MON-309 - Beyond the Classic Triad: An Unusual Presentation of MEN2A with Salivary Gland Carcinoma and Papillary Thyroid Cancer

Introduction
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant syndrome caused by germline gain-of-function mutations in the RET proto-oncogene on chromosome 10q11.21, affecting neural crest-derived tissues including the thyroid, adrenal, and parathyroid glands. It is classified as MEN2A or MEN2B, with MEN2A accounting for 70-80% of cases. Presentation typically occurs before age 35. Medullary thyroid carcinoma (MTC) develops in nearly 98% of patients and is often the initial manifestation. Pheochromocytomas occur in about 50% of cases and are frequently bilateral, while primary hyperparathyroidism affects about 25% of patients, usually later in life. We report a unique case of MEN2A with atypical late presentation and rare associated malignancies.

Case Presentation
A 60-year-old Hispanic male presented with abdominal pain and sepsis secondary to acute cholecystitis, complicated by NSTEMI and newly diagnosed non-ischemic cardiomyopathy. He was undergoing outpatient evaluation for MEN2A due to known RET mutations in his three children. CT imaging revealed bilateral adrenal nodules suspicious for pheochromocytomas in the setting of elevated plasma free metanephrine (520 pg/mL). Following alpha and beta blockade, he underwent right total and left partial adrenalectomy with cholecystectomy. Pathology confirmed bilateral low-grade pheochromocytomas, and postoperative adrenal function remained intact. Subsequent thyroid ultrasound showed bilateral highly suspicious nodules in the setting of elevated plasma calcitonin (4,451 pg/mL). Total thyroidectomy revealed MTC (T2N1a) and incidental papillary thyroid carcinoma (PTC), follicular variant (pT1aN0a). He never developed hyperparathyroidism. Five years later, routine surveillance imaging identified a left parotid mass. Biopsy confirmed salivary duct carcinoma. He received neoadjuvant trastuzumab/pertuzumab followed by parotidectomy, neck dissection, and reconstruction. Tumor sequencing identified pathogenic PIK3CA and RET mutations on exons 10 (p.Q546R) and 11 (p.C634S), respectively, without RET fusion. He is currently receiving adjuvant radiation therapy.

Discussion
This case illustrates an expanded MEN2A phenotype with delayed presentation, pheochromocytoma as the initial manifestation, coexisting PTC, and subsequent salivary gland carcinoma. While RET fusions are implicated in subsets of papillary thyroid and salivary gland tumors, these are somatic events distinct from germline RET mutations in MEN2A. Several case reports document the unusual association between MEN2A and PTC; however, there appears to be no prior reports linking MEN2A with salivary gland carcinoma. This case underscores the importance of recognizing atypical presentations of MEN2A and highlights the role of molecular profiling in guiding lifelong surveillance and individualized management.

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