Therapy-associated Polyposis: Additional Cases in Support of This Novel Form of Acquired Gastrointestinal Polyposis

Abstract

Childhood cancer survivors who received abdominopelvic XRT and/or chemotherapy, are at higher risk for gastrointestinal cancers in adulthood. Recognized hereditary polyposis syndromes that typically present in early to mid-adulthood and lead to gastrointestinal cancers include familial adenomatous polyposis (FAP), attenuated FAP, MYH-associated polyposis, and hamartomatous polyposis syndromes. Yurgelun et al. published a series of 5 childhood cancer survivors who developed gastrointestinal polyposis later in life. None of these patients had detectable APC or MYH mutations. We report two more cases of intestinal polyposis in childhood cancer survivors whose genetic testing and family history were not consistent with a hereditary syndrome. Our cases add to the evidence that chemotherapy and/or radiation exposure may be a risk factor for acquired gastrointestinal polyposis. Case 1 was diagnosed with stage IV adrenal neuroblastoma at age 2, treated with cyclophosphamide and whole body XRT. At 29, he had rectal bleeding with a colonoscopy revealing multiple tubulovillous adenomas >1 cm, one with high grade dysplasia (HGD) and one with multiple foci of HGD and intramucosal adenocarcinoma. He had a sigmoidectomy. Surveillance has found two small colonic tubular adenomas and a 3 cm duodenal serrated adenoma. At 30, he was diagnosed with papillary thyroid microcarcinomas. Case 2 was diagnosed with stage IIIA Hodgkin's lymphoma at age 10, treated with MOPP chemotherapy and mantle/splenic pedicle radiation therapy (40 Gy). Screening colonoscopy at age 45 showed over 30 tubular adenomas and 40 sessile serrated adenomas. He had a right hemicolectomy. Surveillance every 6 months has found more tubular adenomas. At 47, he developed bilateral papillary thyroid cancer. Both patients had no significant family history of gastrointestinal polyps/cancers and genetic testing was negative for APC and MYH mutations. We present two cases consistent with an acquired gastrointestinal polyposis syndrome. Our cases are similar to the 5 patients published by Yurgelun et al, and add to the evidence that childhood exposure to chemotherapy and/or XRT may result in acquired gastrointestinal polyposis in adulthood. The extracolonic and future gastrointestinal polyp risks in these patients may differ from established hereditary polyposis syndromes. Establishing acquired therapy-associated polyposis as a separate entity has important implications for future surveillance in these patients.