Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry

Cheng Liu,Neal I Walker,Barbara A Leggett,Vicki Lj Whitehall,Mark L Bettington,Christophe Rosty

doi:10.1038/modpathol.2017.92

Abstract

Sessile serrated adenomas are the precursor polyp of approximately 20% of colorectal carcinomas. Sessile serrated adenomas with dysplasia are rarely encountered and represent an intermediate step to malignant progression, frequently associated with loss of MLH1 expression. Accurate diagnosis of these lesions is important to facilitate appropriate surveillance, particularly because progression from dysplasia to carcinoma can be rapid. The current World Health Organization classification describes two main patterns of dysplasia occurring in sessile serrated adenomas, namely, serrated and conventional. However, this may not adequately reflect the spectrum of changes seen by pathologists in routine practice. Furthermore, subtle patterns of dysplasia that are nevertheless associated with loss of MLH1 expression are not encompassed in this classification. We performed a morphological analysis of 266 sessile serrated adenomas with dysplasia with concurrent MLH1 immunohistochemistry with the aims of better defining the spectrum of dysplasia occurring in these lesions and correlating dysplasia patterns with MLH1 expression. We found that dysplasia can be divided morphologically into four major patterns, comprising minimal deviation (19%), serrated (12%), adenomatous (8%) and not otherwise specified (79%) groups. Minimal deviation dysplasia is defined by minor architectural and cytological changes that typically requires loss of MLH1 immunohistochemical expression to support the diagnosis. Serrated dysplasia and adenomatous dysplasia have distinctive histological features and are less frequently associated with loss of MLH1 expression (13 and 5%, respectively). Finally, dysplasia not otherwise specified encompasses most cases and shows a diverse range of morphological changes that do not fall into the other subgroups and are frequently associated with loss of MLH1 expression (83%). This morphological classification of sessile serrated adenomas with dysplasia may represent an improvement on the current description as it correlates with the underlying mismatch repair protein status of the polyps and better highlights the range of morphologies seen by pathologists.

Highlights

The histological criteria for the diagnosis of sessile serrated adenoma with dysplasia are not well described
We reviewed a large series of sessile serrated adenomas with dysplasia with the aim of better characterizing the spectrum of dysplasia, in particular sessile serrated adenomas with subtle morphological changes that are associated with loss of mismatch repair protein function
Sessile serrated adenomas with dysplasia have been reported in the gastroenterology literature as representing ‘triple threat’ precursors for interval colorectal carcinomas

Summary

Introduction

The histological criteria for the diagnosis of sessile serrated adenoma with dysplasia are not well described. We have identified examples of sessile serrated adenomas with very subtle changes that have lost expression of MLH1 by immunohistochemistry. Because these lesions have advanced molecular changes, their associated risk of malignant progression is likely to be high, despite the relative lack of cytological abnormalities. Failure to identify this risk by the pathologist may result in inadequate surveillance and increases the risk of interval colorectal carcinoma. We reviewed a large series of sessile serrated adenomas with dysplasia with the aim of better characterizing the spectrum of dysplasia, in particular sessile serrated adenomas with subtle morphological changes that are associated with loss of mismatch repair protein function

Methods

Results

Conclusion