ETV6-NTRK3 Fusion-Positive Late-Recurrent Parotid Carcinoma With Contralateral Axillary Metastasis and Early Response to Entrectinib: A Case Report.

Salivary secretory carcinoma is a rare malignancy that is typically driven by ETV6-NTRK3 and related NTRK fusions. Although many tumors follow an indolent course, late recurrence and atypical lymphatic dissemination may occur. A 54-year-old Caucasian man underwent surgery for a right parotid low-grade cystic adenocarcinoma in 2013, followed by completion parotidectomy, neck dissection, and adjuvant chemoradiotherapy for pT4a pN2b M0 disease. After a 12-year disease-free interval, he developed locoregional relapse, bilateral cervical nodal disease, and contralateral left axillary metastasis. Despite repeated surgery, chemotherapy, and radiotherapy, the disease progressed with mediastinal nodal and pulmonary involvement. DNA and RNA sequencing in September 2025 identified an ETV6-NTRK3 fusion. Entrectinib at a total daily dose of 600 mg was associated with rapid clinical improvement and marked metabolic response after three months, with only mild and manageable toxicities. This case illustrates three clinically important features: very late recurrence of parotid carcinoma, contralateral axillary nodal spread after extensive cervical treatment, and substantial early benefit from TRK inhibition once the driver fusion was identified. Comprehensive molecular profiling should be considered in recurrent salivary malignancies, particularly when histology is unusual or treatment options are limited.