Case report and review of duodenal malignant glomus tumor with novel molecular variants

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Frontiers in Medicine Published May 26, 2026 Medically reviewed May 26, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider integrating molecular profiling in rare duodenal tumors, but interpret novel variants with caution due to uncertain significance.

This publication is a case report and literature review of a duodenal malignant glomus tumor in a 47-year-old woman. The authors describe the diagnosis, confirmed by histopathology and immunohistochemistry, and report molecular findings. Two class III variants of uncertain significance were identified: FOXP1 exon7 c.250C>T (p.P84S, VAF 22.27%) and KDM5A exon19 c.2801C>T (p.P934L, VAF 24.59%). Biomarker analysis showed low tumor mutational burden (1.4 mutations/Mb) and microsatellite stability.

The review synthesizes that both mutations have not been previously reported in malignant glomus tumors. The co-occurrence of FOXP1 and KDM5A mutations suggests potential involvement of NOTCH signaling dysregulation in pathogenesis, but this is a hypothesis based on a single case. The authors highlight the importance of integrating molecular profiling into the diagnosis and management of rare tumors.

Key limitations noted include the single-case design and the fact that both variants are of uncertain significance. The review does not report a study population, intervention comparator, or adverse events beyond the surgical resection performed. Practice relevance is restrained, noting that surgical resection remains the cornerstone of therapy while molecular data may inform future management.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

BackgroundMalignant 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 PresentationWe 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 FindingsNext-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.ConclusionThis 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.