CARMN::NOTCH2 Fusion-Positive Malignant Glomus Tumor of the Liver: A Rare Tumor With Review of Literature.

Glomus tumors are rare mesenchymal neoplasms that commonly occur in distal extremities. Primary hepatic involvement is exceedingly uncommon, with only ten tumors reported to date, most of which were benign. Malignant hepatic glomus tumors are exceptionally rare, and their molecular features remain poorly characterized. Recent studies have identified recurrent CARMN::NOTCH2 fusions as potential defining alterations in malignant glomus tumors. We report a 57-year-old man presenting with epigastric pain, reflux, and diarrhea. Imaging revealed a 10 cm left hepatic lobe mass, initially concerning hepatocellular carcinoma, and an incidental subcutaneous hip lesion. Biopsy of the latter confirmed low-grade fibromyxoid sarcoma, considered unrelated. Extended left hepatectomy revealed a multinodular, hemorrhagic hepatic tumor. Histology demonstrated epithelioid to spindle cells with moderate-to-marked atypia, prominent nucleoli, brisk mitotic figures including atypical forms, and focal myxoid stroma. Immunohistochemistry was positive for smooth muscle actin and vimentin, and negative for epithelial, vascular, melanocytic, and gastrointestinal stromal tumor markers. Sarcoma fusion testing identified a CARMN::NOTCH2 fusion, with MDM2 non-amplified and next-generation sequencing showing microsatellite stability and low tumor mutational burden. Based on morphologic, immunohistochemical, and molecular findings, a diagnosis of malignant hepatic glomus tumor was rendered. To our knowledge, this represents only the third reported malignant hepatic glomus tumor with molecular confirmation of CARMN::NOTCH2 fusion. This tumor highlights the diagnostic challenges posed by hepatic glomus tumors, underscores the importance of integrating molecular studies into unusual hepatic neoplasms, and expands the clinicopathologic and molecular spectrum of this exceedingly rare entity.