Duodenal Serrated Adenomas: Evidence for Serrated Carcinogenesis in the Proximal Small Intestine.
Amitabh Srivastava, Tanya A Rege, Kyoung M Kim, Joel A Lefferts, Cheol K Park, Gregory J Tsongalis, Robert D Odze. Dartmouth Hitchcock Medical Center, Lebanon, NH; Brigham & Women's Hospital, Boston, MA; Samsung Medical Center, Seoul, Korea
Background: Primary sporadic duodenal serrated adenomas (SA) are extremely rare. The clinicopathologic and molecular features of sporadic (non-FAP associated) duodenal SA have never been reported. The aim of this study was to evaluate the morphological, immunohistochemical and molecular features of sporadic duodenal SA, and to compare them to conventional tubular adenomas (TA) of the duodenum.
Design: 10 patients, each with a sporadic duodenal SA, were identified via a 5 year search through the pathology files of 3 academic hospitals. Clinical and endoscopic information was obtained by chart review. Immunostaining for MLH-1, MGMT, p53, beta-catenin, SMAD4 and Ki-67 was performed in all cases. DNA from formalin-fixed tissue was analyzed in 7 TaqMan PCR allelic discrimination assays for detection of common KRAS mutations and in two allele-specific SYBR Green PCR assays for detection of BRAF V600E mutation. 14 consecutive conventional TA (11 sporadic; 3FAP) were analyzed as a comparison (control) group.
Results: The 10 patients included 5 males and 5 females, mean age 70.5 yrs, with sessile or pedunculated polyps in the first (n=4) or second (n=6) part of the duodenum. Size range was 0.8-4.6cm. All duodenal SA were morphologically similar to traditional SA of the colon. 8 duodenal SA showed low grade dysplasia and 2 showed high-grade dysplasia (HGD), 1 of which also had an invasive adenocarcinoma.
Nuclear staining for MLH-1, MGMT and SMAD4 was intact in all cases (100%). p53 overexpression was not identified in any polyp (0%). A high proliferative index (>50% positive cells) was present in 1 case (10%) associated with carcinoma. Nuclear beta-catenin was present in 1 duodenal SA (10%) in an area of HGD. KRAS mutations [(G12D (n=4); G13D (n=1)] were present in 5/10 (50%) duodenal SA, and a BRAF V600E mutation was detected in 1 case (10%).
Compared to duodenal SA, conventional TA were present in younger patients (mean age; 62 yrs), more often involved the 2nd or 3rd part of duodenum (86%), and showed significantly higher nuclear beta-catenin staining (86%; p=0.001), higher proportion of cases with >50% proliferative index (93%; p<0.0001) and a lower frequency of KRAS mutation (7%; p=0.009).
Conclusions: This study provides evidence that the serrated pathway of carcinogenesis is also involved in the development of a subset of primary duodenal carcinomas. Duodenal SA are morphologically and molecularly distinct from conventional TA of the duodenum.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 60, Tuesday Afternoon