Serrated Lesions in the Bowel Cancer Screening Programme

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1 Serrated Lesions in the Bowel Cancer Screening Programme Mark Arends Cambridge & Edinburgh

2 Serrated Lesions of Large Bowel 1. Hyperplastic polyp 2. Serrated adenoma 3. Mixed polyp 4. Sessile serrated lesion (polyp) 5. Serrated carcinoma

3 1. Hyperplastic Polyps Formerly: metaplastic polyps Left > right, Male > female Sawtooth / serrated architecture top half Infolded epithelial tufts, microvesicular cells, enlarged goblet cells upper half crypts expanded proliferation zone Thickened subepithelial collagen plate No dysplasia

4 Hyperplastic Polyps Ki-67

5 Hyperplastic Polyps Increase in frequency with age 17 times commoner in colons with carcinoma Similar dietary and lifestyle risk factors to CRC K-ras mutation common Clonal Monocryptal

6 Hyperplastic Polyposis (WHO) aka Serrated Polyposis > 5 hyperplastic polyps proximal to the sigmoid colon of which two are >10mm diameter OR > 30 hyperplastic polyps of any size proximal to the sigmoid colon OR > Any number of hyperplastic polyps with a 1st degree relative with hyperplastic polyposis Familial clustering Association with colorectal cancer with microsatellite instability Proximal Williams et al 1980 Leggett et al 2001

7 Hyperplastic/Serrated Polyposis Hyperplastic polyps Large Villous Complex architecture May resemble atypical juvenile polyps Sessile Serrated adenomas Typical adenomas Mixed adenoma / hyperplastic polyps Cancer in ~25% Barker M et al Gastroenterology 2006; 131: 30-39

8 2. Serrated Adenoma Serrated architecture Dysplasia by definition, usually low grade Eosinophilic cytoplasm Pseudostratified, pencillate nuclei May be tubular, tubulo-villous or villous Invade to give serrated carcinoma Right sided usual type serrated adenoma Left sided traditional serrated adenoma Longacre - usual & Fenoglio-Preiser 1990

9 Traditional Serrated Adenoma Subset Often left sided ~1% of all adenomas Frequently pedunculated, villiform Short, budding, ectopic crypts Filiform variant Torlakovic et al 2003, 2008 Yantiss et al 2007

10 Traditional Serrated Adenoma (TSA) short, budding, ectopic crypts

11 Filiform pattern of Traditional Serrated Adenoma

12 3. Mixed Polyps Originally: collision between hyperplastic polyp and adenoma Currently: Dysplasia in Hyperplastic Polyp Longacre & Fenoglio-Preiser 1990

13 Mixed Polyps

14 4. Sessile Serrated Lesion (Polyp) Confused nomenclature (Previously: sessile serrated adenoma; still called SSA in USA & Europe & literature ) EU Guidelines 2010: Sessile Serrated Lesion Hyperplastic polyp-like - unusual architecture: o o Horizontal orientation of deep crypts (L,T, anchor) Serration down to crypt base (or dilated at base) No conventional dysplasia but may have nuclear atypia or hypermucinous change Right > Left colon Females > males Large, sessile, poorly defined Torlakovic & Snover 1996

15 Sessile Serrated Lesion (Polyp) Crypt dilatation Abnormal proliferation Normal subepithelial collagen plate Some - loss of MLH1 expression Sometimes found in Hyperplastic Polyposis Often express MUC5AC or MUC6 Torlakovic et al 2003 AJSP 27: 65-81

16 Sessile Serrated Lesion

17 Sessile Serrated Lesion Anchor shape, L-shape crypt, dilated crypts

18 Topographical distribution of SSL Gurudu et al. WGL 2010;16:3402

19 5. Serrated Adenocarcinoma 5-10% colorectal cancer Right colon and rectum Serrated, mucinous or trabecular growth patterns Abundant eosinophilic cytoplasm Preserved polarity No dirty necrosis in lumen

20 Serrated Adenocarcinoma Garcia-Solano J et al 2010 Hum Pathol 41:

21 Serrated Adenocarcinoma 2 subtypes: Most arise in traditional serrated adenomas and are Microsatellite Stable (MSS) Distal tumours Poor prognosis (30% 5-year survival) 20% arise in sessile serrated lesions and have Microsat. Instability (MLH1 loss) Proximal tumours Good prognosis (70% 5-year survival) Makinen et al 2001 J Pathol 193:

22 I. Sessile Serrated Neoplasia Pathway (Right) Proximal hyperplastic polyp Sessile serrated lesion Serrated adenoma MLH1 loss & MSI Proximal MSI, CIMP+, non-hnpcc, serrated carcinoma (50% mucinous) Higuchi T & Jass JR 2004 J Clin Pathol 57: 682

23 II. Traditional Serrated Neoplasia Pathway (Left) Distal Hyperplastic polyp Traditional serrated adenoma Distal MSS, CIMP+, non-hnpcc, serrated carcinoma Higuchi T & Jass JR 2004 J Clin Pathol 57: 682

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25 UK Bowel Screening Programme Probably the best database on adenomas, other precursors (including serrated lesions) and early colorectal cancer in the world An opportunity for research to improve understanding and management

26 Acknowledgements Ian Frayling George Poulogiannis Ash Ibrahim David Adams Lisa Happerfield Andrew Wyllie Geraint Williams Fred Bosman