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Gastrointestinal Tumors in Children and Adolescents

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Gastrointestinal Tumors in Children and Adolescents Seminars in Pediatric Surgery (2006) 15, 37-47 Gastrointestinal tumors in children and adolescents Alan P. Ladd, MD, and Jay L. Grosfeld, MD From the Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana. INDEX WORDS Tumors of the pediatric gastrointestinal tract are extremely rare. Their infrequent presentation at Gastrointestinal treatment centers has not allowed for the development of standardized treatment protocols and tumors; prospective review. The most prevalent gastrointestinal neoplasms and malignancies are described, Gastrointestinal including gastrointestinal lymphoma, colorectal carcinoma, carcinoid tumors, gastrointestinal stromal lymphoma; tumors, leiomyomas, juvenile polyps, inflammatory pseudotumors, gastric tumors, and Peutz–Jeghers Adenocarcinoma of polyposis syndrome. Current recommendations for the medical and surgical management of these the colon; tumors are reviewed and summarized for this vast group of gastrointestinal neoplasms in children. Gastrointestinal © 2006 Elsevier Inc. All rights reserved. stromal tumor; Inflammatory pseudotumor Primary tumors of the gastrointestinal tract are rare in care, children’s hospital (Riley Children’s Hospital, India- children. Historical surveys suggest that primary pediatric napolis, IN). Patients treated from 1972 to 2005 were iden- gastrointestinal malignancies represent less than 5% of all tified through search of hospital database and office patient pediatric neoplasms.1 Estimates of the prevalence of chil- files. Only patients whose tumors underwent surgical resec- dren with malignant tumors are 9 to 12 per hundred thou- tion or had a definitive biopsy were included. Some patients sand.2 A more recent study places the occurrence of these included in this review have been described in previous tumors at 1.2% of all pediatric malignancies.3 Therefore, publications.4,5 tumors of the gastrointestinal tract in children present infre- quently at any single medical center or hospital. The true incidence for any specific neoplasm is truly unknown in the pediatric population. It is from the review of small case Results series and anecdotal reports that we hope to gain an im- proved understanding of these rare entities and determine A total of 58 cases of gastrointestinal tumors were identified the most appropriate intervention and treatment. over this 33-year time frame. The average age of the chil- dren was 13.8 years. There were 39 malignant tumors and 19 benign tumors (Figure 1). Lymphomas represented 54% (n ϭ 30) of the cases, including 15 patients with Burkitt’s Methods lymphoma and 15 patients with non-Burkitt’s, Non- Hodgkin’s lymphoma (NB-NHL). Six patients had colorec- A retrospective review of gastrointestinal tumors of child- tal carcinoma, each in advanced stage (Dukes C or D). One hood and adolescence was performed at a single, tertiary of these children had acquired signet-cell colon adenocar- cinoma 4 years following treatment for acute lymphocytic Address reprint requests and correspondence: Alan P. Ladd, MD, Indiana University School of Medicine, 702 Barnhill Drive #2500, India- leukemia (ALL). Four patients had inflammatory pseudotu- napolis, IN 46202. mors (IPT) of the gastrointestinal tract, at the gastroesoph- E-mail: [email protected]. ageal junction, appendix, colon, and rectum.5 Primary neu- 1055-8586/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2005.11.007 38 Seminars in Pediatric Surgery, Vol 15, No 1, February 2006 Other, 3 Juvenile polyp, 2 Carcinoid, 2 NB-NHL, 15 Hemangioma, 2 Ganglioneuroma, 2 Neurofibroma, 4 PJP, 3 IPT, 4 Burkitts, 15 Carcinoma, 6 Figure 1 Gastrointestinal tumors of childhood, 1972 to 2005. Figure 3 Neurofibroma of the colonic wall. NB-NHL, non-Burkitts’s non-Hodgkin’s lymphoma; IPT, inflam- matory pseudotumor; PJP, Peutz–Jegher polyp. syndrome was made in two patients through the identifica- tion of a hamartoma as the lead-point of an intussusception rogenic tumors of the gastrointestinal tract were present in 6 and the additional polypoid lesions within the gastrointes- patients. Four children had neurofibromas within the bowel tinal tract. The remaining lesion presenting as intussuscep- wall and mesentery, and 2 children were diagnosed with tion was that of a small intestinal leukemic infiltrate. ganglioneuromas, including 1 with ganglioneuromatosis of the entire colon (Figures 2 and 3). Hamartomas of Peutz- Jegher syndrome were encountered in 3 patients. Carcinoid Lymphoma tumors were identified in 2 children, with 1 patient having diffuse small intestinal, colonic, and retroperitoneal disease. Non-Hodgkin’s lymphoma (NHL) remains the most com- The remaining tumors identified included juvenile colonic mon malignancy of the GI tract in children. This observa- polyps (2), leukemic infiltrate of the intestine (1), gastric tion, first made in the 1950s, has persisted in various pub- leiomyosarcoma (1), and hemangiomata (2). lications on the subject since that time.3,6-8 Although most Seven of the patients presented with signs of an intestinal commonly encountered in the terminal ileum and ileocecal obstruction due to an irreducible intussusception that re- area, this malignancy can occur in all portions of the gas- quired operative intervention for either resection or reduc- trointestinal tract from the stomach to the rectum.3,9,10 An tion. Subsequent identification of tumor was made by patho- increased incidence of this tumor has been reported in the logic evaluation of the lead-point, either intraoperatively or Columbus Children’s Hospital tumor data registry since on histological analysis of the intussusceptum. Four of the 1982. Concurrent with this observation, the proportion of seven cases of intussusception had Burkitt’s lymphoma as Burkitt’s lymphoma has increased from 10% of reported the pathologic lead-point. The diagnosis of Peutz–Jehger gastrointestinal malignancies before 1982, to 50% currently. Burkitt’s lymphoma remains the most common tumor of the small intestine and the second-most common pediatric tu- mor of the colon, after adenocarcinoma. This relative inci- dence of gastrointestinal tumors in children remains valid internationally. European data registries also show a similar incidence of NHL and anatomic distribution.11 The male- to-female ratio in children is approximately 7:1. Clinical presentation of gastrointestinal lymphoma varies from the presence of an occult abdominal mass to more urgent clinical signs of intestinal obstruction with bilious emesis or abdominal pain from possible perforation3,4 (Fig- ures 4A and B, and 5). As noted, the tumor may act as a lead-point for ileocolic intussusception and a small bowel obstruction6,12 (Figure 6). Surgical intervention is focused on either complete resection or palliative intervention for the relief of bowel obstruction, in addition to a definitive Figure 2 Ganglioneuroma of the small intestine. tumor biopsy. Frozen section analysis of unexpected tumors Ladd and Grosfeld Gastrointestinal Tumors 39 Figure 4 (A) Mesenteric involvement of Burkitt’s lymphoma. (B) Ileocecal involvement of Burkitt’s lymphoma. should be obtained intraoperatively to make a correct diag- Isolated gastric lymphoma in children has been recently nosis and determine appropriate therapy. The mainstay of described in conjunction with infection from Helicobacter treatment for isolated gastrointestinal lymphoma is com- pylori. Although a causal effect has been identified in adults plete surgical resection when possible, including excision of as to the development of a mucosa-associated lymphoid regional lymph nodes. Nearly 50% of children with gastro- tissue (MALT) lymphoma from infection with H. pylori,no intestinal NHL will have tumor infiltrates confined to the formal causation has been proven in children. Malignant gastrointestinal tract with possible regional lymph node degeneration is often isolated to the stomach wall, but cases involvement. Children that are amenable to localized resec- of regional and distant metastasis have been reported.15-17 tion have an 80% survival at 2 years. Those children with Treatment of the inciting H. pylori infection is often cura- more extensive spread of disease have a 33% 2-year sur- tive for localized, low-grade MALT lymphomas in adults vival.11 Historically, children with metastatic gastrointesti- nal NHL have been treated with a combination of surgery, adjuvant chemotherapy, and radiotherapy. Review of these reports offers neither a standard of care for these tumors nor a predictable outcome. Current chemotherapeutic agents employed in treatment often include cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate. Ret- rospective series have touted an improved survival of NHL of the stomach and cecum; however, more recent studies have not validated this observation.11,13,14 Figure 6 Intestinal lymphoma acting as a lead point for intus- Figure 5 Intestinal perforation from Burkitt’s lymphoma. susception. 40 Seminars in Pediatric Surgery, Vol 15, No 1, February 2006 Figure 7 (A) Barium enema showing partial colonic obstruction from “apple core” lesion of ascending colon. (B) Operative speci- men of adenocarcinoma from right hemicolectomy. (C) Near-ob- structing adenocarcinoma of the ascending colon. and children. However, more systemic treatment is required children ranges from 7% to 12%.24-26 This poor prognosis is for recurrent or metastatic disease.15-17 related to delay in diagnosis, a greater virulence of these tumors, and the advanced stage of disease at the
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