Clinical and pathological disagreement upon the cause of death in a teaching hospital: analysis of 100 autopsy cases in a prospective study

The aim of the present study was to analyze the concordance between clinical and autopsy diagnoses. For this purpose, 100 patients submitted to autopsy from July 2000 to April 2001 were studied prospectively. In all cases, clinicians gave the immediate and the underlying causes of death for patients dying under their care. The diagnoses were compared to the macroscopic autopsy diagnoses. Cohen's kappa coefficient of agreement was estimated. Sixty-four men and 36 women were submitted to autopsy. The most frequent pathological diagnosis of underlying cause of death were diseases of the circulatory system (35%), infections and parasitic diseases (20%) and diseases of the digestive system (11%). The kappa coefficient for immediate cause of death was 0.40 (95% confidence interval (CI): 0.29–0.50); for underlying cause it was 0.38 (95%CI: 0.18–0.44), and for basic cause codified by group according to ICD-10 it was 0.55 (95%CI: 0.44–0.67). Major disagreement occurred in 10 cases involving pathological causes of death as circulatory diseases, in which the clinicians diagnosed a digestive system disease as the cause of death ( n  = 5), or infectious and parasitic diseases ( n  = 5). The present study shows that agreement between clinical and pathological causes of death are moderate, proving that the autopsy is still a very important procedure.     

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.     

Clinical diagnosis of mycobacterial diseases versus autopsy findings in 350 patients with AIDS

Three-hundred fifty consecutively autopsied AIDS patients in Milan, Italy, were studied to determine the frequencies of clinical and postmortem diagnoses of mycobacterial diseases, to evaluate the clinical histories of those patients with mycobacterial diseases, and to investigate the reasons for nondiagnosis of mycobacterial diseases during life. Seventy-eight patients (22.3%) had mycobacterial diseases. In 64 cases (18.3%) the diagnosis was made antemortem and in 50 (14.2%) at autopsy; there were 36 cases of concordant clinical and postmortem diagnoses. Nontuberculous mycobacterioses (NTM) were diagnosed in 41 patients (20 clinical/postmortem diagnoses, 11 clinical diagnoses, and 10 postmortem diagnoses), extrapulmonary tuberculosis (TB) in 19 patients (7 clinical/postmortem, 8 clinical, 4 postmortem), and pulmonary TB in 18 patients (9 clinical/postmortem, 9 clinical). Patients with a clinical diagnosis of mycobacteriosis but with no pathological evidence of disease at autopsy were considered to have recovered on the basis of negative culture findings and prolonged antimycobacterial treatment. In Italian patients with AIDS, NTM occurs less frequently and TB more frequently than in American AIDS patients. At least some of the patients reported in this study seemed to have recovered from mycobacterial disease after prolonged treatment. The lack of diagnosis during life can be attributed to aspecific symptoms, a rapidly terminal course, and the presence of concomitant opportunistic diseases.     

Autopsy as a tool for quality assurance: Leipzig

Autopsy rates have declined throughout the world although autopsy serves as an important tool in quality management. Working together with the Department of Heart Surgery of the Heart Centre in Leipzig clinical and autopsy diagnoses were compared. Between 2000 and 2003 an autopsy was performed in 468 patients. Data from clinical and postmortem examinations were prospectively analysed regarding causes of death, concomitant diseases and postoperative complications. Discrepancies between clinical and postmortem cause of death were identified in 23.1% of these patients. In 99.1% of the patients concomitant diseases (e.g. myocardial hypertrophy, pulmonary embolism, former stroke) could be identified, 57.6% were unknown pre-mortem and 19.2% were considered to be of relevance for surgical therapy. Autopsy is the final and most comprehensive physical examination. Autopsy is also the basis of training for pathologists in interpreting interrelated diagnoses. Therefore the task of pathologists is to enhance the appreciation of autopsy among clinical colleagues by working closely side by side. By communication an autopsy can deliver an effective achievement in terms of being relevant for praxis.     

Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru

There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed.     

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.     

Radiography in post-mortem examinations of fetuses and neonates. Findings on plain films and at arteriography

During the last decade there has been an increasing interest in radiological investigation of stillborns and neonates as a supplement to autopsy. A consecutive series of 137 fetuses and neonates is presented. Prior to autopsy plain X-ray films were taken, and in 50% arteriography was performed by injecting contrast medium into an umbilical or femoral artery. On the plain films only 41% were normal. The major part of the abnormal radiographs exhibited minor abnormalities such as transverse lines or "stress-lines" of the bones, cercival ribs or an abnormal numbers of ribs. Major abnormalities were seen in 9%. Most of these were abnormalities of the spine. The arteriographs were very detailed and were abnormal in 29% of the cases. The technique was not suitable for demonstration of heart malformations. It is concluded that plain film X-ray of soft tissues and bones is recommendable as a routine procedure, whereas arteriography should be limited to cases suspected of vascular malformations or if an autopsy cannot be performed.     

The Role of Invasive and Non-Invasive Procedures in Diagnosing Fever of Unknown Origin

Background: The etiology of fever of unknown origin has changed because of the recent advances in and widespread use of invasive and non-invasive diagnostic tools. However, undiagnosed patients still constitute a significant number.Objective: To determine the etiological distribution and role of non-invasive and invasive diagnostic tools in the diagnosis of fever of unknown origin.Materials & Methods: One hundred patients who were hospitalized between June 2001 and 2009 with a fever of unknown origin were included in this study. Clinical and laboratory data were collected from the patients'' medical records retrospectively.Results: Fifty three percent of the patients were male, with a mean age of 45 years. The etiology of fever was determined to be infectious diseases in 26, collagen vascular diseases in 38, neoplastic diseases in 14, miscellaneous in 2 and undiagnosed in 20 patients. When the etiologic distribution was analyzed over time, it was noted that the rate of infectious diseases decreased, whereas the rate of rheumatological and undiagnosed diseases relatively increased because of the advances in imaging and microbiological studies. Seventy patients had a definitive diagnosis, whereas 10 patients had a possible diagnosis. The diagnoses were established based on clinical features and non-invasive tests for 61% of the patients and diagnostic benefit was obtained for 49% of the patients undergoing invasive tests. Biopsy procedures contributed a rate of 42% to diagnoses in patients who received biopsies.Conclusion: Clinical features (such as detailed medical history-taking and physical examination) may contribute to diagnoses, particularly in cases of collagen vascular diseases. Imaging studies exhibit certain pathologies that guide invasive studies. Biopsy procedures contribute greatly to diagnoses, particularly for malignancies and infectious diseases that are not diagnosed by non-invasive procedures.     

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.     

Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature

To identify causes of death (COD) in propositi with Cornelia de Lange syndrome (CdLS) at various ages, and to develop guidelines to improve management and avoid morbidity and mortality, we retrospectively reviewed a total of 426 propositi with confirmed clinical diagnoses of CdLS in our database who died in a 41-year period between 1966 and 2007. Of these, 295 had an identifiable COD reported to us. Clinical, laboratory, and complete autopsy data were completed on 41, of which 38 were obtainable, an additional 19 had autopsies that only documented the COD, and 45 propositi had surgical, imaging, or terminal event clinical documentation of their COD. Proband ages ranged from fetuses (21-40 weeks gestation) to 61 years. A literature review was undertaken to identify all reported causes of death in CdLS individuals. In our cohort of 295 propositi with a known COD, respiratory causes including aspiration/reflux and pneumonias were the most common primary causes (31%), followed by gastrointestinal disease, including obstruction/volvulus (19%). Congenital anomalies accounted for 15% of deaths and included congenital diaphragmatic hernia and congenital heart defects. Acquired cardiac disease accounted for 3% of deaths. Neurological causes and accidents each accounted for 8%, sepsis for 4%, cancer for 2%, renal disease for 1.7%, and other causes, 9% of deaths. We also present 21 representative clinical cases for illustration. This comprehensive review has identified important etiologies contributing to the morbidity and mortality in this population that will provide for an improved understanding of clinical complications, and management for children and adults with CdLS.     

Open-lung biopsy in patients with undiagnosed lung lesions referred at a tertiary cancer center is safe and reveals noncancerous, noninfectious entities as the most common diagnoses

We evaluated the diagnostic yield of open-lung biopsies (OLBs) in a large tertiary cancer center to determine the role of infectious diseases as causes of undiagnosed pulmonary lesions. All consecutive adult patients with either single or multiple pulmonary nodules or masses who underwent a diagnostic OLB over a period of 10 years (1998–2007) were retrospectively identified. Their risk factors for malignancy and clinical and radiological characteristics were reviewed, and their postoperative complications were assessed. We evaluated 155 patients with a median age of 57 years (range, 19–83 years). We identified infectious etiologies in 29 patients (19 %). The most common diagnosis in this group was histoplasmosis (12 [41 %]), followed by nontuberculous mycobacterial infection (7 [24 %]) and aspergillosis (4 [14 %]). The majority of the 126 remaining patients had nonmalignant diagnoses, the most prevalent being nonspecific granuloma (26 %), whereas only 17 % had malignant diagnoses. We observed no significant differences among the patients with infectious, malignant, or both noninfectious and nonmalignant final diagnoses regarding their demographic, laboratory, and clinical characteristics. Six percent of the patients had at least one post-OLB complication, and the post-OLB mortality rate was 1 %. OLB is a safe diagnostic procedure which frequently identifies a wide variety of infectious and inflammatory diseases.     

An analysis of the quality of the clinical diagnosis based on autopsy data

The findings from 4359 autopsies made in 4 Moscow hospitals during 1986 were analyzed with two proposed tables. The primary materials were processes with a computer. Table 1 includes data on the total number of unrecognized cases by the main disease, major complications, concomitant and underlying diseases in terms of their category and cause of diagnosis discrepancy. The rate of the discrepancy between clinical and postmortem diagnoses averaged 21.6 +/- 4.7% by the main disease, that of unrecognized fatal complications and major concomitant and underlying diseases was found to be 7.6 and some 2%, respectively. By the categories, the analysis of diagnosis discrepancy indicated 35, 58.6, and 6.4% in Categories I, II, and III, respectively. Table 2 (combined correlational one) makes it possible to study the range of diagnostic errors in various diseases and to find typical mistakes made by clinicians. Analyzing the quality of clinical diagnosis according to the given pattern is of advantage in routine practice to obtain comparable consistent data, to make a thorough examination, and to generalized discrepancy cases of clinical and postmortem diagnoses.     

Antemortem diagnosis of gastrointestinal mucormycosis in neonates: report of two cases and review of literature

Gastrointestinal mucormycosis has been reported more frequently in adults than in children. Due to high mortality diagnosis is usually made at autopsy. Only 3 cases of neonates surviving this disease have been described. We report two cases of preterm neonates presenting clinically with symptoms of necrotizing enterocolitis (NEC), but lacking radiological characteristics of NEC where histopathology confirmed the diagnosis of gastrointestinal mucormycosis involving caecum and appendix.     

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.     

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.     

Molecular autopsy by trio exome sequencing (ES) and postmortem examination in fetuses and neonates with prenatally identified structural anomalies

PurposeTo determine the diagnostic yield of combined exome sequencing (ES) and autopsy in fetuses/neonates with prenatally identified structural anomalies resulting in termination of pregnancy, intrauterine, neonatal, or early infant death.MethodsES was undertaken in 27 proband/parent trios following full autopsy. Candidate pathogenic variants were classified by a multidisciplinary clinical review panel using American College of Medical Genetics and Genomics (ACMG) guidelines.ResultsA genetic diagnosis was established in ten cases (37%). Pathogenic/likely pathogenic variants were identified in nine different genes including four de novo autosomal dominant, three homozygous autosomal recessive, two compound heterozygous autosomal recessive, and one X-linked. KMT2D variants (associated with Kabuki syndrome postnatally) occurred in two cases. Pathogenic variants were identified in 5/13 (38%) cases with multisystem anomalies, in 2/4 (50%) cases with fetal akinesia deformation sequence, and in 1/4 (25%) cases each with cardiac and brain anomalies and hydrops fetalis. No pathogenic variants were detected in fetuses with genitourinary (1), skeletal (1), or abdominal (1) abnormalities.ConclusionThis cohort demonstrates the clinical utility of molecular autopsy with ES to identify an underlying genetic cause in structurally abnormal fetuses/neonates. These molecular findings provided parents with an explanation of the developmental abnormality, delineated the recurrence risks, and assisted the management of subsequent pregnancies.     

尸体解剖病理诊断和临床诊断的差异分析

目的 分析尸体解剖病理诊断(简称尸检诊断)与临床诊断在不同类型医院和入院后病程时间(24 h内外)上的差异.方法 回顾性分析188例尸体解剖资料,比较尸检诊断与临床诊断的差异及疾病分布.结果 188例尸检的误诊率为48.9%(92/188),一级医院的误诊率(25/33,75.8%)显著高于三级医院(38/96,39.6%;x2=12.861,P=0.000)和二级医院(29/59,49.2%;x2=6.179,P=0.016).入院24 h后误诊率明显低于入院24 h内(x2=20.991,P=0.000).漏诊率为34.6%(65/188),一级医院明显高于三级医院(x2=8.241,P=0.006).入院24 h内各级别医院的漏诊率差异无统计学意义,入院24 h后三级医院的漏诊率显著低于一级医院(x2=5.181,P=0.047).误诊和漏诊的疾病分布以心脏病变、感染性疾病、动脉病变和肺栓塞等为主.结论 各级医院的临床诊断和尸检诊断差异较大.一级医院的误诊率和漏诊率显著高于三级医院,并与入院后病程时间密切相关.应提倡积极开展尸检工作和临床病理讨论,以提高临床诊断水平.     

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.     

Autopsy and the internal medicine department.

The accuracy of major clinical diagnoses and causes of death was estimated from the analysis of clinical diagnoses and autopsy findings of patients deceased at the internal medicine department of a large university hospital in two different periods (1965-1967 and 1985-1987). The autopsy cases from the second period were subdivided in two groups i.e. less and more than seven days of hospital stay prior death. From 100 randomly selected autopsy cases in each period there was no statistically significant variability in clinico-pathological concordance. In three groups studied (1965-1967, 1985-1987 < seven days and 1985-1987 < seven days hospital stay) the major clinical diagnosis was confirmed in 85, 94 and 86% respectively. A decrease of nearly 27% in the number of autopsies performed is shown between analysed periods. Clinico-pathological conferences are regularly held weekly, this being one of the reasons for a stable and extremely high clinico-pathological concordance.