[Morphology of the gastroesophageal reflux disease]

The present definition of gastroesophageal reflux disease is based on clinical criteria that are difficult to reproduce accurately. Pathologists are supposed to confirm the presence of morphological changes induced by gastroesophageal reflux. Traditional evaluation of injury, inflammatory and reactive changes of esophageal squamous epithelium lacks both sufficient sensitivity and specificity, and thus the modern diagnostic focuses on chronic metaplastic changes of esophageal mucosa defined as any mucosal type proximal to the upper border of oxyntic mucosa (also called fundic mucosa of the stomach). In the setting of gastroesophageal reflux the esophageal mucosa, under normal conditions lined with squamous epithelium, undergoes columnar metaplasia. According to morphology and immunophenotype of columnar cells, the columnar metaplasia may be further subdivided to oxyntocardiac mucosa, cardiac mucosa, intestinal metaplasia, and an intermediate type of cardiac mucosa expressing intestinal transcription factor CDX2, but devoid of goblet cells. The latter two mucosal types are currently thought to represent the most probable candidates for neoplastic transformation, whereas oxyntocardiac mucosa is believed to represent a stable compensatory change with no risk of further progression. An evaluation of dysplastic changes (intraepithelial neoplasia) in the setting of columnar lined esophagus necessitates correlation with the second opinion of a GI expert to prevent potentially harmful under- or over-treatment of the patient. Regarding invasive adenocarcinoma, the pathologist should avoid overdiagnosis of the infiltration of the space between the two layers of columnar lined esophagus - associated split muscularis mucosae as invasion of submucosa, as it is associated with different prognosis. Critical evaluation of the real impact of acid suppression on neoplastic transformation in the setting of gastroesophageal reflux disease may represent the greatest challenge for future studies.