LYMPHOMA PRESENTING AS MALABSORPTION

GASTROENTEROLOGY Copyright 1968 by The Williams & Wilkins Co. Vol. 54, No.3 Pnnted in U.S.A. LYMPHOMA PRESENTING AS MALABSORPTION HORACIO JINICH, M.D., EDMUNDO ROJAS, M.D., JOHN A. WEBB, M.D., AND JOHN R. KELSEY, JR., M.D. Departments of Gastroenterology and Pathology, Instituto Nacional de la Nutricion, Mexico, D. F., and Departments of Pathology and Gastroenterology, Kelsey-Seybold Clinic, Houston, Texas Eidelman et al. l, 2 in 1966 reported a study of 9 cases of abdominal lymphoma which presented initially as a malabsorption syndrome occurring in young non European Jews or Israeli Arabs. After analysis of these cases and a review of the literature, they proposed that the etiological common denominator of this group was geographic rather than ethnic or genetic, all of the patients and their ancestors having lived in or near the Middle East for generations. We recently had the opportunity to observe a similar case. The patient was a young, male, non-european Jew with abdominal lymphoma presenting initially as malabsorption. However, although both of his parents were of Syrian origin, the patient was born and had lived all of his life in Mexico City. The case is of interest because of its occurrence in a geographical area widely separated from those observed in Israel, giving credence to the role of factors other than geographic in this unusual disease syndrome. Case Report We first saw this 31-year-old male patient in Mexico City in September 1962. Eighteen months before, he had experienced epigastric pain extending to the left upper quadrant, pyrosis, and weakness. He had been told that he had a peptic ulcer. The symptoms had improved when he followed the pre- Received March 13, 1967. Accepted November 9, 1967. Address requests for reprints to: Horacio Jinich, M.D., Kelsey-Seybold Clinic, 6624 Fannin Street, Houston, Texas 77025. This investigation was supported in part by a grant from the Joe and Jessie Crump Fund. 421 scribed regimen for ulcer, only to reappear 6 months later accompanied by nausea, vomiting, flatulence, and diarrhea. He reported the stools were bulky, frothy, pale, and numbered six to eight per day. During this period he had lost 22 lb. Past history revealed that he was a weak and "sickly" child whose mental and physical development was much slower than that of his siblings. There was nothing further in the early history to suggest celiac disease. He complained of frequent upper respiratory infections. At age 12 he had lead poisoning which developed during his employment in a paint factory. Although born and living in Mexico, his dietary habits in the home followed Arabic culinary tradition. This diet included considerable portions of veal, lamb, or raw beef, goat cheese, fermented milk, and numerous spices such as sesame seeds, oil of cumin, and Indian nut. This was frequently supplemented by highly seasoned Mexican dishes eaten outside the home. The patient's father was born in Damascus, Syria, and, although his mother was born in Cuba, her parents were Syrian immigrants. Three brothers, 3 sisters and both parents were then and are now in good health. None has exhibited symptoms suggesting malabsorptive disease. On physical examination the patient was emaciated, dehydrated, and hypotensive (85/ 60). Laboratory studies were as follows: fecal fat excretion, 31 g per 24 hr on a 100-g fat diet; d-xylose urinary excretion, 0.58 g in 5 hr after administration of 25 g. In the serum the concentration of calcium was 8.8 mg per 100 ml, phosphorus was 1.93 mg per 100 ml, albumin was 2.15 g per 100 ml, and globulins: Il'l 0.31, 1l'2 0.38, f3 1.2, and y 3.6 g per 100 ml. The blood count and differential white cell count were normal. No ova or parasites were found in six stool examinations. X-ray studies of the chest and colon were normal, but the

422 CASE REPORTS Vol. 54, No.3 small bowel X-ray showed thickening of the mucosal folds and dilation of the lumen with some segmentation and pudding. A biopsy of the small intestine failed to provide adequate material. When the patient followed a prescribed gluten-free diet and took prednisone, 20 mg daily, for 15 days, he experienced a remarkable temporary improvement. He felt well enough to return to work, there was some gain in weight, and the diarrhea diminished. His condition, however, fluctuated. Although never completely free of abdominal distress, there was no diarrhea during favorable periods. Episodes involving more pain and accompanied by diarrhea were attributed, at the time, to his failure to follow the gluten-free diet. In mid-1966 he became progressively worse with recurrence and aggravation of the previous symptoms. He reported having had abdominal distension after each meal for approximately 1 year and that his legs hurt constantly. In October he went to Houston, Texas, for examination. He was cachectic; his blood pressure was low, and he was experiencing pain FIG. 1. Upper gastrointestinal X-ray showing widened small bowel with thickened mucosal folds. and tenderness over the entire abdomen, more marked in the left lower quadrant. Results of laboratory tests were essentially the same as those obtained in Mexico. Gastrointestinal X-rays revealed an increase in the gastric rugal folds; the small bowel loops were widened, and there was thickening of the mucosal folds (fig. 1). A small bowel biopsy (fig. 2, A and B) showed blunted, shortened, and thickened villi. There was a moderate cellular infiltrate consisting primarily of lymphocytes and plasma cells. The patient was advised to adhere faithfully to a gluten-free diet and to take prednisone, 20 mg, daily. When the patient returned to Mexico City, his pain became worse. A mass was felt in the left upper quadrant of the abdomen; X-rays revealed a loop of jejunum persistently dilated and rigid, suggesting organic obstruction. Following the radiological study, the patient developed complete intestinal obstruction and emergency surgery was performed. The entire small intestine was found to be thickened and edematous; the mesenteric lymph nodes were enlarged, and there were three tumor masses located respectively 30 cm distal to the angle of Treitz, at midjejunum, and 50 cm proximal to the terminal ileum. The proximal mass was obstructing the lumen of the bowel. Two segments of intestine containing the masses and totaling 50 cm in length were resected. Continuity was reestablished through terminoterminal anastomosis. The patient died of peritonitis consecutive to dehiscence of the anastomosis. Autopsy was denied. Microscopic study of the resected segment provided the following information. Sections of the intestinal wall in the ulcerated areas showed extensive loss of substance with necrosis and intense lymphocytic infiltration extending toward the subjacent areas. Marginal zones showed obliteration or marked decrease in the number of glands, secondary to the infiltrative process. Still other sections showed infiltration to such high degree that it was difficult to differentiate between the mucosa and subjacent layers. No Reed-Sternberg cells were identified. There were numerous erythrocytes, polymorphonuclear leukocytes, lymphocytes, macrophages, and plasma cells (figs. 3 and 4). Discussion This case appears t8 be another example of abdominal lymphoma presenting as malabsorption and occurring in a young

March 1988 CASE REPORTS 423 FIG. 2, A and B. Small bowel biopsy showing thinning of mucosa. Villi are shortened, thickened, and atrophic to a moderate degree. Cellular infiltrate is composed of moderate numbers of plasma cells and lymphocytes. No pleomorphism of infiltrate is noted. (A, X 100; B, X 200). male of non-european Jewish OrIgm as described by Eidelman et al. l 2 There is one significant difference, that of its geographic area of origin. Although the geographic location was cited as the primary common denominator in the Israel study, the authors also speculated that environmental factors such as diet or intestinal microorganisms might start a chain reaction resulting in lymphoma in intestinal mesenteric lymphoid tissue. Most of our patient's food and its preparation were similar to traditional Middle East cuisine, particularly during the early years of his life. Also, the ecology of the human intestine in Mexico might be comparable to that in the Middle East, because intestinal infections and infestations are common to both areas. Our patient's genetic background is comparable to that of 6 of the 9 patients in the Eidelman study, suggesting a possible genetic connection. When additional cases are recognized and reported, it is conceivable that some pattern will develop to clarify the importance of genetic, geographic, or environmental factors in the etiology of this unusual disease syndrome. The continuing controversy whether cases of this type represent celiac disease with the coincidental or secondary development of abdominal lymphomas or whether the presence of lymphoma itself accounts for the syndrome of malabsorption l 2 is, at the present time, unanswered. It would appear that the latter is the most reasonable probability in this particular case. The question warrants further investigation and will probably be solved only by long term prospective biopsy studies of patients with celiac sprue. Summary A case of abdominal lymphoma presenting as a malabsorption syndrome and occurring in a young non-european Jew born and reared in Mexico is reported. It is similar to cases occurring in non-european

424 CASE REPORTS Vol. 54, No.3 FIG. 3. Low magnification view of section of small intestine removed at surgery. Note straight, essentially normal villi with heavy cellular infiltrate of the lamina propria (x 80). FIG. 4. Same section as in figure 3 at higher magnification showing numerous lymphocytes, plasma cells, macro phages, erythrocytes, and polymorphonuclear leukocytes. A moderate number of cells show nuclear pleomorphism (X 280). Jews and Israeli Arabs studied by Eidelman et al. in Israel. Although geographic factors were proposed in the reference study as playing a possible role in the etiology and pathogenesis of the syndrome, the occurrence of this case in Mexico suggests that factors other than geographic must also be considered.

March 1968 CASE REPORTS 42.5 REFERENCES 1. Eidelman, S., R. A. Parkins, and C. E. Rubin. 1966. Abdominal lymphoma presenting as malabsorption. A clinico-pathological study of 9 cases in Israel and a review of the literature. Medicine (BaIt.) 45: 111-137. 2. Eidelman, S., R. A. Parkins, and C. E. Rubin. 1966. Lymphoma presenting as malabsorption. Gastroenterology 51: 731. 3. Harris, O. E., W. T. Cooke, H. Thompson, and J. A. H. Waterhouse. 1967. Malignancy in adult coeliac disease and idiopathic steatorrhoea. Amer. J. Med. 42: 899-912.