Myoepithelial Carcinoma Ex-Pleomorphic Adenoma Exposing a RET Germline Mutation: A Rare Genetic Event

Myoepithelial carcinoma (MECA) is a malignant neoplasm composed exclusively of myoepithelial cells and accounts for less than 1% of all salivary gland tumors. Its diagnosis is often challenging due to histologic overlaps with benign lesions and its variable morphologic presentation. Although molecular profiling has emerged as a valuable tool in salivary gland tumor classification, the genetic landscape of MECA remains incompletely defined. We report a case of a 65-year-old male with a history of chronic lymphocytic leukemia who presented with otalgia, sore throat, and dysphagia, ultimately diagnosed with a high-grade MECA of the submandibular gland following excision. Preoperative imaging revealed extensive regional lymphadenopathy and likely metastases to the lungs and ribs, and next-generation sequencing (NGS) identified a RET p.V804M variant, well-known to be pathogenic in medullary thyroid carcinoma but previously unreported in MECA. After this genetic change was subsequently found to be germline, this finding expands the implications for the breadth of RET as a tumor driver, particularly given the patient's older age at presentation, with RET alterations in salivary tumors most commonly associated with genetic fusion events.