Microphthalmia transcription factor - Not a sensitive or specific marker for the diagnosis of desmoplastic melanoma and spindle cell (non-desmoplastic) melanoma

Microphthalmia transcription factor (Mitf), a melanocytic nuclear protein c ritical for the embryonic development and postnatal viability of melanocyte s, is a master lineage regulator and modulates extracellular signals. Recen tly, Mitf expression was shown to be both a sensitive and specific marker o f epithelioid melanoma. Because loss of specific melanocytic markers in mel anomas with spindle cell morphology is more common compared with those tumo rs with epithelioid morphology, we investigated the sensitivity of D5, an a nti-Mitf antibody, for diagnosis in this diagnostically problematic subset of melanomas. Twenty of 21 (95%) spindle cell and desmoplastic melanomas ex amined were reactive for S-100 protein. Only 4 of 21 (19%) spindle cell and desmoplastic melanomas were reactive for HMB-45. Six of 21 tumors (29%) we re reactive for D5, including one case that was non-reactive for S-100 and HMB-45. Melan-A reactivity was seen in 2 of 13 cases (15%) studied. Eight o f 24 (33%) non-melanocytic spindle cell tumors were reactive for D5, includ ing 4 of 6 dermatofibromas, 1 of 6 schwannomas, 1 of 2 leiomyomas, and 2 of 6 leiomyosarcomas. Although D5 was shown in a previous study to be a highl y sensitive and specific marker for epithelioid melanomas, the results of t his study show it is not a sensitive or specific marker of spindle cell and desmoplastic melanomas. Nevertheless, we believe that diffuse positive sta ining for D5 when taken in clinical, histologic and immunohistochemical con text may be diagnostically useful in selected eases of melanoma.