Intramuscular Myoepithelioma-Like Hyalinizing Epithelioid Tumor With OGT::FOXO3 Intraexonic DNA Fusion Confirmed by...

Myoepithelioma-like hyalinizing epithelioid tumor (MHET) is a rare mesenchymal neoplasm characterized by rearrangements of the OGT gene. MHET typically presents as a small tumor in the subcutis and generally follows a benign clinical course. Histologically, MHET is characterized by a hyalinized stroma exhibiting a distinctive "two-tone" appearance, epithelioid tumor cells with cellular processes encircling matrix globules, and a minor spindle cell component. The tumor also demonstrates rich vasculature with occasional fringe-like vessels, accompanied by perivascular concentric spindle cell proliferation and hyalinization. Nearly all documented OGT fusions in MHET are intraexonic; however, their precise genomic DNA breakpoints and the mechanisms underlying fusion transcript generation remain unclear. We report a case of MHET in a 17-year-old boy and investigate the genomic breakpoint of the fusion gene. Although the tumor showed atypical features, including large size, intramuscular location, and focal cytokeratin (CAM5.2) expression, the histologic findings were characteristic of MHET. Reverse transcription-polymerase chain reaction (RT-PCR) identified an intraexonic, in-frame OGT::FOXO3 fusion transcript. To clarify the genomic breakpoint, nanopore DNA sequencing demonstrated that the DNA breakpoint was identical to the fusion junction in the mRNA transcript. These findings demonstrate that the fusion transcript was generated directly from rearranged genomic DNA without splice site involvement. This mechanism may contribute to the rarity of MHET and warrants further investigation.