The Expanding Spectrum of DICER1-Associated Gynecologic Neoplasms

DICER1 tumor predisposition syndrome is a rare autosomal-dominant disorder resulting from heterozygous germline pathogenic variants in DICER1, a critical regulator of microRNA biogenesis and RNA interference. The syndrome predisposes individuals to a broad spectrum of benign and malignant neoplasms, primarily affecting pediatric and young adult populations. Gynecologic manifestations are notably heterogeneous and include the well-established associations with embryonal rhabdomyosarcoma and Sertoli-Leydig cell tumor. DICER1 alterations have also been identified in gynandroblastoma, a subset of adenosarcomas, and emerging entities such as DICER1-related Wilms-like uterine tumor and, less consistently, in rare examples of juvenile and adult granulosa cell tumor, Sertoli cell tumor, germ cell tumors, and carcinosarcoma. Despite their diverse anatomic sites, some of these neoplasms share recurrent morphologic hallmarks, including primitive mesenchyme, fetal-type epithelium and cartilage, rhabdomyosarcomatous and neuroectodermal differentiation, and anaplasia. Recent evidence has broadened the morphologic, molecular, and clinical understanding of DICER1-associated neoplasms. Recognition of these distinctive morphologic features is essential for prompting timely testing for DICER1 alterations and facilitating appropriate genetic counseling, surveillance, and early detection strategies for patients and their families. This review synthesizes current knowledge with emerging insights to enhance the diagnostic recognition of these rare yet clinically significant entities.