Differential diagnosis of traditional serrated adenomas and tubulovillous adenomas : a compartmental morphologic and immunohistochemical analysis

Aim: Traditional serrated adenomas are the rarest member of the serrated polyps, that have endoscopic and morphologic similarities with conventional adenomas, tubulovillous adenomas, in particular. We aimed to compare the histopathologic and immunohistochemical features of TSAs showing overt dysplasia with conventional TVAs in a compartmental manner using digitalized images.

Patients and methods: For 25 TSAs and 25 TVAs, extent of the morphologic features including cytoplasmic eosinophilia, mid-zonal nuclei, ECFs, slit-like serration, brush border, gastric foveolar-like epithelium and goblet cells were evaluated. Immunohistochemistry was perfomed using primary antibodies including CK7, CK20, MUC2, MUC5AC, MUC6, B-catenin, Ki67, p53, p16, MLH1, MSH2, MSH6 and PMS2.

Results: Eosinophilic cells, mid-zonal nuclei, slit-like serration and ECF were significantly more extensive in TSAs compared to TVAs (p<0,001) while gastric epithelium was also more extensive in TSA cohort with a lower significance (p<0,01). Cut-offs for these features yielding the highest sensitivity and specificity in discriminating TSAs from TVAs were determined ; mid-zonal nucleus resulted as the best discriminating histopathologic feature (100%, 92%) followed by eosinophilia (88%, 92%),and slit-like serration (84%, 92%) with highest sensitivity and specificities, respectively. Compartmental immunohistochemical evaluation revealed that CK20 and CK7 were mainly expressed in ECF while MUC5AC together with CK7 were found in epithelial compartment more frequently in TSAs compared to TVAs. P16 was more common in TSAs in all compartments whereas Ki67 and p53 were restricted to dysplastic compartments in both polyp groups.

Conclusions: The present study demonstrated that mid-zonal nuclei, eosinophilic cells and slit-like serration followed by ECF proved to be the most discriminatory features for TSAs.The correct diagnosis of TSAs will allow to develop appropriate treatment and follow up modalities which seem to be crucial as their progression rate may be different from TVAs.

Keywords: colonic polyps, traditional serrated adenoma, tubulovillous adenoma, overlap histology.