Importance Merkel cell carcinoma (MCC) is a rare neuroendocrine malignant neoplasm often affecting the head and neck. Sentinel lymph node biopsy (SLNB) is routinely performed; however, the accuracy and reliability of SLNB for head and neck MCC remains unknown. Objective To determine the accuracy of SLNB in head and neck MCC and inform pre- and post-SLNB risk stratification. Design, Setting, and Participants This was a single-center cohort study of patients with clinically node-negative head and neck MCC who underwent SLNB from January 2006 to January 2025; median (IQR) follow-up was 1.9 (0.8-4.6) years. Data analysis was conducted from April to November 2025. Interventions SLNB outcome and nodal disease status. Main Outcomes and Measures SLNB accuracy measured by sensitivity, negative predictive value (NPV), and false negative (FN) rate. FN SLNB was defined as regional nodal recurrence at the first site of recurrence after a negative SLNB without concurrent local or in-transit recurrence. Factors associated with failed SLNB (defined as nonvisualization on lymphoscintigraphy, inability to identify the sentinel lymph node intraoperatively, or absence of nodal tissue in the pathology specimen) were evaluated using effect-size measures. Cox proportional hazards model identified factors associated with nodal disease, comparing patients who developed nodal disease (identified by SLNB or subsequent clinical and/or imaging evaluation) with those who did not develop nodal disease during follow-up. Results Of 86 participants (mean SD age, 75.6 9.6 years; 36 female 41.9% and 50 male 58.1% individuals) with clinically node-negative head and neck MCC, 69 (80.2%) underwent SLNB. Occult nodal disease was identified in 19 participants (27.5%). SLNB sensitivity was 52.6% (10 of 19 patients), NPV was 88.6% (31 of 35 patients), and FN rate was 26.7% (4 of 15 patients). SLNB failed in 29.0% (20 of 69 patients), with tumor location, female sex, and older age having medium to large effect on SLNB failure. Lymphovascular invasion, infiltrative growth pattern, and tumor size had the largest effect size on nodal disease with Cox analysis. Conclusions and Relevance In this large single-site cohort study, SLNB remained a useful tool in head and neck MCC, identifying more than half of occult nodal disease. Given reduced performance in this region, patients with failed SLNB or negative SLNB plus high-risk features may benefit from tailored management, including intensified therapy and surveillance.
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