A Rare Case of Synchronous Multiple Primary Malignancies of the Pancreas, Skin, and Thyroid

Multiple primary malignancies (MPMs) are defined as the occurrence of two or more distinct malignant neoplasms in a single individual, arising either simultaneously or successively. With advancements in targeted therapies and improvements in overall survival, the observed incidence of MPMs has increased, likely reflecting both improvements in oncologic treatments and enhanced surveillance. We report the case of a 63-year-old man with synchronous pancreatic neuroendocrine tumor, anal melanoma, and papillary thyroid carcinoma. His prior oncologic history is notable for prostate adenocarcinoma treated with prostatectomy and renal cell carcinoma managed with right partial nephrectomy. Over a 1-year period, he underwent surgical resection of the neuroendocrine tumor, anal melanoma, and papillary thyroid carcinoma. He is currently receiving pembrolizumab for management of anal melanoma. Germline testing using Ambry's CustomNext Cancer panel was negative across 33 genes associated with hereditary cancer predisposition syndromes. Synchronous MPMs pose substantial challenges for clinical management, including complexities in treatment prioritization, sequencing, and integration of multimodal therapies. These challenges are compounded by limited evidence to guide concurrent or sequential multicancer regimens, with implications for efficacy, toxicity, and long-term outcomes. This case underscores the need for multidisciplinary coordination, individualized risk-benefit assessment, and prospective data to inform evidence-based strategies in the care of patients with MPMs.