Clinical history: 53 y/o female with remote history of ovarian tumour. Now has a large retroperitoneal mass.
What is your diagnosis?
Discussion and answer
Diagnosis: Adult granulosa cell tumour (AGCT) with ovarian primary
This tumour is the most frequent among sex cord-stromal tumours with an annual incidence of 0.5–1.5 cases per 100,000 women and accounts for approximately 2–3% of primary ovarian tumours.
Adult granulosa cell tumours can occur at any age, but are most common in peri- and postmenopausal women. They are the most common ovarian tumour associated with estrogenic manifestations. Because of estrogen production, patients frequently present with menometrorrhagia or postmenopausal bleeding, and they are at risk for concurrent endometrial hyperplasia (up to 50%) and adenocarcinoma (up to 10%).
Other common presentations include abdominal pain and the presence of a pelvic mass.
The vast majority of these tumours are unilateral (> 95%). They range from microscopic incidental findings to 30 cm in maximum dimension, with an average size of 12 cm. The tumours are predominantly solid or solid and cystic with a yellow to white cut surface. Occasional tumours consist of uni- or multilocular cysts which tend to be smooth-walled and filled with serous to sanguineous fluid.
The neoplastic cells can be arranged in a number of different patterns and frequently there is a combination of patterns in the same tumour. A diffuse or solid growth of cells is most frequent, followed by trabecular (cords), microfollicular, macrofollicular, and insular patterns; gyriform and watered silk patterns are less common. Call–Exner bodies, the hallmark of the microfollicular pattern, are microcystic spaces that can contain deeply eosinophilic basal lamina material.
The neoplastic granulosa cells generally have scant cytoplasm and round to oval or angular nuclei with a longitudinal groove. Nuclear grooves, however, are not limited to AGCT (also seen in Brenner tumours, some Sertoli cell tumours, cellular fibromas, and transitional cell carcinomas) and may be present only in scattered cells in some cases. Mitotic activity is variable, but typically < 5/10 HPFs in the majority of AGCTs.
Inhibin and calretinin are sensitive markers of AGCT. While one or the other may be negative or sparsely expressed, it is unusual to find a tumour negative for both markers. Vimentin is universally expressed and WT1 and CD99 stain the majority of tumours, showing nuclear and membranous staining respectively. These tumours have also been reported to be CD56 positive. Cytokeratin AE1/3-Cam5.2 (punctate), smooth muscle actin, desmin, S100, ER, and PR also show variable positivity, but EMA and CK7 are typically negative. Areas of hepatic differentiation are CEA, EMA, Cam 5.2, and AFP positive but negative for Inhibin and Vimentin.