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

Abstract

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

Letter: proton pump inhibitor‐responsive oesophageal eosinophilia – more than just gastro‐oesophageal reflux disease. Authors' reply

“…Thus, according to current guidelines and reviews, 3,4 EoE or PPI-REE were excluded by both distal and proximal histological assessment. More importantly, we have previously demonstrated that the presence of neutrophils/eosinophils in distal oesophagus is very common in patients with GERD, particularly in case of erosive oesophagitis or true NERD, as in our present investigation, [5][6][7][8] and their detection confirms the existence of microscopic oesophagitis as further demonstration of GERD. 9 Accordingly, we decided to include as controls those patients with proven GERD and distal oesophageal eosinophilia in order to have a group of individuals presenting as many similarities as possible with EoE and PPI-REE patients in terms of histological findings, although they had different and distinct diagnoses (EoE, PPI-REE, GERD).…”

Histopathological Analysis of Esophageal Mucosa in Patients with Achalasia

“… 12 Furthermore, there was a recent study that showed a significant increase of intraepithelial T lymphocytes in nonerosive reflux disease compared to normal controls. 17 This might be related with the failure to prove the significant difference of CD3-positive lymphocyte count between the achalasia and control groups, since we included controls with esophageal symptoms who had some possibilities for nonerosive reflux disease.…”

The dynamics of the oesophageal squamous epithelium ‘normalisation’ process in patients with gastro‐oesophageal reflux disease treated with long‐term acid suppression or anti‐reflux surgery

“…[9][10][11] Previous work evaluating biopsy samples at 2 cm above the Z-line and at Zline for the same GERD-associated histological lesions used immunohistochemistry for T lymphocytes, B lymphocytes, NK cells, macrophages, mast cells and Langerhans cells. 12 It was found that only intraepithelial T lymphocytes correlated with the histological lesions both in reflux oesophagitis and non-erosive disease; the other cell types had a limited role in GERD. However, concern has been raised regarding the relevance of these morphological changes.…”

“…Histological assessment of the distal oesophageal mucosal lining has been advocated using basal cell thickness, size of intercellular spaces and papillary length, because changes in these reportedly occur as a consequence of reflux‐induced damage . Previous work evaluating biopsy samples at 2 cm above the Z‐line and at Z‐line for the same GERD‐associated histological lesions used immunohistochemistry for T lymphocytes, B lymphocytes, NK cells, macrophages, mast cells and Langerhans cells . It was found that only intraepithelial T lymphocytes correlated with the histological lesions both in reflux oesophagitis and non‐erosive disease; the other cell types had a limited role in GERD.…”