Intratesticular Serous Borderline Tumor: A Clinicopathologic and Molecular Analysis of Four Tumors With Literature Review

Abstract

Ovarian-type epithelial tumors of the testis are uncommon, with serous borderline tumors (SBTs) representing the most. Intratesticular localization is exceptionally rare, with fewer than 20 tumors described in the literature. We report 4 intratesticular SBTs and provide a clinicopathologic and molecular characterization along with a literature review. The patients ranged from 16 to 83 years and presented with scrotal swelling, discomfort, or a palpable mass. Serum tumor markers were within normal limits in all patients. Imaging studies revealed well-circumscribed cystic lesions with internal papillary projections. Gross examination of the tumors showed unilocular cystic lesions containing serous to hemorrhagic fluid within the testis. Histopatholologically, the tumors showed complex intracystic papillary projections lined by ciliated pseudostratified columnar or cuboidal epithelium with minimal atypia and no stromal invasion. Psammoma bodies and focal heterotopic ossification were variably observed. Immunohistochemically, all tumors were diffusely positive for WT1, estrogen receptor, and progesterone receptor, with variable PAX8 and keratin 7 (KRT7) expression, and were negative for calretinin and D2.40, confirming Müllerian differentiation. Targeted next-generation sequencing revealed pathogenic alterations in AKT1 (p.E17K), CHEK2 (p.D438Y), and TERT promoter (c.-124C > T) in one patient, expanding the molecular spectrum of testicular SBTs; the remaining sequenced tumors were wild-type. All patients remained disease-free during follow-up. Intratesticular SBTs are rare Müllerian-type neoplasms that can closely mimic other more aggressive neoplasms. Recognition of their characteristic morphology and immunoprofile, together with emerging molecular insights, is helpful to avoid misdiagnosis and overtreatment.