Adult Granulosa Cell Tumors of the Ovary With Tubular Differentiation

Occasional ovarian sex cord-stromal tumors exhibit features suggestive of more than 1 subtype, including some with areas of both "female" (granulosa) and "male" (Sertoli and/or Leydig) cell types. These tumors, historically often referred to as "gynandroblastomas," are frequently difficult to classify due to considerable clinical and morphologic heterogeneity. Herein, we describe a particular pattern of differentiation in which tubules occurred within tumors whose overall clinicopathologic features indicate that they are best characterized as adult granulosa cell tumors (AGCT). Eighty tumors were identified. Patient ages ranged from 15 to 87 (median: 52) years, and 28 had endocrine manifestations (25 estrogenic; 3 androgenic). Follow-up was available in 13 patients and ranged from 10 to 266 (median: 60) months, disclosing recurrence in 2. Microscopically, all tumors not only contained areas of typical granulosa cell morphology (diffuse, trabecular, corded, and others), which often dominated, but also contained variable amounts of hollow and/or solid tubules resembling those seen in Sertoli cell tumors. Next-generation sequencing was successful in 11 tumors. Two of these harbored FOXL2 p.C134W variants, and 2 others had FOXL2 copy number gains; none had DICER1 mutations. On the basis of the average age of the patients, frequency of estrogenic manifestations, abundance of standard AGCT morphology, and occasional late recurrences, we suggest that these tumors form a distinct group and propose the term "AGCTs with tubular differentiation" to denote them.