[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.167.149.128. Please contact the publisher to request reinstatement.
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
Download PDF
Table 1.—Number of Undiagnosed or Misdiagnosed Malignant Tumors Found at Autopsy, by Site
Image description not available.
Table 2.—Number of Undiagnosed or Misdiagnosed Malignant Tumors Found at Autopsy, by Type
Image description not available.
Table 3.—Number of Incidental Undiagnosed or Misdiagnosed Malignant Tumors Found at Autopsy, by Tumor Site and Tumor Type
Image description not available.
Table 4.—Number of Discordant Autopsy Cases (Undiagnosed or Misdiagnosed Malignancies) Where Cause of Death Was Attributed to Malignancy
Image description not available.
Table 5.—Number of Discordant Autopsy Cases (Undiagnosed or Misdiagnosed Malignancies) Where Cause of Death Was Not Attributed to Malignancy
Image description not available.
Table 6.—Study Comparision of 3 Most Common Sites of Undiagnosed or Misdiagnosed Malignant Tumors Found at Autopsy
Image description not available.
1.
Marwick C. Pathologists request autopsy revival.  JAMA.1995;273:1889-1891.
2.
Kajiwara JK, Zucoloto S, Manco AR, Muccillo G, Barbieri MA. Accuracy of clinical diagnoses in a teaching hospital: a review of 997 autopsies.  J Intern Med.1993;234:181-187.
3.
Bauer FW, Robbins SL. An autopsy study of cancer patients, I: accuracy of the clinical diagnoses (1955 to 1965) Boston City Hospital.  JAMA.1972;221:1471-1474.
4.
Wells HG. Relation of clinical to necropsy diagnosis in cancer and value of existing cancer statistics.  JAMA.1923;80:737-740.
5.
Suen KC, Lau LL, Yermakov V. Cancer and old age: an autopsy study of 3535 patients over 65 years old.  Cancer.1974;33:1164-1168.
6.
Stevanovic G, Ticakovic G, Dotlic R, Kanjuh V. Correlation of clinical diagnoses with autopsy findings: a retrospective study of 2145 consecutive autopsies.  Hum Pathol.1986;17:1225-1230.
7.
Sarode VR, Datta BN, Banerjee AK.  et al.  Autopsy findings and clinical diagnoses: a review of 1000 cases.  Hum Pathol.1993;24:194-198.
8.
Gobbato F, Vecchiet F, Barbierato D, Melato M, Manconi R. Inaccuracy of death certificate diagnoses in malignancy: an analysis of 1405 autopsied cases.  Hum Pathol.1982;13:1036-1038.
9.
Manzini VD, Revignas MG, Brollo A. Diagnosis of malignant tumor: comparison between clinical and autopsy diagnosis.  Hum Pathol.1995;26:280-283.
10.
Britton M. Clinical diagnostics: experience from 383 autopsied cases.  Acta Med Scand.1974;196:211-219.
11.
Rothwell DJ, Cote RA, Brochu L. The systematized nomenclature of human and veterinary medicine. In: SNOMED International Microglossary for Pathology . Northfield, Ill: College of American Pathologists; 1993.
12.
SAS Institute Inc.  SAS Users Guide, Statistics, Version 6.  4th ed. Cary, NC: SAS Institute Inc; 1990.
13.
Cameron HM, McGoogan E. A prospective study of 1152 hospital autopsies: inaccuracies in death certification.  J Pathol.1981;133:273-283.
14.
Eley JW, Hill HA, Chen VW.  et al.  Racial differences in survival from breast cancer: results of the National Cancer Institute Black/White Cancer Survival Study.  JAMA.1994;272:947-954.
Original Contribution
October 14, 1998

Autopsy Diagnoses of Malignant NeoplasmsHow Often Are Clinical Diagnoses Incorrect?

Author Affiliations

From the Louisiana State University Medical Center, New Orleans.

JAMA. 1998;280(14):1245-1248. doi:10.1001/jama.280.14.1245
Context.—

Context.— Autopsy often reveals new diagnoses of malignant neoplasms, but as technological advances to improve diagnosis during life have improved, autopsy rates have declined dramatically.

Objective.— To determine if there is still a high discordance rate between clinical and autopsy diagnoses of malignant neoplasms despite increasing technological advances in diagnostic methods.

Design and Setting.— A 10-year retrospective study (1986-1995) of all autopsies performed at the Medical Center of Louisiana at New Orleans.

Participants.— All patients autopsied, excluding preterm fetuses, at the Medical Center of Louisiana at New Orleans, by both Tulane and Louisiana State University Schools of Medicine in which consent was obtained or authorization given from the Orleans Parish Coroner's Office.

Main Outcome Measures.— Discordance between clinical and autopsy diagnoses of malignant neoplasms.

Results.— A total of 1625 cases were reviewed of which 520 preterm fetuses were excluded. Of the remaining 1105 cases, 654 were male and 451 were female. The mean age was 48.3 years (range, 1-98 years). A total of 433 neoplasms were diagnosed, 250 of which were malignant. One hundred eleven malignant neoplasms in 100 patients had been either undiagnosed or misdiagnosed, and in 57 patients, the immediate cause of death could be attributed to the malignant neoplasm. The discordance between clinical and autopsy diagnoses of malignant neoplasms in this study is 44%, which is similar to previously reported studies.

Conclusion.— The discordance rate between clinical and autopsy diagnoses of malignant neoplasms is large and confirms the importance of the postmortem examination.

THERE IS much debate among clinicians as to the usefulness of autopsies. One argument is that with advancing technology, autopsy is an unnecessary diagnostic tool. This point of view has contributed to the decline in postmortem examinations during the past several decades. Autopsy rates have declined from an estimated 50% in the 1960s to an average of 10% today in teaching hospitals and as low as 5% in community-based hospitals.1 Despite technological advances, the number of inaccurate clinical diagnoses (attributed to both malignancies and all other causes) remains alarmingly high.210 The last large-scale study3 comparing clinical and autopsy diagnoses of malignant tumors reported in the United States was in 1972. Several more recent studies have been conducted in other areas of the world.8,9 Of the 2 studies conducted in the United States, an incorrect diagnosis of malignant tumors was shown in 36.5% of cases studied by Wells4 in 1923 and 41% of cases studied by Bauer and Robbins3 in 1972. These earlier findings are similar to those found in the present study.

METHODS

To compare more recent data with data of the past, a 10-year retrospective study was conducted at the Medical Center of Louisiana at New Orleans (MCLNO). The MCLNO (formerly Charity Hospital) is a large teaching hospital encompassing 2 medical schools, Louisiana State University and Tulane University Schools of Medicine. Our objective was to evaluate whether there was a continuing need for postmortem examination despite advances in diagnostic methods.

A 10-year retrospective study examining autopsy protocols from autopsies performed at MCLNO from 1986 through 1995 was conducted. Autopsies were performed by residents under the direct supervision of attending pathologists. All neoplasms were coded using the SNOMED international coding system.11 Both a morphological and topographical code were given to each neoplasm. A database was established using SAS software12 with demographic data, including autopsy and hospital identification numbers, age, race, sex, hospital service, dates of admittance, death, and autopsy examination and diagnoses using SNOMED codes. All demographic data were obtained from autopsy protocols. One thousand six hundred twenty-five autopsy protocols were reviewed and entered into the database. Of the 1625 cases, 520 (32%) were fetuses, subsequently excluded. The remaining 1105 cases (68%) were used in the study set. Of the 1105, 654 (59%) were male and 451 (41%) were female. The age range was 1 to 98 years. All neoplasms were reviewed and categorized as "benign" or "malignant." Because of unreliability of diagnoses from death certificates,8,13 clinical diagnoses were gathered from surgical pathological reports, cytological reports, and patient charts. The malignant neoplasms were reviewed for concordance between clinical and autopsy diagnoses. The discordant malignant neoplasms were further subdivided into a category of "misdiagnosed" (incorrect histopathological diagnosis of malignancy or incorrect primary site) or "undiagnosed" (no histopathological diagnosis).

RESULTS

In the 1105 cases studied, 225 (20%) were diagnosed as having a malignancy at autopsy (approximately 1 of every 5 patients). There were 250 malignancies diagnosed in 225 patients, an average of 1.1 malignancies per patient. The average age of all patients autopsied was 48.3 years (range, 1-98 years). The average age of patients having no diagnoses of malignancy was 46.6 years, while the average age of patients diagnosed as having malignancy was 54.3 years. Of those diagnosed as having malignancy, 33% were 65 years or older. The youngest patient was 4 years old and had a clinically undiagnosed medulloblastoma. The oldest patient was 92 years old and had a clinically undiagnosed lung adenocarcinoma. The sex distribution in both groups (nonmalignancies and malignancies) is similar, with both having more men than women. In the group having no diagnosis of malignancy, the ratio is 6:4 (58% men, 42% women), and for those diagnosed as having malignancy, 6:5 (63% men, 47% women). In the group diagnosed as having no malignancy, the black to white ratio is 4:1; while in the group diagnosed as having malignancy, the ratio is 7:3. All other races constitute 3% in both the nonmalignancy and malignancy group. Age, race, and sex data reflect the demographics of patients admitted to MCLNO.

Of the 250 malignant neoplasms diagnosed at autopsy, 111 (44%) were undiagnosed or misdiagnosed. These 111 malignant tumors were identified in 100 patients. Ten of these patients had multiple malignancies, 9 with 2 and 1 with 3 different primaries. The clinically undiagnosed or misdiagnosed malignant tumors found in these 100 patients were categorized based on site of origin (Table 1) and tumor type (Table 2). The most common sites of occurrence were the respiratory tract with 37 malignant tumors, the gastrointestinal tract (including hepatobiliary tract) with 37 tumors, and the genitourinary tract with 18 tumors. The common tumor types included 44 adenocarcinomas, 17 undifferentiated carcinomas, and 13 carcinomas (which include hepatocellular carcinomas, cholangiocarcinomas, and mesotheliomas). Fifty-four percent of these 100 patients had tumor metastases, with 15% locally invasive and 39% with distant metastases.

One hundred three of the malignant tumors were undiagnosed, while 8 were misdiagnosed. All 8 of the misdiagnosed tumors had histopathological diagnoses. Six had a different histopathological diagnosis at autopsy, and 2 had histopathological evidence with an incorrect primary site. Of the 103 undiagnosed malignant tumors, only 34 (33%) of these tumors were clinically suspected. In 21 of the clinically suspected malignancies, radiological studies were obtained that supported the clinical suspicion. Two cases had either cytological or surgical pathological diagnoses that were obtained with inconclusive results (ie, poor preservation of sample, sampling error). In 6 of the cases, both radiological studies and cytological or surgical pathological samples were obtained. In these 6 cases, all showed radiological evidence; however, pathological results were inconclusive. In 5 of the cases with clinical suspicion, there was either a history of malignancy (unconfirmed by patient medical record) or a palpable lesion.

There were 24 malignant tumors designated as incidental at the time of autopsy (Table 3), all undiagnosed prior to death. The majority of these tumors were renal cell carcinomas, with 2 cases reporting bilateral tumors. Adenocarcinoma of the prostate was evident in 4 cases. Three of the 4 cases had microscopic foci of adenocarcinoma. One of the 4 cases, in a 57-year-old black man, was diagnosed as "Gleasons grade IIIB" adenocarcinoma of the prostate. All of these incidental findings in time could result in significant morbidity and mortality.

Of the 100 patients with undiagnosed or misdiagnosed malignancies, in 57% of the cases, the underlying cause of death was due to the malignant neoplasm, and the immediate cause of death could be attributed to the malignant neoplasm (ie, respiratory tract failure due to widespread lung metastasis or infection due to bone marrow metastasis) diagnosed at the time of autopsy (Table 4). In the remaining 43% of the cases, the underlying cause of death documented at autopsy was not attributed to the malignancy (Table 5).

COMMENT

Studies examining discordance between clinical and autopsy diagnoses have shown varying results, with ranges from 6% to 65%10; however, studies looking at discordance between clinical and autopsy diagnoses of malignancies have been more consistent with a range of 26% to 46%.310 Several studies have been conducted comparing clinical and autopsy diagnoses of malignancies throughout the world, with the most recent done at the Montfalcone Hospital in Montfalcone, Italy.9 In a review of studies conducted in the United States, only 2 were found, those by Wells in 1923 and Bauer and Robbins in 1972. The 1972 study is the most recent study conducted in the United States. Both studies used extensive reviews of autopsy records as the basis for each study. Wells further categorized cancers by those "correctly and incorrectly diagnosed antemortem" and those "erroneously called cancer."4 Bauer and Robbins further subdivided antemortem diagnoses of cancer into "undiagnosed" (no suspicion of malignancy prior to death), "incompletely diagnosed cancer" (clinical suspicion but no confirmation or clinically unknown primary site), "diagnosed cancer with no residual cancer at autopsy," and "incorrectly diagnosed cancer" (incorrectly diagnosed or incompletely diagnosed). In the study by Bauer and Robbins, the autopsy rate at Boston City Hospital, Boston, Mass, from 1955 to 1965 was 47%. The study by Wells did not disclose an autopsy rate. Wells' study found a 36.5% discordance rate between clinical and autopsy diagnoses, while Bauer and Robbins found a discordance rate of 41%. Decades had separated the 2 studies, yet the rate of discordance is similar despite technological advances in diagnostic methods. Wells and Bauer and Robbins found inaccuracies in clinical diagnoses of malignancies and supported convincingly the need for autopsy in determining the accuracy of these diagnoses. This current study documents a discordance rate of 44% and other more recent data within the United States.

In the study by Wells, malignancies were found in 15% of autopsies, by Bauer and Robbins 25%, and by us 20%. The explanation by Bauer and Robbins for the 10% difference between their study and Wells' was increased prevalence of malignancy in the United States. The 5% difference between this study and Bauer and Robbins' could likely be explained by differences in autopsy rates, differences in patient populations, and autopsy-referral patterns unique to the 2 different institutions.

The MCLNO is a level I trauma center and a 746-bed hospital, of which 643 beds are used. The MCLNO's autopsy rate was approximately 42% (9034 deaths, 3766 autopsies) of all deaths recorded by the hospital from 1986 through 1995. Because MCLNO is a level I trauma center, all trauma-related deaths are also recorded by the hospital. The 42% autopsy rate includes coroners' cases, which were transported to and autopsied at the coroner's facility. Excluding those cases autopsied at the coroner's facility, the autopsy rate at MCLNO for this period was 24%. As in most hospitals, the number of postmortem examinations has decreased during the past few decades. The number of autopsies performed at our hospital decreased to the lowest number (109) in 1992; however, in recent years an increasing trend has been observed for several reasons. The MCLNO has striven to improve the autopsy service by improving the working environment, improving communication with clinicians, and emphasizing the importance of the postmortem examination. Even though many deaths classified as "natural" (not due to homicide, suicide, or unintentional injuries) are under the jurisdiction of the Orleans Parish Coroner's Office, they cooperate with the hospital and allow many of the cases to be autopsied at the MCLNO. Included are those occurring within 24 hours of hospital admission, those with a history of alcohol or other drug abuse, and perioperative deaths. Suspicious deaths or deaths due to trauma are transported to and autopsied at the coroner's facility. Those deaths autopsied at the coroner's facility are not included in this study set. Excluding the cases autopsied at the coroner's facility, the overall autopsy rate at our hospital (and of our study set) was 24%. The affiliation between the coroner's office and the MCLNO is important for several reasons. Of the autopsies with undiagnosed or misdiagnosed malignancies in this study set, 39% were authorized by the coroner. Without this affiliation, these autopsies may not have been performed. If these autopsies were not performed, a significant number of clinically undiagnosed malignancies may not have been recorded. Also, without this cooperation, the overall autopsy rate at the MCLNO would decline dramatically. During the study period from 1986 through 1995, the autopsy rate would have been as low as 10% without coroner's authorization of many of the cases.

In the 111 undiagnosed or misdiagnosed malignant neoplasms found, the most common sites of occurrence were the respiratory tract with 37 malignant tumors, the gastrointestinal tract (including hepatobiliary tract) with 37 tumors, and the genitourinary tract with 18 tumors. These findings differ from those found in the studies by Manzini et al9 and Bauer and Robbins (Table 6). The 3 systems are the most common in all 3 studies, but the ranking differs markedly. These 3 systems account for approximately 83% of the undiagnosed or misdiagnosed tumors in our study set. Manzini et al included tumors of the hepatobiliary system in their categorization of tumors of the gastrointestinal tract; therefore, for comparison, hepatobiliary tract tumors have also been included in Bauer's statistics and our study. Tumors of the genitourinary tract are third in our study. A possible reason for this may be due to the average age of the patient populations studied. The average age of patients autopsied in our study was 48.3 years, while the average age of patients with malignant tumors was 54.3 years. In the study by Bauer and Robbins, the average age of patients autopsied was 68.9 years, while the average age of patients autopsied with malignant tumors was 59.7 years. In comparison, the average age of patients autopsied in the study by Manzini et al was 75 years. The latter study did not provide the average age of patients found to have malignant tumors. Increasing age may contribute to the increased number of malignant tumors found in the genitourinary tract and thus account for differences in tumor sites observed in the 3 studies compared. Both our study and Bauer and Robbins' study include microscopic foci of genitourinary tumors. Manzini et al distinguished between microscopic foci (their stage 0) and localized tumors of the genitourinary tract. Given the average age (75 years) of the patients studied by Manzini et al, it is not surprising that tumors of the genitourinary tract are first. When looking at these 2 categories, by excluding stage 0 tumors (as was explained in the article by Manzini et al), the percentage of genitourinary tract tumors declines to second in the list of top 3 tumor sites; comparing more closely with the study by Bauer and Robbins.

In addition to being the most common malignancies undiagnosed or misdiagnosed, malignancies of the respiratory, gastrointestinal, and genitourinary tract systems also have the highest undiagnosed or misdiagnosed rate. For malignancies of the gastrointestinal tract, of 56 total cases, the rate of undiagnosed or misdiagnosed malignancies was 76%. For the respiratory tract, of 71 cases, the rate was 89%. For the genitourinary tract, of 28 cases, the rate was 64%.

The underlying cause of death in 57% of these 100 patients was directly related to malignancy. In the remaining 43% of the cases, the most common immediate cause of death was cardiovascular disease. Deaths attributed to cardiovascular disease included such diagnoses as myocardial infarction, myocardial ischemia, coronary occlusion, and fatal arrhythmia. Seven of the deaths attributed to cardiovascular disease were diagnosed with acute myocardial infarction. The second leading cause other than malignancy was pulmonary disease, including diagnoses of pulmonary embolism, pneumonia, chronic obstructive lung disease, and pulmonary infarction.

Possible explanations for the high discordance rate in our study include the patient population. Our hospital serves a mainly indigent population and, on presentation, malignancies may be masked by other more acute problems.3,14 Many of our patients present with far advanced disease. In cases of suspected malignancy, a complete medical workup is initiated but not completed because of patient mortality. Given the average age of the patients autopsied in our study of 48 years, clinical suspicion of malignancy may have been less often considered in younger patients. The discordance between clinical and autopsy diagnoses of malignancies remains high despite the technological advances in medicine. In the evolution of health care system reform in this country, more emphasis has been placed on equal access to care and in preventive medicine, but the autopsy seems to be of low priority. This study confirms the importance of the postmortem examination. All physicians share responsibility in the fate of the autopsy. Clinicians have the strongest impact on whether an autopsy is performed and are instrumental in obtaining autopsy consent from the family members. Instead of discarding the autopsy, we should recognize its importance in our understanding of disease. Autopsies are important in recording vital statistics. Autopsy diagnoses could allow for correction of death certificates and improve mortality statistics as well as cancer statistics recorded by national tumor registries. Autopsies have a role in quality assurance and in the advancement of medical care by monitoring diagnostic accuracy and treatment. Autopsies are important as an educational tool in teaching medical students, residents, and physicians and are vital in the study of disease and in our understanding of disease processes.

References
1.
Marwick C. Pathologists request autopsy revival.  JAMA.1995;273:1889-1891.
2.
Kajiwara JK, Zucoloto S, Manco AR, Muccillo G, Barbieri MA. Accuracy of clinical diagnoses in a teaching hospital: a review of 997 autopsies.  J Intern Med.1993;234:181-187.
3.
Bauer FW, Robbins SL. An autopsy study of cancer patients, I: accuracy of the clinical diagnoses (1955 to 1965) Boston City Hospital.  JAMA.1972;221:1471-1474.
4.
Wells HG. Relation of clinical to necropsy diagnosis in cancer and value of existing cancer statistics.  JAMA.1923;80:737-740.
5.
Suen KC, Lau LL, Yermakov V. Cancer and old age: an autopsy study of 3535 patients over 65 years old.  Cancer.1974;33:1164-1168.
6.
Stevanovic G, Ticakovic G, Dotlic R, Kanjuh V. Correlation of clinical diagnoses with autopsy findings: a retrospective study of 2145 consecutive autopsies.  Hum Pathol.1986;17:1225-1230.
7.
Sarode VR, Datta BN, Banerjee AK.  et al.  Autopsy findings and clinical diagnoses: a review of 1000 cases.  Hum Pathol.1993;24:194-198.
8.
Gobbato F, Vecchiet F, Barbierato D, Melato M, Manconi R. Inaccuracy of death certificate diagnoses in malignancy: an analysis of 1405 autopsied cases.  Hum Pathol.1982;13:1036-1038.
9.
Manzini VD, Revignas MG, Brollo A. Diagnosis of malignant tumor: comparison between clinical and autopsy diagnosis.  Hum Pathol.1995;26:280-283.
10.
Britton M. Clinical diagnostics: experience from 383 autopsied cases.  Acta Med Scand.1974;196:211-219.
11.
Rothwell DJ, Cote RA, Brochu L. The systematized nomenclature of human and veterinary medicine. In: SNOMED International Microglossary for Pathology . Northfield, Ill: College of American Pathologists; 1993.
12.
SAS Institute Inc.  SAS Users Guide, Statistics, Version 6.  4th ed. Cary, NC: SAS Institute Inc; 1990.
13.
Cameron HM, McGoogan E. A prospective study of 1152 hospital autopsies: inaccuracies in death certification.  J Pathol.1981;133:273-283.
14.
Eley JW, Hill HA, Chen VW.  et al.  Racial differences in survival from breast cancer: results of the National Cancer Institute Black/White Cancer Survival Study.  JAMA.1994;272:947-954.
×