Highlights in Pathology - Dying to learn more: what’s new in the medical autopsy literature? (June 2021)
Dr. Michael Seidman, University Health Network
There has been a general decline in the number of hospital autopsies over the decades.
Some proposed reasons include the increased power of pre-mortem diagnostics, and cost pressures (medical autopsy is generally not funded by governments or health insurance, of particular concern with siloed pathology budgets). Although likely not having changed much, there are also remain portions of the population with societal, cultural, or religious prohibitions against autopsy. Nonetheless, autopsy still has numerous valid indications, including learning, teaching, research, public health, epidemiology, etc. But, in a cost-conscious medical environment, one indication stands out.
Although some shy away from autopsies because of the potential for identifying grounds for litigation, the greatest value of autopsy may, in fact, lie with the quality assurance role it provides.
Knowing fully what happened in a particular medical case enables the system to understand, explain, take ownership of, and propose improvements for events with unexpected or undesired outcomes.
Frequently, questions around mechanism of death, particularly following medical interventions, are the driver for hospital autopsies.
Here are two articles that speak to the ongoing value of autopsy:
- van den Tweel JG, Wittekind C. The medical autopsy as quality assurance tool in clinical medicine: dreams and realities. Virchows Arch (2016), 468: 75–81. DOI: 10.1007/s00428-015-1833-5. PMID: 26316183. PMCID: PMC4751188.
- De Cock KM, Zielinski-Gutiérrez E, Lucas SB. Learning from the Dead. N Engl J Med (2019), 381(20):1889-1891. DOI: 10.1056/NEJMp1909017. PMID: 31722148.
Autopsies during COVID-19
Although autopsy remains a common tool for a wide range of clinical studies, in 2021 the pandemic is certainly forefront in our minds.
Many studies have described the specific safety procedures that centres employ, the findings in tissues following the disease, and anecdotal cases of striking findings (few of which stand the test of statistical significance).
I have chosen but one review on the subject. In particular, the study summarizes some of the major findings (be they specific or not) associated with COVID-19. It also, however, alludes to possible biases in the findings, some of which may impact future learning and public health statistics.
- Hooper JE et al. A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study. Arch Pathol Lab Med (2021), 145(5):529-535. DOI: 10.5858/arpa.2020-0786-SA. PMID: 33449998.
I have also included one article on the practicalities of performing autopsies on emerging infections. The safety practices summarized here show the feasibility (particularly for well-funded services) but also the limitations for older or more resource-limited operations.
- Fu L, Zak T, Shanes E. A Framework for Maintaining a Fully Operational Autopsy Service at a Large Academic Teaching Institution During a Global Pandemic. Acad Pathol (2021), 8:23742895211006821. DOI: 10.1177/23742895211006821. PMID: 33884293. PMCID: PMC8040610.
So-called molecular autopsy has been emerging as a tool for over a decade, but is limited by the availability of appropriate equipment, specimen storage constraints (blood and tissue take up space and require a freezer), and cost.
Some systems have adapted well to this challenge (particular recognition is due to the Ontario Forensic Pathology Service (OFPS), where in-house DNA extraction allows for high-density storage). Other programs struggle to even find an appropriate freezer.
One approach to robust post-mortem genetics using routine formalin-fixed paraffin-embedded tissue, in this example for cardiovascular disease, follows. Of note, personal experience and communication have revealed that post-mortem interval and time in aqueous formalin are variables under-emphasized in this work – the success with samples from Canadian centres by this group has been quite low.
- Baudhuin et al. Technical Advances for the Clinical Genomic Evaluation of Sudden Cardiac Death: Verification of Next-Generation Sequencing Panels for Hereditary Cardiovascular Conditions Using Formalin-Fixed Paraffin-Embedded Tissues and Dried Blood Spots. Circ Cardiovasc Genet (2017), 10(6):e001844. DOI: 10.1161/CIRCGENETICS.117.001844. PMID: 29237689.
Modern radiologic techniques, in particular CT and MRI, have been adapted into some autopsy workflows, particularly forensic (again, props to the OFPS), to provide context and focus to cases.
Trauma and foreign objects are particularly well visualized (although caution should probably be used with metal objects and MRI – start with the CT). In the medical setting, however, the value is limited. Particular concerns include poor penetration of vascular contrast, limited by lack of blood flow and post-mortem intravascular clot, and by equilibration of water across tissues, eliminating much of the required resolution.
In some limited settings, specimen imaging, e.g. for cardiac devices, has value after removal, but whole-body imaging remains expensive (the machines start at a $1M cost for clinical calibre, and require special staffing, interpretation, space, …), and thus not likely cost-effective for routine use. The following summarizes the current opportunities and challenges:
- Norberti N et al. State of the art in post-mortem computed tomography: a review of current literature. Virchows Arch (2019), 475(2):139-150. DOI: 10.1007/s00428-019-02562-4. PMID: 30937612.
A practical summary of an approach to post-mortem imaging is provided here:
- Filograna et al. A Practical Guide to Virtual Autopsy: Why, When and How. Semin Ultrasound CT MR (2019), 40(1):56-66. DOI: 10.1053/j.sult.2018.10.011. PMID: 30686369.