Malignant Glomus Tumor of the Uterus With Cyclin D1 Expression and CARMN::NOTCH2 Fusion

Glomus tumors of the female genital tract are rare, and to our knowledge, malignant glomus tumors (MGTs) of the female genital tract have not been previously reported. The diagnosis of MGTs is challenging, given their morphologic and immunophenotypic overlap with other common uterine mesenchymal tumors, especially in the absence of classic benign glomus tumor components. Here, we report a case involving a 34-year-old woman with uterine MGT that was positive for smooth muscle actin, h-caldesmon, cyclin D1, and synaptophysin, and negative for desmin. CARMN::NOTCH2 fusion was identified using hybrid capture-based next-generation sequencing. The presence of CARMN::NOTCH2 fusion combined with supportive immunohistochemical and morphologic features validated the diagnosis of MGT. The patient underwent 4 courses of chemotherapy with ifosfamide and pirarubicin. She had no evidence of tumor recurrence or metastasis at 20 months, as confirmed at the latest follow-up visit. The findings from this case highlight the morphologic and immunohistochemical features that are diagnostic of this rare uterine tumor. Furthermore, this report summarizes the morphologic criteria for malignancy and the key points for its differential diagnosis.