Oral epithelial reactive atypia/dysplasia: An underestimated true atypia/dysplasia?

Abstract

Several clinical and histological features, usually associated with chronic inflammation could complexify the diagnosis of oral epithelial dysplasia (OED). These changes in response to inflammatory stimuli, or re-epithelialization events, are described as reactive epithelial atypia or dysplasia (REA/D). Within a REA/D scenario (for example in the edges of chronic traumatic ulcers), the diagnosis of OED could be challenging for oral pathologists due to an unfeasibility to accurate the true nature of that changes. Due to a reactive profile, REA/D suggests an evolutionary pattern of reversibility once the source that generates those changes is suppressed. However, there are no studies that address the nature or evolution of REA/D. In this context, how might reactive atypia diagnosis modify the therapeutic approach of an oral condition? Could the follow-up protocol of an oral lesion be modified with a diagnosis of REA/D? We hypothesized that there are epithelial changes, usually diagnosed as REA/D in a context of inflammation and chronic irritation, whose dysplastic potential is underestimated, or at least unknown. A biased pathophysiological conception could lead to erroneous or insufficient decisions, especially in the follow-up of these cases. The link between chronic inflammation and carcinogenesis is unquestionable. Oral mucosa is frequently exposed to inflammatory sources. Many conditions such as oral lichen planus, lichenoid lesions, and non-healing chronic traumatic ulcers were previously related to oral carcinogenesis. The diagnosis of REA/D within these entities is often underestimated. However, experimental models and epidemiological studies demonstrated that precursor lesions of some malignancies were initially diagnosed as reactive changes. Furthermore, a subset of oral reactive lesions associated with chronic mechanical irritation showed early carcinogenesis biomarkers. Nevertheless, further studies are needed to understand this issue. The controversial terminology Reactive Atypia vs True Atypia was also a debatable topic in other fields of medical evidence. Since some patients may not fit the strict criteria diagnosis given for each disease, we proposed the term: Oral Epithelial Atypia of Unknown Significance to characterize cellular and dysplastic changes possibly related to chronic inflammation but without a true certainty of its evolution. This term could encourage the clinician to perform a careful follow up of cases of REA/D and also readdress the focus of research regarding oral carcinogenesis. Finally, if all microscopic findings linked to inflammation are diagnosed as REA/D, may lead to underestimation of the potential of inflammation in the multifactorial context of oral carcinogenesis.