Absence of S-100 protein immunoreactivity in cellular blue nevus: A potential diagnostic pitfall

Cellular blue nevus (CBN) is a relatively rare melanocytic neoplasm that oc curs in the deep dermis and frequently extends into the subcutaneous adipos e tissue. CBN may feature a broad range of morphologic findings and, becaus e of its cellularity, may appear histologically worrisome. Immunohistochemi cal analysis plays an important role in confirming the morphologic diagnosi s, and S-100 protein immunopositivity has been regarded as a constant and h elpful finding. Yet the authors were puzzled by the relatively frequent occ urrence of S-100 protein negativity in otherwise typical examples of CBN. A series of 20 cases of CBN was therefore investigated immunohistochemically . At variance with common belief, absence of S-100 protein immunoreactivity was observed in nearly half of the cases. In contrast, all cases analyzed reacted with HMB45, melan A, and tyrosinase. Considering the importance of S-100 protein immunoreactivity in the diagnosis of melanocytic neoplasms, a wareness of these findings may avoid potential diagnostic misinterpretation s. S-100 immunoreactivity in CBN should be evaluated in conjunction with at least another marker of melanocytic differentiation such as HMB45, melan A , or tyrosinase.