Autopsy-based Studies Research Articles

Splenic abscess: a rare presentation

Splenic abscess is a rare clinical entity with an incidence of 0.2–0.7% in autopsy-based studies. When untreated, splenic abscess is associated with nearly 100% mortality; in treated patients, the mortality rate is 16.6% during the first 90 days. It mostly occurs in patients with neoplasia, immunodeficiency, trauma, diabetes or splenic infarct. The incidence of splenic abscess is thought to be growing because of the increase in the number of immunocompromised patients who are particularly at risk for this disease and also because of the widespread use of diagnostic modalities. However, the optimal treatment for this remains unclear. We present a case of a 42-year-old man diagnosed with multiloculated splenic abscess and was subjected to splenectomy.

The pathogenesis of pediatric cerebral malaria: eye exams, autopsies, and neuroimaging.

Several advances in our understanding of pediatric cerebral malaria (CM) have been made over the past 25 years. Accurate clinical diagnosis is enhanced by the identification of a characteristic retinopathy, visible by direct or indirect ophthalmoscopy, the retinal changes (retinal whitening, vessel color changes, white-centered hemorrhages) being consistently associated with intracerebral sequestration of parasites in autopsy studies. Autopsies have yielded information at tissue levels in fatal CM, but new insights into critical pathogenetic processes have emerged from neuroimaging studies, which, unlike autopsy-based studies, permit serial observations over time and allow comparisons between fatal cases and survivors. Brain swelling has emerged as the major risk factor for death, and, among survivors, brain volume diminishes spontaneously over 24-48 hours. Studies of life-threatening and fatal malaria are suggesting new approaches to identifying and caring for those at highest risk; potential adjuvants should be evaluated and implemented where they are most needed.

Prevalence of mixed pathologies in the aging brain.

The spectrum of mixed brain pathologies expands beyond accompanying vascular pathology in brains with Alzheimer’s disease-related pathology. Co-occurrence of neurodegenerative non-Alzheimer’s disease-type proteinopathies is increasingly recognized to be a frequent event in the brains of symptomatic and asymptomatic patients, particularly in older people. Owing to the evolving concept of neurodegenerative diseases, clinical and neuropathological diagnostic criteria have changed during the last decades. Autopsy-based studies differ in the selection criteria and also in the applied staining methods used. The present review summarizes the prevalence of mixed brain pathologies reported in recent community-based studies. In these cohorts, irrespective of the clinical symptoms, the frequency of Alzheimer’s disease-related pathology is between 19 and 67%, of Lewy body pathology is between 6 and 39%, of vascular pathologies is between 28 and 70%, of TDP-43 proteinopathy is between 13 and 46%, of hippocampal sclerosis is between 3 and 13% and, finally, of mixed pathologies is between 10 and 74%. Some studies also mention tauopathies. White-matter pathologies are not discussed specifically in all studies, although these lesions may be present in more than 80% of the aging brains. In summary, community-based neuropathology studies have shown that complex constellations of underlying pathologies may lead to cognitive decline, and that the number of possible combinations increases in the aging brain. These observations have implications for the prediction of the prognosis, for the development of biomarkers or therapy targets, or for the stratification of patient cohorts for genome-wide studies or, eventually, for therapy trials.

Magnetic resonance imaging during life: the key to unlock cerebral malaria pathogenesis?

Understanding the mechanisms underlying the pathophysiology of cerebral malaria in patients with Plasmodium falciparum infection is necessary to implement new curative interventions. While autopsy-based studies shed some light on several pathological events that are believed to be crucial in the development of this neurologic syndrome, their investigative potential is limited and has not allowed the identification of causes of death in patients who succumb to it. This can only be achieved by comparing features between patients who die from cerebral malaria and those who survive. In this review, several alternative approaches recently developed to facilitate the comparison of specific parameters between fatal, non-fatal cerebral malaria and uncomplicated malaria patients are described, as well as their limitations. The emergence of neuroimaging as a revolutionary tool in identifying critical structural and functional modifications of the brain during cerebral malaria is discussed and highly promising areas of clinical research using magnetic resonance imaging are highlighted.

Role of virtopsy in the post-mortem diagnosis of drowning

Due to admitted limits of autopsy-based studies in the diagnosis of drowning, virtopsy is considered the new imaging horizon in these post-mortem studies. The aim of our study was to evaluate the role of virtopsy performed through computed tomography (CT) in the forensic diagnosis of drowning. We retrospectively examined the CT data of four cadavers recovered from sea water and suspected to have died by drowning. Each patient underwent a full-body post-mortem CT scan, and then a traditional autopsy. All the cadavers showed fluid in the airways and patchy ground-glass opacities in the lung. Only one patient had no fluid in the digestive tract; this patient had a left parietal bone fracture with a large gap and other multiple bone fractures (nose, clavicle, first rib and patella). One of the three patients who had fluid in the digestive tract had no fluid in the paranasal sinuses. This latter patient showed cerebral oedema with subarachnoid and intraventricular haemorrhage, multiple bone fractures (orbital floor, ribs, sacrum and acetabular edge) and air in the heart, in the aorta and in bowel loops. To date, there are no autopsy findings pathognomonic of drowning. This study proves that virtopsy is a useful tool in the diagnosis of drowning in that it allows us to understand if the victim was alive or dead when he entered the water and if the cause of death was drowning.

1772 – Difficulties in the recognition of the wernicke-korsakoff syndrome in a general hospital. Three cases and a review

Wernicke-Korsakoff (W-K) syndrome is a neuropsychiatric disorder resulting from thiamine deficiency, which is associated with significant morbidity and mortality. According to autopsy-based studies, it is still greatly underdiagnosed. In this case study and review, we focus on late diagnosed W-K related with alcohol misuse, and we give a short review about the topic focusing on its prompt diagnosis and adequate treatment. We intend to underline that W-K syndrome, a preventable neurological condition and even treatable in its early phase if suspected, is underdiagnosed, with critical consequences for the patient's prognosis. Using a case-report format, we describe three cases of W-K syndrome which were initially misdiagnosed in different general hospitals. We summarize complementary explorations, therapeutic management and evolution, and after that we shortly review the topic. The three patients were diagnosed of W-K syndrome in the psychiatry unit, weeks after being visited in the emergency facilities, where it was not suspected nor detected or prevented. All of them ended up with cognitive disabilities of a different degree, always with a remarkable impact in their functioning. One of them achieved some amelioration with thiamine in high doses, despite its late detection. W-K can be prevented and treated if early detected, but it is underdiagnosed, with severe consequences for the patients. We suggest some measures that could enhance its detection and prevention, like modifying emergency room protocols, both diagnostic and therapeutic.

Epidemiology of neurodegeneration in American-style professional football players

The purpose of this article is to review the history of head injuries in relation to American-style football play, summarize recent research that has linked football head injuries to neurodegeneration, and provide a discussion of the next steps for refining the examination of neurodegeneration in football players. For most of the history of football, the focus of media reports and scientific studies on football-related head injuries was on the acute or short-term effects of serious, traumatic head injuries. Beginning about 10 years ago, a growing concern developed among neurologists and researchers about the long-term effects that playing professional football has on the neurologic health of the players. Autopsy-based studies identified a pathologically distinct neurodegenerative disorder, chronic traumatic encephalopathy, among athletes who were known to have experienced concussive and subconcussive blows to the head during their playing careers. Football players have been well represented in these autopsy findings. A mortality study of a large cohort of retired professional football players found a significantly increased risk of death from neurodegeneration. Further analysis found that non-line players were at higher risk than line players, possibly because of an increased risk of concussion. Although the results of the studies reviewed do not establish a cause effect relationship between football-related head injury and neurodegenerative disorders, a growing body of research supports the hypothesis that professional football players are at an increased risk of neurodegeneration. Significant progress has been made in the last few years on detecting and defining the pathology of neurodegenerative diseases. However, less progress has been made on other factors related to the progression of those diseases in football players. This review identifies three areas for further research: (a) quantification of exposure - a consensus is needed on the use of clinically practical measurements of blows to the head among football players; (b) genetic susceptibility factors - a more rigorous set of unbiased epidemiological and clinical studies is needed before any causal relationships can be drawn between suspected genetic factors, head injury, and neurodegeneration; and (c) earlier detection and prevention of neurodegenerative diseases.

A systematic literature review on first aid provided by laypeople to trauma victims

Death from trauma is a significant and international problem. Outcome for patients suffering out-of-hospital cardiac arrests is significantly improved by early cardiopulmonary resuscitation. The usefulness of first aid given by laypeople in trauma is less well established. The aim of this study was to review the existing literature on first aid provided by laypeople to trauma victims and to establish how often first aid is provided, if it is performed correctly, and its impact on outcome. A systematic review was carried out, according to preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines, of all studies involving first aid provided by laypeople to trauma victims. Cochrane, Embase, Medline, Pubmed, and Google Scholar databases were systematically searched. Ten eligible articles were identified involving a total of 5836 victims. Eight studies were related to patient outcome, while two studies were simulation based. The proportion of patients who received first aid ranged from 10.7% to 65%. Incorrect first aid was given in up to 83.7% of cases. Airway handling and haemorrhage control were particular areas of concern. One study from Iraq investigated survival and reported a 5.8% reduction in mortality. Two retrospective autopsy-based studies estimated that correct first aid could have reduced mortality by 1.8–4.5%. There is limited evidence regarding first aid provided by laypeople to trauma victims. Due to great heterogeneity in the studies, firm conclusions can not be drawn. However, the results show a potential mortality reduction if first aid is administered to trauma victims. Further research is necessary to establish this.

Neuropathology-Based Risk Scoring for Dementia Diagnosis in the Elderly

Current neuropathologic consensus criteria for diagnosis of dementia yield a classification of processes that likely contributed to dementia in that individual. While dementia diagnosis currently relies on clinical criteria, practicing neuropathologists and researchers might benefit from a simple, accurate risk scoring protocol for the neuropathologic diagnosis of dementia. Using 232 consecutive autopsies from the population-based Adult Changes in Thought study, we developed two logistic regression-based risk scoring systems; one solely using neuropathologic measures and a second additionally including demographic information. Inverse-probability weighting was used to adjust for inherent selection bias in autopsy-based studies of dementing illnesses. Both systems displayed high levels of predictive accuracy; bias-adjusted area-under-the-curve statistics were 0.78 (95% CI 0.71, 0.85) and 0.87 (95% CI 0.83, 0.92), indicating improved performance with the inclusion of demographic characteristics, specifically age and birth cohort information. Application of the combined neuropathology/demographic model yielded bias-adjusted sensitivity and specificity of 81% each. In contrast, application of NIA-Reagan criteria yielded sensitivity and specificity of 53% and 84%. Our proposed scoring systems provide neuropathologists with tools to make a diagnosis, and interpret their diagnosis in the light of known sensitivity and specificity estimates. Evaluation in independent samples will be important to verify our findings.

Sudden cardiac death in athletes

The entity of sudden cardiac death in young athletes has been known since the year 490 B.C. when young Greek soldier Phidipides had run the distance from Marathon to Athens and suddenly fell down dead. In the last twenty years, sudden death of famous athletes have attracted huge attention of medical and social community; afterwards both American and European Cardiology Societies started to publish periodically guidelines for preparticipation screening. These guidelines have focused on both identifying athletes with potential cardiovascular risk for sudden death and eligibility conditions for athletes participating in competitive sports. Structural and functional abnormalities causing sudden cardiac death in young athletes have been identified by autopsy-based studies. Unrecognized congenital cardiovascular abnormalities associated with excessive physical effort create background for electrophysiological instability and occurrence of malignant ventricular tachyarrhythmia and consequent death. The most frequent causes of sudden cardiac death in young athletes include hypertrophic cardiomyopathy, anomalies of the coronary arteries and idiopathic left ventricular hypertrophy. Current ACC/AHA & ESC guidelines should be widely used in order to reduce potential sudden cardiac death in young athletes.

Mechanisms of Disease: pathophysiological concepts of stroke in hemodynamic risk zones—do hypoperfusion and embolism interact?

The pathophysiology of cerebral ischemia in the borderzones between the large cerebral arteries has been the topic of considerable debate since this disease entity was defined in the first half of the twentieth century. Hemodynamic failure and microembolization were two seemingly mutually exclusive pathophysiological concepts that were proposed to explain the phenomenon of borderzone infarction in patients with arterial occlusive disease. Sufficient evidence has now accumulated, however, to indicate that borderzone infarcts are in fact caused by an interaction between hypoperfusion and microembolization. In this Review, we summarize the historical background of borderzone infarction and current knowledge regarding the various possible pathophysiological concepts. We present a representative survey of publications from the 1950s to the present day, starting with early autopsy-based studies, followed by later anatomical and in vitro studies, as well as CT-based and MRI-based investigations. The clinical symptoms of borderzone infarction and the possibility of a clinical distinction between borderzone and territorial infarcts are discussed. In addition, we consider techniques to localize hemodynamic risk zones in patients with arterial occlusive disease, such as perfusion-weighted MRI, and techniques to identify a hemodynamic component of stroke, such as investigation of the cerebrovascular reserve capacity with transcranial Doppler ultrasound.

Measuring Hip Development Using Magnetic Resonance Imaging

Abnormal hip development can have severe consequences if not detected and treated early. Previous studies have shown that if the abnormality is detected early, the outcome is good. Much is known about embryological hip development (weeks 1-10 after conception) from postmortem examination. For ethical reasons, information about hip development in the fetal stage of pregnancy (10 weeks to term) is less certain as it is largely gained from animal studies and from early radiograph studies. A few autopsy-based studies have been reported looking at hip development, but no one has shown, to our knowledge, that postmortem magnetic resonance is able to provide the same and possibly more information. The aim of this study was to assess the value of magnetic resonance imaging in providing information on fetal hip development. Measurements of 30 patients (gestation, 17-42 weeks) were made regarding the width and depth of the acetabulum and the radius and diameter of the femoral head; volume and area were calculated. With the exception of the acetabular width, each dimension showed little development until week 20 when growth rose exponentially. The acetabular width showed a slow rate of growth, despite changes in the femoral head. Levels of observer agreement were high for all but depth (intraclass correlation coefficients, 0.90). The measurements were in line with previous postmortem studies. Magnetic resonance imaging is a valid alternative to postmortem in the assessment of hip development. Magnetic resonance imaging has the potential to alert clinicians to the possible abnormal development, allowing early intervention. Cross-sectional study with purposive sampling.

How should we screen competitive athletes for cardiovascular disease?

This editorial refers to ‘Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol’† by D. Corrado et al. , on page 516 The sudden unexpected deaths of young trained athletes are highly visible events which have a substantial impact on the physician and lay communities.1 Although initially a focal point in the United States in the early 1980s, this issue has now become a matter of concern in most parts of the industrialized world (particularly in Europe). Evidence of this is the highly publicized recent sudden deaths of several elite professional athletes from Europe, South America, and Africa, including Sergio Serginho (Brazil; football), Sergei Zholtok (Latvia; hockey), Marc-Vivian Foe (Cameroon; football), Sergei Grinkov (Russia; skating), Miklos Feher (Hungary; football), Cristiano de Lima, Jr (Brazil; football), and Trevor Borysuk (Canada; hockey), at least one of whom had a cardiac diagnosis made previously. Interest in athletic field deaths has also accelerated because of the recognition that these catastrophic events are probably more common than previously thought, may occur in athletes of both genders and all races including under-served minorities, and that the responsible (but usually clinically unsuspected) structural cardiovascular diseases may be clinically identifiable.1–8 At this juncture, the large number of cardiac diseases that can pre-dispose athletes to lethal ventricular tachyarrhythmias have been well documented in a number of autopsy-based studies, largely from the United States and Italy.1,2 Although the specific cardiac diseases cited in these studies are the same, the frequency with which … *Corresponding author. Tel: +1 612 863 3996; fax: +1 612 863 3875. E-mail address : hcm.maron{at}mhif.org

Scientific progress and a Hardy paradigm—the ‘amyloid cascade hypothesis’ revisited

When we did our study, we simply wanted to see what comes first: plaque or tangle. And we found tangles preceding plaques. And this is not supporting the ‘amyloid cascade hypothesis’ as outlined [8] and has been ardently discussed previously [3]. In this respect, we think that our findings refute the above-mentioned ‘amyloid cascade hypothesis’. The findings do not disprove a major pathogenic role of A especially of some of its subforms [10]. We did not say that all A (e.g. as oligomeric A ) is ‘innocent’. Of course, the problem which causes what is not solved because it is an impossible task to decide on with autopsy-based descriptive studies. These studies can only disprove a given prediction such as ‘plaques antecede tangles’. Though, based upon the empiric facts, we prefer the idea that either tangles cause plaques or both pathological features may develop independently (with tangles first) but having the potential to influence the development of the other. And as tangles form earlier they may contribute to the connectivity-related organised spread whereas plaques may be more related to the speed of progression. And we further did not claim to rank the relationship between the pathological entity and the clinical symptomatology. In this sense—and for sake of space limitations—we will not comment on the peer’s contributions dealing with these latter aspects. John Hardy raises in his ‘critique of counting’ [7] the argument that the pathological structure does not ‘wait to be counted’. The argument emphasises that plaques and tangles may have quite different half-lives. If plaques had a considerably shorter half-life than tangles, these plaques may already have been cleared before tangles were formed. At first instance this argument suggests a substantial flaw. However, it is only convincing in its general form if one shared an implicit assumption, namely, that different plaques (and

Review of death certificate diagnosis of coronary heart disease and heart failure in Japan.

Vital statistics for coronary heart disease (CHD) were dramatically influenced by the tenth revision of the International Classification of Diseases (ICD-10) in 1995. To better understand the accuracy of death certificate diagnosis of CHD and heart failure, validation studies in Japan were reviewed. Positive predictive values and sensitivity, calculated as validation measures, varied widely between studies, differing with regard to autopsy rates, amount of information on medical records, and period investigated. However, heart failure, which has been frequently assigned on death certificates in Japan, was validated in some studies. Half of these were evaluated to be sudden deaths, including coronary deaths. Because autopsy-based studies on sudden deaths indicated that 30-50% of these were accounted for by CHD deaths, deaths assigned to heart failure should be taken into consideration in order to determine the actual number of CHD deaths in Japan. Focusing on changes in vital statistics after the 1995 ICD revision, the Oita Cardiac Death Surveys (OCDS) allowed interpretation of its effects on CHD and heart failure. Much of the increase in CHD deaths on vital statistics reflects more false positive cases, particularly for out-of-hospital deaths. Considering the Japanese features of vital statistics for CHD, further epidemiological validation studies are needed in order to confirm the accuracy of CHD death certificate diagnoses and to monitor actual CHD trends in Japan.

Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease

To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations.Forty research teams contributed data on APOE genotype, sex, age at disease onset, and ethnic background for 5930 patients who met criteria for probable or definite AD and 8607 controls without dementia who were recruited from clinical, community, and brain bank sources.Odds ratios (ORs) and 95% confidence intervals (CIs) for AD, adjusted for age and study and stratified by major ethnic group (Caucasian, African American, Hispanic, and Japanese) and source, were computed for APOE genotypes epsilon2/epsilon2, epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon4, and epsilon4/epsilon4 relative to the epsilon3/epsilon3 group. The influence of age and sex on the OR for each genotype was assessed using logistic regression procedures.Among Caucasian subjects from clinic- or autopsy-based studies, the risk of AD was significantly increased for people with genotypes epsilon2/epsilon4 (OR=2.6, 95% CI=1.6-4.0), epsilon3/epsilon4 (OR=3.2, 95% CI=2.8-3.8), and epsilon4/epsilon4 (OR=14.9, 95% CI= 10.8-20.6); whereas, the ORs were decreased for people with genotypes epsilon2/epsilon2 (OR=0.6, 95% CI=0.2-2.0) and epsilon2/epsilon3 (OR=0.6, 95% CI=0.5-0.8). The APOE epsilon4-AD association was weaker among African Americans and Hispanics, but there was significant heterogeneity in ORs among studies of African Americans (P<.03). The APOE epsilon4-AD association in Japanese subjects was stronger than in Caucasian subjects (epsilon3/epsilon4: OR=5.6, 95% CI=3.9-8.0; epsilon4/epsilon4: OR=33.1, 95% CI=13.6-80.5). The epsilon2/epsilon3 genotype appears equally protective across ethnic groups. We also found that among Caucasians, APOE genotype distributions are similar in groups of patients with AD whose diagnoses were determined clinically or by autopsy. In addition, we found that the APOE epsilon4 effect is evident at all ages between 40 and 90 years but diminishes after age 70 years and that the risk of AD associated with a given genotype varies with sex.The APOE epsilon4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women. The association between APOE epsilon4 and AD in African Americans requires clarification, and the attenuated effect of APOE epsilon4 in Hispanics should be investigated further.

Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium

To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations. Forty research teams contributed data on APOE genotype, sex, age at disease onset, and ethnic background for 5930 patients who met criteria for probable or definite AD and 8607 controls without dementia who were recruited from clinical, community, and brain bank sources. Odds ratios (ORs) and 95% confidence intervals (CIs) for AD, adjusted for age and study and stratified by major ethnic group (Caucasian, African American, Hispanic, and Japanese) and source, were computed for APOE genotypes epsilon2/epsilon2, epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon4, and epsilon4/epsilon4 relative to the epsilon3/epsilon3 group. The influence of age and sex on the OR for each genotype was assessed using logistic regression procedures. Among Caucasian subjects from clinic- or autopsy-based studies, the risk of AD was significantly increased for people with genotypes epsilon2/epsilon4 (OR=2.6, 95% CI=1.6-4.0), epsilon3/epsilon4 (OR=3.2, 95% CI=2.8-3.8), and epsilon4/epsilon4 (OR=14.9, 95% CI= 10.8-20.6); whereas, the ORs were decreased for people with genotypes epsilon2/epsilon2 (OR=0.6, 95% CI=0.2-2.0) and epsilon2/epsilon3 (OR=0.6, 95% CI=0.5-0.8). The APOE epsilon4-AD association was weaker among African Americans and Hispanics, but there was significant heterogeneity in ORs among studies of African Americans (P<.03). The APOE epsilon4-AD association in Japanese subjects was stronger than in Caucasian subjects (epsilon3/epsilon4: OR=5.6, 95% CI=3.9-8.0; epsilon4/epsilon4: OR=33.1, 95% CI=13.6-80.5). The epsilon2/epsilon3 genotype appears equally protective across ethnic groups. We also found that among Caucasians, APOE genotype distributions are similar in groups of patients with AD whose diagnoses were determined clinically or by autopsy. In addition, we found that the APOE epsilon4 effect is evident at all ages between 40 and 90 years but diminishes after age 70 years and that the risk of AD associated with a given genotype varies with sex. The APOE epsilon4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women. The association between APOE epsilon4 and AD in African Americans requires clarification, and the attenuated effect of APOE epsilon4 in Hispanics should be investigated further.

Deep-Vein Thrombosis

Credit for fundamental studies leading to our current understanding of deep-vein thrombosis should be given to Bauer, who used phlebography to diagnose deep-vein thrombosis complicating fractures of the tibia,1 and to Sevitt and Gallagher for their autopsy-based studies of the prevalence of venous thromboembolism in patients with other injuries2,3. The development of objective methods for the diagnosis of deep-vein thrombosis has facilitated the investigation of its natural history and has provided a rational basis for its prevention and treatment.DiagnosisMost venous thrombi are clinically silent when they are first detectable by objective methods,2,4 probably because they . . .

Active and Passive Smoking and Pathological Indicators of Lung Cancer Risk in an Autopsy Study

The association between involuntary smoking and lung cancer has been supported by most epidemiologic studies, but a number of authors and interest groups claim that the possibility of bias has not been excluded. Few autopsy-based studies have explored the role of active smoking and other exposures in lung carcinogenesis, and none has been previously done to examine the role of passive smoking. We have undertaken such an autopsy-based study in Athens, Greece. Lung specimens were taken at autopsy from 400 persons 35 years of age or older, of both genders, who had died within 4 hours from a cause other than respiratory or cancer in Athens or the surrounding area. For each person at least seven tissue blocks were taken from the main and lobar bronchi and at least five blocks from the parenchyma, including an average of about 20 smaller cartilaginous bronchi and membranous bronchioles. The specimens were examined without knowledge of the exposures of the particular subject in Turin, Italy. For 283 (71%) of the subjects the preservation of the bronchial epithelium was satisfactory for pathological examination, and for 206 among them (73%) an interview could be arranged with their next of kin, focusing on smoking habits of the deceased and their spouses, as well as other variables. The interviewers were not aware of the results of the pathological examinations. Specimens were examined for basal cell hyperplasia, squamous cell metaplasia, cell atypia, and (in membranous bronchioles and bronchiolo-alveolar airways) mucous cell metaplasia, ie, pathological entities that may be lung cancer risk indicators or epithelial, possibly precancerous, lesions (EPPL). The gland and wall thicknesses were also measured and their ratio calculated (Reid Index). In comparison with nonsmokers, EPPL values were significantly higher among current smokers and higher, but not significantly so, among former smokers. Furthermore, EPPL values were significantly higher among deceased nonsmoking women married to smokers rather than to nonsmokers. In this set of data neither occupation nor residence was associated with EPPL, but this could be due to the poor correlation of residential history with exposure to air pollution and the lack of adequate standardization of contemporary Greek occupations. The Reid Index was higher among smokers and former smokers in comparison with nonsmokers, among subjects with mainly urban residence in comparison with those with mainly rural residence, and among nonsmoking women married to smokers in comparison with those married to nonsmokers, but none of these differences was statistically significant. These results provide support to the body of evidence linking passive smoking to lung cancer, even though they are based on a study methodologically different from those that have previously examined this association.