The contribution of intraepithelial inflammatory cells to the histological diagnosis of microscopic esophagitis

Background: Diagnosis of gastro-esophageal reflux disease (GERD) is mainly based on symptom evaluation, possibly coupled with various invasive investigations (endoscopy, pH-metry, and impedance). New input has recently come from histology: in this context, the diagnostic role of inflammatory cells other than eosinophils and neutrophils is still debated. Aim of the study is to evaluate the diagnostic relevance of intraepithelial lymphocytes, mast cells, and Langerhans cells in GERD-associated microscopic esophagitis (GAME). Methods: Twenty healthy volunteers and 119 patients with GERD symptoms were prospectively recruited and subdivided, on the basis of endoscopy and pH-metry, in erosive (ERD, 48) and non-erosive disease (NERD, 71). Biopsy samples at 2 cm above the Z-line and at Z-line were evaluated for GERD-associated histological lesions (basal cell hyperplasia, papillae elongation, intercellular space dilatation, intraepithelial eosinophils, and neutrophils). Immunohistochemistry for T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), NK cells (CD56), macrophages (CD68), mast cells (c-Kit), and Langerhans cells (S100) was performed. Results: Among inflammatory cells, only intraepithelial T lymphocytes (ITLs) showed statistical correlation with the other histological lesions both in ERD and NERD. ITLs distinguished GERD patients from controls with good sensitivity and specificity (85.5 and 85 % at 2 cm above Z-line; 89.5 and 75 % at Z-line) when a cut-off of 20 cells was applied. An analysis of the T subpopulations found a CD4+/CD8+ ratio close to 1:1; B cells, mast cells, Langerhans cells, NK cells, and macrophages showed a limited role in GERD. Conclusions: ITL evaluation represents an additional useful parameter in the histological evaluation of GAME