Herniation of crypts in hyperplastic polyp and sessile serrated adenoma: a prospective study

Presence of colonic crypts in submucosa was previously termed as herniation of crypts, pseudoinvasion, epithelial-misplacement, or inverted hyperplastic-polyp. It is considered as an important criterion for diagnosing sessile serrated adenoma (SSA), which links to a higher risk of synchronous and future colorectal cancers compared with hyperplastic polyp (HP). Here, we aimed to study the frequencies, diagnostic specificity and synchronous neoplasms of herniation of crypts in HP and SSA. We prospectively included all HP and SSA cases and 514 randomly-selected colorectal polyps of normal histology diagnosed from 2013 to 2015 at our institution. We calculated the frequencies of herniation of crypts by histology, sex, age, size, race, location, prior polyp-history and synchronous neoplasms (including colorectal cancers and adenomas). Binary and ordinal (ordered) logistic regression analyses were used to identify potential associations. Among the 2,560 colorectal polyps in the subjects with average-risk of colorectal cancer, the frequencies of herniation of crypts were 1.79% (10/559) in SSA, 0.2% (3/1487) in HP and 0% (0/514) in polypoid normal tissue. The specificity of herniation of crypts for diagnosing serrated polyp (HP and SSA versus normal tissue) was 100% (514/514), but its sensitivity was 0.64% (13/2046), while the specificity of herniation of crypts for diagnosing SSA (versus HP and polypoid normal tissue) was 99.85% (1998/2001) and its sensitivity was 1.79% (10/559). Our multivariate analyses identified an independent association between herniation of crypts and diagnosis of SSA (Odds ratio [OR]=9.37, P=0.015 for versus HP and normal tissue, and OR=11.47, P=0.009 for versus HP). We also found that herniation of crypts in SSA and HP did not independently link to race or synchronous neoplasms (including cancers and adenomas). In summary, our data show that, while herniation of crypts is rare, its presence is highly suggestive of SSA.