Genomic profiling guided therapy for synchronous SCC and CLL of the parotid gland: a rare case report.

Synchronous squamous cell carcinoma (SCC) and chronic lymphocytic leukemia (CLL) in the parotid gland is rare, with limited evidence on personalized treatment. We report a 75-year-old male with prior cutaneous SCC who presented with a hypermetabolic parotid mass and cervical lymphadenopathy; fine needle aspiration confirmed SCC. Surgery revealed poorly differentiated SCC and CLL in multiple lymph nodes. He underwent radiotherapy but developed regional SCC relapse without systemic CLL symptoms. Recurrence in the ear required extensive surgical resection and reconstruction. Genetic profiling showed high tumor mutational burden (>50 mutations/Mb) and mutations in ARID1B, CDKN2A, MSH2, PMS2, and TP53. He received six cycles of cemiplimab followed by cetuximab-based targeted therapy, based on rising circulating DNA levels. This case emphasizes the value of genetic profiling and tools like TMB, FISH, and immunohistochemistry for risk stratification and personalized treatment in managing advanced or complex parotid malignancies, including synchronous SCC and CLL, to optimize patient outcomes.