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Context: This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. Objective: To accurately reflect the pre-existing diseases and pathologic conditions of decedents with Sars-CoV-2 infection through autopsy. Design: Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple choice and openended survey responses. Results: Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than one preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. Conclusions: Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of co-morbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.

Background: The impact of COVID-19 on heart transplant (HTx) recipients remains unclear, particularly in the early post-transplant period. Methods: We share novel insights from our experience in five HTx patients with COVID-19 (three within 2 months post-transplant) from our institution at the epicenter of the pandemic. Results: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID-19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C-reactive protein, procalcitonin, and ferritin. All had bilateral ground-glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged.

The patient had multiple sclerosis while receiving ocrelizumab monotherapy. EXPOSURES Ocrelizumab monotherapy.RESULTS A 78-year-old man with progressive multiple sclerosis treated with ocrelizumab monotherapy for 2 years presented with 2 weeks of progressive visual disturbance and confusion. Examination demonstrated a right homonymous hemianopia, and magnetic resonance imaging revealed an enlarging nonenhancing left parietal lesion without mass effect. Cerebrospinal fluid revealed 1000 copies/mL of JC virus, confirming the diagnosis of PML. Blood work on diagnosis revealed grade 2 lymphopenia, with absolute lymphocyte count of 710/μL, CD4 of 294/μL (reference range, 325-1251/μL), CD8 of 85/μL (reference range, 90-775/μL), CD19 of 1/μL, preserved CD4/CD8 ratio (3.45), and negative HIV serology. Retrospective absolute lymphocyte count revealed intermittent grade 1 lymphopenia that preceded ocrelizumab (absolute lymphocyte count range, 800-1200/μL). The patient's symptoms progressed over weeks to involve bilateral visual loss, right-sided facial droop, and dysphasia. Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated. The patient nevertheless declined rapidly and ultimately died. PML was confirmed at autopsy. CONCLUSIONS AND RELEVANCEIn this case report, PML occurrence was likely a result of the immunomodulatory function of ocrelizumab as well as age-related immunosenescence. This case report emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections such as elderly patients.

The use of TBL promotes teamwork and learning in a pathology residency program. Residents scored higher on the readiness assurance tests when working in teams, demonstrating the effectiveness of team learning and achievement. In addition, the Accreditation Council for Graduate Medical Education competencies of professionalism and interpersonal and communication skills were further enhanced by incorporating TBL into pathology residency training.

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Placental mesenchymal dysplasia (PMD) is characterized by placentomegaly and grapelike vesicles resembling a partial molar pregnancy and in most cases, a phenotypically normal fetus. Hepatic mesenchymal hamartoma (HMH) is a benign hamartomatous proliferation of mesenchymal liver tissue. PMD has been associated with HMH. Although rare, in combination, it is known to carry a poorer prognosis than in fetuses without structural abnormalities. There are only a few reported cases of PMD and associated HMH with varying management strategies and outcomes, precluding ascertainment of the most appropriate treatment plan. We present a case of PMD with associated cystic HMH resulting in fetal death. We also reviewed the published literature on this issue and explored possible management strategies to prevent adverse fetal and neonatal outcomes.

Objectives: Aortic atresia (AA) in hypoplastic left heart syndrome (HLHS) has been associated with increased mortality in several prior studies. We reviewed our autopsy series to explore the relationship of coronary abnormalities to anatomic subsets of HLHS with AA. Methods:We retrospectively reviewed all pathology specimens with AA/MS (mitral stenosis) and AA/MA (mitral atresia) in the Cardiac Registry of Children's Hospital Boston between 1955 and 2009 including autopsy reports, operative notes, and imaging studies. Formalin-fixed hearts were examined, and cases found to have macroscopic coronary artery abnormalities were sectioned at mid-left ventricular level in the transverse plane and at mid-right ventricular level in the longitudinal plane for histologic analysis of coronary arteries using tissue sections stained with hematoxylin and eosin.Results: A total of 216 autopsy cases were identified with AA/MS (134) and AA/MA (82). Coronary anomalies were found in 49 cases, left ventricle-coronary fistula in 39, all in AA/MS, and 10 other coronary abnormalities, all in AA/MA. Histologic study confirmed fistulas only in the AA/MS group with no evidence of fistulas in the AA/MA group. Conclusions:The occurrence of left ventricle-coronary fistulas appears limited to the AA/MS group, and coronary fistula specimens were disproportionately more prevalent in postoperative specimens. Further clinical studies are required to validate this finding and to identify subgroups that carry a higher mortality risk.