Neuropathology of Pediatric SARS-CoV-2 Infection in the Forensic Setting: Novel Application of Ex Vivo Imaging in Analysis of Brain Microvasculature.

Two years into the COVID-19 pandemic, there are few published accounts of postmortem SARS-CoV-2 pathology in children. We report 8 such cases (4 infants aged 7-36 weeks, 4 children aged 5-15 years). Four underwent ex vivo magnetic resonance neuroimaging, to assist in identification of subtle lesions related to vascular compromise. All infants were found unresponsive (3 in unsafe sleeping conditions); all but 1 had recent rhinitis and/or influenza-like illness (ILI) in the family; 1 had history of sickle cell disease. Ex vivo neuroimaging in 1 case revealed white matter (WM) signal hyperintensity and diffuse exaggeration of perivascular spaces, corresponding microscopically to WM mineralization. Neurohistology in the remaining 3 infants variably encompassed WM gliosis and mineralization; brainstem gliosis; perivascular vacuolization; perivascular lymphocytes and brainstem microglia. One had ectopic hippocampal neurons (with pathogenic variant in DEPDC5). Among the children, 3 had underlying conditions (e.g., obesity, metabolic disease, autism) and all presented with ILI. Three had laboratory testing suggesting multisystem inflammatory syndrome (MIS-C). Two were hospitalized for critical care including mechanical ventilation and extracorporeal membrane oxygenation (ECMO); one (co-infected with adenovirus) developed right carotid stroke ipsilateral to the ECMO cannula and the other required surgery for an ingested foreign body. Autopsy findings included: acute lung injury in 3 (1 with microthrombi); and one each with diabetic ketoacidosis and cardiac hypertrophy; coronary and cerebral arteritis and aortitis, resembling Kawasaki disease; and neuronal storage and enlarged fatty liver. All 4 children had subtle meningoencephalitis, focally involving the brainstem. On ex vivo neuroimaging, 1 had focal pontine susceptibility with corresponding perivascular inflammation/expanded perivascular spaces on histopathology. Results suggest SARS-CoV-2 in infants may present as sudden unexpected infant death, while in older children, signs and symptoms point to severe disease. Underlying conditions may predispose to fatal outcomes. As in adults, the neuropathologic changes may be subtle, with vascular changes such as perivascular vacuolization and gliosis alongside sparse perivascular lymphocytes. Detection of subtle vascular pathology is enhanced by ex vivo neuroimaging. Additional analysis of the peripheral/autonomic nervous system and investigation of co-infection in children with COVID-19 is necessary to understand risk for cardiovascular collapse/sudden death.

Complex (Multimodality) Suicides in New York City: 2008-2017.

ABSTRACT: Complex (or multimodality) suicides pose a challenge for forensic pathologists, because they are infrequent and can be mistaken for the more frequent multiple-injury homicides. Complex suicides are suicides in which 2 or more self-inflicted injurious modalities are used. Among all suicides, this specific type has an incidence of 1.5% to 5%. 1 Few publications exist that examined complex suicides, with the largest review discussing only 19 cases. 2,3 To address the need for better characterization of complex suicides, a 10-year retrospective review was conducted of the database of the New York City Office of Chief Medical Examiner. This is the largest case review to date, with 93 complex suicide cases studied and the first American study contributing to this field. Results provide information regarding the demographics of decedents, incidence of mechanisms used, and mechanisms used in series. Results show that in New York City (NYC), complex suicides predominantly include asphyxia, blunt trauma, and drug toxicity. In addition, suicides in NYC occur at a similar incidence to their US national incidence, and demographics of decedents and most common injury mechanisms mirror those of simple suicides in NYC. However, injury mechanisms do not mirror those that are most common nationally. This contrasts with published data and provides a novel insight into suicide modalities in NYC.

Autopsy-Diagnosed Injury Deaths in Persons With Acute or Chronic Alcohol Use: A Review of 1000 Deaths With History of Alcohol Use.

ABSTRACT: Acute and chronic alcohol use is associated with injury, and autopsies may be performed to ascertain injury deaths in persons with acute or chronic alcohol use. This study sought to determine how many decedents with a history of acute or chronic alcohol use had an internal physical injury diagnosed only at autopsy that caused or contributed to the death. The study reviewed medicolegal investigation and autopsy reports at the New York City Office of Chief Medical Examiner between January 1 and October 11, 2018, to identify 1000 consecutive persons with suspected acute or chronic alcohol use who were autopsied to ascertain whether internal physical injury caused or contributed to the death. Of 1000 persons with known or suspected acute or chronic alcohol use, 390 (39.0%) had an external injury. Although 115 (11.5%) had an internal injury at autopsy, only 29 (2.9%) had an injury that caused or contributed to the death. Only 1 decedent had an internal injury that caused the death with no associated external evidence of injury (0.1%). This study demonstrates the rarity of occult lethal injury diagnosed at autopsy in persons with acute or chronic alcohol use.

Molecular diagnostics of cardiovascular diseases in sudden unexplained death.

The most challenging type of sudden cardiac death is sudden unexplained death. The etiologies for sudden unexplained death are diverse and not necessarily confined to the cardiovascular system. Nevertheless, certain cardiovascular diseases, particularly cardiac channelopathies and cardiomyopathies, are known to play significant roles in sudden deaths. The purpose of the review is to provide autopsy pathologists with an actionable guide through illuminating the clinically relevant molecular basis of cardiac channelopathies and cardiomyopathies, as well as the changing landscape of molecular diagnostics.

Extranodal Rosai-Dorfman disease arising in the right atrium: a case report with literature review.

Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder that commonly affects the lymph nodes. Although extranodal involvement has been reported in diverse sites, manifestation in the cardiovascular system is extremely uncommon. Specifically, the involvement of the heart by Rosai-Dorfman disease is an extraordinarily infrequent event. Here, the authors present a case of Rosai-Dorfman disease arising in the right atrium in a symptomatic 61-year-old man who initially presented with pleuritic chest pain and was found to have a large, lobulated, and circumscribed right atrial mass. The lesion exhibited an exuberant histiocytic and chronic fibroinflammatory process with focal emperipolesis within histiocytes. Immunohistochemical studies demonstrated strong S100 positivity in CD68+ CD1a- histiocytes. Although rare, Rosai-Dorfman disease should be considered in the differential diagnosis of a right atrial mass.

Pancreatic carcinoma with multilineage (acinar, neuroendocrine, and ductal) differentiation.

The preponderance of pancreatic tumors is adenocarcinoma of the ductal type; carcinomas with multiple lineage differentiation are extremely rare. We report an unusual case of pancreatic carcinoma with combined acinar and neuroendocrine differentiation and minor ductal component with concurrent acinar-ductal metaplasia (ADM), an early lesion implicated in ductal carcinogenesis. The patient is a 56-year-old man with vague complaints of dull left upper quadrant pain with radiation across the mid-portion of his abdomen. A computer tomography scan revealed an irregular enlargement of the distal 3.2 cm of the pancreatic body. A distal pancreatectomy was then performed. Histologic examination revealed a pancreatic carcinoma with cellular features of eosinophilic granular cytoplasm and salt-pepper nuclei. The acinar differentiation of the carcinoma was confirmed by positivity on periodic acid-Schiff stain resistant to diastase digestion (dPAS), positivity for antitrypsin on immunohistochemistry (IHC), and presence of zymogen granules on electron microscopy (EM). The neuroendocrine differentiation was evident by positive synaptophysin and chromogranin stain on IHC and neuroendocrine granules on EM. The ductal component was only visible by PAS stain and immunostains for CEA and CK19A and accompanied by a number of the acinar-ductal metaplasia lesions adjacent to the main tumor. Thus, the histological, histochemical, immunohistochemical and electron-microscopic evidence all suggested that the pancreatic carcinoma underwent trilineage differentiation.