Which histologic findings are characteristic of granulosa cell tumors (GCTs) of the ovaries?

Updated: Aug 30, 2018
  • Author: David C Starks, MD, MPH; Chief Editor: Warner K Huh, MD  more...
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Grossly, tumors can be cystic, solid, or a mixture of both. On cut section, they usually are multicystic and may contain areas of hemorrhage. Solid tumors appear grayish if they are nonsteroidogenic or yellow if they are steroid-producing neoplasms. Androgen-producing tumors more commonly are unilocular or solid in contrast to the multilocular tumors that make up most GCTs.

Microscopically, GCTs are composed of granulosa cells, theca cells, and fibroblasts in varying amounts and combinations. The term granulosa-theca cell tumor had been applied to all tumors in which both cell types were identified, regardless of the amounts present. Young and Scully proposed a system that required a tumor to be composed of at least 25% of the second cell type before the tumor could be designated as a true granulosa-theca cell tumor. [11] Otherwise, the tumor would be designated as a granulosa cell tumor or a theca cell tumor based on the predominant cell type. This has led to some confusion in the literature because some theca cell tumors, which are essentially benign neoplasms, have been given the dual designation of granulosa-theca cell tumors, suggesting a malignant potential among this benign group of tumors.

AGCTs have multiple histomorphologies, including well-differentiated and less well-differentiated types. The well-differentiated group is composed of microfollicular, macrofollicular, trabecular, and insular patterns. Microfollicular is the most common pattern of all of these subtypes and contains characteristic Call-Exner bodies. These bodies consist of small rings of granulosa cells surrounding eosinophilic fluid and basement membrane material (see image below).

Microfollicular pattern of an adult granulosa cell Microfollicular pattern of an adult granulosa cell tumor at 100X magnification. Inset is characteristic Call-Exner bodies and nuclear grooves (400X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.

Macrofollicular GCTs are composed of a large cyst or collection of large cysts, each lined by a single layer of granulosa cells. Trabecular and insular patterns have cells arranged in nests and bands, with an intervening fibrothecomatous stroma found in the trabecular type.

The less well-differentiated group includes diffuse and watered-silk (moiré) or gyriform patterns. Monotonous sheets of cells arranged in no distinguishable pattern characterize the diffuse subtype (see image below).

Less well-differentiated diffuse pattern of adult Less well-differentiated diffuse pattern of adult granulosa cell tumor. Monotonous pattern can be confused with low-grade stromal sarcoma (200X). Inset is high-power magnification demonstrating nuclear grooves and nuclear atypia. Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.

Watered-silk and gyriform patterns have cells that often line up single-file in undulating lines (see image below).

Gyriform pattern of adult granulosa cell tumor. Un Gyriform pattern of adult granulosa cell tumor. Undulating single-file rows of granulosa cells (200X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.

The nuclear appearance is the same in both groups of adult GCTs. The nuclei usually are large pale ovoid or angular structures containing nuclear grooves that give them a "coffee-bean" appearance (see image below).

Microfollicular pattern of an adult granulosa cell Microfollicular pattern of an adult granulosa cell tumor at 100X magnification. Inset is characteristic Call-Exner bodies and nuclear grooves (400X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.

Usually only a small amount of cytoplasm is present, although luteinization of the tumor, characterized by larger amounts of dense cytoplasm with occasional vacuoles, sometimes can be found. Mitotic figures generally are few in number, and only mild nuclear atypia is found in most cases. Nuclear appearance and mitotic rate often are the key elements differentiating GCTs from other malignant tumors. Low-grade stromal sarcomas, small cell carcinomas, carcinoid tumors, and melanomas may look similar to GCTs on low power, but these other tumors lack nuclear grooves, are more hyperchromatic, and often contain more mitotic figures than GCTs.

JGCTs have little morphologic similarity to those of the adult type. However, their gross appearance can be similar to AGCTs in that they often are a mixture of solid and cystic components with many areas of hemorrhage. Microscopically, they have a distinct appearance with round hyperchromatic nuclei, most often lacking the nuclear grooves found in the adult type (see image below). Nuclear atypia often is more severe with more mitotic figures than are found in the adult type, consistent with their more aggressive phenotype. The cytoplasm often is more abundant and dense in JGCTs.

Juvenile granulosa cell tumor. Multiple follicles Juvenile granulosa cell tumor. Multiple follicles in various shapes and sizes (200X). Inset shows nuclei that are rounded, hyperchromatic, lacking grooves and showing atypia, and are abnormal mitotic figures (400X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.

Thecomas usually are tan or yellow with an average size of 7-8 cm. These tumors are bilateral in fewer than 3% of cases. Microscopically, they are composed of round or ovoid cells with pale nuclei and a lipid-rich cytoplasm. Mitoses usually are less than 4 per 10 high-power fields. Hyaline bands often are found interspersed between cells (see image below).

Theca cell tumor. Typical thecoma with lipid-rich Theca cell tumor. Typical thecoma with lipid-rich cytoplasm, pale nuclei, and intervening hyaline bands (200X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.

Luteinized thecomas also contain cells with a lipid-rich cytoplasm but are set within a more fibromatous stroma (see image below). Most of these tumors are hormone-producing tumors and cause postmenopausal bleeding in as many as two thirds of patients. Luteinized thecomas also may be androgenic and, if so, tend to occur in younger women.

Luteinized thecoma. Vacuolated theca cells with an Luteinized thecoma. Vacuolated theca cells with an abundant fibromatous stroma (200X). Image courtesy of James B. Farnum, MD, TriHealth Department of Pathology.

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