Advances in Immunohistochemistry for Mohs Surgery: A Comprehensive Review for Precision Control and Personalized Surgical Approach

Immunohistochemistry (IHC) has become an increasingly valuable adjunct in Mohs micrographic surgery (MMS), particularly in the assessment of complex, recurrent, or histologically ambiguous cutaneous tumors. While routine hematoxylin and eosin (H&E) staining remains the foundation of intraoperative margin evaluation, IHC techniques can enhance diagnostic accuracy in cases complicated by dense fibrosis, prior surgical alteration, or infiltrative tumor growth patterns. This in-depth review provides a comprehensive overview of the current applications of IHC in MMS, with a focus on commonly utilized markers and their clinical utility across a range of cutaneous malignancies. A structured review of the literature was conducted to identify relevant studies evaluating IHC in the context of MMS and dermatopathology. Several IHC markers demonstrate consistent and accepted utility in Mohs practice, particularly when frozen-section H&E assessment is limited by subtle tumor morphology, inflammation, fibrosis, or ambiguous cellular lineage. Areas of consensus, as well as ongoing controversies related to marker specificity, interpretation variability, cost, and workflow integration, are discussed. Attention is given to the distinction between IHC markers suitable for same-day frozen-section use in outpatient MMS and those better suited for formalin-fixed paraffin-embedded sections or delayed diagnostic confirmation. Limitations of IHC, including potential diagnostic pitfalls and lack of standardized protocols, are highlighted. Finally, emerging markers, advances in digital pathology, and future research directions are explored, emphasizing the evolving role of IHC in optimizing surgical margin assessment and improving patient outcomes.