Sessile Serrated Polyps

Transcription

1 Årsmøtet i Den norske Patologforening 2014 Sessile Serrated Polyps Tor J. Eide Oslo Universitetssykehus

2 The term serrated include a group of lesions with a sawtoothlike appearance of the crypts and the surface epithelium.

3 Historikk JF Arthur: Structures and significance of metaplastic nodules in the rectal mucosa, 1968 N Lane et al: Minute adenomatous and hyperplastic polyps of the colon, 1971 TA Longarce and CM Fenoglio-Preiser: Mixed hyperplastic adenomatous polyps/serrated adenomas. A disitinc form of colorectal neoplasia, 1990 EE Torlakovic and DC Snover: Serrated adenomatous polyposis in humans, 1996 WHO Classification of tumours of the digestive system, 2010

4 Serrated Polyps of the Colon and Rectum Classification Hyperplastic polyp Microvesicular type Goblet cell rich type Mucin poor type Traditional serrated adenoma Sessile serrated adenoma

5 Sessile serrated polyp Sessile serrated lesion Sessile Serrated Adenoma Synonyms

6 Sessile Serrated Adenomas General features Predilection for the right colon (proximal to the left flexure). Usually larger than 0,5 cm. Tendency to be flat or sessile. Frequently covered with bile-stained mucus. Account for 10-20% of all colonic polyps Typical appearance of a sessile serrated adenoma of the ascending colon seen as a smudge of bile-stained mucus.

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11 Sessile serrated polyps has architectural dysplasia rather than cytologic dysplasia, the latter being sometimes referred to as adenomatous change. architectural dysplasia cytologic dysplasia

12 Sporadic Colorectal Cancer MSI-H 15% Approximately 15% of sporadic colorectal adenocarcinomas present microsatellite instability-high (MSI-H). Sessile serrated adenomas are thought to be the precursor lesion in this group of adenocarcinomas.

13 Microsatellite Instability High (MSI-H) Colorectal Cancer Associated Clinicopathologic Features Older age (~70 y). Female sex (60-70%). Cigarette smoking. Low folate intake. Right sided anatomical location (~ 85%). Poorly differentiated (~ 60%). Mucinous histology (~ 60%).

14 BRAF mutation BRAF takes part of the RAS-RAF-MAP kinase signaling pathway, implicated in the regulation of cell growth, differentiation and apoptosis.

15 Are very frequent in: BRAF mutation Sessile serrated polyps (75 82%) Hyperplastic polyposis (88%). BRAF mutation is an early genetic event in sessile serrated adenomas. The mutated BRAF inhibitis apoptosis multiplying the chances for more genetic alterations to occur. Later, when cells acquire other mutations, the effect of activated BRAF is to drive proliferation.

16 DNA Methylation DNA methylation involves the addition of a methyl group at CpG dinucleotides In general, DNA methylation is an effective mechanism for silencing gene expression in mammals.

17 The consequences of aberrant methylation depend on the target genes involved. Genes frequently involved in the the sessile serrated pathway include: MLH1, a DNA repair gene which is associated with MSI-H Cell cycle inhibitors genes P14 and P16 EPHB2 (Ephrin receptor B2. Ephrin receptors are membrane proteins that are important regulators of the spatial organization of various cells in tissues).

18 The Sessile Serrated Adenoma Pathway Sessile Serrated Adenoma LGD HGD Cancer BRAF Mutation CIMP-High MSI-H

19 The Sessile Serrated Adenoma Pathway The rate and incidence of progression of sessile serrated adenoma to carcinoma is unknown. In general sessile serrated adenomas do not demonstrate a rapid growth rate. Sessile serrated adenoma has been misdiagnosed as hyperplastic polyps for most of the past four decades without evidence for a strong association with carcinoma. The fact that MSI-H colorectal cancer is more common in older age (mean 73.5 y) is in favour of a slow progression. Sessile serrated adenoma with cytologic dysplasia mixed polyps may rapidly progress to colorectal cancer.

20 a b c d A slighly elevated sessile serrated adenoma of the ascending colon with a nodular surface that is partially covered with mucus (a). The u-turn maneuver reveals that the lesion is growing on the oral side of the fold. (b). Dye spraying depicts a granular surface (c). Close-up view demostrates a cerebriform (type IV) pit pattern through the whole lesion.

21 Serrated lesions of the colorectum: review and recommendations from an expert panel Rex et al 2012, Am J Gastroenterology

22 Key conclusions (Rex et al 2012) Pathology: Serrated lesions should be classified as HP,TSA and SSP SSP and TSA are precancerous lesions SSP is distinguished from HP by crypt distorsion. A single distorted, dilated and/or horizontal branched crypt is sufficient for a diagnosis of SSP.

23 Recommended Guidelines (Rex et al 2012) Histology Size No Localization Surveillance (Years) HP < 10 mm > 3 Rectosigmoid 10 HP < 5 mm > 4 Prox. c.sigmoid 10 HP All > 1 Prox. c.sigmoid. 5 HP > 5 mm > 1 Prox c.sigmoid. 5 SSP/TSA < 10 mm >3 All 5 SSP/TSA > 10 mm 1 All 3 SSP/TSA < 10 mm > 3 All 3 SSP > 10 mm > 2 All 1-3 SSP w/ dyspl All All All 1-3

24 Analysis New polyps, old tricks: controversy about removing benign bowel lesions G. Hoff, M. Bretthauer, K. Garborg, TJ Eide BMJ 2013; 347 Colorectal cancer screening programmes have increased the number of benign lesions being detected. Geir Hoff and colleagues argue that we need more evidence about their malignant potential to be sure that the risks of following current recommendations for removal do not outweigh the benefits of screening

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26 Prevalence of polyps at baseline NORCCAP study Type of polyp Total (%) Serrated polyp > 10 mm 88 Hyperplastic polyp 64 (73) Traditionally serrated polyp 2 (2) Sessile serrated polyp 73 (82) -Without dysplasia 68 (76) -With dysplasia 5 (6) Unclassifed polyp 44 (49) Non-advanced adenoma 41 (46) Holme et al 2014 (unpublished data)

27 Risk for ColoRectal Cancer among individuals with Serrated and Non-Serrated Polyps Polyp type Hazard ratio for CRC Large sarrated polyps Hazard ratio; 3,0 95% CI (1,1-7,8) Advanced adenomas Hazard ratio; 0,6 95% (0,4-1,0) Non-advanced adenomas Hazard ratio; 0,6 95% (0,5-0,7) Holme et al 2014 (unpublished data)

28 NORCCAP study Holme et al 2014 (unpublished data)

29 NORCCAP study Twenty-three large serrated polyps found at screening were left in situ in 21 individulas for a medium of 11.0 years. None developed CRC and only one developed a sessile serrated polyp with dysplastic features. Holme et al 2014 (unpublished date)

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