Fundic Gland Polyposis in Patients Without Familial Adenomatosis Coli: Its Incidence and Clinical Features
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1 GASTROENTEROLOGY 1984;86; ALIMENTARY TRACT Fundic Gland Polyposis in Patients Without Familial Adenomatosis Coli: Its Incidence and Clinical Features MITSUO IIDA, TSUNEYOSHI YAO, HIDENOBU WATANABE, HIDEAKI ITOH, and AKINORI IW ASHIT A Departments of Internal Medicine II, Pathology II, and Surgery I, Faculty of Medicine, Kyushu University, Fukuoka, Japan Thirty-five cases of fundic gland polyposis detected by roentgenographic examination, gastrofiberscopy, and endoscopic biopsy were divided into two groups, The first group consisted of 23 cases without familial adenomatosis coli and is termed the nonadenomatosis coli group; the second group contained 12 cases with familial adenomatosis coli and is termed the familial adenomatosis coli group, Incidence of fundic gland polyposis was only 0.085% (23 of 27,000 cases) in the non-adenomatosis coli group but 38.7% (12 of 31 cases) in the familial adenomatosis coli group. In both groups, fundic gland polyps were multiple, small «8 mm in diameter), and located in the body and fundus of the stomach. A solitary or large polyp was occasionally observed in the non-adenomatosis coli group. Histologic examination revealed simple hyperplasia of the fundic glands and microcysts in both groups. The age range was 51.6 ± 12.3 yr (mean ± SD) in the non-adenomatosis coli group and 25.3 ± 8.6 yr in the familial adenomatosis coli group. The ratio of males to females was 5: 18 in the non-adenomatosis coli group, and 7: 5 in the familial adenomatosis coli group. The number of fundic gland polyps was smaller in the non-adenomatosis coli group than in the familial adenomatosis coli group. Our observations suggest that this lesion frequently coexists with familial adenomatosis coli, but that it is not specific to this disease. Fundic gland polyposis was detected for the first time by Japanese investigators (1-3) in patients with Received May 13, Accepted December 16, Address requests for reprints to: Mitsuo Iida, M.D., Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi Higashi-ku Fukuoka 812, Japan. The authors thank M. Ohara for his comments on the manuscript by the American Gastroenterological Association /84/$3.00 familial adenomatosis coli (FAC). Watanabe et al. (4) described this disorder as a gastric lesion with hamartomatous properties specific to F AC. This lesion has been reported since then as a rare occurrence in patients without FAC (5-8). The details of the clinical picture have not been clarified. We have detected 35 cases of fundic gland polyposis by roentgenographic examination of the stomach and by endoscopy with biopsy. The purpose of the present study was to clarify the incidence and clinical features of fundic gland polyposis in 23 patients without F AC as compared with the incidence and features in 12 patients with F AC. Materials and Methods Between 1973 and 1982, 35 consecutive patients were diagnosed as having fundic gland polyposis by means of gastric radiography, endoscopy, and biopsy done in our department. Twelve of the patients had adenomatosis coli whereas 23 did not. The 23 cases of fundic gland polyposis in non-adenomatosis coli patients were detected from among 27,000 consecutive patients subjected to gastric endoscopic examination. The presence of polyposis coli was ruled out by both sigmoidoscopy and barium enema in 21 of the 23 patients and by only sigmoidoscopy in the remaining 2 patients. In addition, family history was negative, and physical examination failed to reveal such Gardner's stigmata as bone and soft tissue tumors in these 23 patients. Results of laboratory studies including complete blood count, blood chemistry, and serologic examinations were all normal. Upper gastrointestinal series revealed no polypoid lesions in the duodenum in all cases without F AC. The 12 cases of fundic gland polyposis accompanied by FAC were detected from among 31 patients with FAC examined by gastric radiography and endoscopy. The diagnosis of F AC was confirmed by the resected colon Abbreviations used in this paper: F AC, familial adenomatosis coli.
2 1438!IDA ET AL. GASTROENTEROLOGY Vol. 86, No. 6 specimens which showed 100 or more adenomas in all patients but one (No. 31), in whom the diagnosis was made by barium enema and endoscopic biopsy. Nine of these 12 patients had family histories of adenomatosis coli. Physical examination, systemic bone survey, and panorex radiography revealed Gardner's stigmata in 10 of 12 patients. Hypotonic duodenography and duodenofiberscopy revealed multiple adenomas in the duodenum in all those with FAC. Both radiography and endoscopy of the stomach were performed in all patients. Fundic gland polyposis was detectable in all cases by both methods. The number of gastric polyps was directly counted under endoscopic observation. Size of the lesions was measured on the x-ray films. The distribution of polyps was evaluated by both radiography and endoscopy. In all patients, the histologic picture of gastric polyps was confirmed by endoscopic biopsy. In 3 cases (Nos. 24, 25, and 26) of FAC, pathological examination of the stomach was carried out at autopsy. Results Table 1 summarizes the clinical features of the 35 patients. Incidence. Fundic gland polyposis was found in 0.085% or 23 of the 27,000 patients in the nonadenomatosis coli group and in 38.7% or 12 of 31 in the FAC group. Symptoms. Upper digestive tract symptoms such as epigastric pain, epigastric discomfort, heartburn, and nausea were present in 14 of 23 patients in the non-adenomatosis coli group. Nine patients without F AC exhibited no symptoms and were incidentally detected by mass screening for gastric cancer. On the other hand, the 12 patients in the F AC group had no symptoms related to upper digestive tract, but their stomachs were examined because they were diagnosed as having F AC. Table 1. Clinical Features of Patients With Fundic Gland Polyposis Fundic gland polyps Patient Age Upper gastrointestinal Size No. (yr) Sex symptoms Number (mm) Location Non-adenomatosis coli group 1 33 F Epigastric pain, nausea Body, fundus 2 27 F None Body, fundus 3 64 M None Body, fundus 4 52 M Heartburn Body, fundus 5 48 F Fatigue Body, fundus 6 67 F Epigastric discomfort Body, fundus 7 61 F Epigastric discomfort Body, fundus 8 45 F Epigastric pain Body, fundus 9 42 F Epigastric discomfort, nausea Body, fundus F None Body F None Body, fundus F Epigastric pain, nausea Body, fundus M Heartburn ~ Body, fundus F None ~ Body, fundus F Fatigue ~ Body F None ~ Body M None Body, fundus M Epigastric pain Body F None Body F Epigastric pain Fundus F Nausea, vomiting 1 7 Body F Belching 1 6 Body F None 1 3 Body Familial adenomatosis coli group F None Body, fundus F None Body, fundus M None Body, fundus M None > Body, fundus M None > Body, fundus M None > Body, fundus F None > Body, fundus M None > Body, fundus F None > Body, fundus F None > Body, fundus M None Body, fundus M None Body, fundus a The number of gastric lesions was noted in the autopsied specimen.
3 June 1984 CLINICAL FEATURES OF FUNDIC GLAND POLYPOSIS 1439 Figure 1. Double-contrast study of patient No.9 (non-adenomatosis coli group). Multiple polypoid lesions are distributed sparsely from the body to the fundus (A and B). Endoscopically, polyps were distributed more densely in the body than in the fundus.
4 1440 IIDA ET AL. GASTROENTEROLOGY Vol. 86, No. 6 Histology of polyps. In both groups, the histologic picture of the gastric polyps was identical, consisting of simple hyperplasia of normal fundic glands with microcysts (Figure 4). In addition, biopsy of the mucosa surrounding the polyps revealed normal fundic glands and no foci of intestinal or pseudopyloric metaplasia. Figure 2. Gastrofiberscopic feature of patient No.9 shows multiple small sessile polyps in the body. The polyps have a smooth surface with little change in color. Age. The age was 51.6 ± 12.3 yr (mean ± SD) (range yr) in the non-adenomatosis coli group and 25.3 ± 8.6 yr (range yr) in the FAC group. Sex. The ratio of males to females was 5: 18 in the non-adenomatosis coli group, and 7: 5 in the F AC group. There was a female preponderance in the non-adenomatosis coli group. Number of polyps. The number of polyps was < 50 in all of the 23 patients in the non-adenomatosis coli group, and >80 in 11 of 12 patients in the F AC group (Figures 1, 2, and 3). A solitary polyp was found in 3 patients in the non-adenomatosis coli group. Examination of the stomach obtained at autopsy (Nos. 24, 25, and 26, FAC group) revealed polyps, of which the distribution was limited to the portion of the stomach with fundic glands. Size and shape of polyps. Only sessile or semi pedunculated polyps measuring < 8 mm in diameter were found in all patients but one (No. 13, non-adenomatosis coli group), in whom three pedunculated polyps measuring mm in diameter were mixed among multiple small sessile polyps. Endoscopically, most of the polyps had a smooth or slightly uneven surface with little change in color from that of normal gastric mucosa (Figure 2). However, relatively large semipedunculated or pedunculated polyps revealed mild erythema. Distribution of polyps. The polyps were all located in the body and fundus, and none were found in the antrum. In 14 of 23 patients in the nonadenomatosis coli group, polyps were distributed sparsely from the body to the fundus, and in the remaining g, they were located in either but not both areas (Figures 1 and 2). In all 12 patients in the FAC group, the polyps were distributed diffusely or densely from the body to the fundus (Figure 3). Discussion Fundic gland polyposis without F AC was apparently reported for the first time in Europe (5,6). In these papers, however, the presence of F AC was not completely ruled out, in that the colon was not examined. Only in 4 cases of fundic gland polyposis reported by Tatsuta et al. (7) and 3 cases reported by the authors (8) was polyposis of the colon excluded by barium enema examination. In the present study, the absence of polyposis coli was established by both sigmoidoscopy and barium enema in all but 2 patients in the non-adenomatosis coli group, in whom only sigmoidoscopy was performed. Furthermore, in our non-adenomatosis coli patients, family history was negative, and physical examination failed to reveal Gardner's stigmata. As for the incidence offundic gland polyposis, g of 15,000 patients subjected to routine gastroscopy (0.06%) (6) and 6 of 22 patients with FAC (27.3%) (4) represent the only data available. In the present study, fundic gland polyposis was found in 0.085% of patients in the non-adenomatosis coli group and in 38.7% of patients with F AC. These findings are somewhat higher than the incidence reported to the present. The fact that fundic gland polyposis is common in F AC and rare in the general population indicates that it is an integral extracolonic manifestation of F AC but not specific to that disease. Fundic gland polyposis in non-adenomatosis coli patients tends to appear more frequently in middleaged females (5-8). In our series of cases of nonadenomatosis coli, a similar tendency was also noted. Among patients with fundic gland polyposis in the FAC group, however, no definite sex difference was noted. The reason for female preponderance in the non-adenomatosis coli group remains to be determined. The size and shape of the fundic gland polyps were similar in the two groups. However, the number of polyps in the F AC group was far greater than in the non-adenomatosis coli group. Inasmuch as a few reports (3,8) have described regression of fundic gland polyps with time, and in that the non-adenomatosis coli group was on average much older than the F AC patients, it is possible that polyp regression accounts for the difference in polyp numbers. Nevertheless, this explanation appears unlikely in view of
5 June 1984 CLINICAL FEATURES OF FUNDIC GLAND POLYPOSIS 1441 Figure 3. Double-contrast study of patient No. 25 (FAC group). Innumerable polypoid lesions are distributed diffusely and almost uniformly from the body to the fundus. The number of gastric polyps is much larger than that shown in Figure 1. Histologic finding of the biopsy specimen from the polyps was the same as shown in Figure 4.
6 1442 IIDA ET AL. GASTROENTEROLOGY Vol. 86, No. 6. /. ~.'.. ' ~-. '..-.. " ~-.... " -'..,' -. Figure 4. Histologic finding of the biopsy specimen from the gastric polyps of patient No.9 reveals fundic gland polyp composed of simple hyperplasia of fundic glands with micro cysts (H&E, x 120). the striking numbers of polyps present in all but one of the F AC patients but in none of the non adenomatosis coli patients. Tatsuta et al. (7) pointed out two possibilities with regard to the relationship of fundic gland polyposis to F AC. First, this abnormality could be an independent disease of the stomach. Second, this condition might represent a variant of F AC. Our present data do not provide strong support for either of these hypotheses. Long-term follow-up of these patients and investigation of their relatives should yield pertinent data. References 1. Ohsato K, Watanabe H, Itoh H, Yao T, Nishimura M. Simultaneous occurrence of multiple gastric carcinomas and familial polyposis of the colon. Jpn J Surg 1974;4: Utsunomiya J, Maki T, Iwama T, et al. Gastric lesion of familial polyposis coli. Cancer 1974;34: Ushio K, Sasagawa M, Doi H, et al. Lesions associated with familial polyposis coli: studies of lesions of the stomach, duodenum, bones, and teeth. Gastrointest Radiol 1976;1: Watanabe H, Enjoji M, Yao T, Ohsato K. Gastric lesions in familial adenomatosis coli: their incidence and histologic analysis. Hum Pathol 1978;9: Elster K, Eidt H, Ottenjann R, Rosch W, Seifert E. Drusenkorperzysten, eine polypoide Lasion der Magenschleimhaut. Dtsch Med Wochenschr 1977;102: Sipponen P, Siurala M. Cystic "hamartomatous" epithelial polyps of the stomach. Acta Hepato-Gastroenterol 1978; 25: Tatsuta M, Okuda S, Tamura H, Taniguchi H. Gastric hamartomatous polyps in the absence offamilial polyposis coli. Cancer 1980;45: Iida M, Yao T, Watanabe H, Imamura K, Fuyuno S, Omae T. Spontaneous disappearance of fundic gland polyposis: report of three cases. Gastroenterology 1980;79:725-8.
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