Gastric xanthomas (GX) are yellow mucosa (inner lining of a few organs and tissues) lesions formed due to lipid-laden histiocyte (phagocytic cells derived from monocytes and help in immune regulations) accumulation in the stomach's lamina propria (connective tissue of mucosa that provides for immune defense and helps the epithelium to move freely over the deep structures). Gastric xanthomas are seen in chronic gastritis, hyperplastic polyps, gastric cancer, and Helicobacter pylori infection and are not associated with hyperlipidemia.
Which Are the Frequently Affected Sites of Gastric Xanthoma?
Gastric xanthomas are rare lesions of the gastrointestinal tract. The stomach is the most affected part of
the gastrointestinal tract, while the duodenum and colon have rare involvement. The antrum, the lowermost part of the stomach, is frequently involved.
What Is the Pathogenesis of Gastric Xanthoma?
The pathogenesis of gastric xanthoma is still not fully understood, but it is thought that it is an inflammatory response to the intestinal mucosa. Fat-laden debris is believed to be left behind due to chronic inflammation and during the healing process of the gastric mucosa. Histiocytes phagocytose them, resulting in foam cells.
What Are the Risk Factors of Gastric Xanthoma?
The specific etiology of gastric xanthoma is unknown; however, several factors that can cause gastric xanthoma have been reported. The risk factor includes
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Dyslipidemia- It is an abnormal lipid level of the blood in which mainly cholesterol, triglycerides, and LDL (low-density lipoproteins) increase. At the same time, there is a decrease in HDL (high-density lipoproteins), which is one of the risk factors for xanthelasma growth. As per research studies, gastric xanthoma is higher in patients with high triglyceride and glucose levels.
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Previous Gastric Surgeries- Atrophy of the tissue can be seen due to previous gastric surgeries, hence one of the risk factors for gastric xanthoma.
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Atrophy and Intestinal Metaplasia- Gastric xanthoma was observed in patients where intestinal metaplasia was discovered. These patients have a high degree of atrophic changes in the intestines.
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Gastric Cancer- Research studies have proven that gastric xanthoma is a marker for higher gastric cancer.
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Hyperplastic Polyps- These are the non-cancerous growth of the intestinal lining. Research studies showed a close relationship had been found between hyperplastic polyp and gastric xanthoma. The coexistence of both conditions has been attributed to inflammatory reactions due to mucosal damage.
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Reflux Gastritis- This is a condition in which bile washes back into the stomach as the valve is not closed, leading to inflammation of the stomach lining. Reflux gastritis causes inflammation of the gastric mucosa and hence can cause gastric xanthoma.
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Weak Immune System or Immunosuppression- Weak immunity can also be a predisposing clinical feature for gastric xanthoma.
What Are the Endoscopic Findings in Gastric Xanthoma?
Gastric xanthomas are asymptomatic and are coincidentally discovered during routine endoscopic examination. An upper gastrointestinal tract endoscopy examines the upper gastrointestinal (stomach, esophagus, and upper portion of the duodenum) tract. This investigation is also called an esophagogastroduodenoscopy since it examines all three organs. Upon investigation, gastric xanthomas appear in the upper gastrointestinal tract. These small-sized (less than 1 cm) plaques appear yellow-white and have a rough surface. These can be single or multiple lesions. Once gastric xanthomas have been confirmed during routine endoscopic diagnosis, a biopsy is advisable to rule out the chances of gastric cancer.
What Are the Histological Findings in Gastric Xanthoma?
The histological appearance of gastric xanthomas shows histiocyte aggregates. They are uniform polygonal cells with foamy cytoplasm that fills the lamina propria and have a pavement-like pattern. As they grow in size, they invade deep into the submucosa. Lymphocytes, plasma cells, and macrophages are present along with the foam cells. The histiocytes show the presence of cholesterol or neutral lipids.
What Is the Differential Diagnosis of Gastric Xanthoma?
Many gastrointestinal lesions show similar characteristics to gastric xanthoma, histologically and upon endoscopic diagnosis. These lesions have different clinical significance from gastric xanthoma. Hence it is essential to provide a correct differential diagnosis.
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Russell Body Gastritis (RBG)- It is a rare inflammatory disorder that mainly affects the gastric antrum of the stomach. Histologically, polygonal plasma cells that contain Russell bodies are found. The eosinophilic globules displace the nucleus. Inflammatory cell infiltration occurs in the nucleus. The plasma cells do not show the presence of nuclear atypia, cytokeratin, or muciramine. Endoscopically, large whitish lesions are visible that can be misdiagnosed for xanthoma, signet cell carcinoma, and malignant lymphoma. Plasma cell infiltration in the nucleus is marked by plasma cell markers CD138 and CD79A.
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Singet-Cell Adenocarcinoma- Histologically, it shows the presence of foamy cells along with a centrally placed nucleus. Atypical cells are also found.
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Pseudoxanthoma Elasticum (PXE)- It is a genetic metabolic disorder characterized by calcium and other mineral deposition in the elastic fibers (the connective tissue that provides power and flexibility to the body tissues) of the body. Mutations occur in the ABCC6 gene. This gene regulates the production of MRP6 protein, mainly found in the liver and kidney cells, with a minimal amount found in the skin, eyes, stomach, and blood vessels. MRP6 protein helps to transfer a few substances across the cell membrane and thus to release adenosine triphosphate (ATP) from the cells. Pseudoxanthoma elasticum lesions are related to high incidences of gastrointestinal bleeding due to the defective vascular component.
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Xanthogranuloma- It is a benign condition characterized by nodules found in the skin of infants, neonates, and adults. It is observed as light-yellow nodules. Histologically, the lesion is made up of foamy histiocytes along with inflammatory cells (both chronic and acute). Stomach xanthogranuloma is very rare, and very few cases have been reported. Xanthogranuloma can also affect the colon and uterus. Gastric mucosa and the pancreas.
What Are the Signs and Symptoms of Gastric Xanthoma?
Unclear symptoms are presented in gastric xanthoma and do not represent specific symptoms of gastric xanthoma; hence other diagnostic tools are used to confirm the diagnosis.
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Dyspepsia (discomfort of the upper abdomen presented as bloating and burning sensation).
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Abdominal pain.
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Nausea.
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Vomiting.
Conclusion
The clinical significance of gastric xanthoma is unclear; however, gastric cancer incidences are relatively higher in patients with gastric xanthoma. Gastric xanthoma is also seen in the inflammatory response to intestinal focal mucosal damage. Histological confirmation is mandatory to rule out the possibility of any precancerous lesion of the gastric mucosa or gastric cancer.
