Anaplastic Juvenile Granulosa Cell Tumor: A Report of 10 Cases of an Unemphasized Variant With Adverse Prognostic...

Ten anaplastic juvenile granulosa cell tumors (JGCT) with architectural and cytologic features that differ from those seen in conventional JGCTs were identified from patients who ranged from 7 to 44 (median 13) years. The tumors measured from 8.3 to 28 (median 21) cm. FIGO stage was IA (n=3), IC3 (n=2), II (n=1), IIIA (n=3), or unknown (n=1). All tumors had conventional areas with solid/nodular growth usually punctuated by follicles. However, all demonstrated areas (median 50%, range: 10% to 90%) with effacement of this architecture, characterized by diffuse growth, marked cytologic atypia, and brisk mitoses (up to 40/10 HPFs). In contrast, the conventional component exhibited significantly less atypia and mitoses. Next-generation sequencing was performed in 7 tumors and all harbored TP53 mutations; the remaining 3 showed aberrant p53 expression by immunohistochemistry. MYC family ( MYC and MYCN ) amplifications were identified in 4 tumors, while other alterations included AKT1 in-frame duplications (n=4) and DICER1 mutations (n=2). Follow-up was available for 9 patients (median 22 mo); 4 died of disease (all stage II/III with MYC/MYCN amplifications), one was alive with disease (stage IA), and 4 were alive and well (stages IA/IC). Anaplastic JGCTs have a distinct morphologic appearance and consistently demonstrate TP53 inactivation, with MYC family amplification evident in advanced-stage tumors. Although it cannot be determined whether MYC family amplifications are an independent predictor of behavior, they are important to recognize as such patients may benefit from MYC inhibitors. Tumors with the features described herein should be distinguished from conventional JGCTs because of the prognostic implications. In addition, the architectural deviations from that usually encountered and pleomorphism further add to diagnostic challenges in evaluating JGCTs.