Micropthalmia transcription factor (MITF) as a diagnostic marker for metastatic melanomas negative for other melanoma markers

• Published in: International journal of clinical and experimental pathology Vol. 6; no. 8; pp. 1658 - 1664
• Main Authors: Guo, Ruifeng, Franco-Palacios, Maria, Russell, Madison, Goddard, Lindsey, Hassell, Lewis, Gillies, Elizabeth, Fung, Kar-Ming
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2013
• Subjects: Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Case Report; Humans; Immunohistochemistry; Male; Melanoma - diagnosis; Melanoma - metabolism; Microphthalmia-Associated Transcription Factor - analysis; Microphthalmia-Associated Transcription Factor - biosynthesis; Skin Neoplasms - diagnosis; Skin Neoplasms - metabolism; Microphthalmia Transcription Factor; Melanoma; immunohistochemistry
• ISSN: 1936-2625

Metastatic malignant melanoma has a wide spectrum of histopathologic patterns and often lacks melanin pigment. Without a known primary tumor, the diagnosis of metastatic malignant melanoma relies on a combination of morphology and immunohistochemical profile. Infrequently, commonly used markers for melanoma (S100, HMB45, Melan-A and Tyrosinase A) are negative. These cases pose critical diagnostic challenges. Recent studies show that Microphthalmia Transcription Factor (MITF) has high sensitivity (88-100%) and specificity for metastatic melanoma. We are reporting here three cases of high grade tumors that were studied by a comprehensive immunohistochemical panel including cytokeratins, S100, HMB-45, Melan A, Tyrosinase, and MITF. All three tumors were also analyzed for the presence of BRAF mutations. All three metastatic tumors were negative for S100, Melan A, HMB-45 and Tyrosinase but positive for MITF. Subsequent to the diagnoses, previously existing or concurrent primary melanomas were identified in 2 of the 3 cases. Interestingly, S100, Melan A, and HMB-45 were positive in the primary tumors. No BRAF (V600E) mutations were identified in the three metastatic melanomas and CD 117 (c-kit) was positive in one of the cases. In summary, our experience shows that MITF can be a valuable adjunct in the diagnosis of metastatic tumors that are suspicious for melanoma but negative for other melanoma markers.