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Lymphocytic Esophagitis: Shedding Fresh Light on a Mysterious Histopathologic Pattern

You may have received pathology reports with a diagnosis of “lymphocytic esophagitis pattern of injury” and asked youself two perfectly reasonable questions: 1. “Well, what does that mean?” 2. “Is it even a real disease?” The answer to the first question is that no one knows exactly what it means with regard to its clinical significance. The answer to the second question is that lymphocytic esophagitis (LE) is currently best described as a histologic pattern of injury, the underlying etiology of which remains uncertain. Although this finding is relatively rare, it is reported with sufficient frequency at Miraca Life Sciences to warrant the presentation of a brief review of the subject to our clinicians.

LE was first described by Rubio et al in 2006. 1 The histologic features laid out in that paper continue to accurately define this pattern of injury: a dense, patchy lymphocytic infiltrate in the esophageal squamous epithelium that is most pronounced in the peripapillary areas (see image from the “Under the Microscope Section” above). There is also accompanying intercellular edema, or spongiosis, in the affected areas, as well as an absence of significant eosinophilic or neutrophilic inflammation. The original study by Rubio and a more recent report 2 suggest that LE may be a manifestation of Crohn’s disease, but it is important to note that the evidence only supports this association with any strength in pediatric patients. Another study by Purdy et al 3 could not demonstrate a significant correlation with any other disease state. Nonetheless, gastriointestinal pathologists continue to observe this pattern, and the lack of unequivocal clinical correlates in the literature to help define LE prompted Dr. Salima Haque and Dr. Robert Genta of Miraca Life Sciences to review a large number of cases from the formidable Miraca database. 4

The most interesting finding in this recent Miraca study is that lymphocytic esophagitis may mimic eosinophilic esophagitis (EE), both clinically and endoscopically. About one third of the patients in the study presented with dysphagia or odynophagia, eliciting a clinical suspicion of EE. Less commonly, significant reflux was the presenting symptom. One-third of patients had endoscopic findings that included rings, white plaques, and strictures, but furrows seemed to be less common than in eosinophilic esophagitis. One less common clinical finding was that of a motility disorder. A small proportion of patients were found to have esophagitis (usually LA grade A), while many had an endoscopically normal esophagus. Demographically, most patients with a histologic diagnosis of LE were women in their 7th decade (median age 63 years; 60% female). The vast majority of patients with LE had a medication history that included PPI use, but as the study is retrospective, no conclusions regarding causality can be made. Although no significant associations with other diseases were identified, the finding that lymphocytic esophagitis can be a mimic of eosinophilic esophagitis is intriguing.

In conclusion, both the etiology and clinical significance of lymphocytic esophagitis remain elusive. Although it has been linked with Crohn’s disease in children, no firm correlates with other diseases have been established in adult patients. The recent study by Drs. Haque and Genta should raise awareness of LE, especially regarding its potential to mimic eosinophilic esophagitis clinically and endoscopically. Continued collaboration between clinicians and pathologists will be needed to arrive at a more complete understanding of LE, which, as Haque and Genta point out in their new study, is “a condition in search of a disease.”5

References

1. Rubio CA, Sjodahl K, Lagergren J. Lymphocytic esophagitis: a histologic subset of chronic esophagitis. Am J Clin Pathol 2006;125:432-437.

2. Ebach DR, Vanderheyden AD, Ellison JM, Jensen CS. Lymphocytic esophagitis: a possible manifestation of pediatric upper gastrointestinal Crohn’s disease. Inflamm Bowel Dis 2011;17:45-49.

3. Purdy JK, Appelman HD, Golembeski CP, McKenna BJ. Lymphocytic esophagitis: a chronic or recurring pattern of esophagitis resembling allergic contact dermatitis. Am J Clin Pathol 2008;130:508-513.

4. Haque S and Genta RM. Lymphocytic Esophagitis: a Clinicopathologic study. Gut, (in press); 2011.

5. Loch J. Pirandello: Six Characters in Search of an Author. Cambridge, UK: Cambridge University Press, 2005.

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The eleven-year relationship between our medical staff and the gastrointestinal pathology specialists of Miraca Life Sciences has served both our patients and physicians very well.
— Tom Deas, Jr. MD


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