Clinicopathologic, genomic, and outcome analysis of primary skin adnexal carcinomas: the Mayo Clinic experience

Background Primary skin adnexal carcinomas (SACs) are rare, histologically diverse tumors with diagnostic overlap with other cutaneous and metastatic malignancies. Standardized treatment guidelines are limited. This study characterizes the clinical, pathologic, and molecular features of SACs to clarify diagnostic distinctions and identify factors associated with prognosis. Materials and methods We carried out a retrospective cohort study of histologically confirmed SACs treated at Mayo Clinic from 2000 to 2025. Clinical, histopathologic, immunohistochemical, and available molecular data were analyzed to evaluate subtype-specific features, recurrence patterns, and survival outcomes. Results Among 117 patients, sebaceous carcinoma was the most common subtype (44.4%), followed by eccrine (25.6%) and apocrine (6.0%). Apocrine tumors showed the highest rates of nodal (85.7%) and distant metastases (14.3%), whereas sebaceous carcinomas were largely localized (94.2%) and frequently associated with mismatch repair deficiency (26.9%). Recurrent genomic alterations included TP53, CDKN2A, and KMT2D. Five-year overall and recurrence-free survival were 62.5% and 78.0%, respectively. Worse overall survival was independently associated with older age, poor performance status, poor differentiation, and increased number of involved lymph nodes. Recurrence risk was highest in apocrine (67%) and eccrine (35%) tumors and was significantly linked to nodal disease, poor differentiation, and positive margins. Patients receiving immunotherapy after progression demonstrated improved survival compared with those treated with other systemic regimens (62 versus 21 months, P = 0.04). Conclusions SACs show distinct subtype-specific behavior and molecular profiles. Findings support early systemic staging, risk-adapted surveillance, and consideration of immunotherapy. These data provide a foundation for personalized management and for future multi-institutional studies.