Gastric Siderosis

Abstract

Recently, we encountered 2 cases of diffuse iron deposition in gastric antral and fundic glandular epithelium, which in 1 patient eventually led to the diagnosis of hemochromatosis. Gastric mucosal siderosis (GS) has previously been described in hemochromatosis patients, alcoholics, and in association with iron medications. However, the prevalence of various patterns of iron deposition in the gastric mucosa and their clinical significance have not been studied in detail. The 2 index cases mentioned above and 500 additional consecutive gastric biopsies examined over a period of 8 months at our institution were stained for iron by the Prussian blue method. In addition, all patients with genetic hemochromatosis diagnosed by liver biopsy in our department between 1998 and 2003 who also had gastric biopsies were identified from the surgical pathology files and included in the study (n = 3). The location of iron deposition [stromal cells (endothelium, fibroblasts, macrophages), glandular epithelium, or extracellular] was recorded and subjectively graded as 1+ to 3+ according to the severity of deposition within the mucosa. Relevant histologic changes (inflammation, presence of H. pylori, ulceration) and clinical features were reviewed. Three patterns of GS were identified: A) "nonspecific GS" with predominant iron deposition in the stromal cells including macrophages, and focally in epithelium; B) "iron-pill gastritis" with often mild gastritis and reactive gastropathy type changes, and mostly extracellular deposition with focal stromal cells and epithelial deposition; and C) predominant deposition in antral and fundic glandular epithelium. Of the 500 cases studied, a total of 18 (3.6%) cases were found to have GS. Of these 18 cases, 11 (2.2%) showed pattern A, 4 (0.8%) showed pattern B, and 3 (0.6%) showed pattern C. The GS in patterns A and B was always focal or patchy (1+ to 2+), whereas in pattern C it was generally diffuse and strong (2+ to 3+). A history of oral iron medication was present in 2 (n = 11, 0.4%) patients with pattern A, in all patients with pattern B (n = 4, 100%), and in none of patients with pattern C (n=3, 0%). Varying degrees of mucosal inflammation were noted in patients with pattern A cases, and 2 had evidence of active Helicobacter pylori infection. Of the 3 cases with known hemochromatosis, only one gastric biopsy showed pattern C GS (1+). In conclusion, gastric mucosal siderosis is relatively uncommon (3%) but is important to look for as it may lead to a diagnosis of hemochromatosis in some cases. Three patterns are recognized: A) a "nonspecific" stromal cell predominant pattern, which may be associated with gastric inflammation, possibly prior mucosal hemorrhages or iron medications; B) extracellular coarse clumps of crystalline iron deposition associated with oral iron medications, mild gastritis, and reactive gastropathy type changes ("Iron-pill gastritis"); and C) gastric glandular siderosis, which may be associated with systemic iron overload/hemochromatosis.

Gastric siderosis: An under-recognized and rare clinical entity

“…Since GS has been found in association with hemochromatosis, oral iron medications, alcohol abuse, blood transfusions, hepatic cirrhosis and spontaneous portacaval shunt with esophageal varices, it was interesting that in our cases none of these other factors were involved. 2 Interestingly, the pattern of iron deposition of one of the patients did not meet the pattern previously described in the literature. 2 We believe that identification of iron in gastric mucosa may have some clinical implications, and as such, recognition of this rare clinical entity will alert clinicians to investigate their patients further in order to determine the underlying causes.…”

“…1 The uptake of iron in the gastrointestinal (GI) tract is still not fully understood. 2 It is believed that the only regulated step of the iron metabolism cycle occurs during absorption in the duodenum and jejunum. 2 , 3 If the system becomes overwhelmed due to high iron levels (local or systemic), then iron can be absorbed very quickly in a passive concentration-dependent mechanism.…”

“… 2 It is believed that the only regulated step of the iron metabolism cycle occurs during absorption in the duodenum and jejunum. 2 , 3 If the system becomes overwhelmed due to high iron levels (local or systemic), then iron can be absorbed very quickly in a passive concentration-dependent mechanism. 4 Once there is an excess of iron in the body, it is initially stored as hemosiderin in the liver, and then later in the pancreas, heart and joints ( Figure 1 ).…”

“… 4 Once there is an excess of iron in the body, it is initially stored as hemosiderin in the liver, and then later in the pancreas, heart and joints ( Figure 1 ). 2 , 5 Since ferrous and ferric ions are catalysts for the formation of reactive oxygen metabolites and highly reactive radicals, damage will occur to the various organs and joints where iron accumulates. 2 , 4 , 6 , 7 When iron accumulates in the gastric mucosa, it is known as gastric siderosis (GS).…”

Gastric siderosis as a cause of dyspepsia

“…The literature lacks information concerning the changes of gastric haemosiderin deposits when iron chelation therapy is used. [1][2][3]…”