COLORECTAL ADENOCARCINOMA DEVELOPING IN A YOUNG FEMALE WITH OVERLAP SYNDROME AND VERY EARLY ONSET-INFLAMMATORY BOWEL DISEASE: A CASE REPORT. (21st January 2021) - Kandavel, Prashanthi
Abstract: We present a 4-year-old female diagnosed with very-early onset inflammatory bowel disease (VEO-IBD), ulcerative colitis type, and overlap syndrome based on clinical presentation, blood and stool studies, diagnostic endoscopies and liver biopsy. Her clinical course was complicated by pervasive psychological stressors, non-compliance with medical therapy, and frequent provider changes. Initial treatment included Prednisone, 6-mercaptopurine and Ursodiol. Treatment was escalated to include multiple biological agents which were stopped prematurely due to non-adherence. She developed weight loss and growth stunting, necessitating exclusive enteral nutrition and then parenteral nutrition. Due to medically refractory disease, she underwent a total colectomy with end ileostomy at the age of 13. Pathology revealed stage III colorectal adenocarcinoma (CRC) with lymph node involvement and transmural inflammation diagnostic of Crohn's disease (CD). Genetic testing of the resected colon noted a missense mutation of TP53. Our patient completed 6 cycles of extensive and targeted chemotherapy with no evidence of disease reccurrence. She recently underwent ileal pouch-anal anastomosis and creation of a diverting ileostomy. CRC is exceedingly rare in pediatric IBD (PIBD) patients, with less than 30 reported cases in the available literature 1 . Most cases occurred in males and patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC), where the risk of developing CRC is four times greater 2 . The risk of CRC increases with disease duration, with most PIBD patients developing CRC at 25 years of age 1 . Interestingly, mutations in TP53, a tumour suppressor gene, have been found to occur more frequently in patients with IBD-CRC compared to those with sporadic-CRC or IBD without dysplasia 3 . Mutations in TP53 may not only increase a patients general susceptibility to CRC but may also accelerate its development by contributing to excessive inflammation 4 . Our patient's treatment refractory clinical course and transition in IBD diagnosis from UC to CD highlights the complexity of VEO-IBD management. While rare in pediatric patients, the development of CRC is a life-threatening risk and it should be considered in patients with prolonged and severely refractory IBD with concomitant autoimmune liver disease. Our patient's young age at the time of CRC diagnosis emphasizes the need for vigilant yearly endoscopic screening and development of pediatric guidelines for dysplasia monitoring in this high risk population. Further research is needed to evaluate the role of genetic variant screening in CRC risk stratification. References: 1. Aardoom MA, et al. Inflamm Bowel Dis . 2018;24(4):732–741. 2. Soetikno RM, et al. Gastrointest Endosc . 2002;56(1):48–54. 3. Yaeger R, et al. Gastroenterology . 2016;151(2):278–287. 4. Cooks T, et al. Cancer Cell . 2013;23(5):634–46.