ORIGINAL ARTICLE Microscopic esophagitis in gastro-esophageal reflux disease: individual lesions, biopsy sampling, and clinical correlations Luca Mastracci & Paola Spaggiari & Federica Grillo & Patrizia Zentilin & Pietro Dulbecco & Paola Ceppa & Paola Baccini & Carlo Mansi & Vincenzo Savarino & Roberto Fiocca Received: 24 September 2008 / Revised: 12 November 2008 / Accepted: 13 November 2008 / Published online: 2 December 2008 # Springer-Verlag 2008 Abstract Patients with non-erosive reflux disease may show microscopic damage. This study is aimed to describe distribution, sensitivity, and specificity of histological lesions (i.e., basal cell hyperplasia—BH, papillae elonga- tion—PE, dilatation of intercellular spaces—DIS, intra- epithelial eosinophils—IE, neutrophils, and erosions) and sampling criteria. Four groups were identified on the basis of symptoms, endoscopy, and pH monitoring: (1) erosive esophagitis (n =48), (2) non-erosive esophagitis with ab- normal pH (n =59), (3) non-erosive esophagitis with normal pH (n =12), and (4) controls (n =20). Biopsies were taken at the Z-line and 2 and 4 cm above it. BH, PE, DIS, IE, neutrophils, and erosions were assessed. A global severity score was calculated on the basis of the above parameters and allowed the distinction of patients from controls with 80% sensitivity and 85% specificity. Lesions were more severe at Z-line than proximally and more expressed in erosive than in non-erosive disease, although more than 70% of latter patients still showed histological damage. Esophageal biopsy seems very attractive in non-erosive disease where it may contribute to diagnosis and play a role in the comparative evaluation of different therapies. Keywords Gastro-esophageal reflux disease . Microscopic esophagitis . NERD Introduction The prevalence of gastro-esophageal reflux disease (GERD) is continuously increasing in western countries [1]. The term “esophagitis” currently refers to endoscopic alterations (mucosal breaks) [2] that are classified on the basis of their extent [3]; however, besides patients with endoscopic lesions (erosive reflux disease, ERD), the scenario of GERD includes more than half of patients that show no endoscopic abnormality whatsoever [4]. Patients who have normal endoscopy include those with abnormal acid exposure at prolonged pH-metry in the absence of endoscopic lesions (non-erosive reflux disease pH+, NERD pH+) and others showing typical symptoms but normal endoscopy and pH-metry (non-erosive reflux disease pH-, NERD pH-); both these categories are generally believed to be “functional” diseases [5, 6]. The accurate assessment of NERD has proved difficult, as endoscopy does not provide any useful information, symptoms may be variable or atypical, and even prolonged monitoring of esophageal pH shows no abnormality in about one-third of patients with otherwise typical symptoms [7]. Also, the evaluation of anti-reflux therapies is based on resolution of symptoms in NERD patients, and this suffers greatly from subjectivity. Therefore, an objective diagnostic tool with acceptable sensitivity and specificity remains an unmet need for clinicians facing the task of diagnosing and treating GERD patients. Virchows Arch (2009) 454:31–39 DOI 10.1007/s00428-008-0704-8 L. Mastracci : P. Spaggiari : F. Grillo : P. Ceppa : P. Baccini : R. Fiocca Department of Anatomic Pathology, University of Genova, Genova, Italy P. Zentilin : P. Dulbecco : C. Mansi : V. Savarino Department of Internal Medicine, University of Genova, Genova, Italy R. Fiocca (*) Dipartimento di Discipline Chirurgiche, Morfologiche e Metodologie Integrate (DICMI), Università degli Studi di Genova, Via De Toni 14, 16132 Genova, Italy e-mail: fiocca@unige.it