Utility of Autopsy among Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: One Last Chance to Learn?

Autopsy may confirm clinical diagnoses or identify conditions that were not suspected prior to a patient's death. Previous studies evaluating the utility of autopsy in hematopoietic stem cell transplant (HSCT) recipients yielded conflicting results.We conducted a retrospective cohort study of children (<18 years of age) undergoing allogeneic HSCT at Duke University who died of any cause between January 1, 1995, and December 31, 2016. We evaluated associations between patient characteristics and autopsy performance using chi-square or Fisher exact tests. We reviewed autopsy reports to determine the concordance between preautopsy causes of death and pathological diagnoses identified on autopsy. We classified unexpected diagnoses on autopsy using criteria developed by Goldman et al. We evaluated for temporal changes in the autopsy consent rate and the frequency of unexpected diagnoses on autopsy using Cochran-Armitage tests.During the 22-year study period, 475 patients died and had data available on autopsy performance, and 130 (27%) of these patients underwent autopsy. The autopsy consent rate declined over time (P < .0001), with autopsies being performed for 40% of deaths in 1995 to 1999 and 17% of deaths in 2009 to 2016. White patients were more likely to undergo autopsy than nonwhite patients (P?=?.03). There were no associations between autopsy performance and patient age, sex, HSCT indication, or HSCT donor. Unexpected diagnoses were identified in 31 (24%) autopsies. The proportion of autopsies with an unexpected diagnosis did not change during the study period (P?=?.45). However, infectious diagnoses that would have led to a change in management were more frequently identified on autopsies in 1995 to 2003 than in 2004 to 2016 (20% versus 0%; P?=?.001).The autopsy consent rate for pediatric HSCT recipients at our institution has declined substantially over the past several decades. The utility of autopsy in this patient population remains high despite a reduction in the identification of unexpected infections.     

Autopsy causes of death in HIV-positive individuals in sub-Saharan Africa and correlation with clinical diagnoses

Despite the persistently high HIV-related mortality in sub-Saharan Africa, limited information on the causes of death is available. Pathological autopsies are the gold standard to establish causes of death. In this review we describe the autopsy series performed among HIV-infected individuals in sub-Saharan Africa over the last two decades. We identified nine complete and 11 partial or minimally invasive autopsy series. Complete autopsies were performed in 593 HIV-positive adults and 177 HIV-positive children. Postmortem diagnoses were mainly infectious diseases. Tuberculosis was the most frequent, present in 21-54% of HIV-positive adults and was considered the cause of death in 32-45%. Overall, pulmonary infections accounted for approximately 66% of pathology and central nervous system infections for approximately 20%. A high discordance between clinical and postmortem diagnoses was observed. This review emphasizes the need for reliable information on causes of death in order to improve HIV patient care, guide further research, and inform health policy.     

Concordance between premortem and postmortem diagnosis in the autopsy: results of a 10-year study in a tertiary care center

We describe the concordance between clinical diagnoses and autopsy findings in a tertiary care center. Clinical autopsy is a useful tool for the evaluation of accuracy of the clinical diagnoses. However, autopsy rates have declined around the world recently. We randomly evaluated 500 of 2,211 autopsies performed in the department of pathology of a tertiary care hospital during a 10-year period. We computed the sensitivity, specificity, predictive values, and concordance scores between premortem and postmortem diagnoses. The autopsy diagnoses were used as the "gold standard." Four-hundred twenty-two (84.4%) of the autopsies met inclusion criteria. Diseases of the respiratory tract were diagnosed in 44.1% (186) of all autopsy reports reviewed. The higher sensitivity for diagnosis was observed in congenital anomalies (87.5%), while the higher specificity was observed in diagnosis of complications of pregnancy, childbirth, and the puerperium (98.98%). The higher concordance between premortem and postmortem diagnosis was observed with the diagnoses of neoplasms (kappa = 0.76), and for the group of complications of pregnancy, childbirth, and the puerperium (kappa = 0.76). A clinical diagnosis successfully addressed the cause of death in 40% of the cases Low values for concordance between autopsy reports and clinical diagnoses were present in most of the autopsies reports reviewed. We encourage physicians to continue considering the autopsy as an important tool that extends our understanding of diseases.     

The necessary role of the autopsy in cardiovascular epidemiology

The autopsy rate in the United States today is remarkably low, with proportionally fewer autopsies for natural causes of death. Consequently, most cardiovascular epidemiology studies do not use autopsy data and rely on death certificates, medical records, questionnaires, and family interviews as sources of mortality information. These practices introduce a high degree of variability and uncertainty regarding cause of death. This review illustrates the necessity for increased use of autopsies in cardiovascular epidemiology by critically evaluating other measures of cardiovascular disease (CVD) incidence. We evaluated the literature regarding CVD as cause of death and conducted discussions with cardiologists, pathologists, and epidemiologists. No attempt was made for meta-analysis. This review shows the limited reliability of death certificates, medical records, and interviews as sources of mortality statistics. In addition, the autopsy's role in clearly indicating the presence of CVD is illustrated. The autopsy used in conjunction with medical records is the only reliable means for establishing cause of death from CVD. There is an urgent need to reassess the current dependence of statistical mortality data on death certificates and other inadequate sources of CVD incidence. Death certificates, in general, are inadequately monitored for quality control and appropriate administrative oversight. With an increase in the number of hospitals performing no autopsies to investigate cause of death, a uniform national autopsy database is needed.     

Discrepancies between clinical and autopsy diagnoses: a comparison of university, community, and private autopsy practices

Although it is known that autopsies often disclose unexpected findings, few studies have been published that address the effect of institutional setting, selection bias, and length of hospitalization. Records of medical autopsies from 3 institutional settings were studied for discrepancies between clinical and autopsy findings. The settings were university hospital (n = 85); community hospital (n = 146); and private autopsy (n = 60), which were referred from various community hospitals and paid for by family members. The same prosector performed the autopsies in the community and private settings. The overall rate of major discrepancy that involved the cause of death was 17.2%. Factors that increased the likelihood of missed diagnoses were private setting (P = .0005), community setting (P = .02), and short hospital stay before death (P = .02). Additional major findings were present in 28.5% of autopsies. Length of hospital stay before death, institution, and selection bias all affect the rate of major unexpected findings in hospital-based autopsies.     

Missed diagnosis in hematological patients—an autopsy study

Autopsy findings of missed diagnoses that would probably have changed management or prognosis occur in up to 29% of cases in general hospitals. Such proportions may be higher in subsets of patients with complex diseases. We reviewed 2908 consecutive autopsies performed over a period of 29 months in a large-volume hospital, analyzing 118 autopsies of patients with hematological malignancies or severe aplastic anemia. A review of macroscopic reports as well as microscopic examination of tissue samples was performed. Medical records were reviewed for clinical diagnoses. Discordances between clinical and autopsy diagnoses were classified using Goldmans criteria. Additionally, we searched for clinical parameters correlated with occurrence of class-I discrepancy using a multivariate method. Median age was 46.5 years, and 25.4% had received a hematopoietic stem-cell transplant. Overall, 11.9% (6.6–19.1%) of patients died before conclusion of the hematological diagnosis and 33% (24.6–42.3%) died with no active hematological disease. We found class-I discrepancy in 31.3% (23.1–40.5 %) of cases. The most common among these diagnoses were hematological disease, pneumonia and gastrointestinal bleeding. In a univariate analysis, being elderly (P=0.04) was positively correlated with the finding of class-I discrepancies; while, having received previous specific hematological treatment (P=0.0005) or hematopoietic stem-cell transplants (P=0.013), or being admitted to a specialized hematology unit (P=0.0006) were negatively correlated to the occurrence of such discrepancies. Multivariate analysis showed that care in a specialized hematology unit (OR 0.34, 0.12–0.93) was independently associated with lower occurrence of discrepancies. We concluded that critical diagnoses are often missed in highly complex hematological patients especially in the absence of admission to specialized hematology units.     

The autopsy as a performance measurement tool--diagnostic discrepancies and unresolved clinical questions: a College of American Pathologists Q-Probes study of 2479 autopsies from 248 institutions

OBJECTIVE: To develop a multi-institutional reference database for quality improvement purposes using the autopsy to define clinical diagnostic discrepancies and resolve clinical questions. DESIGN: Using the College of American Pathologists Q-Probes format, institutions prospectively assessed a maximum of 15 consecutive autopsies each, excluding forensic cases and stillborn infants, conducted over a 6-month period. They documented answers to clinical questions provided at autopsy and classified unexpected disease diagnoses according to a standardized system. SETTING AND PARTICIPANTS: Hospital-based autopsies performed at 248 institutions participating in the 1993 College of American Pathologists Q-Probes Quality Improvement Program. MAIN OUTCOME MEASURES: Percentages of clinical questions resolved by the autopsy and percentage of autopsies with unexpected findings of graded clinical impact. RESULTS: In the aggregate database of 6427 questions from 2479 autopsies, overall 93.0% were answered by the autopsy. The 3 most common question categories were (1) identify pathology to account for clinical signs or symptoms (28.0%); (2) establish the cause of death (21.0%); and (3) confirm a clinical diagnosis (19.0%). At least one major unexpected disease finding that contributed to the patient's death was discovered in 39.7% of the total number of autopsies. There were no differences in the percentages of autopsies with these major unexpected findings when the data were stratified by institutional demographics or decedent characteristics. CONCLUSION: This multi-institutional study underscores the clinical relevance of postmortem examination in current medical practice by consistently providing answers to unresolved clinical questions and frequently revealing major unexpected findings that contributed to the patient's death. It is our strong belief that this postmortem-derived clinicopathologic information is a key indicator of effectiveness of care. Integration of this information into institutional quality improvement programs will improve system processes and clinician performance.     

Medical autopsy: whose gain is it? An audit

Medical audit is essential in assessing the efficacy of health care delivery system. Though autopsy services are generally looked upon indifferently and with sceptism by the clinicians, it can form an important part of the medical audit system. The aims of this study were to audit autopsies of deaths within 24 hours of hospital admission by: 1) Comparing premortem and postmortem diagnosis; 2) Comparing postmortem gross diagnosis with postmortem histopathologic diagnosis; 3) Whether deaths could be certified based on clinical judgement and autopsies avoided. The study sample was 99 autopsies. In 45% autopsies, clinical impression did not match the final cause of death. In 14.2% autopsies, final cause of death could have been given by the clinician based on his clinical judgement. In 54.5% autopsies, there was agreement between premortem and postmortem diagnosis. In 67.6% autopsies, gross findings matched with the histopathologic findings.     

Maternal death analysis based on data from the nationwide registration system in Japan (2010–2018)

The maternal mortality rate in Japan was 3.5 per 100 000 live births in 2017, similar to that reported in other developed countries. To reduce the number of maternal deaths, a Japanese nationwide registration and analysis system was implemented in 2010. Between January 2010 and April 2018, 367 maternal deaths were reported. Among them, by reviewing 80 autopsy records, the direct obstetric causes of death were identified in 52 women. The major causes of deaths were amniotic fluid embolism and acute pulmonary thromboembolism. The other 26 maternal deaths were associated with indirect obstetric causes including invasive Group A Streptococcus infection, aortic dissection, cerebral stroke and cardiomyopathies. This review highlights the importance of autopsy in maternal deaths. On analyzing 42 autopsy specimens obtained from registered cases of maternal death during 2012–2015, the 36% of causes of death by autopsy were discordant with the clinical diagnosis. Moreover, of the 38% of non-autopsied maternal death, the cause of death could not be clarified from the clinical chart. We emphasized that detailed autopsies are necessary to clarify the precise pathologic evidence related to pregnancy and delivery, especially causes of unexpected death such as amniotic fluid embolism.     

Malignant neoplasms: discordance between clinical diagnoses and autopsy findings in 3,118 cases

BACKGROUND: During the past few decades, hospital autopsy rates have steadily declined throughout the Western world. This decline is mainly attributed to the introduction of advanced diagnostic techniques. Despite technological developments, discrepancy rates between clinical diagnoses and autopsy findings remain high. Few studies have addressed discrepancy rates exclusively with regard to malignant neoplasms. In the present study, we reviewed the records of 3,118 autopsies performed at Mayo Clinic during a 6-year period (1994-1999) and identified clinically undiagnosed malignancies found at autopsy and clinically diagnosed cancers not confirmed at postmortem examination. MATERIALS AND METHODS: Autopsy protocols, provisional and final anatomic diagnoses, and data from the Mayo Autopsy Pathology Quality Assurance program were reviewed in an attempt to identify discrepancies between clinical diagnoses and autopsy findings regarding malignant neoplasms. RESULTS: In 3,118 autopsies performed at Mayo Clinic between 1994 and 1999, a malignant tumor was identified in 768 cases (25%). In 128 of 3,118 cases (4.1%), the malignancy was not diagnosed clinically. In 14 of 3,118 cases (0.45%), autopsy failed to confirm a clinically diagnosed cancer. A review of the literature is presented. CONCLUSIONS: Autopsy remains an effective tool for the confirmation and refutation of clinical diagnostic findings regarding malignant neoplasms.     

Unexpected autopsy findings arising from postmortem ocular examination

BACKGROUND: A full autopsy at our institution includes removal of the eyes for pathologic examination. To our knowledge, the rate of ophthalmic findings at autopsy has not been documented previously. DESIGN: We retrospectively reviewed 277 consecutive autopsies conducted between 1995 and 1999 in which the eyes were removed for examination. Ophthalmic findings were placed in the following categories: I, major findings included those that contributed to the patient's death, would have changed patient management, and/or may have important medical implications for close relatives; II, expected findings after ophthalmologic surgery and minor findings that may have eventually required treatment; and III, incidental findings. RESULTS: Major findings (category I) were found in 32% of autopsies. Minor findings (category II) and incidental findings (category III) were documented in 62% and 34% of autopsies, respectively. Only 14% of autopsies revealed no ophthalmologic diagnoses. CONCLUSION: In our series, postmortem ocular examination revealed a number of important findings, including several heritable and rare conditions. Eighty-six percent of autopsies disclosed at least one pathologic ophthalmologic finding, approximately one third of which demonstrated findings significant enough to have likely required management. Diabetic retinopathy was the most frequent major finding. Malignant melanoma of the choroid was the most commonly found intraocular neoplasm. Chronic uveitis was the most common minor finding. We conclude that important, often unexpected ophthalmic findings are frequently encountered at autopsy, underscoring the relevance of routine postmortem examination of the eyes.     

Utility of autopsy in uncovering unexpected neuropathology

Autopsy rates have declined in the last several decades for a variety of reasons. The purpose of this study is to compare autopsy neuropathologic findings from 2 periods to assess the prevalence of unexpected neuropathologic findings and unexpected neuropathologic diagnoses determined to be the major cause of death. Retrospective review of autopsies with examination of the central nervous system was performed in 2007 to 2008 (n = 289) and 1984 to 1985 (n = 328). Unexpected neuropathologic diagnoses were found at autopsy in 42.4% of cases from 1984 to 1985 vs 38.8% of cases from 2007 to 2008. The neuropathology was felt to contribute to the cause of death in 22% of cases from 1984 to 1985 vs 19.7% of cases from 2007 to 2008. Unexpected neuropathologic findings were the cause of death in 5.2% of cases from 1984 to 1985 vs 3.1% of cases from 2007 to 2008. These findings underscore the continued use of brain and spinal cord examination at autopsy despite advances in "modern" medicine.     

Pathologists in a teaching institution assess the value of the autopsy

CONTEXT: With the advent of modern diagnostic technology, use of the autopsy as a means of assessing diagnostic accuracy has declined precipitously. Interestingly, during the same period, the rate of misdiagnosis found at autopsy has not changed. OBJECTIVES: To ascertain why an autopsy was requested, whether or not questions asked by clinicians were specifically addressed, and what types of misdiagnoses were found. DESIGN: One hundred forty-two consecutive autopsy records from the University of Arkansas for Medical Sciences Hospital were reviewed. In the same period, 715 deaths occurred, giving an overall autopsy rate of 20.14%. RESULTS: Of the 125 autopsies in which the problem-oriented autopsy request was available for review, a reason for the autopsy was given in only 69 cases (55%). One hundred three clinical questions were asked, and of these, 81 were specifically addressed in the final anatomic diagnosis, 10 were addressed in some part of the autopsy report but not in the final anatomic diagnosis, 10 were not addressed at all, and 2 could not be answered by the autopsy. Sixty-one autopsies revealed 81 misdiagnoses: 47 class I (missed major diagnosis that, if detected before death, could have led to a change in management that might have resulted in cure or prolonged survival) and 34 class II misdiagnoses (missed major diagnosis in which antemortem detection would have not led to a change in management). CONCLUSIONS: The autopsy continues to be a vital part of medical education and quality assurance. It is important for the clinician to provide a clinical summary and specific clinical questions to be addressed or to speak directly with the pathologist and for the pathologist to provide answers that are easily accessible within the autopsy report. In this way, a problem-oriented autopsy can be performed based on questions raised by the clinician and the pathologist as a result of the gross dissection and microscopic evaluation.     

Diagnostic yield from 231 autopsies in a community hospital

Autopsy reports of 231 adult autopsies were examined for clinically unexpected diagnoses. Analysis of data showed that 97 of 188 autopsy diagnoses were clinically unexpected. The diagnosis of pulmonary embolism was clinically the most frequently missed diagnosis relative to its actual occurrence. Also noted was that the proportion of cases with unexpected diagnoses increased from 1983 to 1987.     

A retrospective study of the accuracy between clinical and autopsy cause of death in the University of Malaya Medical Centre

It is well known that diagnostic accuracy of the clinical cause of death has not improved despite advances in diagnostic techniques. We aimed to investigate the accuracy of the clinical cause of death compared with the autopsy cause of death and to see if the Coroner's autopsy can play a role in clinical audit. Our study population consisted of all autopsies where the deceased was hospitalised or resuscitated at the Accident and Emergency Unit of the University of Malaya Medical Centre before death, performed during the period July 1998 to June 2000. The cases were subdivided according to natural and unnatural causes of deaths. Natural deaths were further subdivided in relation to the main organ systems involved while unnatural deaths were subcategorised into trauma, poisoning and burns. The rate of agreement between clinical and autopsy cause of death was further compared with duration of survival in the hospital. Of 132 autopsies included in this study, 115 were Coroner's autopsies. 78% of cases showed agreement between clinical and autopsy cause of death. The agreement rate in Coroner's cases was 80.0%. For natural and unnatural causes, the agreement rate was 56.7% and 84.3% respectively. There were 6 cases (4.5%) where an initial accurate diagnosis might have altered the prognosis of the deceased. In general, the rate of agreement increased with duration of survival of patients. However, this was no longer observed after a survival of more than 28 days. Our findings agree with other similar studies. The diagnostic accuracy of cause of death has not improved despite the modernisation in medical technology. The autopsy still plays an important role in clinical audit and medical education.     

Correlation of clinical diagnoses with autopsy findings: A retrospective study of 2,145 consecutive autopsies

The protocols of 2,145 autopsies were retrospectively reviewed and the findings compared with the clinical diagnoses. A sudden decline in the autopsy rate that occurred during the period studied was followed by a highly statistically significant difference in clinical accuracy (P less than 0.01), in favor of the predecline period. The overall rate of major discrepancies was 29 per cent. The most frequently missed diagnoses were infections, which were found in 26 per cent of all autopsies and had not been diagnosed clinically in 63 per cent of these cases. Malignancies occupied second place among overlooked diagnoses in the selected disease categories; in 99 per cent of the cases the malignancy was the principal diagnosis, and it had been misdiagnosed clinically in 42 per cent of these cases. Cerebrovascular disorders were correctly diagnosed in most cases (87 per cent of the patients in this group). Among autopsy diagnoses labeled as the immediate causes of death, the most frequently overlooked were pulmonary embolism and gastrointestinal hemorrhage, which were not recognized in 84 and 78 per cent, respectively. In cases in which clinicians were not entirely confident in their impressions, their diagnoses were usually confirmed at autopsy. In these cases 15 per cent of the patients died soon after admission to the hospital, with accurate diagnoses in 71 per cent. The discrepancies disclosed should be regarded as sufficiently large to mandate continued emphasis on autopsy evaluation as the basis for the control of the quality of patient care.     

Laparoscopic postmortem examination: a minimally invasive approach to the autopsy

Laparoscopic and thoracoscopic autopsies have previously only been performed on an experimental basis to determine their potential usefulness as a substitute for a conventional postmortem examination. We present the case of a patient with an unusual variant of malignant melanoma (diffuse melanosis) in whom the immediate cause of death clinically was thought to be fulminant hepatic failure, the etiology of which was unknown. The family was unwilling to consent to a conventional autopsy, but would permit a postmortem examination limited to a 2-cm abdominal incision and removal of a sample of liver. In view of the unanswered clinical questions regarding the cause of the acute hepatic failure and its possible relationship to the diagnosis of diffuse melanosis, we decided that more extensive examination of the abdominal cavity, specifically the liver, was required and that the only way that this could be accomplished was by laparoscopic techniques. Laparoscopic examination of the abdominal cavity revealed multiple melanotic nodules on the surface of the liver and studding the omentum. Multiple liver samples were easily obtained; these revealed massive diffuse necrosis of the liver parenchyma with scattered nodular deposits of dark pigment consistent with melanin. We report the first known case in which a laparoscopic autopsy was used to obtain valuable information that answered clinically relevant questions. Laparoscopic autopsy can offer the a family that is unwilling to consent to a conventional postmortem examination an alternative that can potentially provide answers to clinical questions that otherwise would have been unresolved.     

Infectious diseases detected at autopsy at an urban public hospital, 1996-2001

Previous studies have demonstrated significant discrepancy rates between clinical and autopsy diagnoses. However, infectious diseases have not received emphasis in these studies. We conducted a study to determine whether the clinical and autopsy diagnoses of infectious diseases are concordant or discrepant and to determine discrepancy rates. Retrospective reviews of the records of 276 patients (adults, 182; fetuses and neonates, 94) who underwent autopsy during the years 1996 through 2001 were performed. Comparison of clinical and autopsy diagnoses was performed using the Goldman classification scheme. Of 182 adult patients, 137 (75.3%) had an infectious disease at autopsy. In 59 (43.1%) of 137 patients, the infectious disease diagnoses were unknown clinically. Of 94 fetuses and neonates, 45 (48%) had an infectious disease at autopsy. In 26 (58%) of 45 patients, the infectious disease diagnoses were unknown before death. There are substantial discrepancies between clinical and autopsy diagnoses of infectious diseases. In adults, acute bronchopneumonia is the infectious disease most often missed clinically; in fetuses and neonates, it is acute chorioamnionitis.