Variable regional histomorphology of the ascending aorta: Implications for disease classification

Regional differences in the normal histology of the ascending aorta have not been systematically studied, possibly resulting in diagnostic misinterpretation. This study aims to characterize the normal histologic spectrum of the aortic sinus (AS) and tubular aorta (TA) in a normal population. Ascending aortic specimens from 37 autopsy cases (mean age 58.7 years, range 12 to >89 years) without known aortopathy were collected prospectively. Transverse and longitudinal sections from AS and TA were stained with H&E and Verhoeff-Van Gieson. Assessed features included medial and lamellar thickness, lamellar architecture, elastic lamina number, elastic fiber waviness and organization, and features of medial degeneration. Interobserver agreement was assessed using Krippendorff's alpha. The AS had significantly thinner media and lamellae, more woven lamellar architecture, and greater elastic fiber waviness and non-parallel organization compared to the TA. Elastic lamina number was greater in the posterior TA than AS (p < 0.0001). Pathologist agreement was moderate to satisfactory except for lamellar architecture in the left and posterior AS. No significant differences were observed between the measures with age, sex, or body mass index up to 49 kg/m². These results provide the first systematic histologic profile of the AS and highlight key differences from the TA-several of which overlap with degenerative changes. Recognizing these normal regional variations is essential to avoid diagnostic overcalls and unnecessary intervention. Accurate specimen labeling, orientation, and sampling are critical in aortic pathology assessment.