[Colorectal serrated adenoma: diagnostic criteria and clinical implications].
More than 40 years ago Morson (1962) coined the paradigm that adenomas are the main precursors of colorectal carcinoma (CRC) whereas hyperplastic polyps are "non-neoplastic" lesions without cancer risk. Later-on (1988) this was supported by Vogelstein's molecular adenoma-carcinoma progression model with APC mutations being a key-initiating molecular event (classic adenoma-carcinoma pathway). In 1992 a new molecular mechanism, the mutator pathway of CRC was discovered in HNPCC patients. Deficiencies in mismatch repair (MMR-) gene function (mainly of MSH2 and MLH1) cause microsatellite instability (MSI) in about 15% of CRC. It's the merit of Jass (1999) to demonstrate that carcinogenesis in sporadic MSI-positive CRC is associated with serrated polyps. These polyps form the hallmark of a third "serrated (neoplasia) pathway" exhibiting a hyperplastic polyp-like morphology characterized by serrated crypt epithelium. In contrast to adenomatous polyps with readily apparent cytological atypia (dysplasia) the feature of dysplasia in serrated polyps is architectural distortion. Today four categories of serrated lesions can be delineated: (i) the most frequent classic hyperplastic polyp (HP, 80-90%), followed by (ii) sessile serrated adenoma (SSA, 15-20%) and (iii) by the rare traditional serrated adenoma (TSA, < 1%). Whereas HPP are benign, SSA are probably slowly progressing lesions and TSA as well as SSA with APC-type adenomatous atypias (iv. mixed SSA) indicate increased cancer risk. Molecularly serrated polyps seem to share a defect in apoptosis caused by either K-ras or BRAF gene mutation leading to CpG island methylation (CIMP) affecting MLHI (--> MSI type CRC) or non-MMR oncogenes (--> MSI-L or MSS type serrated CRC, Mäkinen 2007).
Rüschoff
J
J
Institut für Pathologie, Klinikum Kassel.
Aust
D
D
Hartmann
A
A
D000236:Adenoma / Q000145:classification / Q000235:genetics / Q000473:pathology*; D003111:Colonic Polyps / Q000473:pathology; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology*; D003937:Diagnosis, Differential; D017491:Genes, APC; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D009154:Mutation