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Int J Clin Exp Pathol 2013;6(8):1658-1664

Case Report
Micropthalmia Transcription Factor (MITF) as a diagnostic marker for metastatic
melanomas negative for other melanoma markers

Ruifeng Guo, Maria Franco-Palacios, Madison Russell, Lindsey Goddard, Lewis Hassell, Elizabeth Gillies, Kar-Ming Fung

Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma

Received June 26, 2013; Accepted July 10, 2013; Epub July 15, 2013; Published August 1, 2013

Abstract: 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. (IJCEP1306028).

Keywords: Melanoma, immunohistochemistry, Microphthalmia Transcription Factor

Address correspondence to: Dr. Kar-Ming Fung, Department of Pathology, University of Oklahoma Health Sciences Center OU Medical Center,
Presbyterian TowerLower Level, Pathology Suite, 700 N.E. 13th St. Oklahoma City, OK 73104, USA. E-mail: karming-fung@ouhsc.edu