ArticleFrontiers in genetics2026
Malignant glomus tumor of the duodenum Harboring novel FOXP1 and KDM5A mutations: a case report and literature review.
Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Malignant glomus tumor (MGT) is an exceptionally rare mesenchymal neoplasm, accounting for less than 1% of all glomus tumors. Gastrointestinal involvement is unusual, and duodenal MGTs are exceedingly rare. Accurate preoperative diagnosis is difficult due to nonspecific clinical manifestations and overlapping histological features. Case Presentation: We report the case of a 47-year-old woman presenting with intermittent upper abdominal pain, aggravated after meals. Imaging revealed a heterogeneous enhancing lesion in the descending duodenum, and endoscopy showed a large ulcerative lesion. Initial biopsy suggested a glomus tumor. Whipple resection was performed, and histopathological examination demonstrated diffuse tumor growth with moderate nuclear atypia, atypical mitoses, and infiltrative extension into the mucosa and muscularis propria. Immunohistochemistry showed positivity for SMA, h-caldesmon, and synaptophysin, with negativity for CD117 and CgA. These findings, consistent with WHO 2019 diagnostic criteria, confirmed the diagnosis of duodenal MGT. Molecular Findings: Next-generation sequencing revealed two class III variants of uncertain significance: FOXP1 exon7 c.250C>T (p.P84S, VAF 22.27%) and KDM5A exon19 c.2801C>T (p.P934L, VAF 24.59%). Both mutations have not been previously reported in MGT. Biomarker analysis indicated low TMB (1.4 mutations/Mb) and microsatellite stability (MSS). The co-occurrence of FOXP1 and KDM5A mutations suggests potential involvement of NOTCH signaling dysregulation in MGT pathogenesis. Conclusion: This case represents a rare duodenal MGT confirmed by histopathology and immunohistochemistry, with novel FOXP1 and KDM5A mutations identified for the first time. These findings broaden the molecular spectrum of MGT and highlight the importance of integrating molecular profiling into the diagnosis and management of rare tumors, while surgical resection remains the cornerstone of therapy.
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