volume 76, no. 5 261

ABSTRACT—Russell body gastritis is character-ized by accumulation of plasma cells, filled with Russell bodies, in the gastric mucosa. Twelve cases have been reported in the English language medical literature. Its association with Helicobacter pylori gastritis or immunosuppression is known. The pres-ent case is the third to be reported in association with HIV infection. An 82-year-old male presented with dyspepsia, loose stools, loss of appetite and weight. Computed tomography scan showed esophageal and gastric wall thickening. Gastrointestinal endoscopy revealed gastritis. Microscopic examination of the biopsy revealed gastric mucosa with diffuse plasma cell infiltration in the lamina propria, associated with large eosinophilic Russell bodies. Immunoperoxi-dase stains revealed positivity for CD 138 and lambda and kappa chains. Special stain for Helicobacter pylori and immunostain for CD68 were negative. The differential diagnoses include plasmacytoma and mucosa associated lymphoid tissue (MALT) lymphoma with plasmacytic differentiation, which are entities with different prognostic and therapeutic implications.

Introduction

The term Russell body gastritis was described for the first time in 1998 as a peculiar lesion of the gastric mucosa characterized by localized accu-

mulation of numerous plasma cells filled with Russell bodies along with inflammatory infiltrate.1 To the best of our knowledge, only twelve cases have been reported in the english language medical literature to date. The present case is the third to be reported in association with HIv infection.2,3 The other cases have been associated with Helicobacter pylori gastritis, epstein Barr virus infection, esophageal candidiasis, gastric adenocarcinoma and renal failure.

Case Report.—An 82-year-old patient presented to the gastroenterology office with complaints of dyspepsia, loose stools, anorexia and significant weight loss of 25 pounds within three months. He denied any blood in the stool and stated that he had a colonoscopy two years prior, which was reported as normal. Past medical his-tory was significant for HIv infection, cerebrovascular accident, chronic kidney disease, peripheral vascular disease, hypertension, depression and diabetes melitus Type 2. Family history was significant for laryngeal cancer. Social history was significant for smoking in the past and social alcohol use.

on physical examination the patient appeared chroni-cally ill but was in no acute distress. vital signs revealed a blood pressure of 110/60 and a BmI of 18.4. The abdo-men was soft, nontender, nondistended and with bowel sounds. The remainder of the physical examination was unremarkable. laboratory findings were remarkable for a sodium level of 137, K of 4.1, Bun of 9, creatinine 1.79 and calcium 10.9. White count and differential were within normal limits.

Russell Body Gastritis in an HIV Positive Patient: Case Report and Review of Literature

AmARPReeT BHAllA, mD, DIAnA moSTeAnu, mD, STeven GoRelIcK, mD AnD HAnI-el-FAneK mD

AmARPReeT BHAllA, mD, PGY-2 Department of Pa-thology and laboratory medicine, Danbury Hospital, DIAnA moSTeAnu, mD, PGY-3 Department of Internal medicine, Danbury Hospital,STeven GoRelIcK, mD, clinical As-sistant Professor, Department of Gastroenterology, Danbury Hospital; HAnI-el-FAneK, mD, clinical Assistant Professor, Department of Pathology and laboratory medicine, Danbury Hospital. Abstract presented at: college of American Pathologists (cAP 2011), Sep 11,Gaylord Texan, Grapevine, Texas: Poster ses-sion 100: Poster #54. Financial support: The case was received and reported at Danbury hospital. no additional expenses were incurred for research purposes. Approved by IRB. no financial interests.

connecTIcuT meDIcIne, mAY 2012262

A computerized tomography (cT) scan of the abdo-men revealed esophageal and gastric wall thickening. An upper gastrointestinal endoscopy revealed gastritis. The microscopic examination revealed fragments of gastric mucosa with plasma cell infiltration. The lamina propria was expanded by prominent diffuse infiltration by plasma cells associated with large eosinophilic Russell bodies. (Fig. 1 & 2). Immunoperoxidase stains revealed strong positivity for cD 138 (Fig. 3), lambda and kappa chains (Fig. 4 & 5). Special stain (Giemsa) for Helicobacter pylori was negative.

The patient continued to have weight loss and loose stools. Subsequent colonoscopy showed erythematous mucosa and biopsies taken revealed microscopic col-lagenous colitis.

DiscussionRussell body gastritis is an extremely rare presenta-

tion of gastritis. clinically, patients with Russell body gastritis usually present with nausea, epigastric pain and dyspepsia. Russell body gastritis is not associated with

Figure 1.—Gastric mucosal biopsy showing expansion of lamina propria with Russell body laden plasma cells. (Hematoxylin and eosin X100).

Figure 2.—Gastric mucosal biopsy, Russell body gastritis (Hematoxylin and eosin X400).

Figure 3.—Gastric mucosal biopsy, CD 138, staining the plasma cells and gastric epithelium. (Immunohistochemical stain X400).

Figure 4.—Gastric mucosal biopsy, kappa cytoplasmic stain for plasma cells (Immunohistochemical stain X400).

Figure 5.—Gastric mucosal biopsy, lambda cytoplasmic stain for plasma cells (Immunohistochemical stain X400).

specific endoscopic findings, but may include hyperemia, mucosal swelling, erosive or ulcerative lesions, single or multiple yellow raised lesions or pangastritis.

volume 76, no. 5 263

found dispersed in small numbers among a larger com-ponent of polymorphous lymphocytic infiltrate. Russell bodies are formed as a result of a block in the normal pathways of immunoglobulin secretion in plasma cells, resulting in sequestration of abnormal immunoglobulin within vesicles.

mott cells are plasma cells whose rough endoplasmic reticulum is stuffed with Russell bodies.

Russell bodies can be found in neoplastic cells of plasmacytoma and lymphoproliferative disorders, B cell lymphomas, Hashimoto’s thyroiditis, rheumatoid arthritis and ulcerative colitis. A small number of Rus-sell bodies are occassionally identified in either chronic follicular gastritis or gastric mucosa-associated lymphoid tissue (mAlT) lymphoma. In these conditions, mott cells and Russell bodies are usually found dispersed in small numbers among a larger component of polymor-phous lymphocytic infiltrate.5,7,8

Plasma cells are an integral component of the gastric lamina propria in chronic gastritis, where they are usu-ally admixed with lymphocytes and a variable amount of neutrophils. The present case revealed positivity for human immunodeficiecy virus. The pathogenesis is related to polyclonal B cell activation present in HIv infection, which leads to plasmacytosis, hypergam-maglobulinemia and formation of circulating immune complexes. It is a consequence of reactivation or reinfec-tion with cytomegalovirus or epstein-Barr virus (eBv). The viral envelope glycoprotein gp 41 promotes B cell growth and differentiation. HIv infected macrophages produce increased amounts of Il-6 which stimulates proliferation of B cells.10 Also cD70 (cD 27 ligand) is expressed spontaneously or by activation on T cells of HIv-infected patients, which stimulates memory B cells via cD27 and promotes their differentiation into plasma cells, resulting in the elevation of serum immunoglobulin levels and the elimination of circulating memory B cells in HIv-infected patients.11

Helicobacter pylori is known to have a causative role in chronic gastritis and mAlT lymphoma. The bac-terium adheres to the surface of the gastric epithelium and generates cellular and humoral responses through antigenic stimulation of mucosal monocytes and T cells. consequently, T cell-driven activated B cells aggregate to form lymphoid follicles and may differentiate into immu-noglobulin (Ig) m, IgA or IgG antibody-producing cells. The lesions disappear following treatment of H. pylori.8

In their original report Tazawa and Tsutsumi favored an associated infection with Helicobacter pylori to be responsible for this unique lesion but they propose the publication of similar cases in order to clarify the nature and biological significance of Russell body gastritis.

The histological features of this lesion are described in various case reports. The lesion is characterized by expansion of lamina propria due to localized accumula-tion of Russell bodies and abundant homogenous cells with eosinophilic cytoplasmic inclusions and eccentric nuclei. The cells resemble plasma cells and mott cells. Dutcher bodies have not been reported in any case. The immunoreactive pattern of the cells to light chains is polyclonal. moderate glandular atrophy may be associ-ated. Few reported cases reveal neutrophilic cryptitis, regenerative crypt hyperplasia, intestinal metaplasia. mitoses and other evidence of proliferative activity is absent. In case there is associated Helicobacter pylori infection, the rod-like bacteria may be found in the mu-cous overlying the foveolar epithelium. Small lymphoid follicles may be found adjacent to but not within the collection of mott cells.4–8

The histological differential diagnoses include plas-macytoma, non-Hodgkin lymphoma, especially mucosa associated lymphoid tissue lymphoma with plasmacytic differentiation, lesions associated with multiple myeloma, signet ring cell carcinoma and granular cell tumor. mott cells may be found in higher number at the periphery of carcinomas. Similar lesions have been described in the esophagus and cervix.9

Immunohistochemically, the cells stain positively for cD79a and cD38, but stain negative for cD20, thus confirming them to be plasma cells. non-Hodgkin lymphoma is ruled out due to the absence of atypia, cen-trocyte-like cells, monocytoid cells and lymphoepithelial lesions. The plasma cells in multiple myeloma stain for either kappa or lambda antibodies owing to monoclonal nature. The signet ring cell carcinoma cells stain for cytokeratin antibodies and are negative for markers of lymphoid lineage. Granular cell tumor stains for S-100, laminin and calretinin.

A summary of reported cases of Russell body gastritis and related lesions is described in Table 1. In one of the reported cases, the patient underwent investigation for associated plasma cell neoplasia. Serum immune and protein electrophoresis, bone marrow trephine biopsy revealed no significant abnormality. The plasma cell ratio was within normal limits.7,8

Plasma cells are an integral component of the gastric lamina propria in chronic gastritis, where they are usu-ally admixed with lymphocytes and a variable amount of neutrophils.

Russell bodies were first described by Russell in 1890. They are spherical eosinophilic structures and represent aggregates of immunoglobulins which are abnormally se-creted and accumulate within dilated rough endoplasmic reticulum cisternae of the plasma cells. They are usually

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82

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volume 76, no. 5 265

In the previously reported cases there was a resolution of symptoms with treatment of the chronic gastritis with no information regarding endoscopic follow up.1

ConclusionAlthough Russell body gastritis is by itself a benign

condition, its long-term effect, such as its possible increased risk for the development of neoplasia, is un-known. It has been reported in three cases with HIv infection and results from hypergammaglobulinemia. clinically, it may be worthwhile to implement Heli-cobacter pylori eradication treatment in this peculiar disease entity. Histologically, awareness of this disease is important in order to prevent confusion with neopla-sia. Doubtful cases require tissue analysis using more sophisticated molecular techniques but clinicopathologic correlations are helpful in establishing a correct diagnosis.

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12. Wolkersdörfer GW, Haase m, morgner A, et al: monoclonal gammopathy of undetermined significance and Russell body formation in Helicobacter pylori gastritis. Helicobacter 2006; oct; 11(5):506–10.

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