTOLI LEYDIG DIFFERENTIATION
RECURRENT SEX CORD STROMAL TUMOR WITH METASTATIC SEROSAL IMPLANTATION OF SIGMOID COLON EPIPLOICA AND OMENTUM
Sex cord stromal tumors represent approximately 8% of all ovarian tumors (1). They may be composed of cells of ovarian origin (e.g. granulosa - stromal cells) or testicular origin (Sertoli - stromal cells). At times the neoplastic cells are immature and show no further differentiation with morphology intermediate between testicular and ovarian cell types or architectural patterns non-specific to either the testis or the ovary (1). In such cases it may be impossible to determine the category of the tumor, whether it belongs to the Granulosa - stromal or Sertoli - stromal category. In such circumstances the term sex cord - stromal tumor, unclassified introduced by WHO can be used (1).
This case is interesting because initial ovarian tumor had combined poorly differentiated juvenile granulosa cells and Sertoli Leydig cell differentiation. However when it recurred, the tumor was less differentiated and showed mostly monotonous arrangements of small cells without Sertoli like tubular structures or Leydig cell nests (Figures 5 &6). This can be a diagnostic dilemma, if the tumor presents as an undifferentiated sex cord stromal tumor, with no definitive features of granulosa stromal cells or Sertoli stromal cells. Most of the sex cord stromal tumor of the ovary can be easily classified. However about 10% of the sex cord stromal tumors are difficult to classify (2) especially when they have a low degree of differentiation with an overall feature that prevents their placement in either the Granulosa or Sertoli Leydig category (2).
This case emphasizes the importance of sampling of gonadal stromal tumors. Undersampling of the neoplasm can lead to classification problems. A clinicopathologic retrospective study of 32 cases of unclassified ovarian gonadal stromal tumors showed that even with two sections per centimeter of maximum tumor dimension, 13 tumors (41%) were undersampled (2).
The commonly available immunohistochemical tests which can be used in the diagnosis of the neoplasm consists of vimentin, keratin, epithelial membrane antigen (EMA), desmin, smooth muscle actin (SMA), S-100 and inhibin (3). Sex cord stromal tumors were previously believed to be neoplasms of mesenchymal or stromal origin and therefore were expected to express vimentin and not keratin or desmin (3). However since sex cord stromal tumors are complex neoplasms which can have smooth muscle phenotype and can variably express cytokeratin, actin and desmin as part of its differentiating phenotype (3). As a result, sex cord stromal tumors can have variable staining with cytokeratin, actin and desmin. Studies have shown that they also show S-100 immunoreactivity, where it is reported to be positive in 33 to 85 % of granulosa cell tumors, but not in other sex cord stromal tumors (3). When using immunohistochemical panel, universal absence of staining of sex cord stromal tumor with epithelial membrane antigen and strong positive inhibin reaction of almost all sex cord stromal tumors and granulosa cell tumors is significant (3). Studies have shown that inhibin greatly improves the accuracy of the diagnosis (3).
Some of the mimickers of sex cord stromal tumors are endometrioid type adenocarcinoma, poorly differentiated primary or metastatic carcinoma and carcinosarcoma (3). All these neoplasm are EMA positive, Inhibin negative (3), while the sex cord stromal tumors are EMA negative, Inhibin positive (3). This is important because the prognosis, treatment and follow-up of the above tumors are different from sex cord stromal tumors (3).
Only 0.1% of all ovarian tumors occur in children (4). Despite their rarity, they are of great clinical interest because of their endocrine effects and possible malignant potential. The endocrine presentation consists of sexual precocity and virilization (4). In a review of 17 cases in Emik Novak Ovarian Tumor Registry (5), 80% of the children with isosexual precocity were diagnosed with granulosa cell and theca cell tumor (5). After the removal of the tumor, the sexual precocity subsided with a physiologic puberty at the normal expected age (5). This patient did not have hormonal manifestations.
Most of the sex cord tumors behave in a benign fashion, except for granulosa cell tumors, which can have late recurrences as well as distant metastasis (6). The most important prognostic factor is the tumor stage at presentation and the degree of differentiation of the tumor. This is important because poorly differentiated tumors require postoperative chemotherapy (6). In a series done by Scully and Young, 59 % of poorly differentiated sex cord stromal tumors had malignant components while only 11 % of tumors with intermediate differentiation and 19% of tumors with heterogenous components of sex cord stromal tumors had evidence of malignancy (6). In this series none of the well differentiated tumors behaved in malignant fashion (6).
In conclusion, the diagnosis of sex cord stromal tumors should be made after excluding the other possible mimicking neoplasms. Immunohistochemistry can aid in the diagnosis. The stage and degree of differentiation is important for further prognosis and follow up.
Contributed by Leena T. Lourduraj, MD, Manju Nath, MD and Dilip Gupta, MD