Polyp Landscape in Serrated Polyposis Syndrome
Christophe Rosty, Daniel Buchanan, Neal Walker, Susan Parry, Joanne Young. Royal Brisbane and Women's Hospital, Brisbane, Australia; Queensland Institute of Medical Research, Brisbane, Australia; Envoi Specialist Pathologists, Brisbane, Australia; Auckland City Hospital, Auckland, New Zealand
Background: Serrated polyposis syndrome (SPS), also known as hyperplastic polyposis, is a syndrome of unknown genetic basis defined by the occurrence of multiple serrated polyps in the large bowel and associated with an increased risk of colorectal cancer (CRC). There is a variety of presentations of SPS, which may encompass a continuum of phenotypes modified by environmental and genetic factors. To explore the phenotype of SPS, we recorded the histologic and molecular characteristics of multiple colorectal polyps in 100 patients with SPS.
Design: Patients were selected from a cohort of individuals recruited between 2000 and 2010 from genetics clinics in Australia, New Zealand, Canada and the USA. Pathology review of polyps was undertaken by 3 specialist gastrointestinal pathologists. Polyps were classified into conventional adenoma or serrated polyp with various subtypes following the criteria from the WHO. Mutations in BRAF and KRAS and mismatch repair protein expression were determined in a subset of polyps.
Results: A total of 100 patients were selected for the study, comprising 58 females and 41 males. The total polyp count per patient ranged from 6 to 150 (median: 30). The vast majority of patients (89%) had polyposis affecting the entire large intestine. From this cohort, 406 polyps were reviewed. Most of the polyps (83%) were serrated polyps: microvesicular HP (n=156), goblet cell HP (n=25), SSA/P (n=110), SSA/P with cytological dysplasia (n=28) and TSA (n=18). BRAF mutation was mainly detected in SSA/P with dysplasia (95%), SSA/P (84.5%), microvesicular HP (76.2%), and TSA (53.8%) while KRAS mutation was present mainly in goblet cell HP (50%) and in tubulovillous adenoma (45.4%). Four of 6 SSA/Ps with high grade dysplasia showed loss of MLH1/PMS2 expression. CRC was diagnosed in 39 patients who were more often found to have a conventional adenoma compared to patients without CRC (p=0.003).
Conclusions: SPS referred to genetics clinics is a pancolonic disease with a wide range of polyp counts, mostly represented by microvesicular HP, SSA/P and occasional TSA with a high rate of BRAF mutation. The occurrence of CRC was associated with the presence of conventional adenoma.
Monday, March 19, 2012 1:00 PM
Poster Session II # 111, Monday Afternoon