Anatomical lymphatic drainage basin and sentinel lymph node positivity in Merkel cell carcinoma: a 37-year single-center cohort study of 400 patients.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine malignancy with increasing incidence due to UV exposure and improved diagnostics. It spreads rapidly via lymphatics and has high mortality, surpassing melanoma in lethality. Management includes surgical excision, sentinel lymph node biopsy (SLNB), radiotherapy, and immunotherapy. SLNB is an established staging tool for detecting occult nodal metastases; however, the influence of anatomical drainage basin location on SLNB positivity and the role of completion lymph node dissection (CLND) remain incompletely understood. This study evaluated patterns of nodal involvement according to drainage basin location and assessed the diagnostic yield of CLND in a large single-center MCC cohort. Methods: A retrospective analysis was performed of 400 patients with MCC treated at a tertiary referral center between 1986 and 2023. SLNB positivity rates were compared across cervical, axillary, and inguinal drainage basins. Associations between anatomical location and nodal involvement were assessed using univariable and multivariable logistic regression models. Adjusted analyses included year of diagnosis, lymphovascular invasion and immunosuppression status, with Firth's penalized regression applied where appropriate. Results: Among 400 patients, 244 underwent SLNB, of whom 71 (29.1%) had at least one positive SLN. In univariable analysis, inguinal SLNB was associated with higher odds of positivity compared with axillary SLNB (OR 3.31, 95% CI 1.49-7.35; p = 0.003) and cervical SLNB (OR 2.10, 95% CI 1.04-4.24; p = 0.040). After adjustment for lymphovascular invasion, immunosuppression, and year of diagnosis, inguinal drainage remained associated with SLNB positivity compared with axillary drainage (OR 3.08; 95% CI 1.36-6.98; p = 0.007). Lymphovascular invasion (OR 3.29; 95% CI 1.66-6.54; p = 0.001) and immunosuppression (OR 2.38; 95% CI 1.12-5.06; p = 0.025) were also associated with SLNB positivity in the adjusted model. Conclusions: SLNB remains a valuable staging procedure in MCC, identifying occult nodal disease in nearly one-third of patients. Inguinal drainage basin remained associated with SLNB positivity after adjustment for clinicopathological factors. These findings may help inform clinical decision-making regarding nodal staging in patients with MCC. The substantial rate of additional nodal involvement detected by CLND supports its continued role as a staging procedure in selected patients with MCC. As this study focuses on lymphatic dissemination assessed by SLNB and lymph node dissection (LND), no conclusions can be drawn regarding hematogenous metastatic spread.