Minimal Lesions of the Small Intestinal Mucosa: More than Morphology

Minimal lesions of the small bowel are mucosal changes characterized by an increased number of intraepithelial lymphocytes (with or without crypt hyperplasia) and normal villous architecture. Such changes are associated with a wide spectrum of conditions, ranging from food intolerances to infections, and from drugs to immune diseases, with different clinical profiles and manifestations, which complicates the formulation of a differential diagnosis. Patient history, symptom evaluation, and histopathology are the diagnostic features needed to establish a correct diagnosis. Physicians should assist pathologists in formulating a precise morphological evaluation by taking well-oriented small intestinal biopsies and collecting informative clinical findings that inform histopathology. In this current clinical controversy, the authors provide the reader with an appraisal of the small intestine minimal lesions through a careful analysis of the major conditions (e.g., celiac disease and other non-celiac disorders) responsible for such changes and their differential diagnosis. Also, we acknowledge that some of the diseases detailed in this article may progress from an early minimal lesion to overt mucosal atrophy. Thus, the timing of the diagnosis is of paramount importance.