183 TOX expression discriminates early Mycosis fungicides from benign inflammatory dermatoses

Abstract

IDH mutations have been identified in many tumor types, including glioma, acute myeloid leukemia, and cholangiocarcinoma, and testing for the mutation can be a valuable diagnostic and predictive biomarker. We identified melanomas with IDH mutations at a single institution and sought to further characterize this cohort. 405 melanoma cases collected at Massachusetts General Hospital between 2015 and 2017 underwent molecular characterization of 91 genes, including IDH1 and IDH2, by next generation sequencing. Demographic and primary site data were recorded. The mean age of the cohort was 69 years with 70% of patients male. An IDH mutation was identified in 20 cases of 405 tested tumors (4.9%). Seventeen of 20 mutant cases (85%) showed an IDH1(R132C) mutation, while the remaining three cases (15%) were hypermutant, with non-hotspot alterations of unknown significance. Of the 17 cases with an IDH1(R132C) mutation, 16 occurred in sun exposed areas (non-acral, nonmucosal) and 14/16 (88%) had co-occurring alterations in the MAPK pathway (BRAF, NRAS, MAPK3), a similar frequency compared to IDH wild-type melanomas in the cohort (329/385, 85%). Histology of 13 IDH1(R132C) mutant cases was reviewed, with 12 exhibiting an epithelioid growth pattern and one with mixed epithelioid and spindled patterns. All cases showed absence of or non-brisk tumor infiltrating lymphocytes. Of the 17 cases with IDH1(R132C) mutation, ten received immunotherapy. Two showed a reduction in tumor burden by imaging, and eight showed progression. At last follow-up (median follow-up time¼32.6 months), five patients were alive with no evidence of disease, nine were alive with disease, and three had died of disease. We identified a small cohort of melanomas that harbor IDH1 mutations with frequent co-existing MAPK mutations. This group represents a distinct molecular subgroup classification of melanoma. Limited data suggests these cases may have a poor response to immunotherapy.