Immunohistochemistry for Skin Cancers: New Insights into Diagnosis and Treatment of Melanoma.

: With its incidence on the rise, a high mortality rate, and great costs associated with its treatment, melanoma represents an important challenge for healthcare systems, clinicians, and pathologists. Therefore, an emphasis should be placed on its early and correct diagnosis, as well as the appropriate assessment of prognostic and predictive factors. Immunohistochemistry (IHC) is an ancillary test that can provide invaluable information for diagnosing melanoma, especially in complex cases. : The aim of this systematic review is to gather the available information regarding the use of IHC markers in the diagnosis, differential diagnosis, prognosis, staging, and treatment of melanoma in a format that is easy to access for clinicians and pathologists. A comprehensive search of the literature was conducted and resulted in one hundred and forty-seven studies being included in this systematic review. The results were grouped thematically by specific IHC markers. : The IHC markers specific to melanocytic differentiation, like S100, SOX10, and Melan-A/MART1, were consistent across studies as being positive in most cases of melanoma, with rare exceptions. HMB-45 and PRAME can provide additional information, especially for differential diagnoses between benign and malignant melanocytic lesions. MITF, Ki67, BRAF, and PD-L1 are associated with prognosis factors, like the Breslow thickness, tumour ulceration, type of inflammatory infiltrate, and response to treatment. : IHC markers are an invaluable tool for the diagnosis and differential diagnosis of melanoma, especially in cases that lack the characteristic histopathological aspects. In addition, IHC provides prognostic factors and can help in predicting the tumour's response to various treatments.