Multiple Gastric Xanthomas in a 3-Year-Old Patient

Gastric xanthomas are uncommon endoscopic lesions that may cause diagnostic confusion in patients at risk for neoplasia. Although population studies have shown an incidence of 0.018% for gastric xanthomas,¹ endoscopic studies have reported an incidence of 2–9%.^2,3 Peak incidence of these lesions increases with age (up to 40%). In addition, gastric xanthomas are more frequently found in patients with both active and healed gastric ulcers and in patients who have undergone gastric resection.

Gastric xanthomas are usually solitary lesions in the gastric antrum or prepyloric areas. Findings may include multiple lesions (in 24% of cases) and plaques. Although involvement in all areas of the gastrointestinal tract have been reported, involvement in the stomach predominates. Size is variable (up to 3 cm), but most gastric xanthomas are less than 1 cm. Histologically, gastric xanthomas are characterized by lipid-laden macrophages, often called foam cells, that infiltrate the lamina propia. Foam cells contain cholesterol with or without neutral fat.^4,5

Identification of the cause of gastric xanthomas has been controversial. Gastric damage is a common association, with a high incidence in ulcer and surgical patients.⁶ The repair of the damage produced by chronic inflammation leaves behind lipid-laden debris, which is phagocytized by histocytes and forms foam cells. Gastric xanthomas were found in 6.3% of nonoperated, age-matched control patients and 6.2% of patients 1–3 years after gastric surgery. Twenty-three years after gastric surgery, the incidence of gastric xanthomas increased to 60%. Cholesterol levels, lipid levels, and the patient's age were unrelated. Intestinal metaplasia with bile reflux has been shown to increase cellular lipid transport. Permanent cellular change was hypothesized and supported by the fact that the lesions did not change in appearance over time. Increased frequency in the elderly (up to 40%), increased gastric atrophy, and decreased pepsinogen production are consistent with this theory.

Helicobacter pylori infection is closely associated with gastric atrophy. Age- and gender-matched patients with and without gastric xanthomas showed a higher incidence of H. pylori infection in patients with gastric xanthomas (94% vs 72%). Extensive gastric atrophy was also more common both endoscopically and histologically in xanthoma patients. The serum pepsinogen I and pepsinogen I/ pepsinogen II ratio were lower in patients with gastric xanthomas, which is a finding that is consistent with proximal gastric atrophy. H. pylori antigens were also found in most gastric xanthoma foam cells (86%), whereas immunoreactivity was not found for H. pylori antigens in H. pylori–negative specimens of gastric xanthomas.⁷

Lipid levels have had an unclear role in gastric xanthomas.⁸ Two cases of profound gastric xanthomatosis have been reported in patients with profound cholestasis. Resolution of the gastric xanthomas occurred with the resolution of cholestasis and the return of normal cholesterol and triglyceride levels. This finding supports the idea that not all xanthomas are permanent.⁹

As both gastric ulceration and gastric resection carry an increased risk for gastric cancer, signet-cell gastric adenocarcinoma is in the differential diagnosis of gastric xanthomas. Standard histology of xanthomas usually shows regular nuclear cells centrally located in the foam cells, though atypical cells can be seen in cytology preparations. Masson trichrome staining can be positive in both entities. Periodic acid Schiff staining is uniformly negative in gastric xanthomas and strongly positive in gastric signetcell adenocarcinoma.¹⁰

Halabi and associates reported the case of a 3-year-old boy with chronic abdominal pain who underwent upper gastrointestinal endoscopy, which revealed multiple xanthomas. Clinical concern for malignancy made the differential diagnosis difficult. Periodic acid Schiff staining and pancytokeratin staining confirmed the diagnosis of gastric xanthoma, though no potential cause for the xanthomas was seen (ie, no inflammation, H. pylori infection, gastric atrophy, or cholestasis). The abdominal pain resolved, though the gastric xanthoma persisted in short-term follow-up. Long-term re-evaluation was not available. This case, which involved multiple lesions, was the first pediatric case reported in the literature, according to the authors.¹¹