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Download Geraint Williams (Cardiff) - Virtual Pathology at the University of Leeds
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Assessment of Adenomas Geraint Williams Pathology Department Cardiff University The great majority of lesions in the Screening Programme are small adenomas and hyperplastic polyps Recognising adenomas Categorising adenomas Invasion Completeness of Excision Serrated lesions Recognising adenomas Categorising adenomas Invasion Completeness of Excision Serrated lesions Size Villousness Dysplasia Frequency of Carcinoma in Adenomas < 1 cm 1479 1.3% 1-2 cm 580 9.5% > 2 cm 430 46.0% Muto et al 1975 Frequency of Carcinoma in Adenomas tubular 1875 4.7% tubulovillous 380 22.4% villous 234 41.9% Muto et al 1975 Frequency of Carcinoma in Adenomas mild dysplasia 1734 5.7% moderate dysplasia 549 18.0% severe dysplasia 223 34.5% Muto et al 1975 High Risk (‘Advanced’) Adenomas > 1 cm villous component severe dysplasia As long as there is no invasive malignancy and excision is complete No worries! Rectosigmoid Adenoma Follow-Up 1618 patients followed for a mean of 14 years after removal of rectosigmoid adenomas: 49 (3%) developed colorectal cancer: 14 rectal SIR 1.2 (CI 0.7-2.1) (11/14 had incompletely excised adenomas) 35 colonic SIR 2.1 (CI 1.5-3.0) Atkin et al 1992 Risk of Subsequent Colon Cancer tubular 1 mild 1.3 tubulovillous 3.8 moderate 3.4 villous 5.0 severe 3.3 <1 cm 1.5 1 tumour 1.7 1-2 cm 2.2 >2 tumours 4.8 >2 cm 5.9 Risk of Subsequent Colon Cancer Patients Cancers SIR Low Risk Adenomas Single Multiple Total 712 64 776 4 0 4 0.6 0 0.5 High Risk Adenomas Single Multiple Total 683 159 842 20 11 31 2.9 6.6 3.6 Advanced Adenoma Patients > 1 cm villous component severe dysplasia multiple polyps Risk of Advanced Neoplasia 5.5yrs No neoplasia Tubular Adenoma <10mm 1-2 3+ Tubular Adenoma >10mm Villous Adenoma High Grade Dysplasia Carcinoma Patients 298 622 496 126 123 81 46 23 Ad Neo 7 38 23 15 19 13 8 8 RR 1 2.56 1.92 5.01 6.40 6.05 6.87 13.56 Lieberman et al 2007 Even if there is no invasive malignancy and excision is complete Grading of dysplasia and assessment of villousness in adenomas that are <10mm will govern surveillance So we’ve got to try hard to get it right! Grading Dysplasia in 2189 Adenomas at 13 Centres min max median mild 29% 88% 42% moderate 10% 67% 43% 1% 24% 4% severe Low grade and high grade High Grade Dysplasia Expected in <5% of all adenomas Equates to ‘intramucosal adenocarcinoma’ Involves more than 1-2 glands High Grade Dysplasia Recognition based primarily on ARCHITECTURE: COMPLEX glandular crowding and irregularity PROMINENT budding CRIBRIFORM ‘back-to-back’ glands INTRALUMINAL papillary tufting Low power diagnosis - epithelium is thick, blue, disorganised and ‘dirty’ High Grade Dysplasia CYTOLOGY: Loss of polarity and nuclear stratification Markedly enlarged nuclei Atypical mitoses Prominent apoptosis Usually more than one of these Histology of 2206 Adenomas at 13 Centres min max median 62% 93% 84% tubulovillous 6% 37% 15% villous 0% 6% 1% tubular Reproducibility of Identifying Villousness – 3 observers – Overall agreement 61% Jensen et al 1995 Tubulovillous Adenomas The 20% Rule Neoplastic Villi Classical Palmate Foreshortened May have prominent low grade mucinous epithelium Flat Adenomas – – – – – – thickness does not exceed twice that of adjacent mucosa more often right sided usually small (<1cm) with tubular growth pattern more often high grade dysplasia 40% contain carcinoma uncommon because no chromoendoscopy Muto et al 1985 National Polyp Study • 1418 patients • Complete colonoscopy with removal of adenomas • No special attempt to identify flat adenomas • Follow up colonoscopy, mean 5.9 years • 97% clinical follow up, 80% colonoscopies • 8401 patient years National Polyp Study • 90% reduction in colorectal cancer incidence • all five colorectal cancers found on follow-up were polypoid Macroscopic Examination & Trimming of Polyps • Size - to nearest millimetre in formalin fixed specimen (whole polyps) • Polypoid lesions • • • • Fixed intact Bisect through stalk if <10mm If larger, trim to leave central intact stalk At least three levels of stalk • Sessile lesions pinned out and all-embedded after inking margins Serrated Lesions Hyperplastic polyp Serrated adenoma Mixed polyp Sessile serrated polyp Serrated carcinoma Hyperplastic Polyps • Formerly metaplastic polyps • Left > right • Male > female • Infolded epithelial tufts and enlarged goblet cells • No dysplasia • Failure of anoikis (shedding of mature cells) Ki-67 Hyperplastic Polyp 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? Serrated Adenoma Dysplasia by definition Eosinophilic cytoplasm Pseudostratified, ‘pencillate’ nuclei May be tubular, tubulovillous or villous Invade to give serrated carcinoma Longacre & Fenoglio-Preiser 1990 ‘Traditional’ Serrated adenoma (TSA) Mixed Polyps Collision between hyperplastic polyp and adenoma Dysplasia in Hyperplastic Polyp Longacre & Fenoglio-Preiser 1990 Sessile Serrated Polyp (Adenoma) • Serrated polyps with unusual architectural features • No conventional dysplasia but may have ‘nuclear atypia’ or ‘hypermucinous’ change • Right colon • Females > males • Large sessile, poorly defined Torlakovic & Snover 1996 Sessile serrated polyp Serrated Adenocarcinoma • Serrated, mucinous or trabecular growth pattern • Abundant eosinophilic cytoplasm • Chromatin condensation • Preserved polarity • No necrosis Tuppurainen K et al 2005 J Pathol 207: 285-94 Tuppurainen K et al 2005 J Pathol 207: 285-94 Serrated Neoplasia Microsatellite instability DNA methylation MLH1 inactivation BRAF mutation Baker K et al J Clin Pathol 2004; 57: 1089 BRAF mutation • • • • • • • • Typical adenomas Typical hyperplastic polyps Sessile serrated adenomas Traditional serrated adenomas Mixed Polyps HNPCC cancers All colorectal cancers MSI-high non-HNPCC cancers 0% 19-78% 75-78% 20-66% 57-89% 0% 15% 76% Serrated Neoplasia Pathway Proximal hyperplastic polyp Sessile serrated polyp Serrated adenoma MSI-high, methylation-rich non-HNPCC “serrated” carcinoma (50% mucinous) Higuchi T & Jass JR 2004 J Clin Pathol 57: 682 1250 Polyps at Colonoscopy Polyp Dysplasia % Adenoma Tubular Tubulovillous Villous + + + 55 15 1 Serrated Hyperplastic polyps Sessile Serrated Polyp Mixed Polyp Serrated Adenoma + + 24.5 2.5 0.8 1.2 NBCSP Hyperplastic polyp Serrated adenoma Mixed polyp Sessile serrated polyp Serrated carcinoma
