DICER1 Syndrome and Tumor Pathology: An Updated Review for Diagnostic Practice

DICER1 syndrome is an autosomal dominant tumor predisposition disorder caused by pathogenic variants in the microRNA-processing gene DICER1. Since its initial recognition in families with pleuropulmonary blastoma, the phenotypic spectrum has expanded to encompass a wide array of benign and malignant neoplasms-including thyroid follicular nodular disease, Sertoli-Leydig cell tumor, cystic nephroma, pituitary blastoma, and embryonal rhabdomyosarcoma of the cervix-often presenting in childhood or early adulthood. This updated review synthesizes current knowledge of DICER1 biology, the historical evolution of the syndrome, the distinctive clinicopathologic features of associated tumors, provides a practical diagnostic algorithm to guide pathologists in recognizing sentinel lesions and initiating germline testing, and recent advances in the study of this syndrome and the DICER1 gene. By integrating molecular mechanisms with evolving clinical practice, this article aims to equip diagnostic pathologists and multidisciplinary teams with diagnostic tools and correlations for the detection and management of DICER1 syndrome.