Bleeding from Ileal Nodular Lymphoid Polyposis Identified by Capsule Endoscopy

Abstract

INTRODUCTION Nodular lymphoid polyposis (NLP) of the intestine is a rare disease in children characterized by multiple sessile polyps in the rectosigmoid colon and ileum formed by hyperplasia of lymphoid nodules. Without immunodeficiency, the course of NLP is relatively benign and self-limiting. Common complications of NLP include recurrent intussusception, recurrent abdominal pain, chronic and recurrent diarrhea, hematochezia and chronic intestinal bleeding. We report a 12-year-old boy with iron deficiency anemia caused by bleeding from NLP of the terminal ileum. The lesions were detected by capsule endoscopy. Intraoperative enteroscopy helped locate the distribution of polyposis in the small intestine and selective ileocecocolectomy was performed. To our knowledge, this is the first symptomatic pediatric case of localized ileal NLP detected by capsule endoscopy and treated by intraoperative enteroscopy-assisted surgery. CASE REPORT A pale 12-year-old boy presented with a 2-year history of chronic iron deficiency anemia, exercise intolerance and mild intermittent abdominal discomfort. An iron profile revealed a serum ferritin of 6.26 ng/ml (17.9–464 ng/ml), serum iron of 22 μg/dl (51–180 μg/dl) and total iron binding capacity of 483 μg/dl (275–332 μg/dl). Initial stool occult blood test was negative. Panendoscopy was performed three times and showed only mild gastritis with no evidence of Helicobacter pylori infection. Despite iron supplementation, the hemoglobin level fluctuated and the patient continued to have intermittent blackish stool. A small bowel follow-through barium meal study also was normal. On admission, the patient had pale conjunctiva. Neither lymphadenopathy nor hepatosplenomegaly was present on physical examination. Intermittently, stool samples contained occult blood. Laboratory results were obtained: hemoglobin 7.5 g/dl (12.0–14.0 g/dl), white blood cell count 4670/μl (4500–7500/μl), platelet count 207 K/μl (150–300 K/μl), reticulocyte count index 2.1%, ferritin 4.26 ng/ml, iron 24 μg/dl and total iron binding capacity 423 μg/dl. Serum immunoglobulin levels revealed immunoglobulin (Ig) G 1060 mg/dl (normal range, 1321 ± 276 mg/dl), IgA 191 mg/dl (normal range, 259.34 ± 82.84 mg/dl) and IgM 137 mg/dl (normal range, 160.57 ± 72.21 mg/dl). Lymphocyte subset, chemiluminescence tests for neutrophil function, gastric parietal cell antibody, anti-microsomal antibody, anti-thyroglobulin antibody and anti-nuclear antibody tests were all normal. Abdominal magnetic resonance imaging, Tc-99m scintigraphy for Meckel’s diverticulum, and colonofibroscopy all showed negative findings. Intravenous Tc-99m labeled red blood cell gastrointestinal tract bleeding study revealed a suspicious hot spot over the abdominal right lower quadrant (Fig. 1).FIG. 1.: Intravenous Tc-99m labeled red blood cell gastrointestinal tract bleeding study showed suspicious bleeder over the abdominal right lower quadrant (arrow).The patient underwent a capsule endoscopy examination to determine whether the bleeding source was in the small bowel. In the terminal ileum, multiple polyps with blood clots were seen (Fig. 2). Laparotomy with intraoperative enteroscopy was performed and multiple sessile polyps 1 – 5 mm in diameter were seen with adherant blood clots in the distal 45 cm of the terminal ileum (Fig. 3A and B). Selective ileocecocolectomy of the 45-cm long terminal ileum and ileocecal valve and partial ascending colon resection were done. Histologically, the polyps were composed of numerous various-sized single or confluent well-defined lymphoid follicles located in the mucosa of terminal ileum, ileocecal valve and part of the ascending colon (Fig. 3C and D). Focal erosion of mucosa overlying the prominent lymphoid follicles was present. Immunohistochemical analysis of the follicles was negative for bcl-2 (DAKO Corporation, Carpinteria, CA). These findings were diagnostic of nodular lymphoid polyposis. The patient had follow-up visits at regular interval with intramuscular hydroxocobalamin acetate supplement and has not had any recurrence of anemia.FIG. 2.: Wireless capsule endoscopy examination (GIVEN Imaging, Israel) showed multiple sessile polyps with blood clots over the terminal ileum and ileocecal valve.FIG. 3. : A, multiple polyps (more than 100 in number), measuring up to 5 mm in size, were found on the terminal ileum, ileocecal valve, and ascending colon. B, close up view of these polyps. C, variable sized and well-defined lymphoid follicles were located in the mucosa (hematoxylin & eosin stain ×40). D, erosion was noted on the mucosa overlying a prominent lymphoid follicle (hematoxylin & eosin stain ×200).DISCUSSION Small intestinal lesions are difficult to evaluate by endoscopy (1). In conventional practice, upper endoscopy, colonoscopy, barium contrast radiography and radionuclide scans may be repeated in patients with obscure gastrointestinal bleeding. Approximately 5% of patients with gastrointestinal bleeding remain undiagnosed after these routine evaluations (2). Small bowel lesions such as a nodular lymphoid polyposis of the terminal ileum may be a cause of obscure GI bleeding difficult to assess by upper endoscopy, colonoscopy or even push-type enteroscopy. Barium contrast studies are the primary procedure for detecting small bowel diseases. However, subtle mucosal lesions such as vascular abnormalities or tiny lymphoid polyps could be missed by routine small bowel radiographic studies (1). This patient had significant gastrointestinal bleeding with severe intermittent iron deficiency anemia. We failed to localize the bleeding source by repeated upper endoscopy, colonoscopy, Tc-99m scintigraphy for Meckel’s diverticulum and small bowel follow-through barium meal study. Finally, an intravenous Tc-99m labeled red blood cell gastrointestinal tract bleeding study showed a suspicious site over the right lower abdominal quadrant. Thus, a small bowel lesion was suspected and capsule endoscopy was performed (3). NLP is characterized by numerous hyperplastic lymphoid nodules larger than 2 mm in diameter within the lamina propria and submucosa of the intestinal wall (4,5). The majority of lesions are detected in the recto-sigmoid colon and terminal ileum (6,7). Hermans first described a syndrome of nodular lymphoid hyperplasia of the small intestine, loss of body weight, splenomegaly, peripheral lymphadenopathy, recurrent diarrhea, frequent respiratory tract infection and cholelithiasis in adults with late-onset immunodeficiency (8). This association has been rarely reported in children (9). Impaired humoral immunity with a slightly decreased serum IgA level and normal or elevated levels of IgG and IgM in children with NLP have been reported in several case series (4,9). An association with adenovirus and echovirus infection in children has also been reported (10). Louw proposed that susceptible individuals with immunodeficiency could develop reactive lymphoid hyperplasia with polyp formation when reacting to irritants such as infections, chemicals or environmental factors (11). In our patient, stool viral isolation was negative. Lymphocyte subset and serum levels of immunoglobulins including IgG, IgA and IgM levels were all normal. Autoantibody screening including thyroglobulin, microsomal, gastric parietal cell and anti-nuclear antibodies were negative. Histological studies confirmed that the polyps were composed of numerous well-defined lymphoid follicles located in the mucosa of the terminal ileum, ileocecal valve and part of the ascending colon. CD3 and CD20 stains demonstrated the well-differentiated lymphoid follicles. Bcl-2 stains were also negative. Thus, the diagnosis of nodular lymphoid polyposis was confirmed. Spontaneous resolution of lymphoid polyps has been reported (12). In children, NLP without underlying disease is usually self-limiting, and no treatment is necessary for uncomplicated patients (13). Local excision is indicated when complications develop (14). Previous reported cases of terminal ileal NLP were all diagnosed after emergent surgery for complications such as intestinal bleeding, recurrent intussusception, abdominal pain, recurrent diarrhea and intestinal obstruction (10,14). This is the first case of NLP in the terminal ileum and ileocecal valve identified before surgery by capsule endoscopy. Selective ileocecocolectomy was then performed with the aid of intraoperative enteroscopy to localize the extent of polyps. Adjustment of the algorithm for obscure gastrointestinal bleeding using capsule endoscopy may avoid repeated unpleasant panendoscopy, colonofibroscopy and radioexposure. In summary, NLP should be included in the differential diagnosis of gastrointestinal bleeding and the application of capsule endoscopy may detect ileal NLP before surgery.