Objectives:To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020. Methods: Complete postmortem examinations were performed according to standard procedures in a negativepressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns. The diagnosis of coronavirus disease 2019 was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs. Results:A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care. He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs. Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough. Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative. Autopsy showed acute bronchopneumonia with evidence of aspiration. Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis.Conclusions: SARS-CoV-2 testing can be performed at autopsy. Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that is responsible for the 2019-2020 pandemic. In this comprehensive review, we discuss the current published literature surrounding the SARS-CoV-2 virus. We examine the fundamental concepts including the origin, virology, pathogenesis, clinical manifestations, diagnosis, laboratory, radiology, and histopathologic findings, complications, and treatment. Given that much of the information has been extrapolated from what we know about other coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), we identify and provide insight into controversies and research gaps for the current pandemic to assist with future research ideas. Finally, we discuss the global response to the coronavirus disease-2019 (COVID-19) pandemic and provide thoughts regarding lessons for future pandemics.
The availability of targeted therapies has created a need for precise subtyping of non-small cell lung carcinomas (NSCLCs). The aim of this study was to assess the utility of immunohistochemical markers in subtyping poorly differentiated NSCLC and to compare the results of immunohistochemical staining on biopsies with the corresponding resections. Thirty-nine cases of NSCLC that could not be further classified on biopsy and had subsequent resection specimens were identified. Classification of the tumor was based on the resection specimen using the World Health Organization criteria. All biopsies and resections were stained with CK7, TTF-1, napsin A (novel aspartic proteinase of the pepsin family), p63, CK5/6, and 34βE12. The specimens included 20 adenocarcinomas (ACs), 15 squamous cell carcinomas (SCCs), and 4 large-cell carcinomas (LCCs). TTF-1 was positive in biopsies from 16 of 20 ACs, 2 of 4 LCCs, and none of the SCCs. p63 was positive in all 15 SCCs, 2 of 20 ACs (both were also positive for TTF-1 and napsin A), and none of the LCCs. CK5/6 was positive in 11 of 15 SCCs (all p63 positive) but none of the ACs or LCCs. Napsin A stained 11 of 19 ACs (all TTF-1 positive) but none of the other tumors. Staining for CK7 was present in 19 of 19 ACs and 9 of 15 SCCs. 34βE12 stained both SCCs (15 of 15) and ACs (12 of 20). The combination of TTF-1, napsin A, p63, and CK5/6 allowed an accurate classification of 30 of39 (77%) cases. Of 232 pairs of slides (biopsy and resection) stained with immunohistochemical markers, 12 (5%) showed discrepancies in immunohistochemical staining between biopsies and their corresponding resections. Immunohistochemical staining using a combination of TTF-1, napsin A, p63, and CK5/6 allows subclassification of poorly differentiated NSCLCs on small lung biopsies in most cases. Discrepancies in immunohistochemical staining between biopsies and resections are uncommon.
Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, −0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.
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