Annals of Surgical Oncology, 5(5):407-410 Published by Lippincott-Raven Publishers © 1998 The Society of Surgical Oncology, Inc.

Gastric Adenocarcinoma Associated with Isolated Granulomatous Gastritis

Christopher Newton, MD, Lucien Nochomovitz, MD, and Jonathan M. Sackier, MD, FRCS, FACS

Background: Granulomatous gastritis is a rarely observed pathological diagnosis. This condition often mimics gastric adenocarcinoma clinically, resulting in gastric resection. However, granulo- matous gastritis has long been viewed as a benign process not observed in association with adeno- carcinoma of the stomach. This article describes a patient with granulomatous gastritis occurring in close proximity to an area of superficially invading gastric adenocarcinoma.

Methods: Acid-fast stains, fungal stains, standard cultures, tuberculosis cultures, and a VDRL serum test were all obtained. Both upper endoscopy and colonoscopy were performed. Chest radiographs were taken and pulmonary consultation was obtained.

Results: The gastric samples obtained from resection showed no evidence of foreign body reaction. The acid-fast stains, fungal stains, cultures, and VDRL were all negative. Endoscopic exams did not show granulomatous inflammation in any other part of the gastrointestinal tract. No pulmonary disease was evident on radiographic or pulmonary exam.

Conclusion: Isolated granulomatous gastritis is a diagnosis of exclusion, The findings in this patient do not support a diagnosis of Crohn's disease, tuberculosis, sarcoidosis, syphilis, histoplas- mosis, berylliosis, or foreign-body reaction. This is a unique case suggesting an association between isolated granulomatous gastritis and metaplastic mucosal changes.

Key Words: Granuloma--Stomach--Granulomatous gastritis--Carcinoma.

Isolated granulomatous gastritis is a rare occurrence. It was first characterized as a separate pathologic entity by Fahimi in 1963,1 and since then, several cases have been reported with various presentations. It is defined by the exclusion of other disease processes which could give rise to granutoma formation in the stomach, including Crohn's disease, sarcoidosis, tuberculosis, histoplasmo- sis, berylliosis, and foreign-body reactions.

Granulomatous gastritis most often presents with clinical and radiologic features similar to gastric carci- noma. With rare exceptions, these patients have not had histologic evidence of neoplasm, and this has not been considered as a premalignant condition. In this unusual case, isolated granulomatous gastritis was discovered

Received April 3, 1997; accepted September 9, 1997. From the Department of Surgery, George Washington University

School of Medicine and Health Sciences, Washington, DC. Address correspondence and reprint requests to: Jonathan M.

Sackier, MD, Dept. of Surgery ACC--6B, George Washington Uni- versity School of Medicine and Health Sciences, 2150 Pennsylvania Ave., NW, Washington, DC 20037.

after subtotal gastr ic resect ion for b iopsy -p roven adenocarcinoma.

CASE REPORT

A 55-year-old black man was admitted in February 1996 for gastric resection of a malignant ulcer that had been seen and biopsied endoscopically two weeks ear- lier. At the time of presentation he was asymptomatic. In 1970 he had undergone surgical repair of a perforated duodenal ulcer; since then he had been followed by a gastroenterologist, experiencing several recurrences of peptic ulcer disease. During the 3 years prior to this admission, he had been symptom-free with daily doses of omeprazole. As a part of his routine follow-up and sur- veillance with the gastroenterologist, an upper endos- copy was performed in 1995; it revealed a prepyloric ulcer that was Hpylori-positive. Following antibiotic and continued omeprazole therapy, a repeat endoscopy re- vealed a refractory 1.5 x 1.5 cm antral ulcer.

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408 C. NEWTON ET AL.

FIG. 1. Adenocarcnoma of the stomach (arrow), seen invading into the submucosa.

Biopsies of the gastric mucosa revealed glandular dys- plasia consistent with adenocarcinoma. Acute gastritis and intestinal metaplasia were noted; at that time, how- ever, there was no detection of granuloma formation in the stomach. Abdominal computed tomography was sug- gestive of gastric carcinoma, with possible regional in- vasion into the celiac and portal hepatic lymph nodes. Chest radiography showed no pulmonary lesions and no evidence of lymphadenopathy.

The patient's past surgical history was significant for a perforated ulcer repair in 1970. His medical history was significant for hypertension, which was treated with clorthalidone. He had a 20 pack-year smoking history, drank alcohol on occasion, and denied any family history of malignancy. His physical examination was benign, without lymphadenopathy or significant abdominal signs, and with hemoccult-negative stool.

He underwent a subtotal gastrectomy and splenec- tomy. Intraoperatively, there was no gross evidence of invasive gastric carcinoma and no metastases. The stom- ach wall was thickened throughout with prominent mu- cosal folds. The stomach, a portion of the greater omen- turn, and gastroepiploic and gastrosplenic nodes were sent for histologic evaluation.

lymph nodes and the spleen were without evidence of carcinoma or granulomatous inflammation. Several gas- troepiploic nodes showed reactive hyperplasia.

Several relatively compact noncaseating granulomas with occasional giant cells were associated with the an- tral lesion (Fig. 2). There was no associated debris, crys- tals, or cytoplasmic or extracellular bodies noted that would suggest a foreign-body-type reaction (Fig. 3). The granulomas were isolated to the mucosa and upper sub- mucosa and were not found in the lymph node samples. H pylori was absent from the surgical specimens.

An upper gastrointestinal series with small-bowel fol- low-through and a colonoscopy were performed to ex- amine the remainder of the GI tract for signs of further granulomatous inflammation. These tests showed no evi- dence of inflammation, ulceration, polyps, or malig- nancy. The disease process appeared to be isolated to superficial layers of the stomach only, which effectively ruled out Crohn's disease.

Acid-fast stains, fungal stains, and tuberculosis cul- tures of the surgical specimens were negative. In addi-

PATHOLOGY

The pathology of the specimens revealed minimally invasive well-differentiated adenocarcinoma in the an- trum of the stomach (Fig. 1). The malignancy was ap- proximately 1.5 x 1.5 cm, with clear surgical margins, invading the uppermost layers of the submucosa. Diffuse follicular gastritis was also noted, with intestinal meta- plasia of the mucosa surrounding the primary lesion. The duodenum was histologically normal. All of the sampled

FIG. 2. Granuloma seen in the submucosa (arrow) with overlying carcinoma in situ in the antrum of the stomach.

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ADENOCARCINOMA AND ISOLATED GRANULOMATOUS GASTRITIS 409

FIG. 3. High-power view showing a granuloma (arrow) in the antral submucosa.

tion, chest radiographs were clear, showing no evidence of infiltration, adenopathy, or pleural anomalies. In light of these findings, tuberculosis, sarcoidosis, and fungal infection were also ruled out.

DISCUSSION

Fahimi's 1963 paper ~ gives a definitive description of three cases of granulomatous gastritis that were not as- sociated with sarcoidosis or regional enteritis. On this basis, he argued for isolated granulomatous gastritis as a separate clinicopathologic entity. While the histologic examination of the granulomas in the patients he de- scribed varied, none of the patients showed evidence of the typical etiologies for granulomatous inflammation. In all of Fahimi's cases, gastric carcinoma was suspected based on clinical and radiologic evidence, and all three patients underwent subtotal gastrectomy. However, none of the cases showed evidence of neoplasm on histologic examination.

Since that time, others have reported similar findings. Although it simulates gastric carcinoma clinically, granulomatous inflammation has not normally been as- sociated with neoplasms. Kahn and associates 2 reported a case of suspected gastric carcinoma, which was found, postresection, to have isolated idiopathic granulomatous gastritis. They suggested that in a patient presenting with clinical and radiologic signs suggestive of gastric carci- noma, isolated granulomatous gastritis should also be suspected in the differential diagnosis. More recently, Brown 3 has further suggested that current endoscopic techniques should permit a more accurate diagnosis pre- operatively, which should avert unnecessary gastric re- sections. In a later paper, Zuckerman 4 reviewed seven patients from the literature who were diagnosed endo- scopically with idiopathic isolated granulomatous gastri- tis and treated medically. Endoscopic ultrasound was not done preoperatively on our patient; while this may have been useful for detecting the granulomas, it would not have altered the clinical management of our patient. For cases when biopsy is equivocal for malignancy, how- ever, endoscopic ultrasound could be invaluable for de- fining isolated granulomatous gastritis. However, in these circumstances we would advocate frequent surveil- lance for the appearance of neoplasms.

Granulomatous gastritis has not been proven to be benign in all cases. There have been some reports of neoplastic findings in patients with isolated granuloma- tous gastritis. Leach and MacLennan 5 reported a case of granulomatous inflammation associated with gastric lymphoma; Rashid and Williams 6 subsequently reported a patient with granulomatous inflammation and mucoid adenocarcinoma with signet ring cells. In the latter re- port, preoperative biopsies did not show evidence of ma- lignancy. However, clinical suspicion prompted a gastric resection which yielded evidence of both granulomas and carcinoma.

The role, if any, of H pylori infection in these cases is unclear. There has been a great deal of speculation con- cerning an association between chronic gastritis caused by H pyIori and gastric carcinoma. In this case, prior exams had shown evidence of H pylori, but the tissue samples from the gastric resection were negative. We know of one episode in the patient's 20-year history of chronic gastritis in which H pylori was diagnosed and successfully treated. It is tempting to speculate that H pylori is related to isolated granulomatous inflammation, which is then associated with gastric neoplasia; although this association would certainly deserve future investiga- tion, however, we must emphasize that such a relation is not evident in this case.

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410 C. NEWTON ET AL.

Isolated granulomatous inflammation of the stomach is a rare finding, and its association with gastric carci- noma even more so. At this point, any link between granulomatous gastritis and adenocarcinoma is unclear. It is also unclear that isolated granulomatous inflamma- tion is or is not a predictor of carcinoma because the majority of patients with these histologic findings have undergone gastric resections for suspected malignancy. What is clear is that accurate preoperative evaluation is extremely important. Endoscopic evidence of granulo- mas with a biopsy negative for malignancy does not require resection. It is also seems clear that the follow-up in these patients should be frequent and aggressive, in the hope of finding any malignancy associated with the granulomas in a resectabte stage.

REFERENCES

1. Fahimi HD, Deren J J, Gottlieb LS, Zamcheck N. Isolated granu- lomatous gastritis: its relationship to disseminated sarcoidosis and regional enteritis. Gastroenterology 1963;45(2):161-75.

2. Kahn MH, Lain R, Tamoney HJ. Isolated granulomatous gastritis. Am J Gastroenterol 1979;71(1):90-4.

3. Brown KM, Kass M, Wilson R Sr. Isolated granulomatous gastri- tis: treatment with corticosteroids. J Clin Gastroenterol 1987;9(4): 442--6.

4. Zuckerman MJ, AI-Samman M, Boman DA. Granutomatous gas- troenteritis: case report with comparison to idiopathic isolated granulomatous gastritis. Dig Dis Sci 1994;39(8):1649-54.

5. Leach IH, MacLennan KA. Gastric lymphoma associated with mucosal and nodal granulomas: a new differential diagnosis in granulomatous gastritis. Histopathology 1990;17:87-9.

6. Rashid A-MH, Williams RM. A new differential diagnosis in granulomatous gastritis. Histopathology 1992;20(3):280-1.

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