Russell body gastritis showing IgM kappa‐type monoclonality

Abstract

We report here a unique case of Russell body gastritis showing localized monoclonal growth in the inflammatory gastric mucosa. A 74 year-old Japanese female with a history of dementia and atherosclerosis obliterans of the lower extremities suddenly complained of hematemesis, and the first gastric biopsy was performed around an open ulcer at the gastric angle. The urease test for Helicobacter pylori was positive, and a proton pump inhibitor was administered. One month later, the patient received follow-up gastroscopic biopsy for the survey of the healing of the gastric ulcer. Microscopically, in the lamina propria of the mildly inflamed, hyperplastic gastric mucosa, benign-looking plasma cells accompanying Russell bodies (‘Mott cells’) were focally clustered in one of the three pieces. There was neither active inflammation, lymphoid follicle formation, lymphoepithelial lesion, nor submucosal extension of the lymphoid infiltration, so that the possibility of mucosa-associated lymphoid tissue (MALT) lymphoma was histologically excluded. Intestinal metaplasia is associated, but H. pylori infection was not observed histologically. Russell bodies were reactive with periodic acid-Schiff reaction and phosphotungstic acid hematoxylin staining. Russell body-containing Mott cells expressed CD38, CD138 and CD79a, and Ki-67 labeling was sparsely noted (Fig. 1). CD20 and cytokeratin (AE1/AE3) were negative. Immunostaining was performed with the amino acid polymer technique. The Mott cells immunohistochemically showed IgM, kappa-type monoclonality (Fig. 2). IgG, IgA, IgD, IgE and lambda chain were unreactive in the Mott cells. The first biopsy specimen was reviewed, but no features of Russell body gastritis were recognized. Serum immunoelectrophoresis revealed a mild increase of immunoglobulin fractions, but no monoclonal peak was noted. Bence-Jones protein was negative in the urine. No clinicopathologic features of lymphoid neoplasia were proven. No disease progression was recorded during a one year follow-up period. Biopsy histology of Russell body gastritis. Accumulation of Russell body-containing plasma cells (Mott cells) is observed in the lamina propria of the metaplastic gastric mucosa (H&E, top left and top right panels). The Mott cells are strongly immunoreactive for CD38 (bottom left). Ki-67 labeling is sparse, with some labeling seen in non-plasma cells in the lamina propria (bottom right). IgM, kappa-type monoclonality seen in Russell body gastritis. Russell body-containing Mott cells demonstrate strong positivity for IgM (top left), while IgG is non-reactive (top right). Kappa chain is diffusely immunoreactive in the Mott cells (bottom left), while lambda chain positivity is seen in some small-sized plasma cells without cytoplasmic globules (bottom right). Since the first report by Tazawa and Tsutsumi in 1998,1 a total of 16 cases of Russell body gastritis have been reported,2-7 and four cases showed monoclonal proliferation.2, 4, 6, 7 Coyne et al.6 described IgM, kappa-type monoclonality in the Mott cells, as seen in the present case. Tabata et al.4 and Miura et al.7 also described kappa chain restriction in the Mott cells. Lambda-type monoclonality was reported by Wolkersdörfer et al.2 Hence, this is the fifth case of Russell body gastritis of monoclonal type. Choi et al.5 and Miura et al.7 most recently reviewed clinicopathological features of Russell body gastritis, summarizing frequent (but not consistent) association with Helicobacter pylori infection and occasional occurrence of candidal esophagitis, gastric carcinoma, gastric MALT lymphoma, and human immunodeficiency virus seropositivity. Monoclonal gammopathy of undetermined significance (so-called benign monoclonal gammopathy) have also been associated with Russell body gastritis, but the antibiotic eradication of Helicobacter pylori did not alter the state of paraproteinemia.2, 3 Monoclonal plasma cell proliferation in our case of Russell body gastritis does not necessarily indicate malignancy, nor predict the future development of true lymphoid neoplasm, we believe. The lesion was focal and non-progressive, and Ki-67-positive cells were scarcely observed. We would like to consider as one of the examples, the case where monoclonal B-cell proliferation is accompanied by chronic inflammation. Monoclonal B-cell growth in chronic inflammation has been reported in Hashimoto's thyroiditis,8 chronic hepatitis C,9 Sjögren's syndrome,10 and Helicobacter pylori-induced chronic active gastritis.11 Fan et al.9 supposed the monoclonality to be a sign of future progression to malignancy. Saxena et al.8 and Hsi et al.12 did not find any relation between the presence of B-cell clonality and later evolution to lymphoma. Saxena et al.8 have supposed that the presence of clonal B-cells in Hashimoto's thyroiditis represents a stage in the natural history of the disease and does not necessarily mean progression to overt lymphoma. Monoclonal B-cell proliferation in Russell body gastritis can be regarded as one of such benign monoclonal conditions, associated with Helicobacter pylori infected chronic gastritis. Diagnostic pathologists should be cautious of giving the diagnosis of neoplastic growth (such as MALT lymphoma), just based upon the immunohistochemical identification of immunoglobulin light chain restriction.