Lymphocytic Esophagitis Is Associated with CD4+ T-Cell-Predominance and Esophageal Dysmotility
Yue Xue, Scott L Gabbard, Richard I Rothstein, Xiaoying Liu, Arief Suriawinata, Mikhail Lisovsky. Dartmouth-Hitchcock Medical Center, Lebanon, NH
Background: The presence of increased intraepithelial lymphocytes (IEL) as a predominant or sole histologic abnormality in the esophageal mucosa is uncommon and has been referred to as “lymphocytic esophagitis” (LE). The features of LE remain poorly defined and its clinical significance is largely unknown. The goal of this study was to characterize clinicopathologic and immunophenotypic features of LE.
Design: Fifteen biopsy cases of LE were identified during routine diagnostic work over the period of 24 months in 2010-2012. LE was diagnosed when conspicuously increased IEL were present in the absence of other features of esophagitis, such as basal hyperplasia, a single intraepithelial eosinophil or neutrophil, and erosion/ulceration. IEL were counted by 2 pathologists (Y.X. and M.L.) in one x400 high power field (HPF) from the most affected area. LE was deemed focal when present in <50% of a biopsy and diffuse when present in ≥50%. Biopsies from 17 patients with reflux esophagitis (RE) and increased IEL comprised the control group. Cases of RE with demonstrated esophageal dysmotility were excluded. CD4 and CD8 T-cell subsets were analyzed by routine immunohistochemistry. Data is presented as mean ± SD.
Results: Patients with LE (age 58.2 ± 12.9) were predominantly females (M:F=1 : 2.8) and presented with dysphagia (11/15), heartburn (3/15) and melena (1/15). Endoscopy was normal in 9/15 patients, all with dysphagia. Eight patients with dysphagia and normal endoscopy underwent manometry and/or barium swallow and all showed abnormal esophageal motility patterns including nutcracker esophagus (n=3) and diffuse esophageal spasm (n=2). Histologically, LE was focal (10/15) and localized to the peripapillary areas in 13/15 cases. There were 183.1 ± 95.7 IEL/HPF and CD4+ T-cells were predominant over CD8+ T-cells (CD4:CD8=3.6 ± 2.7). In comparison, patients with RE did not differ significantly in age, 53.5 ± 13.1 (p=0.312), but were predominantly males (M:F=2.4 : 1, p=0.032). Only 5/17 presented with dysphagia (p=0.032), and only 4/17 had normal endoscopy (p=0.070). In RE, there were 122.4 ± 107.7 IEL (p=0.08) and peripapillary localization of IEL was present in only 2/17 (p <0.001). In contrast to LE, CD4+ T-cells were in minority (CD4:CD8=0.92 ± 0.71, p=0.004), suggesting discrete types of lymphocytic inflammation in LE and RE.
Conclusions: LE is a distinct histologic pattern that is associated with dysphagia, esophageal dysmotility and CD4+ T-cell predominance. The results suggest a possible role of LE in primary motility disorders of the esophagus.
Tuesday, March 5, 2013 8:00 AM
Proffered Papers: Section D, Tuesday Morning