Colonic Dysplasia and Malignancy in Patients with SMAD4 Mutation-Associated Juvenile Polyposis-Hereditary Hemorrhagic Telangiectasia
Zaid S Kamil, Frank Schwenter, Terri Berk, Aaron Pollett, Andrea Grin, Marie E Faughnan, Catherine J Streutker. University of Toronto, Toronto, ON, Canada; McGill University, Montreal, QC, Canada; Mount Sinai Hospital, Toronto, ON, Canada; St. Michael's Hospital, Toronto, ON, Canada
Background: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease, usually associated with mutations in Endoglin and activin receptor like kinase 1 genes, characterized by telangiectasias and arteriovenous malformations. Juvenile polyposis (JP) is a syndrome characterized by hamartomatous polyps throughout the gastrointestinal tract, with increased risk of malignancy. SMAD4 and BMPR1A mutations can be identified in JP. A recently described SMAD4 mutation-associated syndrome combines the features of HHT and JP. In this study, we review the rate and types of dysplastic and malignant lesions in this population.
Design: 15 JP-HHT patients with confirmed SMAD4 mutation were identified from HHT clinic files. All available biopsies and resections were reviewed.
Results: The majority of the patients had only few juvenile polyps detected (3-5 polyps), but one patient had multiple (>100 polyps). Six of our fifteen patients (three male, three female) developed dysplastic and malignant colonic lesions; 26 dysplastic lesions and 2 adenocarcinomas were identified at a mean patient age of 27.5 years. Four patients had lesions developing within juvenile polyps, including low grade and high grade dysplasia and signet ring carcinoma, the remainder of the dysplastic lesions were tubular or villous adenomas. Two patients developed invasive adenocarcinoma one year after dysplastic lesions were identified on colonoscopy.
Conclusions: Though patient numbers are small, the rate of dysplasia and malignancy is elevated and the lesions are developing at an early age. Also, in two patients, the time period between the detection of colonic dysplastic lesions and adenocarcinoma was short (1 year). Patients with SMAD4 mutations and the combined JP-HHT syndrome develop colonic dysplasia and malignancies at an early age: this emphasizes the need for early, close surveillance of this population.
Monday, March 19, 2012 1:00 PM
Poster Session II # 122, Monday Afternoon