Molecular Mechanisms and Clinical Implications in Gastric Glomus Tumors

Riad Chakroun^*
*Correspondence: Riad Chakroun, Department of Molecular Biology Cell, University of Monastir, Monastir 5000, Tunisia, Email:

Introduction

Glomus tumors are rare mesenchymal neoplasms that arise from the glomus body, a specialized arteriovenous anastomosis involved in thermoregulation. Although these tumors most commonly occur in the extremities, especially under the fingernails, their presence in visceral organs such as the stomach is uncommon and poorly understood. Gastric glomus tumors account for a very small percentage of gastrointestinal tumors, but they possess distinct clinicopathological and molecular features that warrant deeper scientific investigation. These tumors typically arise in the gastric antrum and are submucosal in location. Their clinical presentation can range from being asymptomatic to causing abdominal pain, gastrointestinal bleeding, or even gastric outlet obstruction in rare cases [1].

Due to their submucosal origin and vascular nature, gastric glomus tumors are often difficult to distinguish from other gastrointestinal tumors such as Gastro Intestinal Stromal Tumors (GISTs), leiomyomas, or neuroendocrine tumors. Radiological imaging, endoscopic examination and histopathological analysis are typically employed to achieve a diagnosis. However, despite histological similarities, the underlying molecular biology of glomus tumors differs significantly from other gastric neoplasms. With advancements in molecular diagnostics, there is increasing interest in understanding the molecular and genetic basis of these tumors to improve diagnostic accuracy and therapeutic outcomes. Research into the molecular mechanisms governing the development and progression of gastric glomus tumors remains limited but promising. Recent studies have suggested the involvement of various signaling pathways, such as the VEGF (vascular endothelial growth factor) pathway, the PI3K/AKT/mTOR pathway and alterations in key oncogenes and tumor suppressor genes including KRAS, p53 and SMARCB1. The application of Next-Generation Sequencing (NGS) and immunohistochemical profiling has helped identify a number of molecular markers that can aid in diagnosis and potentially serve as therapeutic targets. Moreover, the expression patterns of smooth muscle markers such as actin, desmin and calponin, along with CD34 and vimentin, provide insights into the tumorâ??s cellular origin and behavior.This paper aims to present a comprehensive overview of the current understanding of gastric glomus tumors from a molecular biology perspective. It will explore their clinical manifestations, histopathological features, molecular alterations and implications for diagnosis and treatment. With the growing trend toward precision medicine and targeted therapies, a better understanding of the molecular mechanisms underlying gastric glomus tumors can significantly influence the clinical management and prognosis of affected patients [2].

Description

Gastric glomus tumors are primarily found in the gastric antrum and present as well-circumscribed, submucosal lesions. Most patients are diagnosed incidentally during endoscopic procedures or imaging studies performed for unrelated conditions. Symptomatic patients may report vague upper abdominal discomfort, nausea, or upper gastrointestinal bleeding. In rare instances, when the tumor becomes significantly enlarged, it may result in obstruction or mass effect. Due to these non-specific symptoms, diagnosis based on clinical features alone is virtually impossible. Endoscopy may reveal a submucosal bulge with or without ulceration, while CT scans typically demonstrate a hypervascular mass with homogeneous enhancement, distinguishing it from other submucosal gastric lesions [3].

Histologically, gastric glomus tumors are composed of small, uniform, round cells arranged in sheets or nests surrounding capillary-sized blood vessels. The tumor cells have eosinophilic cytoplasm and centrally located nuclei without significant pleomorphism. Immunohistochemical staining is crucial in differentiating glomus tumors from other neoplasms. These tumors are positive for Smooth Muscle Actin (SMA), vimentin, calponin and collagen type IV, indicating their smooth muscle origin. They are usually negative for CD117 (c-KIT), DOG1 and S-100 protein, which are typically seen in GISTs and other soft tissue tumors. From a molecular perspective, glomus tumors are relatively understudied compared to more common gastrointestinal tumors. However, recent advances in genomic technologies have begun to uncover the molecular alterations associated with these neoplasms. One notable genetic abnormality is the loss of expression of the SMARCB1 (INI1) gene, a tumor suppressor involved in chromatin remodeling and transcriptional regulation. In some cases, mutations in KRAS and BRAF genes have also been reported, suggesting possible dysregulation of the MAPK signaling pathway. Additionally, overexpression of VEGF and related angiogenic factors appears to contribute to the tumorâ??s rich vascular network, offering a potential target for anti-angiogenic therapies [4].

Furthermore, the PI3K/AKT/mTOR pathway has been implicated in the tumorigenesis of glomus tumors, particularly in those with more aggressive histologic features. This pathway regulates cell proliferation, survival and angiogenesis and its activation may confer a growth advantage to tumor cells. Molecular inhibitors targeting this pathway, already in use for other cancers, may offer therapeutic potential in selected cases of gastric glomus tumors, especially those that are malignant or recurrent. Malignant glomus tumors, also known as glomangiosarcomas, are exceedingly rare but do occur and can metastasize to distant organs. Histologically, they exhibit increased mitotic activity, nuclear atypia and infiltrative growth patterns. Molecularly, these malignant forms often harbor additional mutations, including those in TP53, which is associated with genomic instability and poor prognosis. Such malignant tumors are more likely to recur after surgical excision and may benefit from adjuvant therapies, though no standardized regimen exists due to the rarity of cases. From a treatment standpoint, surgical resection remains the mainstay of therapy for gastric glomus tumors. Complete excision is typically curative in benign cases. Minimally invasive approaches such as laparoscopic wedge resection or endoscopic submucosal dissection have shown favorable outcomes. The role of chemotherapy and radiotherapy is limited, especially in benign cases, but may be considered for malignant tumors with aggressive behavior. Given the emerging molecular insights, there is growing interest in exploring targeted therapies, particularly in cases with known genetic mutations or pathway activation. The clinical implications of these molecular findings are substantial. For example, identifying VEGF overexpression or PI3K pathway activation may guide the use of tyrosine kinase inhibitors or mTOR inhibitors, respectively. Moreover, the discovery of specific genetic mutations can help distinguish glomus tumors from GISTs, which often require different treatment strategies, such as imatinib therapy. Ultimately, incorporating molecular diagnostics into the routine evaluation of gastric submucosal tumors can enhance diagnostic precision and therapeutic decision-making [5].

Conclusion

In conclusion, genetic factors are fundamental in shaping human metabolic processes and exert a profound influence on individual health outcomes. From monogenic disorders with well-defined gene mutations to the subtle contributions of polygenic traits, genetics determine how efficiently the body processes nutrients, stores energy and responds to environmental stimuli. While the identification of specific genetic variants has enhanced our understanding of metabolic regulation, it is also evident that these factors do not act in isolation. The interplay between genetic predisposition and environmental influences, including diet, physical activity and epigenetic modifications, defines the complexity of human metabolism. The integration of genetic knowledge into clinical practice through genetic screening, risk prediction and pharmacogenomics holds immense potential to transform the management of metabolic disorders. As research continues to uncover the intricate relationship between our genes and metabolism, the vision of personalized and predictive medicine becomes increasingly achievable. Future efforts should focus on translating genetic insights into effective public health strategies and individualized interventions, ultimately improving metabolic health and reducing the global burden of chronic disease.

Acknowledgement

None.

Conflict of Interest

None.

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