Sex Cord-Stromal and Miscellaneous Tumors of the Ovary

Frequency

Fibroma/thecoma account for approximately 87% of all tumors in the stromal and sex cord–stromal group. These, along with adult granulosa cell tumors, SLCTs, and sclerosing stromal tumors (SSTs), account for approximately 99% of stromal and sex cord–stromal tumors. The remaining are exceedingly rare and are primarily the subject of case reports and small series.

Age

Subsets of stromal and sex cord–stromal tumors predominate in women within four age ranges. These include premenarchal, younger than 25 years old, 25 to 50 years old, and postmenopausal. Those most likely to occur in premenarchal girls are juvenile granulosa cell tumors (JGCTs). Between menarche and 25 years old, JGCTs and SLCTs predominate. In the 25- to 50-year age group, fibroma/thecoma and granulosa cell tumors are most common. Beyond menopause, in addition to fibromas and steroid cell tumors, rare malignancies such as fibrosarcomas emerge. Age incidence is a useful guideline to the pathologist who is faced with a stromal tumor on frozen section. However, all of these tumors can be seen over a wide age range.

Presenting Signs and Symptoms

The most common tumors (fibromas) present simply as a mass or with mass-related symptoms. Granulosa and SLCTs may, in addition, cause symptoms referable to hyperestrinism and hyperandrogenism (virilization), respectively, or in the case of steroid cell tumors, to either of these. Some are associated with specific syndromes or other tumors, such as Meigs or Gorlin syndrome (fibroma), Ollier disease or Maffucci syndrome (granulosa cell tumor), and either Peutz-Jeghers syndrome (PJS) or minimal deviation adenocarcinoma of the cervix (sex cord–stromal tumor with annular tubules).

Outcome

Table 27.2 summarizes the outcomes associated with stromal and sex cord–stromal tumors. These tumors are generally benign or behave as lower-risk malignancies with long survivals relative to epithelial tumors. The high-risk group includes granulosa cell tumors, the more poorly differentiated Sertoli-Leydig tumors, unclassified sex cord–stromal tumors, steroid cell tumors, and sex cord tumors with annular tubules that are not associated with PJS.

Definition

Fibromas are benign fibromatous tumors of varying cellularity with variable collagen deposition. Fibromas, including those showing partial thecomatous differentiation (so-called fibrothecomas), constitute the largest group of sex cord–stromal tumors, accounting for approximately 80% of this group.

The Patient at Risk

Fibromas can occur at any age but are uncommon in women under age 30, predominating in the fifth decade, with a mean age of 48 years old. Most are incidental findings discovered at the time of surgery for other causes, but if they produce symptoms, the most common is abdominal pain. They may be associated with Meigs syndrome (ascites and pleural effusion), particularly when they are large (>10 cm), and nevoid basal cell syndrome (also known as Gorlin syndrome , an autosomal-dominant disorder characterized by developmental defects of the skeletal system and a predisposition to develop multiple basal cell carcinomas and ovarian fibromas) but are not linked to appreciable hormonal activity.

Gross Features

Fibromas are typically unilateral; nevertheless, they represent the most common sex cord–stromal tumor to involve both ovaries. Ovarian fibromas resected at Brigham and Women's Hospital over 1 year ranged in size from less than 1 to 16 cm, with an average size of 3.8 cm. More than 80% were greater than 5 cm, and 9% were bilateral. They typically have a smooth or slightly lobulated surface. They are characteristically solid with a firm, white to tan cut surface ( Fig. 27.7A ). Edema, cyst formation, and calcification are not uncommon; the latter is seen in up to 10% of tumors. Infarction and hemorrhage may be present but are uncommon. Of note, fibromas associated with Gorlin syndrome are more commonly bilateral (≈75%), have a multinodular growth pattern, and are more frequently associated with calcifications (see Fig. 27.7B ).

Histopathology

The bland spindle-shaped tumor cells, which are typically arranged in a swirling (storiform) pattern, are uniformly distributed with varying, but typically mild to moderate cellularity ( Fig. 27.8A ). The nuclei are small and elongated with tapered ends and have inconspicuous nucleoli. Cytologic atypia is absent, and mitotic figures are usually infrequent. Calcified plaques and bands of hyaline fibrosis are common (see Fig. 27.8B ).

A rare finding is the presence of sex cord–like differentiation comprising less than 10% of the tumor, which typically appears as discrete tubules or epithelioid cords within the spindled stroma ( Fig. 27.9 ). Tumors with these features have been termed “fibroma with minor sex cord elements.” Although the presence of sex cord–like structures is a potential cause for confusion in the differential diagnosis with other sex cord–stromal tumors, particularly granulosa and Sertoli cell tumors, their presence in fibromas does not alter patient outcome. Other unusual features include bizarre nuclei, intracytoplasmic hyaline droplets, and Verocay-like areas.

Fibromas are typically positive for SF1, FOXL2 (but lack the mutation), CD56, WT-1, ER, and PR but usually negative for CD10. They may be smooth muscle actin, calretinin, and inhibin positive although typically not diffusely; desmin and CD34 are usually negative.

Differential Diagnosis

Typical fibromas are easily recognized, although small ones may be confused with hypercellular ovarian cortex seen in polycystic ovarian disease or stromal hyperplasia/hyperthecosis. In some instances, it may be impossible to distinguish these latter entities from microscopic fibromas ( Fig. 27.10 ). The preservation of ovarian architecture and atretic follicles in the stroma of these entities will distinguish them from fibroma. However, a diagnosis of “microscopic cortical fibroma” is appropriate if the changes are discrete. Fibromas should also be distinguished from thecoma, although these two tumors may show significant morphologic overlap, which has led to use of the term fibrothecoma . Of note, this terminology is not recognized by the 2014 WHO; however, we still believe it is a practical term in some scenarios. In contrast to thecoma, fibromas typically lack a nodular growth pattern and cells with abundant pale to vacuolated cytoplasm. Moreover, they usually do not show the same degree of positivity for inhibin and are typically negative for CD10.

Management and Outcome

Conventional-appearing fibromas typically do not recur and are cured by simple excision.

Definition and Background

Cellular fibromas and fibrosarcomas will be discussed together, inasmuch as the pathologist must distinguish the two whenever he or she encounters a “fibroma” with increased cellularity and mitotic activity. The term cellular fibroma is used to describe fibromas with increased cellularity similar to that seen in diffuse-type adult granulosa cell tumor. In comparison to the frequency of conventional fibroma, cellular fibroma and fibrosarcoma are much less common, with cellular fibroma accounting for approximately 10% of all ovarian fibromas.

The Patient at Risk

Similar to conventional fibromas, cellular fibroma and fibrosarcoma predominate in the fifth decade, although fibrosarcoma tends to occur in older women; one fibrosarcoma in a child has been linked to the basal cell nevus syndrome.

Gross Features

Cellular fibroma and fibrosarcoma are typically unilateral tumors, and both are usually larger in size than conventional fibromas. Moreover, cellular fibromas may also have a softer consistency and a tan to yellow color rather than the firm, white appearance of a conventional fibroma ( Fig. 27.11A ). In addition, cellular fibromas tend to more commonly be associated with rupture and surface adhesions. Fibrosarcomas, which can be solid or partially cystic, are also usually softer and more commonly associated with hemorrhage and necrosis (see Fig. 27.11B ).

Histology

Cellular fibromas and fibrosarcomas are composed of a densely packed proliferation of spindle cells, with a storiform or herringbone growth pattern. The histologic diagnosis of either requires attention to the following.

Fibroma Versus Cellular Fibroma

In contrast to conventional fibroma, cellular fibromas show increased cellularity similar to that of the diffuse-type adult granulosa cell tumor ( Fig. 27.12A and B ). Often these tumors are not uniformly cellular and have areas typical of conventional fibroma, although they tend to lack the hyaline bands and edema that is frequently associated with the latter.