Atherosclerosis is a chronic, progressive disease of the arterial wall and the principal pathological substrate underlying most cardiovascular diseases, including ischemic heart disease, stroke, and peripheral arterial disease. Despite advances in prevention, imaging, and therapy, atherosclerosis remains the leading cause of cardiovascular morbidity and mortality worldwide. From a pathological perspective, the disease represents a dynamic and heterogeneous process characterized by endothelial dysfunction, lipid retention and modification, chronic inflammation, immune activation, smooth muscle cell phenotypic modulation, extracellular matrix remodeling, and thrombogenic surface alterations. This review provides a comprehensive overview of atherosclerosis from a pathologist’s perspective, integrating classical morphological concepts with contemporary insights into immunopathology, plaque classification, and mechanisms of plaque instability. We summarize the structure and function of the arterial wall, the stepwise pathogenesis of lesion initiation and progression, and the histopathological classification systems established by the American Heart Association and subsequently refined through Virmani’s framework. Particular emphasis is placed on plaque instability, highlighting the qualitative features—such as fibrous cap thinning, necrotic core expansion, macrophage-driven inflammation, plaque erosion, and calcification patterns—that determine clinical outcomes rather than luminal stenosis alone. Furthermore, the review discusses the expanding role of immunohistochemical markers in defining plaque biology, including lineage markers and functional indicators of inflammation, matrix integrity, osteogenic signaling, and local anticoagulant balance. These pathological insights are integrated with contemporary risk assessment tools, imaging modalities, preventive strategies, and therapeutic interventions, including emerging lipid-lowering and RNA-based therapies. In conclusion, pathology remains central to understanding atherosclerosis as a biologically active disease and to refining concepts of plaque instability. Integrating histopathology with molecular profiling, imaging, and clinical data is essential for advancing precision prevention and targeted treatment strategies in atherosclerotic cardiovascular disease.

Isolated splenic peliosis is an extremely rare condition characterized by the presence of multiple blood-filled cavities, occasionally resulting in non-traumatic splenic rupture with fatal bleeding. In our case, a 64-year-old man was brought by ambulance due to weakness and abdominal pain without nausea or febrility. On clinical examination, the patient was sensitive to palpation with significant tenderness over the abdomen but no associated features of peritonitis. He collapsed during the imaging examination and became unconscious and asystolic. Cardiopulmonary resuscitation was not successful. The patient died approximately within 2 hours of admission to the hospital. Postmortal examination showed 2800 ml of intraperitoneal blood with clots and a laceration of the lower pole of the spleen. Macroscopic examination of the spleen revealed huge nodular splenomegaly, measuring 21 cm x 19 cm x 5 cm, weighing 755 g. On the cut surfaces, multiple randomly distributed blood-filled cavities ranging from 0,5 to 2 cm in diameter were seen. At microscopic examination, the specimens showed multiple irregular haemorrhagic cyst-like lesions that were not lined by any epithelium or sinusoidal endothelium, consistent with the diagnosis of peliosis lienis. Although the condition is often clinically silent, the forensic pathological significance arises from the differential diagnosis of resultant intraperitoneal haemorrhage and sudden death, mimicking a violent death.