Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients.

Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.

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Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists.

Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease. The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. A systematic literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed. We found 28 scientific papers; the total amount of cases is 341. The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels. It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed. A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed. In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements.

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Autopsy findings in COVID-19-related deaths: a literature review

Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza: A Systematic Review.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, COVID-19, is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of COVID-19 individuals undergoing postmortem evaluation is provided, with four aims: 1) describe the pathologic spectrum of the myocardium; 2) compare to an alternate viral illness; 3) investigate angiotensin converting enzyme 2 (ACE2) expression; and 4) provide the first description of the cardiac findings in patients with cleared infection. Methods: Study cases were identified from institutional files and included COVID-19 (n=15; 12 active, 3 cleared), influenza A/B (n=6), and non-virally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An ACE2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction (ddPCR). Results: Male sex was more common in the COVID-19 group (p=0.05). Non-occlusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls), and were more common in the active COVID-19 cohort (p=0.006). Four active COVID-19 cases showed focal myocarditis, while one case of cleared COVID-19 showed extensive disease. Arteriolar ACE2 endothelial expression was lower in COVID-19 cases versus controls (p=0.004). ACE2 myocardial expression did not differ by disease category, sex, age or number of patient comorbidities (p=0.69, p=1.00, p=0.46, p=0.65, respectively). SARS-CoV-2 immunohistochemistry showed non-specific staining, while ultrastructural examination and ddPCR were negative for viral presence. Four (26.7%) COVID-19 patients had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. Conclusions: This detailed histopathologic, immunohistochemical, ultrastructural and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.

COVID-19-Associated Nonocclusive Fibrin Microthrombi in the Heart.

Since making its debut on the global stage in December 2019, coronavirus disease 2019 (COVID-19) has afflicted nearly 4 million people and caused hundreds of thousands of deaths. Case reports and case series depicting the clinical effects of the causative virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-have been published, yet few demonstrate the cytopathologic alterations of this disease. We present a clinical-pathologic correlation report of a previously healthy Hispanic woman with laboratory-confirmed COVID-19 who had typical features of acute respiratory distress syndrome (ARDS) and also showed cardiac abnormalities thought to represent fulminant viral myocarditis. Congruent with the ARDS clinical impression, autopsy findings were remarkable for extensive and markedly severe acute lung injury consistent with viral pneumonia, characterized by diffuse alveolar damage, pulmonary infarction, severe pulmonary edema, desquamation of pneumocytes with intra-alveolar aggregation, and pneumocyte morphologic alterations suggestive of viral cytopathic effect. However, there was incongruence between the clinical impression and the cardiovascular pathology findings in that viral myocarditis was not detected on histopathologic evaluation. This case highlights the importance of pathologic corroboration of the clinical impression and, in addition, illuminates the key role autopsy plays during a pandemic by providing valuable insight into viral pathology in tissues.

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Autopsy Report with Clinical Pathological Correlation

Broadening the Age of Incidence of Intracranial Angiomatoid Fibrous Histiocytoma With EWSR1-CREM Fusion: A Case Report.

Fine-needle aspiration of intramammary lymph nodes: a clinical, radiographic, and cytologic review.

Background. Metastasis to parotid gland occurs mostly from skin cancers of the head and neck region. Metastatic neuroendocrine tumors to the parotid gland are rare and not well studied so far. In this study, we undertook a retrospective review of secondary neuroendocrine tumors of the parotid diagnosed in our institution. The most common entities, primary tumor locations, their clinical presentations and histopathological features were analyzed. Methods. Cases of secondary neuroendocrine tumors to parotid diagnosed from August 1995 to Jan 2021 were retrieved from our institution's pathology databases, and their clinicopathological features were reviewed. Results. About 29% (120 of 420 cases) of parotid neoplasms were malignant, including 70 cases of parotid primary malignant tumors and 50 cases of metastases to parotid glands. Among metastatic tumors to the parotid glands, squamous cell carcinoma and melanoma of the head and neck region together accounted for about 78% of the cases. Only 11 of 50 metastatic tumors to the parotid were neuroendocrine carcinomas (22%). The most common primaries were poorly differentiated neuroendocrine carcinoma of lung (5 of 11 cases), including 4 cases of small cell carcinoma and one case of large cell neuroendocrine carcinoma. The second most common secondary tumor was Merkel cell carcinoma (4 of 11 cases, 36%) including one case of direct invasion from overlying skin. Medullary carcinoma of the thyroid comprised the rest of the metastases to the parotid (2 of 11 cases, 18%). Conclusion. Our results show that metastatic neuroendocrine carcinomas to the parotid gland account for about 22% of all metastatic tumors to the organ. Lung is the most common primary neuroendocrine carcinoma location. It is not uncommon for metastatic neuroendocrine carcinoma to present as the first sign of systemic clinical manifestation. Merkel cell carcinoma is the second most common entity that metastasizes to parotid, followed by medullary carcinoma of the thyroid.

Metastatic Neuroendocrine Tumors to Parotid Gland: Where Do They Come From?

Routine histopathological examination of hernia sac in adults remains a controversial topic. We undertook a retrospective study to assess possible clinical benefits of pathological examination of hernia sac specimens. Our pathology database between 1992 and 2020 was searched for adult specimens submitted as hernia sac. The clinical and pathological data of patients with abnormal histopathological findings were reviewed. There were 5424 hernia sac specimens (3722 inguinal, 1625 umbilical, and 77 femoral), 32/5424 (0.59%) with malignancies (28 epithelial and 4 lymphoid) and 25/32 were located in the umbilical region. Twelve out of twenty-five malignancies (48%) presented as primary clinical manifestations of the diseases (5 GI tract carcinomas, 5 gynecological tract carcinomas, and 2 lymphoid neoplasms); and 13/25 (52%) specimens were involved by previously known tumors (8 gynecological carcinomas, 3 colon carcinomas, 1 breast carcinoma, and 1 lymphoma). Among the 7 inguinal hernia sacs with malignancies, 3 (42.9%) were primary presentations of the tumors (2 prostatic carcinomas, 1 pancreatic carcinoma), and 4 (57.1%) were previously known tumors (2 ovarian carcinomas, 1 colon carcinoma, 1 lymphoid). Benign lesions were 12/5424 (0.22%), including 7 adrenal rests, 4 endometriosis, and 1 inguinal sarcoidosis. The incidence of hernia sacs with malignancies was 32/5424 (0.59%), most commonly from nearby organs in gynecological tract. However distant metastases from breast were also present. Near half of the hernia sac with malignancies (15/32, 47%) presented as the first clinical manifestation. Routine histopathological examination of hernia sac in adults is recommended, since it may provide important clinical information.

Lei Yan

Papers

Autopsy Report with Clinical Pathological Correlation

Broadening the Age of Incidence of Intracranial Angiomatoid Fibrous Histiocytoma With EWSR1-CREM Fusion: A Case Report.

Fine-needle aspiration of intramammary lymph nodes: a clinical, radiographic, and cytologic review.

Metastatic Neuroendocrine Tumors to Parotid Gland: Where Do They Come From?

Histopathological Findings in Hernia Sacs: A Clinical and Pathological Review.