ALIMENTARY TRACT:CLINICAL RESEARCH Histologic Study of Colonic Mucosa in Patients With Chronic Diarrhea and Normal Colonoscopic Findings Jose ´ Guilherme Nogueira da Silva, MD,* Thales De Brito, MD,† Ade ´rson Omar Moura ˜o Cintra Damia ˜o, MD,* Anto ˆnio Atı ´lio Laudanna, MD,* and Aytan Miranda Sipahi, MD*‡ Background: There are controversies about the importance of bi- opsies of normal colon mucosa in the investigation of patients with chronic diarrhea. Study: Colonic and terminal ileum biopsies of 167 patients were reviewed. In 5 patients, used as controls, colonoscopy was done due to family history of colon cancer. Results: The 5 patients without symptoms had no histologic abnor- malities. The histologic findings in 162 patients with chronic diarrhea were as follows: 110 patients (67.9%) with normal histology, micro- scopic colitis not otherwise specified, and isolated small granulomas; 17 (10.5%) patients had findings of borderline diagnostic signifi- cance, including possible collagenous colitis, some features of lym- phocytic colitis and melanosis coli; and 35 (21.6%) patients, with diagnostic significant histologic findings as collagenous colitis, lym- phocytic colitis, minimal change microscopic colitis, eosinophilic colitis, pericrypt eosinophilic enterocolitis, intestinal spirochetosis, schisto- somiasis, and Crohn’s disease. Of the 52 patients with either border- line or significant diagnostic abnormalities, in 8 (15.4%) the diagnosis was done only with a proximal study (ascending, transverse, or de- scending colons). Conclusions: Histologic lesions of possible diagnostic value could exist in 32.1% of chronic diarrhea patients with normal colonoscopy, which can justify, in certain cases, mucosa biopsies, which might contribute for a more precise etiologic diagnosis; also, the distribution of these histologic changes has pointed out the importance of having all colon segments biopsied. Key Words: biopsy, colitis, colonic diseases, colonoscopy, diarrhea (J Clin Gastroenterol 2006;40:44–48) C olonoscopy has increasingly been used in the investiga- tion of patients with chronic diarrhea. 1 This procedure enables biopsies to be used for pathologic study as a means of confirming diagnosis. 2 However, the majority of colonoscopic screenings have disclosed a macroscopically normal mucosa. The contribution to diagnosis of histologic studies of macroscopically normal colonic mucosa has already been verified, as in the case of Crohn’s disease, 3,4 collagenous and lymphocytic colitis, eosinophilic colitis, intestinal spirochet- osis, melanosis coli, and colitis caused by cytomegalovirus. 5–9 However, there is still no consensus among gastroenterologists on whether obtaining biopsies of an apparently normal mucosa during colonoscopy do provide a significant increase in the diagnostic elucidation rates. 3,5,6,10–13 The present study aims, therefore, to contribute to the elucidation of these controversies, using uniform inclusion cri- teria for a population exposed to environmental agents that might lead to chronic diarrhea. PATIENTS AND METHODS Histologic slides of the terminal ileum, colon, and rectum from 167 outpatients with normal ileocolonoscopy referred by the Department of Gastroenterology of the Hospital das Clı ´nicas of the Medical School of the University of Sa ˜o Paulo, between 1996 and 2000, were reviewed. A total of 162 patients presented with chronic diarrhea and 5 were asymptomatic. Colonoscopy, for the latter, was justified because of a family history of malignant neoplasia of the large bowel. The histo- logic characteristics of the colonic mucosa and ileum of these 5 patients were used as the basis for analysis of those with chronic diarrhea. Chronic diarrhea was defined for those pa- tients who presented with three or more daily evacuations, with soft or liquid stools, for a period of at least 4 weeks. 7,9,11,12 The patients with chronic diarrhea ranged in age from 16 to 79 years, with an average of 44.2 years. Sixty-six patients (40.7%) were male and 96 (59.3%) were female. Patients who had any macroscopic alteration of the colon or ileal mucosa were excluded, except for those with inflammatory or adeno- matous small polyps, vascular ectasias, and uncomplicated colonic diverticular disease. The same endoscopist (J.G.N.S.) did all the ileocolonos- copies. The examinations reached as far as terminal ileum in all cases. Four biopsy fragments were collected randomly from each segment, ie, the terminal ileum, the ascending, transverse, descending and sigmoid colons, and the rectum. A single Received for publication December 8, 2004; accepted March 29, 2005. From the *Department of Gastroenterology and ‡Medical Investigation Laboratory of Gastroenterology (LIM 07), University of Sa ˜o Paulo Medical School, Sa ˜o Paulo, Brazil; and †Laboratory of Immunopathology, Institute of Tropical Medicine, Division of Pathology, ‘‘Hospital das Clı ´nicas,’’ University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil. Supported by CNPQ (300857/94-NV) and LIM 06 (to T.D.B.). Reprints: Jose ´ Guilherme Nogueira da Silva, MD, Disciplina de Gastro- enterologia, Clı ´nica daFMUSP, Av. Dr. Ene ´as Carvalho de Aguiar, 255/9 andar - sala 9159, Sa ˜o Paulo, SP Brazil (e-mail: jgnogueirasilva@uol.com.br). Copyright Ó 2005 by Lippincott Williams & Wilkins 44 J Clin Gastroenterol  Volume 40, Number 1, January 2006 Copyright ' Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.