Cystic Granulosa Cell Tumors of the Ovary: An Analysis of 80 Cases of an Often Diagnostically Challenging Entity

Abstract

Context.— Granulosa cell tumors (GCTs) of both adult (AGCT) and juvenile (JGCT) types can rarely be completely or dominantly cystic, creating diagnostic difficulty because the cyst lining epithelium is often denuded. Objective.— To describe clinical, gross, microscopic, immunohistochemical, and molecular features of cystic GCTs with an emphasis on their differential diagnosis. Design.— We report 80 cystic GCTs (24 AGCTs and 56 JGCTs) in patients from ages 3 to 83 years (average ages, 35 years for AGCT and 22 years for JGCT). Results.— Nineteen of 43 patients with known clinical information (3 AGCT and 16 JGCT) had androgenic manifestations. All tumors were greater than 8 cm (average, 17 cm) with minimal to absent gross solid component. Denudation of cells lining the cysts was prominent. Invagination of the epithelium into the cyst walls was a key diagnostic feature and was present as cords, trabeculae, solid nests, and small and large follicles and was identified in most tumors (17 AGCTs and 45 JGCTs). Cytologic atypia was essentially absent in AGCTs, whereas 14 JGCTs showed moderate to severe atypia of bizarre type. A theca cell component was present in all tumors and was extensive in 54. A FOXL2 hotspot mutation was identified in 1 of 4 AGCTs tested. Conclusions.— Despite extensive denudation, the finding of typical architectural patterns and cytologic features as well as, in some cases, androgenic manifestations helps differentiate cystic GCTs from follicle cysts, the most common and challenging differential diagnosis, as well as other cystic neoplasms that may enter the differential diagnosis. FOXL2 sequencing may show a false-negative result in cystic AGCT because of the limited number of cells present within the tumor sample.

Adult Granulosa Cell Tumour With Heterologous Adipocytic Differentiation: Report of a Unique Case

“…The presence of these different architectural patterns may be a clue to diagnosis but may also result in consideration of a variety of other neoplasms. Morphologic "variants" of AGCT which may result in problems in diagnosis include luteinized variants, diffuse variants with a spindle cell morphology, predominantly cystic variants, thecoma-like variants, variants with "high-grade" transformation and tumors with a prominent fibrothecomatous component (previously referred to as granulosa-theca cell tumor) (12)(13)(14)(15)(16). As discussed previously, AGCTs may also contain heterologous elements, which in the published literature have been confined to mucinous epithelium and hepatocytes (4-8).…”

Sex Cord-Stromal Tumors of the Ovary: An Update and Review. Part II — Pure Sex Cord and Sex Cord-Stromal Tumors

“…[12][13][14] These tumors are typically unilateral with solid or solid and cystic cut surfaces, although rarely they are predominantly cystic. 15 Solid areas are variably white to tan and/or yellow with foci of hemorrhage; cysts often contain hemorrhagic fluid. Some tumors have pale to golden yellow nodules on a white firm background, at times imparting a pseudolobular appearance.…”

“…Ruptured follicle cysts are almost invariably smaller with a thin and delicate wall, and their lining cells do not show nuclear grooves while AGCTs typically show expansion of the granulosa cell layer, often with focal cords and trabeculae seen within the wall. 15 Cystic AGCTs may show partial attenuation and extensive denudation of the lining granulosa cells, generating a nonspecific appearance and potentially may mimic a simple cyst. Tangential section through a Graafian follicle may mimic a small AGCT, a problem that may be further complicated by its brisk mitotic activity.…”

False‐positive inhibin B leading to oophorectomy for a benign cyst: An unusual trap

“…Most of the tumors encountered present as solid or mixed lesions upon ultrasound, except teratoma and juvenile granulosa cell tumor (JGCT) that may be cystic. 2,3 Surgical strategy, conservative or not, is then chosen according to these complementary exams, keeping in mind the low malignancy prevalence in the pediatric population with adnexal torsion. 4 We report a very unusual case of false-positive inhibin B level, which led to inappropriate oophorectomy.…”

“…The potential cystic nature of JGCT has been reported, although usually the cysts are numerous and voluminous, as opposed to the reported case. 2,9 However, some authors suggest that the diagnosis should be suspected even in unilocular lesions. 2 In our particular situation, recent amenorrhea, which is a classical sign of hormonal disturbance induced by a JGCT but also of an ovarian cyst, triggered the prescription of tumor marker assays.…”