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Colon tumor
Polyps
Serrated polyp / adenoma
Reviewers: Shilpa Jain, M.D. (see Reviewers page)
Revised: 17 September 2012, last major update August 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.
Clinical features
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● First described in 1990 (Am J Surg Pathol 1990;14:524)
● Neoplastic, 1-2% of all polyps
● Combination of hyperplastic and adenomatous polyp
● Usually in sigmoid colon and rectum (Anticancer Res 2000;20:1141)
● Often have microsatellite-instability mutations and DNA methylation
● Right sided lesions may be precursor of sporadic microsatellite-unstable colorectal carcinoma, particularly if large, multiple and part of giant hyperplastic polyposis (J Natl Cancer Inst 2001;93:1282)
● May be associated with attenuated (<100 polyps) familial adenomatous polyposis (Gut 2002;50:402)
● Risk of subsequent carcinoma is 5-6% (Am J Clin Pathol 2005;123:349, World J Gastroenterol 2006;12:2770); relationship to cigarette smoking is unclear (PLoS One 2010;5:e11636)
● 6% of colorectal carcinomas are associated with coexisting serrated adenomas (J Pathol 2001;193:286)
● Inhibition of apoptosis in upper and middle crypts of hyperplastic polyps and serrated adenomas may be due to reduced Fas expression and may cause serrated appearance (Am J Surg Pathol 2002;26:249)
Case reports
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● Developing into carcinoma within 2 years (J Gastroenterol 2002;37:467)
● Polyp with intraepithelial carcinoma (Pathol Int 2001;51:215)
● Associated with multiple “serrated adenocarcinomas” (J Pathol 2000;190:444)
Gross description
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● Mean 6-9 mm
Micro description
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● Variable, ranging from clearly adenomatous to resembling a hyperplastic polyp (Am J Surg Pathol 2003;27:65)
● Proposed definition: surface epithelial nuclear dysplasia (elongation, increased N/C ratio, nucleoli and atypia) and serration of 20%+ of lesional crypts (Mod Pathol 2003;16:417)
● Left sided: have “normal proliferation” - less pronounced adenomatous features; may be vesicular cell type with prominent serration, irregular thickening of muscularis mucosa, decreased or dystrophic goblet cells, mucin in vesicular cells similar to hyperplastic polyp; also goblet cell type with less prominent serration but thick mucosa and thick basal membrane; also mucin poor type (rare) with prominent serration, no mucin
● Right sided: usually large with abundant mucin (intra/extracellular), abnormal proliferation (i.e. adenomatous changes), dilated and distorted crypts and often secondary papillae
● May coexist with colon carcinoma, with transition zone of tubulovillous adenoma (Am Surg 2010;76:E190)
Micro images
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Various images
Various images #1, #2, #3, #4, #5, #6
Serrated adenoma in hyperplastic polyposis #1, #2, #3
Pedunculated serrated adenoma with high grade dysplasia
Virtual slides
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Positive stains
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● CK7 and CK20 (Dig Dis Sci 2005;50:1741)
● Similar mucin profiles as hyperplastic polyp and gastric antral mucosa (Pathol Int 2004;54:401)
● Ki-67 (19%, intermediate between hyperplastic polyp and adenoma, proliferation in basal or intermediate [but not superficial] crypts (Pathol Int 2003;53:277)
● Also p53 (29-50%) and hTERT (46-53%) (Scand J Gastroenterol 2002;37:1194), COX2 (Dis Colon Rectum 2001;44:1319)
Molecular description
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● MLH1 and PMS2 is often lost in zones of dysplasia or early carcinoma (Am J Clin Pathol 2006;126:564)
● K-ras mutations in 40%, particularly in nodular and rectal lesions (Dis Colon Rectum 2003;46:327)
● More highly methylated than tubular adenomas (Am J Pathol 2003;162:815), often BRAF mutations (Virchows Arch 2005;447:597, Cancer Res 2003;63:4878)
● SMAD4 gene frameshift mutations have recently been reported (Clin Genet 2011 Apr 7 [Epub ahead of print])
● Serrated polyp-carcinoma sequence, which includes microsatellite instability, BRAF/KRAS mutations and CpG island methylator phenotype, has been described (Curr Gastroenterol Rep 2008;10:490)
Differential diagnosis
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● Adenoma
● Hyperplastic polyp
● Colchicine effect (Arch Pathol Lab Med 2002;126:615
Sessile serrated adenomas
Clinical features
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● Also called sessile serrated adenoma
● Precedes microsatellite-unstable adenocarcinoma (Am J Clin Pathol 2003;119:778)
● MIB staining not helpful in differentiating (Am J Clin Pathol 2006;125:407)
● Cases with focal invasive adenocarcinoma or high grade dysplasia: most of polyp is non-malignant with abrupt transition to malignancy; hMLH1 negative (Am J Clin Pathol 2006;125:132)
Micro description
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● Expanded crypt proliferative zone, exaggerated serrated architectural outline in basilar crypt region, basilar crypt dilation, inverted crypts and predominance of dysmaturational crypts (crypts with minimal cell maturation)
● Also horizontal extension of the crypt base along the muscularis mucosa (J Clin Pathol 2004;57:682)
● Low grade dysplasia: has stratified "cigar" shaped blue nuclei with "picket-fence" arrangement of adenoma and lack of goblet cells
● High grade dysplasia: Stratified atypical haphazardly arranged nuclei in uppermost level of cell (Am Surg 2010;76:E190)
Micro images
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Sessile serrated adenoma
Ascending colon
Cecum
Positive stains
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● Ki-67, Kras, BRAF and methylation present, but this does not distinguish these polyps from traditional hyperplastic polyps (Am J Clin Pathol 2006;125:407) or serrated adenomas (Am J Surg Pathol 2004;28:1452)
● Also MUC2 and MUC5A (Cesk Patol 2006;42:133)
Negative stains
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● p53 (usually)
● Reduced expression of hMHL1 and hMSH2 (Am J Surg Pathol 2003;27:65)
Virtual slides
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Serrated adenoma with abnormal proliferation
End of Colon tumor > Polyps > Serrated polyp / adenoma
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