Comparison of Clinical Diagnoses and Autopsy Findings: Six-Year Retrospective Study.
MATERIALS AND METHODS
Clinical information of all adult (18 years or older) autopsy cases performed in Jackson Memorial Hospital (Miami, Florida) for 6 years (from January 2009 to December 2014) was retrospectively evaluated. Only cases with a stay longer than 24 hours in Jackson Memorial Hospital were included in the study in order to ensure enough time for initial clinical evaluation and management. Exclusion criteria were: (1) a hospital stay of less than 24 hours, (2) restrictions to single-organ or body cavity dissections, and (3) cases referred from other facilities. Cases from the University of Miami Hospital (Miami, Florida), which shares attending physicians and residents in the adjacent campus and whose full medical records were available, were considered in-house cases.
All cases had consent for autopsy from the legal next of kin, and each autopsy was performed by pathology residents who observed restrictions, if there were any. Attending pathologists directly supervised each case. For each eligible autopsy the autopsy report, including clinical history, was reviewed by 2 pathologists (H.M. and C.M.). Medical records were reviewed if the clinical information provided in the autopsy report was unclear or inadequate. Each case was classified using the Goldman Classification (Table 1).4 When a case could be classified with more than one discrepancy, the higher class (smaller number) was regarded as the final classification. The pathologists reviewed the cases independently, compared their assessments, and came to consensus by discussion if there was discordance.
The study design was reviewed by the Institutional Review Board of the University of Miami and approved to be conducted as nonhuman research.
Of 923 autopsies performed in Jackson Memorial Hospital for the 6 years (2009-2014), 512 cases (55.5%) were performed on adults (age >18 years). A total of 334 of 512 cases (65.2%) were subject to review after excluding those with a short (<1 day) hospital stay, restriction to a single-organ or body cavity dissection, and those referred from other facilities (Table 2). The demographics of the patients included are presented in Table 3.
A total of 33 of 334 cases (9.9%) were identified as a class I discrepancy, where the autopsy revealed a discrepant diagnosis with a potential impact on survival or treatment (Table 4). Various critical findings, such as untreated infection (15 of 33 cases; 45.5%), pulmonary embolism (8 of 33 cases; 24.2%), and undiagnosed malignancy (6 of 33 cases; 18.2%) were identified in cases of this class (Table 5). For the cases with class I discrepancies, the clinical history or impression and critical laboratory or imaging results are listed in Table 6. Major significant findings that had not been clinically detected, whether they might or might not have clinical impact, were found in a total of 65 of 334 cases (class I and II; 19.5%).
This study is a retrospective review of the adult autopsy reports for recent years in the third largest public hospital (1550 beds) in the United States. It excluded cases from outside institutions, patients with short hospital stays, and those in which the autopsy was restricted to a single organ or body cavity, in order to optimize the clinical and pathologic correlation. Even though the exclusion made the size of the study smaller, the entire set of included cases was comprehensively reviewed, unlike in some previous studies which only reviewed randomly sampled cases. (5)
There was a limitation to calculate the exact autopsy rate because: (1) some cases were declared to be under the jurisdiction of the medical examiner, and therefore dropped from the initial data set, and (2) Jackson Memorial Hospital has many branches and affiliated hospitals from which autopsies are requested, and the total number of deaths in each hospital was not available.
Despite intensive modern clinical investigations, autopsies have continued to reveal major antemortem diagnostic errors in as many as 30% of cases. (6-8) Follow-up or meta-analysis studies show that the rate of clinically significant discrepancy is decreasing over decades; however, 4% to 7% of cases still have class I discrepancies. (1,5) This study shows a comparable result of 9.9% of clinically significant findings to the previous studies.
Undiagnosed infections, especially pneumonia, and pulmonary embolism were the 2 most common significant unexpected findings. These are common complications of hospitalization and subsequent immobilization. The character of the study, which excluded the short hospital stay, may make the frequency of those complications more notable by a possible exclusion of sudden cardiovascular accidents, which might have a significant portion in autopsies but have a short time period between the initial clinical presentation and the patient's demise. Because early suspicion and detection may make for a significantly better prognosis in those potentially fatal complications, vigilant management for preventing these conditions is suggested.
Beyond the direct clinical or administrative advantages, autopsies have other virtues, such as educational and epidemiologic values. (9) The autopsy should continue to be the gold standard for quality control in clinical management, including radiologic evaluation, (10-15) in spite of declining requests. (16) The most crucial factors influencing attitudes toward the autopsy have been shown to be the clinician's level of experience with autopsy in training and practice. Therefore, the importance of the autopsy should be emphasized in medical education and postgraduate training so the number of significant diagnostic discrepancies can be reduced and patient care can be optimized.
Please Note: Illustration(s) are not available due to copyright restrictions.
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Hyejong Song Marshall, MD; Clara Milikowski, MD
Accepted for publication December 29, 2016.
Published as an Early Online Release June 28, 2017.
From the Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital/University of Miami, Miami, Florida.
The authors have no relevant financial interest in the products or companies described in this article.
The data and abstract were presented at the annual meeting of the United States and Canadian Academy of Pathology (USCAP); March 14, 2016; Seattle, Washington.
Reprints: Clara Milikowski, MD, Pathology and Laboratory Medicine, Jackson Memorial Hospital/University of Miami, 1611 NW 12th Ave, Holtz Children's Hospital, 2nd Floor, Suite 2042, Miami, FL 33136 (email: CMilikowski@med.miami.edu).
Table 1. Criteria of Goldman Classification Type of Class Discrepancy Definition Example: Death Due to: I Major Directly related to Unsuspected death; if myocardial recognized, may have infarction altered treatment or presenting with survival chest pain II Major Directly related to Unsuspected death; if recognized, myocardial would not have infarction altered treatment or presenting with survival cardiac arrest III Minor Incidental autopsy Known myocardial finding not directly infarction with related to death but unsuspected left related to terminal ventricular mural disease process thrombus IV Minor Incidental autopsy Known myocardial finding unrelated to infarction with cause of death unsuspected lung cancer V No error Clinical and autopsy diagnoses in complete agreement Table 2. Numbers of Cases Included and Excluded by Year Year 2009 2010 2011 2012 Total number of autopsies (A) 204 151 140 154 Cases of age older than 18 y (B) 107 66 76 105 Outside case (C) 6 2 4 6 Short (<1 d) stay (D) 21 14 8 23 Single organ or single cavity only (E) 6 4 8 9 Cases subject to review (B-[C + D + E]) 74 46 56 67 Year 2013 2014 Total Total number of autopsies (A) 137 137 923 Cases of age older than 18 y (B) 74 84 512 Outside case (C) 6 5 29 Short (<1 d) stay (D) 13 17 96 Single organ or single cavity only (E) 13 13 53 Cases subject to review (B-[C + D + E]) 42 49 334 Table 3. Patient Demographics Item No. (%) Sex Male 189 (56.6) Female 145 (43.4) Total 334 (100) Age, y 18-30 38 (11.4) 31-40 22 (6.6) 41-50 43 (12.9) 51-60 89 (26.6) 61-70 85 (25.4) 71-80 42 (12.6) >80 15 (4.5) Total 334 (100) Table 4. Result of Case Classification Class No. (%) of Cases I 33 (9.9) II 32 (9.6) III 12 (3.6) IV 110 (32.9) V 147 (44.0) 334 (100) Table 5. Findings With Potential Impact on Survival or Treatment (Class I Discrepancy) Item and Findings No. (%) Infection 15 (45.5) Fungal pneumonia (1 case with coexisting 6 fungal myocarditis) Viral pneumonia 2 Bacterial pneumonia 2 Miliary tuberculosis and bacterial 1 meningitis Meningitis of unknown etiology 1 Toxoplasmosis involving lung, liver, and 1 brain Candidemia confirmed by postmortem 1 blood culture Renal abscess 1 Pulmonary embolism 8 (24.2) Malignancy 6 (18.2) Lymphoma involving multiple organs 3 Diffuse large B-cell lymphoma Follicular lymphoma Peripheral T-cell lymphoma Pulmonary carcinoma 2 Small cell carcinoma Squamous cell carcinoma Gastric adenocarcinoma 1 Cardiovascular 3 (9.1) Retroperitoneal and/or intraabdominal 2 hemorrhage Cartilaginous emboli 1 Immunologic 1 (3.0) Anaphylactic laryngeal edema 1 Total 33 (100) Table 6. Clinical History or Impression and Critical Labs or Imaging Compared With Class I Autopsy Findings Serial Age, y/Sex Clinical History or Impression 1 34/M History of stroke, shortness of breath, flulike symptoms, possible pneumonia 2 81/M DM, valvular heart disease, fever and chills after procedure for benign prostatic hyperplasia 3 68/F DM, HTN, ischemic cardiomyopathy 4 83/F Myasthenia gravis, pneumonia 5 64/F COPD aggravation 6 56/M DM, HTN, nausea, vomiting, chest pain 7 68/M Pneumonia 8 48/F Mixed connective tissue disease, sepsis by multiple organisms 9 65/F Leukemia, s/p bone marrow transplant 10 65/F s/p liver transplant, transfusion of red blood cells to correct anemia 11 55/M Admitted for schizophrenia, COPD 12 58/M Adrenal mass, steroid therapy for numbness 13 54/M s/p kidney transplant, hematuria and abdominal pain, chest pain 14 43/F HIV, HTN, hypertensive crisis 15 77/M Dementia, HTN, normal pressure hydrocephalus, hematemesis 16 59/M POEMS syndrome, vomiting 17 39/M Neck pain, complicated hospital course including pulmonary embolism 18 57/M DM, s/p kidney and pancreas transplant, nausea and abdominal pain 19 69/M Lymphoma, s/p chemotherapy, rash, fever 20 23/F 36-wk pregnancy, pulmonary infiltrates, emergency cesarean delivery 21 58/M Inguinal hernia, persistent HTN after surgery 22 30/F Anti-NMDA receptor autoimmune/ paraneoplastic encephalitis 23 54/M HTN, DM, s/p kidney transplant, pulmonary edema, acute renal failure 24 58/F DM, HTN, weight loss, lymphadenopathy, shortness of breath 25 50/F Bronchiectasis, cirrhosis due to probable autoimmune hepatitis, hemoptysis 26 41/M HTN, sickle cell trait, after elective lumbar disk surgery, abdominal pain and respiratory failure, renal injury, disseminated intravascular coagulation, possible septicemia 27 62/F HTN, autoimmune hepatitis overlap with primary biliary cirrhosis, varices, hepatorenal syndrome, acute respiratory distress syndrome 28 74/F Cirrhosis, pleural effusion, aspiration pneumonia 29 54/F Asthma, cough, chest pain, antibiotic treatment, diarrhea, biopsy was planned but not done 30 20/M Cerebral palsy, hydrocephalus s/p shunt, hip dislocation s/p replacement. Septic shock. Treated with antibiotics 31 42/M HIV, DM, congestive heart failure, atrial fibrillation 32 58/M Gout, asthma, HTN, atrial fibrillation, extremity weakness, and altered speech 33 76/F Bladder and upper urinary tract cancer, DM, coronary artery disease, sudden collapse in hospital stay for urinary tract infection Serial Critical Lab or Imaging 1 Diffuse nodularity on chest radiograph, MSSA in blood 2 Blood and urine culture negative 3 Atrial fibrillation 4 Pneumonia and pulmonary edema, Proteus bacteremia 5 Hilar lymphadenopathy on imaging, BAL with Candida 6 Hepatitis C virus positive with elevated liver enzymes, cardiac enzyme negative 7 Blood culture negative, pleural effusion, consolidation of lung 8 Rhabdomyolysis, CMV, Klebsiella, Acinetobacter, Enterococcus 9 Elevated liver enzymes, negative blood culture and BAL 10 Bibasilar opacity and pleural effusion on chest radiograph 11 12 Adrenal mass, pleural effusion on imaging, hypercalcemia 13 Nonsignificant electrocardiogram and troponin 14 Pulmonary edema and enlarged cardiac silhouette, positive for cocaine 15 16 Hepatomegaly, spontaneous bacterial peritonitis 17 Edema of spinal cord 18 Leukocytosis 19 Pulmonary interstitial edema on chest radiography, gram- negative rods in bone marrow culture 20 Pulmonary embolism workup with negative results 21 Lung consolidation with mild pleural effusion 22 Infection workup with negative results 23 Leukopenia 24 Pulmonary embolism workup with negative result 25 Soft tissue mass encasing the celiac vessels and pericardium, mild elevation of aspergillosis glucomannan level 26 Decreasing hemoglobin and hematocrit 27 Chronic cholestatic hepatitis on liver biopsy, Klebsiella bacteremia 28 MSSA bacteremia, blood culture positive for Klebsiella, aspiration pneumonia on chest radiograph 29 Lung opacity concerning for infection, multiple enlarged lymph nodes 30 Hypernatremia, coagulopathy 31 Hyponatremia, marked and diffuse cerebral edema, MSSA bacteremia, pulmonary opacity; consolidation versus atelectasis 32 Brain CT with no intracranial hemorrhage 33 Mild interstitial pulmonary edema on chest radiograph Serial Significant Autopsy Findings 1 Pulmonary embolism 2 Pulmonary embolism 3 Pulmonary embolism 4 CMV pneumonia and colitis, not bacterial 5 Small cell carcinoma of lung with metastasis to lymph nodes and bone 6 Acute retroperitoneal hemorrhage extending into abdominal cavity 7 HSV pneumonia, not bacterial or fungal 8 Fungal pneumonia, not just viral and bacterial 9 Toxoplasmosis involving lung, liver, and brain 10 Laryngeal edema 11 Squamous cell carcinoma of lung 12 Diffuse large B-cell lymphoma, meningeal malignant lymphomatosis 13 Pulmonary embolism 14 Chronic meningitis of undetermined etiology 15 Bacterial pneumonia 16 Follicular lymphoma 17 Cartilaginous emboli to cervical spinal cord, recent hematoma of thalamus 18 Intra-abdominal and retroperitoneal hemorrhage 19 Fungal pneumonia 20 Pulmonary embolism 21 Pulmonary embolism 22 Pulmonary embolism 23 Abscesses of transplanted kidney 24 Poorly differentiated adenocarcinoma of stomach with metastasis to vertebral bone marrow 25 Fungal pneumonia and myocarditis 26 Fungal pneumonia 27 Fungal pneumonia 28 Fungal pneumonia 29 Peripheral T-cell lymphoma 30 Candidemia confirmed by postmortem blood culture 31 Miliary tuberculosis. Acute meningitis suggestive of bacterial etiology 32 Pulmonary embolism 33 Bacterial pneumonia Abbreviations: BAL, bronchoalveolar lavage; CMV, cytomegalovirus; COPD, chronic obstructive pulmonary disease; CT, computed tomography; DM, diabetes mellitus; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTN, hypertension; MSSA, methicillin/sensitive Staphylococcus aureus; NMDA, N/methyl/D/aspartate; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes; s/p, status post.
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|Title Annotation:||Original Article|
|Author:||Marshall, Hyejong Song; Milikowski, Clara|
|Publication:||Archives of Pathology & Laboratory Medicine|
|Date:||Sep 1, 2017|
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