The serrated pathway to colorectal carcinoma: current concepts and challenges. Issue 3 (22nd January 2013)

• Record Type: Journal Article
• Authors: Bettington, Mark; Walker, Neal; Clouston, Andrew; Brown, Ian; Leggett, Barbara; Whitehall, Vicki
• Is Part Of: Histopathology. Volume 62:Issue 3(2013)
• Page Start: 367
• Page End: 386
• Publication Date: 2013-01-22
• Subjects: Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12055
• Languages: English
• ISSNs: 0309-0167

Abstract

<abstract abstract-type="main" xml:lang="en" id="his12055-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Approximately 30% of colorectal carcinomas develop via a serrated neoplasia pathway, named for the pattern of crypts in the precursor polyps. Molecular abnormalities consistently involve methylation of CpG islands [CpG island methylator phenotype (CIMP)] of low degree (CIMP‐L) or high degree (CIMP‐H), and activating mutations of the mitogen‐activated protein kinase pathway components <italic>BRAF</italic> or <italic>KRAS</italic>. Microsatellite instability (MSI) of a high level (MSI‐H) is often present, allowing for a molecular classification of serrated pathway carcinoma as: (i) <italic>BRAF</italic> mutant/CIMP‐H with either a) MSI‐H or b) microsatellite stable (MSS); and (ii) <italic>KRAS</italic> mutant/CIMP‐L/MSS. Precursor polyps include sessile serrated adenoma (SSA), characterized by proximal location, crypt architectural disturbance, and <italic>BRAF</italic> mutation. Microvesicular hyperplasic polyp (MVHP) probably precedes the development of SSA, and borderline lesions between MVHP and SSA occur. Cytological dysplasia in SSA portends advanced genetic abnormality and a high risk of progression to carcinoma. The traditional serrated adenoma has a predilection for the left colon, tubulovillous architecture, eosinophilic cytoplasm, and frequent <italic>KRAS</italic> mutation. Serrated morphology carcinoma is a new World Health Organization subtype with well‐differentiated, mucinous or trabecular patterns. It has frequent <italic>KRAS</italic> or <italic>BRAF</italic> mutations and a poor prognosis. This review provides an insight into the histology and molecular mechanisms driving these serrated pathway lesions.</p> </abstract>