The emerging spectrum of cardiopulmonary pathology of the Coronavirus disease 2019 (COVID-19): Report of three autopsies from Houston, Texas and review of autopsy findings from other United States cities

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m2). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy

Cardiovascular pathology: guide to practice and training

This chapter addresses the scope of practice and training in cardiovascular pathology. The importance of the autopsy for the documentation of cardiovascular diseases is discussed, including expanding roles for diagnostic imaging and molecular and genetic testing. The surgical pathology of cardiac and vascular specimens is reviewed. Indications and interpretation of endomyocardial biopsy (EMB) are described in relationship to EMB as a major diagnostic procedure for cardiovascular diagnosis. The role of cardiovascular pathology is discussed in the evaluation and management of patients with advanced heart failure including organ transplantation. A section is included summarizing basic information for pathologists regarding cardiovascular functional and diagnostic imaging studies. Criteria for training in cardiovascular pathology are presented. Roles of the cardiovascular pathologist as diagnostician, teacher, consultant, and care team member are discussed

The Terrible Triad of Checkpoint Inhibition: A Case Report of Myasthenia Gravis, Myocarditis, and Myositis Induced by Cemiplimab in a Patient with Metastatic Cutaneous Squamous Cell Carcinoma

Background. We report a case of a patient with squamous cell carcinoma (SCC) who developed myasthenia gravis (MG), myositis, and myocarditis after receiving cemiplimab, an anti-PD-1 immune checkpoint inhibitor (ICI). Case Presentation. An 86-year-old man with metastatic periocular SCC presented with decreased vision in the left eye, severe fatigue, and lower back and bilateral hip pain 3 weeks after receiving cemiplimab. Within hours, he developed dysphonia, pharyngeal secretions, and dysphagia, necessitating intubation. Endomyocardial biopsy revealed active lymphocyte-mediated necrosis consistent with ICI-induced myocarditis. Anti-striated muscle and anti-acetylcholine receptor antibodies were elevated, consistent with myositis and myasthenia gravis. Despite plasma exchange therapy, steroids, and intravenous immunoglobulin, he died from cardiac arrest. Conclusions. The presence of myasthenia gravis, myocarditis, or myositis should prompt evaluation for all three toxicities as they may represent an overlap syndrome. The severity of these immunotoxicities highlights the need for clinicians to suspect multiple simultaneous adverse effects of ICIs