Skeletal muscle invasion identifies aggressive merkel cell carcinomas beyond tumor size-based risk stratification: a...

The American Joint Committee on Cancer (AJCC) staging system for MCC defines pT1-pT3 disease by tumor size and pT4 disease as disease invading deep structures, including skeletal muscle. However, the prognostic significance of skeletal muscle invasion in MCC remains incompletely characterized, especially in the head and neck (H&N), where the dermis and subcutis are often thin and even small tumors may invade skeletal muscle. We evaluated the clinicopathologic significance of skeletal muscle invasion in H&N and non-H&N MCC. MCCs diagnosed at a tertiary cancer center during 2002-2025 were stratified by anatomic site and presence of skeletal muscle invasion. Clinicopathologic features, Merkel cell polyomavirus (MCPyV) status, treatment parameters, and clinical outcomes were analyzed. The study included 65 cases: 23 H&N skeletal-muscle-invasive, 18 H&N non-skeletal-muscle-invasive, 4 non-H&N skeletal-muscle-invasive, and 20 non-H&N non-skeletal-muscle-invasive MCCs. Muscle-invasive tumors were significantly larger and thicker than non-muscle-invasive tumors and required more surgical procedures to achieve negative margins. In the H&N, skeletal-muscle-invasive tumors had higher rates of vascular invasion and distant metastasis (3-year rate: 31% versus 0%; p = 0.027) and a higher frequency of MCPyV positivity (65% versus 0%; p < 0.001). The median size of H&N muscle-invasive tumors was 16 mm, indicating that many would have been classified as pT1 in the absence of muscle invasion. Skeletal muscle invasion was not significantly associated with overall or MCC-specific survival in H&N or non-H&N MCCs. Skeletal-muscle-invasive H&N MCCs are more aggressive despite small tumor size. These findings support keeping MCCs with skeletal muscle invasion in the AJCC pT4 category.