Micropthalmia transcription factor (MITF) as a diagnostic marker for metastatic melanomas negative for other melanoma markers.
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.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma 73104, USA.
Ruifeng
R
Guo
Maria
M
Franco-Palacios
Madison
M
Russell
Lindsey
L
Goddard
Lewis
L
Hassell
Elizabeth
E
Gillies
Kar-Ming
KM
Fung
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000032:analysis / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism
D014408:Biomarkers, Tumor; D051739:Microphthalmia-Associated Transcription Factor
Melanoma; Microphthalmia Transcription Factor; immunohistochemistry