Diffuse esophageal hyperkeratosis (DEH) is a very intriguing and impressive mucosal finding that is quite easily identified on endoscopy and histology. A distinction must be made between microscopic/focal hyperkeratosis and endoscopically visible DEH. Microscopic hyperkeratosis is not uncommon in histological studies, while diffuse hyperkeratosis is seen very rarely. Over the past century, only a handful of cases have been reported.
The endoscopic appearance of hyperkeratosis is of thick, white, piled-up mucosa. On histology, there is a prominent thickening of the stratum corneum, the squamous cells are anuclear, and there is no hyperplasia of the squamous epithelium. These histological characteristics distinguish benign orthokeratotic hyperkeratosis from other premalignant entities such as parakeratosis or leukoplakia where hyperplastic squamous cells retain pyknotic nuclei, lack keratohyalin granules, and also lack complete keratinization in superficial epithelial cells. The clinical presentation of hyperkeratosis includes gastroesophageal reflux, hiatal hernia, and associated symptoms.
Our case highlights a very rare endoscopic finding associated with a common clinical presentation. The nearly 10-year follow-up reinforces the benign nature of ortho-hyperkeratosis and our report underscores the features that distinguish DEH from premalignant conditions. It merits additional research into factors that lead to hyperkeratinization of the esophageal mucosa as opposed to the more common columnar metaplasia. The concomitant presence of Barrett’s esophagus in some patients is even more intriguing. Animal models with variable pH and content of the refluxate may shed light on the role played by duodenogastric/non-acid reflux in this condition. Larger, prospective, multicenter studies may provide the answers.