Grading gastrointestinal dysplasia and what to call it when you don't know what it is

Dysplasia in the gastrointestinal tract is defined as intraepithelial neoplasia (IEN) according to the WHO nomenclature. Neoplastic growth in the gastrointestinal tract evolves through stepwise tumour progression in which consecutive morphological stages are characterized by increasing genetic instability accompanied by specific genetic alterations. Invasive cancer is preceded by non-invasive precursor stages and the clonal epithelial cell proliferation in these pre-invasive stages is diagnosed as dysplasia or IEN. Dysplasia is therefore a marker for cancer risk and guides surveillance. Dysplasia is conventionally graded using a two-tier system and low- and high-grade dysplasia convey different connotations regarding cancer risk. This perspective argues that the critical differential diagnosis is the one between neoplastic and non-neoplastic epithelial cell proliferations and the relevance of grading dysplasia is questionable. It is furthermore expected that a molecular signature will predict the propensity to invasive carcinoma more accurately than routine histopathology in the near future. Research in this field needs to focus on a combination of biomarkers representing genetic instability, clonal mutations, and genetic clonal divergence.