Microphthalmia transcription factor and melanoma cell adhesion molecule expression distinguish desmoplastic/spindle cell melanoma from morphologic mimics

Desmoplastic/spindle cell melanoma is a rare variant of melanoma. A number of factors complicate the diagnosis of desmoplastic/spindle cell melanoma, including the variable absence of a lentiginous component, its spindle cell morphology, and its many morphologic mimics, including scars, malignant peripheral nerve sheath tumor, neurofibroma, atypical fibroxanthoma, and spindled carcinoma. The immunohistochemical confirmation of desmoplastic/spindle cell melanoma may also be difficult, because the majority of tumors are negative for specific melanocytic markers such as HMB-45 and Melan-A, despite their usual expression of S-100 protein. Two new and potentially promising melanocytic markers, microphthalmia transcription factor (MiTF) and melanoma cell adhesion molecule (Mel-CAM), have been shown to be sensitive markers of epithelioid melanoma, but have not been tested in desmoplastic/spindle cell melanoma or in other rare melanocytic neuroectodermal tumors such as clear cell sarcoma. We immunostained 79 tumors (20 desmoplastic/spindle cell melanomas, 10 scars, 10 neurofibromas, 12 malignant peripheral nerve sheath tumors, 10 atypical fibroxanthomas, 10 clear cell sarcomas, 3 melanotic schwannomas, and 4 cellular blue nevi) for MiTF and Mel-CAM. MiTF expression was seen in 11 of 20 desmoplastic/spindle cell melanomas, 0 of 10 scars, 2 of 10 neurofibromas, 0 of 12 malignant peripheral nerve sheath tumors, 1 of 10 atypical fibroxanthomas, 7 of 10 clear cell sarcomas, 3 of 3 melanotic schwannomas, and 3 of 4 cellular blue nevi. Mel-CAM expression was present in 14 of 17 desmoplastic/spindle cell melanomas, 0 of 10 scars, 4 of 10 neurofibromas, 3 of 11 malignant peripheral nerve sheath tumors, 0 of 10 atypical fibroxanthomas, 9 of 10 clear cell sarcomas, 3 of 3 melanotic schwannomas, and 0 of 4 cellular blue nevi. MiTF and Mel-CAM were coexpressed in 6 of 17 desmoplastic/spindle cell melanomas and in no other tumor. Regarding desmoplastic/spindle cell melanoma, scar, neurofibroma, malignant peripheral nerve sheath tumor, and atypical fibroxanthoma, the sensitivity and specificity of MiTF for desmoplastic/spindle cell melanoma were 55% and 91%, respectively. For this same group of tumors, Mel-CAM had a sensitivity of 82% and a specificity of 83%. We conclude that the sensitivity and specificity of MiTF for desmoplastic melanoma equals or exceeds that of such markers as HMB-45 or Melan-A, and that MiTF should be part of the initial immunohistochemical panel for the