Adult granulosa cell tumors with tubular differentiation were proposed as a distinct variant characterized by merging Sertoliform tubules, infrequent FOXL2 mutations with occasional copy gains, and absent DICER1 alterations, according to a recent study.
Researchers described 80 ovarian tumors that combined adult granulosa cell morphology with tubular structures. Patient ages ranged from 15 to 87 years. Endocrine manifestations were documented in 28 patients and were predominantly estrogenic; androgenic features were uncommon. Follow-up was available for 13 patients (10 to 266 months), with 2 recurrences in ovary-confined tumors, at 60 and 77 months.
Adult granulosa cell tumor (AGCT) patterns were present in every case and typically dominated. Sex cord-stromal tumor elements formed hollow and solid tubules that often merged with adjacent granulosa components, published in The American Journal of Surgical Pathology. Hollow tubules showed columnar cells with basally oriented nuclei and apical cilia were seen in 38 tumors; solid tubules lacked lumina and resembled prepubertal seminiferous tubules. A minority of tumors contained annular tubules resembling sex cord tumor with annular tubules. Tumors were unilateral, measured 0.4 to 29.6 cm (median 10 cm), and were usually confined to the ovary. Fibromatous stroma was common, hemorrhage occurred in some tumors, and luteinized cells were variably present. Immunohistochemistry supported sex cord differentiation: steroidogenic factor 1, calretinin, and inhibin were frequently positive; keratin AE1/AE3, when positive, often highlighted the tubular component. Reticulin demonstrated an epithelial pattern outlining granulosa nests and individual tubules.
Targeted next-generation sequencing was successful in 11 tumors using clinically validated assays (PGDx elio tissue complete, OncoPanel, or MSK-IMPACT). FOXL2 alterations included two p.C134W variants and two copy number gains. DICER1 alterations were not identified. Additionally, variably observed changes involved EP300, FGFR1, HNF1A, RUNX1, POLE, and JAK2, along with recurrent chromosomal gains, such as chromosome 12, and losses, such as 22q. The frequency of FOXL2 mutation appeared lower than reported in typical AGCT, a finding previously noted in some AGCT variants.
Differential diagnostic considerations included Sertoli-Leydig cell tumor and endometrioid adenocarcinoma with sex cord-like areas. In this series, the clinical profile (older age, frequent estrogenic manifestations, and potential for late recurrence), the merging of tubular and granulosa elements, and the absence of DICER1 alterations aligned with AGCT rather than Sertoli-Leydig cell tumor.
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