Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis

0016-5107/90/3601-0010$02.00 GASTROINTESTINAL ENDOSCOPY Copyright © 1990 by the American Society for Gastrointestinal Endoscopy

Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis Shuji Tada, MD, Mitsuo lida, Akinori Iwashita, MD, Toshiyuki Matsui, Tadahiko Fuchigami, MD, Tsutomu Yamamoto, Tsuneyoshi Yao, MD, Masatoshi Fujishima,

MI MI MI Ml

Fukuoka, Japan and Matsuyama, Japa

Endoscopic and biopsy findings of the esophagus, stomach, duodenum, and colorectum were studied in 37 patients with amyloidosis involving the gastrointestinal tract. Endoscopic examinations revealed fine granular appearance, polypoid protrusions, erosions, ulcerations, and mucosal friability in many cases. These findings were most marked and noticed most often in the second portion of the duodenum. The frequency of amyloid deposition in the biopsy specimens was as follows; 100% in the duodenum, 95% in the stomach, 91% in the colorectum, and 72% in the esophagus. The degree of amyloid deposition in the duodenum, which was the highest of the entire gastrointestinal tract, significantly correlated with the frequency of endoscopic findings such as fine granular appearance and polypoid protrusions. Therefore, the two endoscopic findings described above are characteristic of this disease and may reflect amyloid deposition in the mucosa or submucosa of the alimentary tract. Our results indicate that for a diagnosis of amyloidosis, it is important to examine the upper gastrointestinal tract, especially the duodenum, using endoscopy and biopsy techniques. (Gastrointest Endosc 1990; 36:10-14)

Amyloidosis is a relatively rare disease caused by the deposition of insoluble protein fibrils in organs and tissues of the body. In recent years, amyloid deposition has been ascertained by biopsy of various organs. 1- 5 Rectal biopsy has been widely used as a diagnostic procedure because amyloid deposition frequently occurs in the digestive tract. 5 - 9 However, there are few reports describing the value of endoscopy and biopsy of the upper digestive tract for diagnosing this disease. 1O- 15 In this study, we examined endoscopic and biopsy findings of the upper digestive tract in 37 patients with amyloidosis and compared the findings with those of the colorectum. Received February 15, 1989. For revision April 12, 1989. Accepted July 17, 1989. From the Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan; Divisions of Pathology and Gastroenterology, Matsuyama Red Cross Hospital, Matsuyama, Japan; and First Department of Internal Medicine, School of Medicine, Fukuoka University, Fukuoka, Japan. Reprint requests: Shuji Tada, MD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812, Japan. 10

PATIENTS AND METHODS

During the period from 1978 to 1988, 37 consecutive Japanese patients were diagnosed as suffering from amyloidosis which involved the gastrointestinal tract. Five patients had primary amyloidosis, 3 had myeloma-associated amyloidosis, and 29 had secondary amyloidosis (rheumatoid arthritis in 20, Crohn's disease in 3, unclassified intestinal ulcers in 1, multiple myositis in 1, adult Still's disease in 1, Chediac-Higashi syndrome in 1, ankylosing spondylitis in 1, and pulmonary tuberculosis in 1). According the method of Wright et a1./ 6 principal amyloid proteins consisted of amyloid light chain protein (AL) in 6 patients and amyloid A protein (AA) in 31. The average age of the patients was 50 years (range, 20 to 80 years). The male to female ratio was 13:24. At the time of examination, symptoms relating to the digestive tract, such as abdominal pain, vomiting, hematemesis, and diarrhea were present in 36 patients. None of them had ingested alcohol, anti-inflammatory drugs, or other drugs, such as antimetabolites, reserpine, histamine, and caffeine. The diagnosis of amyloidosis was not known at the time of endoscopy of the digestive tract, except in two patients, in whom biopsy of the kidney had already revealed a!llyloid deposition. GASTROINTESTINAL ENDOSCOPY

Endoscopy of the esophagus, stomach, and duodenum was erformed in all 37 patients, using forward-viewing (models :IF-P3, GIF-QW, GIF-Q10, and GIF-Q20) and side-viewing models GF-B3 and GF-1O) instruments (Olympus, Tokyo, apan). Of these, 35 patients underwent endoscopic examitation of the colon and rectum (Olympus models CF-LB3, ~F-IBW, CF-LB3W, CF-10I, and CF-10L). A sprayed dye 0.2% indigo carmine) technique was used to visualize fine nucosal appearance. The biopsy specimens taken from each part of the alinentary tract were fixed in 10% formalin, and histologic xamination was carried out using 5-~m thick sections tained with hematoxylin and eosin and Congo red. One of he authors (A. I.) examined the degree of amyloid deposition vithout !lny knowledge of the endoscopic appearance. Ac:ording to the amount of amyloid deposition, histologic indings of the biopsy specimens were divided into two

groups: (1) marked, amyloid deposition was observed easily via low magnification (Fig. 1A) and (2) slight, amyloid deposition was observed barely via high magnification (Fig. IB).

RESULTS

Table 1 summarizes the endoscopic and biopsy findings of the esophagus, stomach, duodenum, and colorectum in 37 patients. Endoscopic findings

Esophagus. Endoscopy of the esophagus revealed a fine granular appearance (Fig. 2A) in six patients (6%), erosions in two (5%), shallow ulcerations in one (3%), and mucosal friability in one (3%).

Table 1. Endoscopic and biopsy findings in patients with amyloidosis

Endoscopic findings Fine granular appearance Polypoid protrusions Erosions Ulcerations Mucosal friability No remarkable change Biopsy findings Positive Negative "N

Esophagus (N = 37)

Stomach (N = 37)

Duodenum (N = 37)

Colorectum (N = 35)

6 (16%) 0(0%) 2 (5%) 1 (3%) 1 (3%) 31 (84%)

13 (35%) 0(0%) 23 (62%) 6 (16%) 5 (14%) 11 (30%)

26 (70%) 2 (5%) 21 (57%) 5 (14%) 6 (16%) 9 (24%)

12 (34%) 0(0%) 4(11%) 3 (9%) 3 (9%) 16 (46%)

21 (72%)" 8 (28%)

35 (95%) 2 (5%)

37 (100%) 0(0%)

32 (91 %) 3 (9%)

= 29.

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Figure 2 . A, Endoscopy of the esophagus shows multiple white minute elevations. B, Endoscopy using a sprayed dye technique reveals innumerable fine granules in the antrum of the stomach. C, Multiple erosions and mucosal friability are seen in the antrum. D, Endoscopy using a sprayed dye technique shows a small ulcer in the body of the stomach. The ulcer is surrounded with slightly erythematous and elevated mucosa. Figure 3 . A, Endoscopy reveals a coarse mucosal appearance consisting of innumerable fine granular elevations in the second portion of the duodenum. B, Endoscopy using a sprayed dye technique shows even more clearly the findings illustrated in A. C, Multiple yellowish white polypoid protrusions are seen in the second portion of the duodenum. D, Colonoscopic view showing fine granular appearance in the sigmoid colon.

Stomach. A fine granular appearance (Fig. 2B) was seen in 13 patients (35%). Multiple erosions (Fig. 2C) were noticed in 23 patients (62%), ulcerations in 6 (16%), and mucosal friability in 5 (14%). The ulcerations were often surrounded with mucosal reddening 12

and elevation (Fig. 2D). Residual food was observed in-five patients, thereby suggesting gastric retention. Duodenum. A fine granular appearance was seen in 26 patients (70%), most frequently and most marked in the second portion of the duodenum. The granules GASTROINTESTINAL ENDOSCOPY

:omposing the fine granular appearance were whitish md less than 1 to 3 mm in diameter (Fig. 3, A and B). vtultiple polypoid protrusions (Fig. 3C) which were rellowish white and larger (4 to 10 mm in diameter) ;han the granules were observed in two patients (5%). :n addition, endoscopy revealed erosions in 21 patients :57%), ulcerations in 5 (14%), and mucosal friability n 6 (16%). Colorectum. A fine granular appearance (Fig. 3D) Nas detected in 12 patients (34%), erosions in 4 (11 %), Jlcerations in 3 (9%), and mucosal friability in 3 (9%). The degree of these findings was slight compared with those of the duodenum. Follow-up study. Eleven patients were followed up for an average of 32 months (range, 13 to 61 months) by endoscopic examination. Erosions, ulcerations, and mucosal friability were found to improve, disappear, or grow worse during the follow-up period, while the fine granular appearance and polypoid protrusions remained unchanged. Biopsy findings

Amyloid deposits were located in the vascular walls and the stroma of the lamina propria, mucosa, muscularis mucosa, and submucosa. The frequency of amyloid deposition detected by histologic examination of the biopsy specimens was 72% in the esophagus, 95% in the stomach, 100% in the duodenum, and 91 % in the colorectum (89% in the rectum). In three patients, the biopsy specimens taken from the colorectum contained sufficient submucosal tissue, but revealed no amyloid deposition. Marked amyloid deposition was observed in 4 patients (14%) in the esophagus, in 13 (35%) in the stomach, in 25 (68%) in the duodenum, and in 7 (20%) in the colorectum. Endoscopic findings and degree of amyloid deposition

Table 2 shows the relationship between endoscopic findings and degree of amyloid deposition in the duodenum. In 84% of the 28 patients with fine granular appearance or polypoid protrusions on endoscopy, bi-

Table 2. Relationship between endoscopic findings and degree of amyloid deposition in the duodenum Degree of amyloid deposition

Endoscopic findings Fine granular appearance or polypoid protrusions (N =

Slight

Marked

5

23 (84%)

(16%)

28)

No remarkable change (N = 9)

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7

2

(78%)

(22%)

opsy specimens revealed severe amyloid deposition, while in 78% of the 9 patients without such findings, there was slight amyloid deposition. The difference between both groups was statistically significant (p < 0.005, Fisher's direct probability method). In two patients with multiple polypoid protrusions, biopsy specimens of the duodenum showed massive amyloid deposits in the mucosa and submucosa. DISCUSSION

In order to make a definite diagnosis of amyloidosis, histologic examination is essential and biopsy specimens have been taken from many organs such as kidney, liver, lymph node, muscle, tendon, and rectum. Systemic amyloidosis, even in early stages, often involves the gastrointestinal tract,G, 14, 17-19 and, therefore, rectal biopsy has been recommended as a routine diagnostic procedure.1, 5. 7-9 In previous publications, some authors have reported endoscopic findings of the upper gastrointestinal tract in patients with amyloidosis, and they have described several features, such as prominent folds, small mucosal hemorrhages or friability,1O-12 and yellowish white nodular lesions. 13 However, there have been few reports assessing the characteristic endoscopic features of the upper gastrointestinal tract in a considerable number of patients with amyloidosis. In our study, 37 amyloidosis patients with gastrointestinal involvement had endoscopic findings, including fine granular appearance, polypoid protrusions, erosions, ulcerations, and mucosal friability. Of these, the latter three findings changed with time, suggesting they were secondary, possibly ischemic changes, associated with amyloid deposition in vascular walls. 13, 17,20-22 On the other hand, fine granular appearance and polypoid protrusions remained unchanged during the follow-up period. In patients who had such endoscopic findings, biopsy specimens revealed marked deposits of amyloid in the mucosa and submucosa of the duodenum. This suggests that these two endoscopic findings may directly reflect amyloid deposition in the mucosa and submucosa and that they are the most characteristic endoscopic features of gastrointestinal amyloidosis. Gilat et a1. 17 reported that amyloid was deposited in the mucosa more frequently in the small bowel than in the stomach or colon on the basis of postmortem findings. In our series also, histologic examination of biopsy specimens taken from various sites revealed that the most frequent and most marked amyloid deposits were found in the duodenum, especially in the second portion of the duodenum. Therefore, these results suggest that both endoscopy and biopsy of the duodenum may greatly contribute to the diagnosis of this disease. 13

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