Purpose Acute appendicitis may present as uncomplicated and complicated and these disease forms differ both epidemiologically and clinically. Complicated acute appendicitis has traditionally been defined as an appendicitis complicated by perforation or a periappendicular abscess, and an appendicolith represents a predisposing factor of complicated disease. There are histopathological differences between uncomplicated acute appendicitis and the previously established traditional forms of complicated acute appendicitis, but to our knowledge, the histopathological differences between uncomplicated acute appendicitis and complicated acute appendicitis presenting with an appendicolith have not yet been reported. The study purpose was to assess these differences with two prospective patient cohorts: (1) computed tomography (CT) confirmed uncomplicated acute appendicitis patients enrolled in the surgical treatment arm of the randomized APPAC trial comparing appendectomy with antibiotics for the treatment of uncomplicated acute appendicitis and (2) patients with CT-verified acute appendicitis presenting with an appendicolith excluded from the APPAC trial. Methods The following histopathological parameters were assessed: appendiceal diameter, depth of inflammation, micro-abscesses, density of eosinophils, and neutrophils in appendiceal wall and surface epithelium degeneration. Results Using multivariable logistic regression models adjusted for age, gender, and symptom duration, statistically significant differences were detected in the depth of inflammation ≤ 2.8 mm (adjusted OR 2.18 (95%CI: 1.29-3.71, p = 0.004), microabscesses (adjusted OR 2.16 (95%CI: 1.22-3.83, p = 0.008), the number of eosinophils and neutrophils ≥ 150/mm 2 (adjusted OR 0.97 (95%CI: 0.95-0.99, p = 0.013), adjusted OR 3.04 (95%CI: 1.82-5.09, p < 0.001, respectively). Conclusions These results corroborate the known clinical association of an appendicolith to complicated acute appendicitis.

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