Anatomic Pathology / THE ATTRIBUTION OF LUNG CANCERS

We studied a series of 924 nonselected surgical cases of lung carcinoma (without occupational history in clinical records) by histologic examination and light microscopic determination of asbestos body (AB) concentration to determine cancers attributable to asbestos exposure. Lower lobes showed higher concentrations, but no significant associations were recorded between concentrations and histologic type of the lung carcinomas. Histologic asbestosis was demonstrated in 56 cases considered definitely asbestos-related. In 12 of them, the demonstration of asbestosis was attained only after repeated examination of additional sections, suggested by the finding of more than 1,000 ABs per gram of dry weight (gdw), an indicator of occupational asbestos exposure. In the 56 cases, the median AB concentration was 3,281/gdw. In 5 other cases without demonstration of ABs in histologic sections, concentrations higher than this median and interstitial fibrosis were observed. The AB count after digestion of pulmonary tissue may show greater sensitivity than the search in histologic sections as an indicator of substantial asbestos exposure. Extrapolation of our estimate on a national scale suggests about 2,000 cases per year of asbestos-related cancers of the lung in Italy; 281 cases were reported (from all occupational causes) in the years 1990-1995. Attributable risk for lung cancer in Europe has been reported as between 2% and 50% for asbestos exposure in males, but after exclusion of the extreme values, most of the remaining estimates are within the range of 10% to 20%.1 The wide interval reflects the different extension of asbestos use and, therefore, the different prevalence of exposure and the different definition of exposure. The attributable fraction, evaluated with a method based on the correlation of incidence rates of lung cancer and mesothelioma, was estimated as 5.7% in Glasgow2 and 3.9% in our region.3 Surveys conducted in the Nordic countries and in the United Kingdom in general populations indicated a proportion of asbestos-related lung cancer in the range of 7% to 36% among men, with differences related to the age distribution of respondents and the economic profile of the area.1 Since population studies suggest probabilities but do not allow conclusive evidence in individual cases, several criteria have been proposed for the attribution of a lung cancer to definite asbestos exposure. Despite this, a serious underreporting of these occupationally related cancers is being recognized.4 At present, the balance of evidence supports the proposition “the asbestos load itself in lung tissue is the main determinator of lung carcinogenesis,”5 but forensic medicine still debates whether the asbestosis is a prerequisite for the attribution or whether it is just an indicator of substantial exposure. The discussion of this topic is beyond the purposes of this article. Anyway, the pathologic demonstration of asbestosis is considered, beyond dispute, as decisive proof of linkage (at least contributing if smoking is associated) between a lung cancer and previous exposure to asbestos: we have found no contradictory evidence in the literature. The criteria for the histologic diagnosis of asbestosis, therefore, are crucial in this respect. Anatomic Pathology / ORIGINAL ARTICLE Am J Clin Pathol 2002;117:90-95 91 © American Society for Clinical Pathology The minimal features that permit the diagnosis of asbestosis have been described, in the Report of the Pneumoconiosis Committee of the College of American Pathologists (CAP) and the National Institute for Occupational Safety and Health (NIOSH), as discrete foci of fibrosis in the walls of respiratory bronchioles associated with accumulations of asbestos bodies.6 Bellis et al7 validated the applicability of these criteria in the Piedmont region (northwestern Italy). The fibrosis with possible pigmentation of the walls of respiratory bronchioles was defined as “small airway lesions” (SALs), and these features were considered as “asbestosis grade 1” (AG1) when associated with asbestos bodies (ABs) on the sections. In fact, similar lesions have been regarded as a form of interstitial fibrosis.8,9 Fibrotic thickening with possible carbon and iron pigmentation of the walls of the respiratory bronchioles and of alveolar ducts has been observed in patients who had been exposed to asbestos and named “asbestos airway disease” by other authors.10 In the series of Bellis et al,7 the AG1 cases compared with subjects without SALs were associated significantly with indicators of asbestos exposure such as bilateral pleural plaques, high concentrations of ABs in the digested lung, and a history of occupational exposure. The criteria settled by the International Expert Meeting on Asbestos, Asbestosis and Cancer convened in Helsinki in 199711 are not very much different in substance from those described by CAP and NIOSH for the diagnosis of asbestosis on histologic sections. However, a new concept was introduced by the Helsinki Criteria, that is, the acceptability of the diagnosis of asbestosis when, together with interstitial lung fibrosis, the count of lung asbestos fibers by electron microscopy was in the range recorded for asbestosis by the same laboratory. According to this statement, when interstitial fibrosis is present, the demonstration of a substantial asbestos burden in the digested tissue examined by electron microscopy may replace the finding of ABs in the histologic sections examined by light microscopy. Even in absence of interstitial fibrosis, concentrations higher than 1,000 ABs per gram of dry weight of lung tissue (ABs/gdw) by light microscopy indicate exposures of the occupational type. This proposition results from pathologic studies in various countries, including our region,12-15 and has been validated by international workshops.16,17 But until now, the light microscopic counts of ABs have not been systematically taken into consideration along the diagnostic path for the recognition of asbestosis in a fibrotic lung. The objective of the present study was the pathologic assessment of the prevalence in our region of asbestosrelated carcinomas, recognized because of the association with histologic asbestosis according to CAP and NIOSH criteria, in a large surgical series of unselected lung cancers. In a previous study, Mollo et al18 found histologic asbestosis in 6.7% of 165 hospital autopsy cases with lung carcinoma, but this result could seem to be biased by postmortem selection. Materials and Methods We studied 924 unselected cases of pulmonary carcinomas, consecutively examined at the Department of Biomedical Sciences and Human Oncology, Turin (northwestern Italy), after pneumonectomy or lobectomy, from December 1992 through December 1998. These surgical specimens were sent to the laboratory of pathology without records about occupational histories. There were 345 pneumonectomies and 579 lobectomies (359 upper lobes and 220 intermediate and/or lower lobes). Pathologic Investigations The identification of ferruginous bodies as true typical ABs was performed according to the criteria described on the basis of the comparison between light and electron microscopic findings.19,20 The concentration of ABs/gdw was determined in samples of “normal” lung tissue taken from each available lobe. The optical count was performed after membrane filtration of the material obtained by hypochlorite digestion of the pulmonary tissue.21 When 2 or 3 samples were examined, the count was expressed as the mean value resulting from the different counts. We screened 2 to 5 sections of lung tissue without neoplastic invasion for SALs and for features of histologic asbestosis according to the CAP and NIOSH criteria and previous experience7 ❚Image 1❚. When the diagnosis of histologic asbestosis was not justified according to these criteria because ABs were not evident on the sections, 2 to 4 additional sections were prepared and carefully screened if interstitial fibrosis (IF) was present and the AB count was higher than 1,000/gdw. As for minimal interstitial fibrosis, the CAP and NIOSH criteria6 were applied; furthermore, particular attention was given to recommendations suggested for the differential diagnosis between interstitial fibrosis due to asbestos and that attributable to other diseases.22