A case‐control study was carried out on 145 male lung‐cancer patients diagnosed at autopsy and 178 controls, in order to investigate the relationship between asbestos exposure and the cell type of pulmonary carcinoma. Adenocarcinomas (AD) were individually matched with other cell types and with controls. The relative risk (RR) of developing AD in relation with lung asbestos body (AB) content as the exposure indicator was calculated by using logistic‐regression analysis for matched sets. Two cutoff levels, 1,000 and 10,000 asbestos bodies per gram dry weight (AB/gdw), were used in the analysis. In addition, AB counts were treated as a continuous variable (log AB + 1). A significant association was found between AD and asbestos exposure, using levels and logarithmic transformation. However, an association of asbestos exposure with cell types other than AD could not be ruled out. © 1995 Wiley‐Liss, Inc.

This investigation was carried out on 851 consecutive judicial autopsies of drug addicts who died mostly of heroin overdose from 1977 to 1996. Research of anti-HIV/HBV/HCV antibodies was performed, and histologic sections were retrospectively reviewed. More than 65% were HBV/HCV-positive and about 17% HIV-positive; females were HIV-positive more often than males. Intracranial microhemorrhages were frequently found; cerebral infectious diseases were rare. Inflammatory heart lesions, myocardial fibrosis, and acute ischemia were common. Interstitial nephritis (found in about 8%) was more frequent in females, in older patients, and in those carrying HIV infection; glomerular sclerosis was detected in about 12%. Acute bronchitis and/or pneumonia was demonstrated in 12%, without significant association with HIV infection; pulmonary hemorrhages, foreign body granulomas, and food aspiration were also commonly seen; hyperplasia of pulmonary perivascular lymphatic tissue was rather characteristic. Liver was carrying steatosis in 66.3% and/or hepatitis in 64.5%; acute hepatitis was more frequent in females, chronic hepatitis in older subjects and in those proven positive for hepatotropic viruses; cirrhosis occurred more often in older patients, in those carrying virus infection, and in consumers of nonnarcotics drugs such as ethanol. No pathologic finding was clearly related to drug abuse; therefore, during autopsy, drug addiction can be suspected, but anamnestic and circumstantial data are needed to lead pathologists to request toxicologic analysis to ascertain the cause of death. The present investigation emphasizes that, in addition to the risk of death by overdose, the high incidence of acute and chronic diseases could seriously undermine the health status of heroin and/or other drug consumers.

BACKGROUND:During a wider study in progress at the Turin University with the cooperation of the Departments of Anatomy, Pharmacology and Forensic Medicine, and of Biomedical Sciences and Human Oncology, anti-HCV antibodies were determined in the blood of drug-addicts submitted to judicial autopsy.METHODS:This investigation was carried out on blood samples taken at postmortem from 793 subjects submitted to judicial autopsy in Piedmont from 1977 to 1996. This is a retrospective investigation and these cases represented 93.9% of the total autopsies, and 98.6% of them came from Turin and province.RESULTS:The percentage of subjects for whom the search for anti-HCV antibodies proved positive was 75.8% (74.5% among males, and 86.5% among females). These data remained relatively unchanged through the years, with a range 64.3% to 85.3%. They are close to those recorded in the international literature with regard to living subjects admitted to public health institutions for the prevention and treatment of drug addiction.CONCLUSIONS:As the positivity related to age, lower values were found among the 15-20-year olds as compared to the older ones: 57.1% among the former, and 85.5% among the latter. This difference may be due to a longer period of drug addiction among subjects deceased at an older age, with a more prolonged risk of infection.

The authors discuss the influence of postmortem tissue decomposition on the lung asbestos body (AB) burden, with the aim of evaluating the reliability of data obtained from autopsies performed for medicolegal purposes several months after deaths in possible connection with asbestos-related pathology. Eight autopsy cases were selected, each one with occupational exposure considered very probable on the basis of the history or pathologic findings. In each case the AB concentrations were assessed soon after death in one lung and after periods of 1 to 18 months in the others, which had been stored in sealed containers without fixation. AB concentrations consistently decreased with time in rotten lungs. The counts in some cases became negative a few months after death, even in cases with very high AB counts at first examination. It may be reasonably inferred that, in putrefied lungs from corpses exhumed after months of interment, the counts in digested tissues and the screening of histologic sections for AB may give false-negative results.

BACKGROUND:Cardiac myxomas have varying clinical presentation, uncertain histogenesis, and debatable immunohistochemical profile. A few malignant cases have been previously reported. METHODS:Fifty-three consecutive cardiac myxomas were histologically investigated and results compared with clinical data. The main goal of the study was to investigate the immunohistochemical differentiation and the clinicopathologic correlations. RESULTS:Stromal cells were characterized by the expression of the von Willebrand factor endothelial marker (12 of 53 cases) and diffuse cytoplasmic neuropeptides such as protein gene product 9.5 (50 of 53 cases), S100 protein (47 of 53) and neuron-specific enolase (30 of 53), all of which were expressed in 30 (57%) of 53 tumors. Stromal cells did not show endocrine granules, epithelial, or smooth muscle immunoreactivity. Non-cardiac-related symptoms were observed in 7 of 53 patients and promptly disappeared after tumor excision; median values and percentages of total immunoreactivity scores for neuropeptides were higher in these 7 cases, but data analysis showed no statistical significance. Glands were detected in 2 myxomas, and they showed epithelial (cytokeratins and carcinoembryonic antigen), protein S100, and neuron-specific enolase immunoreactivity; this pattern has been previously detected in human gut. All tumors showed benign behavior, and no mitosis was detected. CONCLUSIONS:The results of this study support the hypothesis that stromal cells originate from multipotent mesenchyme capable of neural and endothelial differentiation; rare myxoma glands would represent entrapped foregut rests. A correlation could exist between neuroendocrine differentiation and non-cardiac-related symptoms.

Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.

OBJECTIVE:The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs).METHODS:The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4.RESULTS:Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL.CONCLUSION:The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.

More than 1,000 asbestos bodies/gram dry weight (AB/gdw) were found by light microscopy in lung tissues, out of 429 non selected cases of pulmonary carcinoma (264 from surgery and 165 from autopsy). Asbestosis was detected by histology in 28% of the cases with AB > 1,000/gdw (in 19% of the surgical cases, and in 38% of the autopsy cases). A proportion of 4% of the total cases may be related to asbestos exposure.

The reproducibility of the histopathological diagnosis of pleural malignant mesothelioma (MM), after supple menting routine H&E stain by immunohistochemistry (IH) in 77 cases of original diagnoses of MM, was assessed by examining interobserver variation between five pathologists. A battery of commercial antibodies (cytokeratins, vimentin, HMFG-2, anti Leu-M1 [CD15], BerEP4, B72.3 [TAG-72], carcinoembyonic antigen), considered to be useful in enhancing diagnostic accuracy, was used. The number of definitively classified tumors (accepted MM plus rejected MM) increased from 57 on H&E stain to 60 after IH, with 59 (76.6%) cases being accepted as true MM. Based on IH, the chance-adjusted interobserver agreement was poor (kappa w = 0.29) and lower than that observed on previous H&E alone. The intraobserver agreement for four of the five pathologists was rather good (kappa w = 0.54-0.56). The inter-and intraobserver concordance was higher in accepting than excluding the cases as MM. A larger number of cases were classified by all reviewers as mixed or sarcomatous variants after IH. In the interpretation of each immunostain, kappa values ranged from 0.19 for B72.3 to 0.62 for HMFG-2, which were respectively the least and the most consistently interpreted immunostains. The information additionally contributed by IH did not seem to change the pathologists' diagnoses very much in comparison with those made by routine H&E stain. Until highly specific and sensitive probes for the positive identification of MM become available, a careful scrutiny of routinely stained preparations still remains the most rewarding component of the diagnostic pathway.

Objective.-To evaluate the prevalence of myocarditis in a general hospital in Turin, Italy.Design.-We retrospectively reviewed 17162 postmortem records from autopsies routinely performed at San Giovanni Battista General Hospital, Turin, between 1965 and 1994.Results.-Applying the so-called Dallas criteria, myocarditis was histologically found in 91 cases (0.53%, 95% Cl 0.4 to 0.7). The prevalence increased, reaching a peak between 1985 and 1994 (1.2 %, 95 % Cl 0.9 to 1.6). The disease was found more frequently in patients from 20 to 39 years of age, with no difference between males and females. The present data were compared to those of a previous study, performed in 1985 and 1993 to 1994, in which we had prospectively taken into account 605 autopsies (not comprised in the present retrospective study) with standardized myocardial sampling for histological examination: a 5.1% prevalence was found (nearly five times as high as that retrospectively detected in the same period).Conclusions,-If a standardized method of myocardial samples for microscopic examination is not followed, it is possible that myocarditis is overlooked in an unsuspected number of cases.

The presence of human cytomegalovirus DNA was investigated in 103 unfixed endomyocardial biopsies, performed during the first 4 months in 17 heart transplant recipients by polymerase chain reaction. Results were correlated with human cytomegalovirus systemic infection, as detected by the test for the viral lower matrix phosphoprotein pp65 (antigenemia) and by polymerase chain reaction for viral DNA in blood leukocytes (DNAemia). Three patients out of 17 did not develop cytomegalovirus infection and 14 did: 5 had symptomatic disease treated with ganciclovir and 9 developed asymptomatic infection and were not treated. Viral DNA was detected in 24 out of 103 biopsies (23%) from 13 patients: 5 with symptomatic infection during the acute phase of disease (mean levels of pp65: 125+/-232 pp65 positive leukocytes/200,000 examined cells) and 8 patients with asymptomatic infection when the mean antigenemia was 5+/-15/200,000 (4 patients) or when DNAnemia was present in the blood (4 patients). No histological evidence of myocarditis was shown in viral DNA-positive biopsies. No difference in acute rejection was found in viral DNA-positive and DNA-negative biopsy specimens in symptomatic and asymptomatic infected patients. Our experience suggests that during systemic symptomatic and asymptomatic cytomegalovirus infection, polymerase chain reaction can detect a relatively frequent myocardial involvement, but this involvement is not associated with myocarditis or with a higher incidence of acute rejection. THe presence of viral DNA in myocardial biopsies can be a result of high viremia, but it also can be due to low level of viral DNA in circulating infected leukocytes. Polymerase chain reaction is the most sensitive method for cytomegalovirus DNA detection in biopsies, but its results need to be evaluated together with morphology-preserving methods and systemic markers of infection in order to make a correct diagnosis.

We have undertaken an autopsy-based study to evaluate the etiologic importance of active and passive smoking, as well as socio-demographic variables, in the development of pathologic precursors of lung cancer. Lung specimens were taken at autopsy from 531 persons who had died within four hours from a cause other than respiratory or cancer in Athens (Greece) or the surrounding area. Specimens were examined blindly for basal cell hyperplasia, squamous cell metaplasia, cell atypia and mucous cell metaplasia, i.e., pathological entities considered as epithelial, possibly precancerous, lesions (EPPL). Interviews were conducted with next of kin of the deceased. Suitable autopsy specimens as well as completed interviews were eventually available for 275 subjects. EPPL score was regressed on the available independent variables. EPPL score was higher among active smokers than among nonsmokers, while ex-smokers occupied an intermediate position. Conditional on smoking habits, EPPL score was higher among women than among men and higher among manual than among non-manual workers, in agreement with the corresponding patterns with respect to lung cancer. Nonsmoking women married to ever smokers had significantly higher EPPL score than those married to never smokers. The overall findings of this study suggest that EPPL is a valuable indicator of lung cancer risk and that exposure to environmental tobacco smoke is associated with higher EPPL levels and therefore with higher lung cancer risk.

We report a case of myxoid leiomyosarcoma originating from the interventricular septum in the outflow tract of the right ventricle. Although the gross features suggested a benign myxoma, histologic examination demonstrated features of a smooth muscle tumor, which was characterized by low mitotic index and a bland degree of atypia with few cells immunoreactive for cell cycle-associated Ki-67 antigen. The tumor relapsed twice, and the patient (a 61-year-old woman) died 18 months after the first diagnosis. This case demonstrates that myxoid leiomyomatous proliferations of the heart must be considered potentially malignant, even when the gross features and degree of cellular atypia seem to suggest otherwise.

This report concerns the pathologic findings observed at autopsy in a 10-year-old heterotopic heart transplant under cyclosporine treatment. The allograft showed a diffuse multivessel atherosclerotic disease whereas in the recipient heart coronary arteries and aorta were focally affected by atherosclerosis. The proliferating cell nuclear antigen had significantly increased expression in the allograft vessels in comparison with the recipient.

AIMS--To assess the consistency of histopathological diagnosis of pleural malignant mesothelioma by estimating interobserver agreement between five pathologists. METHODS--Eighty eight histological sets pertaining to original diagnoses of pleural malignant mesothelioma were reviewed separately by each pathologist. Diagnostic likelihood was graded as definite (A), probable (B), possible (C), improbable (D), and definitely not (E) malignant mesothelioma. The following indexes were estimated: observed proportion of agreement (Po), kappa statistics and proportion of agreement for "positive" (Ppos) and "negative" (Pneg) diagnoses. RESULTS--Sixty cases (68.2%) were rated by at least three reviewers as A or B and by none of the others as D or E. Five (5.7%) were rated by at least two reviewers as D or E and by none of the others as A or B. Nine (10.2%) showed a serious disagreement, rated A or B and D or E. Agreement for sets obtained at necropsy/surgery (median kappa w = 0.57) was similar to that for endoscopic material (median kappa w = 0.54). Agreement was poor on material obtained by needle biopsy (median kappa w = 0.21). The median value of Ppos varied between 0.94 (necropsy/surgery) and 0.67 (needle biopsy) and that of Pneg between 0.78 (necropsy/surgery) and 0.34 (unspecified biopsy). Interobserver agreement on histological typing was good overall (median kappa = 0.59). CONCLUSIONS--Of the original histological diagnoses, 70% were consistently reproduced through panel review. Most indexes of agreement between pathologists ranged from poor (needle biopsy) to moderate (necropsy/surgery). Agreement in confirming malignant mesothelioma was greater than that regarding exclusion of this diagnosis. Of the cases finally considered to have malignant mesothelioma, the reproducibility of histological typing was relatively satisfactory.

A 26-year-old woman developed critical stenosis of the left main coronary artery 10 years after radiation treatment for Hodgkin's disease. She was operated on but died in the immediate postoperative period. At autopsy the pathological findings were indistinguishable from those described in ''typical'' atherosclerotic plaques.

We studied 605 necropsies carried out in a general hospital (San Giovanni battista in Turin), during the years 1985-86 (405 cases) and 1993-94 (200 cases). A standardized sample of myocardium was systematically taken and submitted to histological examination. Thirty-one cases of myocarditis were found (5.1%). Th disease was more frequently observed in the age group from 30 to 49 years and in people dying of malignancies: females showed higher frequency than males (7.4% vs. 4%), with differences nearly significant from a statistical point of view. None of these cases was recognized by the physicians. The prevalence rate of myocarditis in the present series is higher than in retrospective reviews, where microscopic examination of myocardium was not systematically performed. The discrepancies between clinical results and pathological findings confirm that myocarditis is often unsuspected by the physicians.

A case of pneumoconiosis with unknown occupational history was examined both pathologically and mineralogically by means of a variety of techniques, including analytical scanning and transmission electron microscopy with electron diffraction and energy dispersive x-ray analysis, and electron resonance spectroscopy. The pathologic features consisted of a diffuse interstitial fibrosis with deposits of amorphous and crystalline particles and granulomatous reaction. The identification of minerals, mainly talc, halloysite, coal and chlorite, allowed a definite diagnosis of mixed silicate pneumoconiosis to be made. This is an example of complete pathologic, mineralogic and physico-chemical analysis of a case of pneumoconiosis.

We describe a case of malignant peritoneal mesothelioma arising in a 17-year-old boy. The diagnosis was based on a comprehensive study including light microscopy, histochemistry, immunohistochemistry, evaluation of the clinical course, and autopsy examination. Analytical transmission electron microscopy showed a concentration of 510,000 asbestos fibers/g dry lung tissue. The fibers were represented by chrysotile (62%) and tremolite (38%) asbestos. About 40% of the total fibers were longer than 5 μm. The presence of tremolite fibers was probably due to environmental exposure to contamined cosmetic talc. This is the first reported case of pathologically proven exposure to asbestos dust in malignant mesothelioma of childhood and adolescence.

A case of malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease (MID) is presented. The patient had mesenteric and omental lesions characterized at biopsy by extensive fibrosis of fat tissue with mild to moderate inflammation. One year later, post-mortem examination revealed a well-differentiated epithelial mesothelioma. Immunohistochemical stains for keratin and vimentin were diffusely positive, whereas EMA showed a membranous staining of scattered cells. CEA, Ber-EP4, B72.3 and Leu-M1 were negative. In addition, actin monoclonals decorated groups of cells pertaining to the tumoural component. Immunostains of sections from retrieved paraffin blocks of the previous biopsy showed that the bulk of the spindle-shaped and histiocytic-like cells present in the fibrous streams was strongly labeled by low-molecular-weight keratin, and coexpressed vimentin and actin. EMA showed a membranous staining of sporadic spindle and round cells. The other immunostains were invariably negative. This immunohistochemical pattern closely corresponded to the immunophenotype of the mesothelial tumour detected at autopsy and was very suggestive of myofibroblastic/submesothelial cell origin. The quantitative evaluation of silver nucleolar organizer regions (Ag-NORs) demonstrated high levels of cell proliferation in both surgical and autopsy tissue samples.