Adenoma serrato e polipi intestinali: nuovi aspetti e
implicazioni cliniche
Stefano Crippa
Istituto Cantonale di Patologia
Lugano, 7 marzo 2007
• Torlakovic et al. (1996) Serrated adenomatous polyposisin humans
• Longacre, Fenoglio-Preiser (1990) Mixed hyperplasticadenomatous polyps/serrated adenomas: a distinct form ofcolorectal neoplasia
• Urbanski et al. (1984) Mixed hyperplasticadenomatous polyps: an underdiagnosed entity.
• Cooper et al. (1979) Adenomatous and carcinomatouschanges within hyperplastic colonic epithelium
Serrated lesions pathway
Response to tissue injury Genetic mechanism(Kras, BRAF, MLH1…)
« The hyperplastic polip can be defined as a lesion causedby the inibition of programmed cell death or apoptosis »J. R. Jass (2004)
« Despite decades of research into the behaviour of adenoma, we still do not know which adenomas are aggressive »J. R. Jass (2004)
serrated neoplasia pathway
vs
APC pathway (Vogelstein)
« Inhibition of apoptosis characterises serrated polips, whereasloss of inhibition of proliferation is the mechanism underlyingtubular adenomas » J. R. Jass (2004)
serrated
villous
tubulo-villous
tubular
adenocarcinomaMSI-H
(Mucinous-poorly
differentiated)
normalmucosa
adenocarcinomaMSS
(Mucinous-poorly
differentiated)
metastasis(~85% of CRCsaneuploidy)
metastasis(~15% of CRCsaneuploidy)
Colon cancer stratification
Diagrammatic Representation of the Serrated Neoplasia Pathway
Proximal ColonNormal
Hyperplastic Polyp Hyperplastic Polyp
Serrated Adenoma
MSI-H carcinoma
MLH1 methylation
Proliferation
Mutation of TGF-B, IGF and BAX genes
K-ras Mutation BRAF Mutation
Growthfactor
P
P
P
P
PPP
GRBSOS RAS
OUT
Changes ingene expression
CyclicAMP
Nucleus
Cytoplasm
P
BRAF
MEK
ERK1 ERK2
Adenylatecyclase
Growthfactor
G-protein
G-protein-coupledreceptor
The RAS-RAF-MAPK signalling pathway
TyrosineKinase
receptor
P P
Clinical relevance
• Separate traditional hyperplastic polyp from sessile serratedadenoma which is truly a neoplastic lesion that can progress tocarcinoma
• Nomenclature
• Follow-up guidelines
Nomenclature
• Polipo iperplastico
• Adenoma dentellato sessile (usualmente displasia di basso grado)
• Adenoma dentellato (displasia di basso o alto grado)
• Polipo misto iperplastico/adenomatoso
Summary
• Sessile serrated adenoma, used to be called hyperplastic polyp, but evidence exists that have precancerous potential through serrated neoplasia pathway
• It has high growth rate, and has similar risk of developingcolorectal cancer as TA
• Optimal treatment is complete endoscopic removal and probably managed as conventional adenoma