Mucoid extracellular matrix accumulation as a histopathological marker of aortic fragility: Two autopsy cases and a literature review

Medial degeneration of the aortic wall represents a critical substrate for the development of acute aortic syndromes, particularly dissection, in both clinically healthy individuals and those with known cardiovascular disease or syndromic features. Among these alterations, Mucoid Extracellular Matrix Accumulation (MEMA) has emerged as a key histopathological marker of aortic fragility, with implications not only for clinical practice but also for forensic investigations of sudden and unexpected deaths. This study presents two autopsy case reports of 41-year-old and 44-year-old individuals who died from acute aortic dissection with no prior evidence of cardiovascular disease or other macroscopic findings that could explain the death. Detailed histopathological examination revealed mucoid extracellular matrix accumulation and associated medial changes; in one case, acute cocaine intoxication was identified as a plausible hemodynamic trigger acting upon an intrinsically vulnerable aortic wall. Furthermore, a narrative review on MEMA and its role in medial layer alteration was conducted, allowing comparison of our findings with existing literature. These cases highlight the forensic significance of identifying medial degenerative lesions in sudden aortic deaths. Comprehensive autopsy and histopathological assessment (hematoxylin-eosin staining) allow the recognition of MEMA and other medial alterations even in individuals without history of cardiovascular disease, support differentiation between intrinsic structural vulnerability and potential external precipitants, and contribute to a more accurate reconstruction of the mechanisms underlying unexpected aortic fatalities. Systematic evaluation of the aortic wall also improves differentiation between intrinsic aortic pathology and external triggers, contributing to scientific understanding and to forensic accuracy, and may support medico-legal evaluations of potential medical malpractice in appropriate contexts.