Diagnosis
Diagnosis
Glomus tumor of the stomach
Discussion
Gastric glomus tumors are rare mesenchymal neoplasms composed of modified smooth muscle cells, representing the visceral counterpart of the perivascular glomus body. Within the gastrointestinal tract, the stomach is the most common involved site, accounting for approximately 1% of all gastric mesenchymal tumors. These tumors show a predilection for the gastric antrum, more frequently than the gastric body.
Gastric glomus tumors show a female predominance, with a median age at diagnosis of approximately 55 years. They typically present as solitary masses and are often difficult to distinguish preoperatively from other gastric subepithelial lesions, particularly gastrointestinal stromal tumors (GISTs). Clinically, patients may present with upper gastrointestinal bleeding, epigastric pain, or symptoms of gastric outlet obstruction; however, many lesions are detected incidentally on endoscopy or imaging studies. Endoscopically, they usually appear as round to oval submucosal nodules. On H&E, glomus tumors are composed of solid nests and sheets of uniform round cells arranged around thin-walled blood vessels. The tumor cells have round nuclei with delicate chromatin, inconspicuous nucleoli, and a moderate amount of eosinophilic to clear cytoplasm with well-defined cell borders. Cytologic atypia is minimal, and mitotic activity is generally low. The stroma may show focal hyalinization or myxoid change.
Immunohistochemically, tumor cells show diffuse positivity for SMA, with frequent expression of caldesmon. Tumor cells are typically negative for cytokeratins, desmin, chromogranin, S100, CD56, CD34, CD117 (KIT), and DOG1. Focal synaptophysin expression may be seen and can represent a diagnostic pitfall in distinguishing these tumors from neuroendocrine neoplasms.
Most gastric glomus tumors pursue a benign clinical course, and surgical resection is generally curative. Rare malignant variants have been described. Proposed criteria for malignancy include deep location and size greater than 2 cm, atypical mitotic figures, moderate to marked nuclear atypia, and/or increased mitotic activity (≥5 mitoses per 50 high-power fields), Tumors meeting these criteria may demonstrate increased risk of metastasis and mortality.
Molecular studies in sporadic cases have identified recurrent rearrangement involving NOTCH signaling pathway most commonly CARMN::NOTCH2 fusion, as well as BRAF mutations. In contrast, multiple familial glomus tumors are associated with inactivating mutations in the GLMN gene and are inherited in an autosomal dominant pattern.
The differential diagnosis includes epithelioid GIST, which usually arises from the muscularis propria, lacks prominent dilated vessels, and expresses KIT and DOG-1. Neuroendocrine tumors are characterized by expression of cytokeratins, chromogranin, synaptophysin, and INSM1, and lack SMA and caldesmon expression. Paraganglioma, typically occurs in the retroperitoneum, shows a Zellballen growth pattern, expresses neuroendocrine markers, and demonstrates sustentacular S100 positivity, without SMA expression. Leiomyoma may also be considered; however, it typically shows spindle cell morphology with strong desmin and SMA expression and lacks a prominent perivascular growth pattern
References
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