The most likely diagnosis is lymphocytic colitis, a form of microscopic colitis. Microscopic colitis (MC) accounts for 10% to 15% of patients with chronic, watery diarrhea. In contrast to inflammatory bowel disease, MC is more common in older persons and does not cause endoscopically visible inflammation. The symptoms of MC are similar to other chronic causes of nonbloody diarrhea, such as celiac disease and irritable bowel syndrome; therefore, colonic mucosal biopsies are required for diagnosis. Lymphocytic and collagenous colitis are the two subtypes of MC, and they are distinguishable only by histology. The diagnosis of MC is made by histologic evaluation of colonic biopsies; the classic finding is intraepithelial lymphocytosis (>20 intraepithelial lymphocytes per 100 epithelial cells). In collagenous colitis, the increase in intraepithelial lymphocytes may be less pronounced than in lymphocytic colitis, and the main histologic feature is thickening of the subepithelial collagen band (usually >10 µm). This patient's histologic findings are pathognomonic of lymphocytic colitis. Microscopic colitis often is idiopathic, but in a small subset of patients it may be a side effect of medications. A diagnosis of microscopic colitis should prompt a careful review of prescription and over-the-counter medications such as NSAIDs, aspirin, proton pump inhibitors, and others. Celiac disease should also be considered, as it can be associated with microscopic colitis.

The hallmark of Clostridium difficile colitis is watery diarrhea that is frequently associated with fever and abdominal pain or cramps. Diarrhea may be absent in patients with significant ileus or toxic megacolon, leading to a delay in diagnosis. Grossly bloody stools are rare. Risk factors for C. difficile infection include use of antibiotics or chemotherapeutic agents in the 8 weeks preceding infection because this causes alterations in enteric flora that allow bacterial overgrowth and toxin production. Typical symptoms of ischemic colitis are the acute onset of mild, crampy abdominal pain with tenderness on examination over the affected region of colon. Bleeding may not occur early but often occurs within a few days of pain onset. This patient does not have clinical features or colonoscopic findings of either C. difficile colitis or ischemic colitis.