Serrated polyps of the colorectum: is sessile serrated adenoma distinguishable from hyperplastic polyp in a daily practice?

Traditionally, the two principal categories of colorectal polyps have been adenomas and HP. Conventional adenomas are well-identified precursor lesions of the tumor suppressor pathway first proposed by Vogelstein et al. [26]. In contrast, HP have been considered as benign and innocent mucosal lesions for many years, with no involvement in colonic carcinogenesis [12, 13, 27]. However, reassessment of the HP through clinical and epidemiological reports combined with the genetic alterations has led to a reinterpretation of its significance in colorectal carcinogenesis [13, 15]. The serrated polyps demonstrate a “saw-toothed” infolding of the crypt epithelium, probably as a consequence of inhibition of programmed cellular apoptosis of the surface mucosa or more precisely of anoïkis, which is the inhibition of programmed cell exfoliation, leading to prolonged cell life [15]. But to date, no consensus has been established about what classification or nomenclature to use when dealing with serrated polyps. SSA has been described by Torlakovic and Snover in 1996 [25] but has been ignored for several years and designated with different names, rendering this entity quite confusing. Recently, Snover et al. [23] reported an excellent morphologic and molecular review about serrated polyps of the large intestine.

In the present study, we tested the ease of use of this classification on the basis of the described morphological aspects and tried to apply them to the daily practice. We found that the incidence of SSA is very low, as they represent 7% of the serrated polyps and only 2% of all colonic polyps of our series, which is in the range of previously published data [10]. The distinction between HP and SSA was based mainly on architectural features, which seem to be due to abnormal proliferation and probably also decreased apoptosis [24]. These architectural features can be better recognized when a well-oriented polypectomy has been performed. We found that the diagnostic was more difficult when the biopsy specimens were superficial and tangentially cut, when the polyp was addressed fragmented, and when the polyp was small. However, even if the orientation of the biopsy was not optimal, we could distinguish between HP and SSA in the majority of the cases (94%) mainly due to the presence of a great number of undifferentiated cells in the lower third of HP crypts, contrasting with the predominance of goblet or gastric foveolar cells in SSA. Only in six polyps, the differential diagnosis between HP and SSA could not be resolved due to the above-mentioned reasons. The fact that the polyps in the category of indefinite diagnosis (HP/SSA) had the smallest median size (−2.5 vs 4 and 11 mm for the HP and SSA, respectively) appears to indicate that the size of the polyp is an important factor in the distinction of SSA from HP. The smaller the lesion, the more SSA and HP histologically overlap. Intermingling features of HP and SSA in a same serrated polyp, which was observed in three out of seven SSA, might add more difficulty to the distinction between both types of lesions. These findings support the idea that serrated polyps might constitute a continuous spectrum of lesions.

We found that the absence or presence of undifferentiated cells, location of the serration, branchment, horizontalization, and herniation of the crypts appeared to be good discriminators between HP and SSA.

Beside size and morphological features, other parameters seem to be discriminators between HP and SSA. HP are reported to be more frequently located in the distal colon and rectum [3, 6, 10]. Our results are in agreement with these data because we found that the majority of HP were left sided, whereas most SSA were right sided.

For Snover et al. [23], cytological dysplasia is not needed for the diagnosis of SSA, which is in contradiction with the generally accepted consensus about diagnostic criteria in gastrointestinal adenomas. Therefore, some authors do not fully agree with this concept and prefer to label SSA as “atypical HP” or “sessile serrated polyp” [2]. However, in our series, we found one case of SSA showing a low-grade dysplasia, and recently, Goldstein [5] reported eight cases of SSA with incidental high-grade dysplasia or invasive adenocarcinoma. This supports that dysplasia may emerge in SSA and that they are probably precursors of the serrated adenocarcinoma [21]. Molecular studies will probably be able to elucidate the link between morphologic features and molecular changes. Serrated mucosal lesions of the colorectum have emerged as an important concept supporting the existence of an alternate polyp–neoplasia pathway in addition to the classical adenoma–carcinoma sequence [1, 7, 9, 11, 26]. The most common genetic changes seem to be BRAF-activating mutation and CpG island mutation [1, 4, 10, 17, 18, 20, 22]. However, most of the molecular results already published have to be interpreted with caution because the serrated polyps studied were heterogeneous and the diagnostic criteria were poorly defined [4, 6, 17, 19]. To our knowledge, only one recent study analyzed the molecular features of morphologically well-defined serrated polyps of the colorectum [16]. However, molecular studies will be helpful only when a consensual classification will be established to be sure to study specific morphologic sub-types of SP and not a broad range of lesions.

In summary, SSA has clinic and morphologic features distinctive from that of HP. In our view, correct morphologic identification of SSA is essential to enable further studies that are required to assess molecular basis and clinical impact of these lesions.