*Pediatric Gastroenterology and Nutrition Unit, France
‡Department of Pathology, France
§Surgery Department, Armand-Trousseau Hospital, France
†Department of Digestive Disease, Lariboisière University Hospital, Paris, France
Received 20 November, 2006
Accepted 10 February, 2007
Address correspondence and reprint requests to Dr Sheila Viola, Pediatric Gastroenterology and Nutrition Unit, Armand-Trousseau Hospital, 26, avenue du Dr Arnold Netter, 75571 Paris Cedex 12, France (e-mail: email@example.com).
In childhood 15% to 27% of gastrointestinal (GI) bleeding remains unexplained after conventional exploration (esogastroduodenoscopy, colonoscopy, small bowel barium follow-through, and/or enteral CT) (1,2). In these cases further investigation of the small bowel is necessary. We report a case of jejunal GI stromal tumor (GIST) revealed by wireless capsule endoscopy in a young girl with obscure GI bleeding.
A nonmenstruating 14-year-old girl was referred to our institution in January 2004 for a 3-year history of iron-deficiency anemia, without overt GI bleeding. No pertinent medical history or familial known diseases were reported. In August 2001 she presented with asthenia and dyspnea, with recurrent episodes of pallor and vertigo. The results of physical examination, including a gynecological examination, were normal, and her hemoglobin and hematocrit rates were 9 mg/dL and 30%, respectively, associated with an iron deficiency, with normal rates of vitamin B12 and folate plasma concentrations. Coagulation and inflammatory biochemical parameters were normal. A Hemoccult test was performed, and occult blood was found in the stools. The results of esogastroduodenoscopy and colonoscopy were normal. The girl was first treated with oral iron supplements for 6 months without any clinical improvement. Her hemoglobin dropped to 6.7 mg/dL, requiring transfusion with 2 units of blood in January 2002. A second endoscopic examination by esogastroduodenoscopy and colonoscopy again showed no abnormality. The results of gastric, duodenal, and colonic biopsy were normal. Enteral computed tomography was considered to be normal. A 99mTc pertechnetate radionuclide scan showed mild bleeding into the right lower quadrant of the abdomen, which suggested a Meckel diverticulum. Thus, surgical laparoscopy was performed without intraoperative enteroscopy but did not reveal any GI abnormality. The girl was recurrently treated with iron supplements, which allowed transient improvement. In January 2004 symptoms of asthenia, dyspnea, and vertigo recurred. Physical examination showed conjunctival pallor and orthostasis. The hemoglobin was 8 mg/dL. The patient was referred for wireless capsule endoscopy (Given Imaging, Yoqneam, Israel), which revealed a regular submucosal mass (Fig. 1A) in the proximal part of the jejunum, approximately 20 minutes after the capsule crossed the pylorus. Active bleeding was observed around the jejunal mass (Fig. 1B), without any evidence of mass ulceration. No other abnormality was noted in the remaining small bowel capsule examination. Interpretation of capsule images was difficult in the distal part of the jejunum and in the ileum because of the presence of a large amount of dark fluid. A push enteroscopy was then performed and confirmed the presence of a jejunal 2-cm ulcerated bleeding mass approximately 30 cm beyond the duodenojejunal ligament (Fig. 2). No other mucosal lesion was detected in the jejunum, with a total length of approximately 150 cm of small bowel explored. Biopsy of the jejunal mass was performed, and the histological examination revealed a tumor composed of alternating hypocellular and cellular areas, with plump spindle cells, and a positive smooth muscle anti-actin staining. Immunohistochemical study showed overexpression of CD117. A diagnosis of jejunal GIST was suspected. Surgical exploration showed a submucosal round tumor 20 centimeters beyond the duodenojejunal ligament, with adventitial retraction. A segmental 15-cm jejunal resection was performed, and the tumor was excised. Macroscopic examination (Fig. 3) showed a 2.5 × 2 × 1.5-cm rounded submucosal tumor with mucosal ulceration, without stricture. Histologic examination showed a transmural tumor, with histologic abnormalities similar to those described in the perendoscopic biopsy analysis. No nuclear atypia was observed, and the mitotic index was low. Immunohistochemical study showed strong CD117 and vimentin overexpression in the tumoral cells. The final diagnosis was benign jejunal GIST. The girl's postoperative progress was satisfactory. Iron supplementation was stopped, and no recurrence of anemia was noted during the 48-month follow-up period despite the occurrence of menstruation in August 2005.
To our knowledge, this is the first reported case of pediatric jejunal GIST diagnosed by wireless capsule endoscopy. This case report emphasizes the fact that obscure GI bleeding challenges diagnosis. In childhood overt upper GI bleeding is usually related to esophagitis, gastritis, gastroduodenal ulcers, or esophageal varices, usually diagnosed by conventional upper endoscopy (1). However, various and age-related causes of pediatric lower GI bleeding (including acute intestinal invagination, necrotizing enterocolitis, anal fissures, Meckel diverticulum, allergic colitis, Henoch-Schönlein purpura, colonic polyposis, angiomas, and intestinal tumors) often challenge diagnosis. The first-line diagnostic strategy includes upper and lower GI tract endoscopy, followed by radiological examination (small bowel barium through radiography and/or enteral CT and/or 99mTc pertechnetate radionuclide scan) (2). Until recently, suspected pediatric small bowel bleeding often led to laparoscopic examination with or without intraoperative enteroscopy, although some authors reported the use of push enteroscopy in adolescents (3). Wireless capsule endoscopy can now be proposed as a noninvasive diagnostic tool in many small bowel diseases in children, including obscure GI bleeding, suspected enteropathy (eg, Crohn disease), or small bowel tumors (4–6). The capsule is either swallowed, if the child is older than 8 years, or placed endoscopically. It has been recently shown that capsule endoscopy correctly diagnosed or excluded a bleeding source in 29 of 30 children over the age of 10 years with obscure GI bleeding (5). Thus, capsule endoscopy allows an accurate noninvasive approach for diagnosing obscure small bowel lesions in children over the age of 10 and could change the first step of the diagnostic strategies in suspected small bowel bleeding. Indeed, this step may now include a 99mTc pertechnetate radionuclide scan, an esogastroduodenoscopy, a coloscopy, and simultaneous endoscopic placement of the capsule in the stomach. Only patients younger than 8 or 10 years or those with persistent acute bleeding will require a laparoscopic approach with intraoperative enteroscopy. In our reported case of pediatric chronic obscure iron-deficiency anemia, capsule endoscopy showed a bleeding jejunal tumor and led to the diagnosis and successful treatment of a benign GIST, after the classic diagnostic strategy based on repeated endoscopic procedures and laparoscopy had failed.
A GIST is a nonlymphoid mesenchymal tumor derived from interstitial cells of Cajal, known to be GI pacemaker cells of mesodermal origin. Histological examination shows sheets of spindle cells of smooth cell origin or, as seen in our patient, epithelioid tumors with abundant and sometimes vacuolated cytoplasm. Most GISTs overexpress CD117 (c-Kit protein), a cell surface antigen on the extracellular domain of the tyrosin kinase receptor. Immunohistochemical staining is therefore confirmatory, being positive in most cases for both CD34 and CD117 (7). The prevalence of GIST is estimated to be 15 to 20/million; it is usually diagnosed in adults over the age of 40 without gender predilection. In childhood, although the prevalence of GIST is not clearly known, the disease is believed to be rare. The pediatric literature on GISTs covers only reports and small series (8). The clinical presentation of the disease, tumor location, histological features, and immunohistological features are similar in children and adults. In the St Jude Hospital series, 7 children with diagnoses of GIST (9) had a mean age at diagnosis of 11. Abdominal symptoms were frequent with abdominal pain (4 cases), meteorism (3 cases), or abdominal mass (4 cases). GISTs were located to the stomach (2 cases), the small bowel (2 cases), the colon (2 cases), and the peritoneum (1 case). The malignant potential of GISTs depends on the mitotic count, the tumor size, and extragastrointestinal spread (10). Malignant GISTs arising from the small bowel have a less favorable prognosis than those arising from the stomach. None of these criteria were found in our patient. Surgery remains the main treatment for patients with GIST. In patients with unresectable or metastatic disease overexpressing c-Kit CD117, treatment with a specific tyrosine kinase inhibitor (imatinib, Gleeve, Novartis, Basel, Switzerland) is recommended. Lifelong follow-up of all patients, even those treated with complete surgical resection, is mandatory. This follow-up can be made by capsule endoscopy when the GIST is in the small bowel.
Wireless capsule endoscopy followed by push enteroscopy led to the diagnosis and successful treatment of a jejunal GIST in a 14-year-old girl with unrecognized long-standing iron-deficiency anemia. This case report emphasizes the usefulness of capsule endoscopy in children with obscure GI bleeding before invasive diagnostic and therapeutic procedures are undertaken.
1. Fox VL. Gastrointestinal bleeding in infancy and childhood. Gastroenterol Clin North Am 2000; 29:37–66.
2. Hyams JS, Leichtner AM, Schwartz AN. Recent advances in diagnosis and treatment of gastrointestinal hemorrhage in infants and children. J Pediatr 1985; 106:1–9.
3. Benaroch LM, Rudolph CD. Introduction to pediatric esophagogastroduodenoscopy and enteroscopy. Gastrointest Endosc Clin North Am 1994; 4:121–142.
4. Mallet E, Cron J, Stoller J. Wireless-capsule video-endoscopy: preliminary results in children. Arch Pediatr 2003; 10:244–245.
5. Guilhon de Araujo Sant'Anna AM, Dubois J, Miron MC, et al
. Wireless capsule endoscopy for obscure small-bowel disorders: final results of the first pediatric controlled trial. Clin Gastroenterol Hepatol 2005; 3:264–270.
6. Seidman EG, Sant'Anna AM, Dirks MH. Potential applications of wireless capsule endoscopy in the pediatric age group. Gastrointest Endosc Clin North Am 2004; 14:207–217.
7. Miettinen M, Kopczynski J, Makhlouf HR, et al
. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol 2003; 27:625–641.
8. Haider N, Kader M, Mc Dermott M, et al
. Gastric stromal tumors in children. Pediatr Blood Cancer 2004; 42:186–189.
9. Cypriano MS, Jenkins JJ, Pappo AS, et al
. Pediatric gastrointestinal stromal tumors and leiomyosarcoma. Cancer 2004; 101:39–50.
10. Pierie JP, Choudry U, Muzikansky A, et al
. The effect of surgery and grade on outcome of gastrointestinal stromal tumors. Arch Surg 2001; 136:383–389.