[Immunohistochemistry of melanocytic tumours]

Immunohistochemistry has an essential role in the diagnosis and differential diagnosis of benign and malignant melanocytic lesions, and underlying molecular changes are reflected by several newly characterized antibodies. Given the limited sensitivity and specificity of classical immunohistochemical markers (S-100 protein, Melan‑A, HMB-45, Sox10, MITF), a panel of these antibodies should always be used. Loss of p16 expression, a variable increased expression of p21, expression of 5‑hmC, and a strong nuclear expression of PRAME are helpful in the diagnosis of melanomas in distinction from benign nevi. Nuclear expression of β‑Catenin and LEF1 is seen in WNT-activated melanocytomas, a reduced expression of PRKAR1A in many pigmented epithelioid melanocytomas, and a loss of nuclear BAP1 expression in BAP1-inactivated melanocytomas. Similarly, immunohistochemical antibodies (ALK, NTRK1, NTRK3, ROS1) allow the diagnosis of benign, atypical, and malignant Spitz tumours characterized by different genetic changes in comparison to melanocytic naevi and usual melanomas. Desmoplastic melanoma stains positively for S‑100 protein, Sox10, p75, WT‑1, p16, and nestin, whereas Melan‑A and HMB-45 are usually negative. The expression of Collagen type IV, CD68, and MDM2 in desmoplastic melanoma is helpful in the distinction from spindle cell melanoma. Cases of malignant peripheral nerve sheath tumours are, in contrast to desmoplastic melanoma S‑100 protein negative or express this marker only focally, and show a decreased nuclear expression of H3K27. Desmoplastic melanoma shows a focal nuclear expression of p53 in contrast to neurofibroma.