PD-L1 in Merkel Cell Carcinoma: From Tumor Microenvironment to Pathological Interpretation

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma in which Merkel cell polyomavirus (MCPyV) oncoproteins and ultraviolet-induced mutations provide distinct sources of tumor immunogenicity. This narrative review examines the biological determinants, immunohistochemical assessment, and prognostic and therapeutic relevance of programmed death ligand 1 (PD-L1) in MCC, linking tumor immunobiology to pathological interpretation. PD-L1 expression on tumor and immune cells is often concentrated at tumor–immune interfaces, consistent with interferon-γ-driven adaptive immune resistance. Reported associations with survival and treatment response vary across studies, partly reflecting differences in tissue sampling, assays, scoring compartments, and treatment context. Immune checkpoint blockade can produce durable responses in both PD-L1-positive and PD-L1-negative tumors, while baseline PD-L1 expression alone is not a validated criterion for treatment selection. Resistance mechanisms and emerging biomarkers are discussed alongside viral status, T-cell architecture, antigen-presentation defects, and alternative immune checkpoints. A reporting framework should emphasize specimen characteristics, assay documentation, separate assessment of PD-L1 expression in tumor and immune cells, and spatial heterogeneity. Interpreting PD-L1 within this biological and pathological context supports informative reporting and highlights the potential of integrated spatial biomarkers to improve understanding of immune responsiveness in MCC.