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Sessile Serrated Polyps
Tor J. Eide
Oslo Universitetssykehus
Årsmøtet i Den norske Patologforening 2014
The term ‘‘serrated’’ include a group of lesions with a sawtooth-
like appearance of the crypts and the surface epithelium.
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
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
Sessile Serrated Adenoma Synonyms
Sessile serrated polyp
Sessile serrated lesion
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
Sessile Serrated Adenomas General features
Typical appearance of a sessile serrated adenoma of the ascending colon
seen as a smudge of bile-stained mucus.
Sessile serrated polyps has “architectural dysplasia” rather than
“cytologic dysplasia,” the latter being sometimes referred to as
“adenomatous change.”
cytologic dysplasia architectural dysplasia
MSI-H
15%
Sporadic Colorectal Cancer
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.
Older age (~70 y).
Female sex (60-70%).
Cigarette smoking.
Low folate intake.
Right sided anatomical location (~ 85%).
Poorly differentiated (~ 60%).
Mucinous histology (~ 60%).
Microsatellite Instability High (MSI-H)
Colorectal Cancer Associated Clinicopathologic Features
BRAF mutation
BRAF takes part of the RAS-RAF-MAP kinase signaling pathway,
implicated in the regulation of cell growth, differentiation and
apoptosis.
BRAF mutation
Are very frequent in:
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.
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.
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).
BRAF Mutation
CIMP-High
MSI-H
Sessile Serrated Adenoma LGD HGD Cancer
The Sessile Serrated Adenoma Pathway
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.
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.
a b
c d
”Serrated lesions of the colorectum: review and recommendations from an expert panel”
Rex et al 2012, Am J Gastroenterology
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.
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
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
Prevalence of polyps at baseline NORCCAP study 1999-2001
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)
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)
NORCCAP study
Holme et al 2014 (unpublished data)
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)
