Document wgdpOa4jeDJrdxzy8nzagMgB6

British Journal of Industrial Medicine 1987;44:402-406 Non-malignant chest x ray changes in patients with mesothelioma in a large cohort of asbestos insulation workers RUTH LILIS, JRIBAK,* YSUZUKI, LPENNER, NANCY BERNSTEIN, IJSELIKOFF From the Division of Environmental and Occupational Medicine, Department of Community Medicine, Mount Sinai School of Medicine of the City University ofNew York, New York 10029, USA abstract To assess the prevalence of non-malignant chest x ray abnormalities in cases of meso thelioma 184 cases of mesothelioma (72 pleural and 112 peritoneal) which had occurred in a cohort of asbestos insulation workers followed up since 1967 were studied. Chest x ray films of satisfactory quality, on which the presence or absence of non-malignant radiological changes indicating inter stitial pulmonary fibrosis or pleural fibrosis or both, could be assessed with a high degree of cer tainty were available. In some cases (20% for pleural mesothelioma, 11-6% for peritoneal mesothelioma) non-malignant radiological changes were not radiologically detectable. Parenchy mal interstitial fibrosis (small irregular opacities) only was found in a proportion of cases (25-4% of pleural mesotheliomas, 12*5% of peritoneal mesotheliomas). Pleural fibrosis only was detected in 17% of cases of pleural mesothelioma and 27% of cases of peritoneal mesothelioma. Most patients had both parenchymal and pleural fibrosis. Although these results tend to indicate that in peritoneal mesothelioma the proportion of pleural fibrosis is significantly higher, these findings might have been due to the fact that in most cases of pleural mesothelioma non-malignant changes were inter preted in one hemithorax only. In 46 cases (21 pleural, 25 peritoneal) in which sufficient lung tissue was available histopathology of lung parenchyma indicated the presence of interstitial fibrosis; in 20 (43-5%) of these the chest x ray film had been read as negative. Thus the absence of radiologically detectable small opacities on the chest x ray film does not exclude the existence of interstitial pulmonary fibrosis in cases of mesothelioma among insulation workers. With lower levels of exposure (such as in family contacts of asbestos workers) it is conceivable that mesothelioma might occur in the absence of interstitial pulmonary fibrosis. Mesothelioma, pleural and peritoneal, occurred in 356 members of a large cohort1 of asbestos insulation workers. Non-malignant abnormalities on the chest * ray film indicating the presence of interstitial pul monary fibrosis, pleural fibrosis, and pleural calcifications, preceding the development of the malignant mesothelioma or detectable on the hemithorax opposite to that in which the tumour devel oped, were of interest, given the widely accepted opinion that mesothelioma can occur after relatively short and low exposure to asbestos2 "5 (R Lilis et al, Present address: Tel-Aviv University, Department of Preventive & Social Medicine, Sackler School of Medicine, Ramat Aviv, Tel-Aviv, Israel. Accepted 27 August 1986 VI International Pneumoconiosis Conference, Bochum, May 1983, abstracts ppl6, 30). POPULATION AND METHODS Mesothelioma had occurred in 356 members of a large cohort of 17 800 insulation workers in the United States and Canada, established in 1967.1 6 The diagnosis of malignant mesothelioma was ascertained by thorough review of pathology in all cases by one of us (YS). In 184 cases chest x ray films of satisfactory quality were available for review: 112 cases of peritoneal mesothelioma and 72 of pleural mesothelioma. The chest .v ray films were interpreted for non-malignant abnormalities of the lung parenchyma, or of the pleura, by following the criteria of the International 402 Non-malignant chest x ray changes in patients with mesothelioma in a large cohort ofasbestos insulation workers 403 Table 1 Peritoneal mesothelioma (n -- 112) No % Presence of non-malignant pulmonary and pleural abnormalities None 13 Parenchymal interstitial fibrosis only (small irregular opacities) 14 Pleural fibrosis only 30 Parenchymal and pleural fibrosis 55 11 *6 12-5 26-8 49-1 Parenchymal interstitialfibrosis (irregular opacities) Profusion 0/0-0/1 1/0-1/2 2/1-2/3 3/2--3/3 43 38-4 45 40-21 J20 17-8 ^ 61-6% 4 3-6 Classification of Radiographs of Pneumoconioses.7 In the 112 cases of peritoneal mesothelioma the full chest x ray film was interpreted for non-malignant abnormalities (parenchymal or pleural, or both). In most of the 72 cases of pleural mesothelioma the interpretation of non-malignant radiological pleuropulmonary changes were made on the hemithorax contralateral to that in which the tumour had devel oped (60 cases); in 12 cases full chest jc ray films preceding the mesothelioma by a relatively short period (several years) were available and were used for interpretation. Findings in the 112 cases of peritoneal meso thelioma were compared with those in the 72 cases of pleural mesothelioma. Results PERITONEAL MESOTHELIOMA Radiological changes indicating the presence of inter stitial pulmonary fibrosis (small irregular or rounded opacities, or both) or pleural fibrosis were absent in 13 (11*6%) of the 112 cases of peritoneal meso thelioma. Pleural fibrosis was present in one or more locations in 76 0% of all cases: chest wall, tangential, or face on, or both, and diaphragmatic plaques. In 30 (26*9%) cases changes consistent with pleural fibrosis were the only abnormalities detected, whereas in 55 (49* 1 %) small irregular opacities indicating the presence of interstitial fibrosis were associated with pleural fibrosis (table 1). Small, mostly irregular but sometimes also roun ded opacities were radiologically detectable in 69 (61*6%) cases; the majority, almost two thirds, showed opacities of type s (according to the ILO classification), and in one third of cases the predom inant shape and size of radiologically detectable small opacities was t. The profusion of radiologically detectable small opacities was 1/0-1/2 in 45 cases (40-2%), 2/1-2/3 in 20 cases (17-8%), and reached a 3 grading (3/2--3/3) in only four cases (table 1). Tangential pleural fibrosis was found with similar prevalence on the right in 44 (39-4%) and on the left in 50 (44-6%) cases. The extent and width of tan gential pleural fibrosis were also similar. Pleural fibrosis face on was a relatively frequent finding, present in one third of all cases affecting the left hemi thorax (in cases of right pleural mesothelioma). The extent (1, 2, or 3) of pleural fibrosis face on was rela tively evenly distributed; for tangential pleural fibrosis, extents 1 and 2 were more prevalent than extent 3, and widths A and B were more prevalent than width C (table 2). Circumscribed pleural fibrosis was found roughly twice as often as diffuse pleural fibrosis (table 3). Diaphragmatic plaques (table 4) were observed with a similar frequency on the right and on the left hemidiaphragms, in almost half of cases (47-3% right diaphragmatic plaques and 49-1% left). They were radiologically non-detectable in 39 (34*9%) cases, bilateral in 35, present on the left only in 20, and on the right only in 18. The costophrenic angle was blunted in less than 20% of cases, both on the right and on the left hemithorax (table 4). Pleural Table 2 Peritoneal mesothelioma: tangential pleuralfibrosis (in profile) andface on (n = 112) Pleuralfibrosis (tangential) Right Left No % No None Present Extent 1 2 3 Width A B C 68 60-7 62 44 (39-4)* 50 17 15 2 20 23 20-5 24 4 3-6 6 20 17 9 22 18 16 1 22 6 5-4 6 *No (%) out of 112 cases of peritoneal mesothelioma. Pleuralfibrosis (face on) % 55-3 None (44-6)* Present 17-9 Extent 1 21-4 2 5-3 3 19-6 19-6 5-4 Right No 83 29 10 11 8 Left % No 74-1 (25-9)* 8-9 9-8 7-1 74 38 12 12 14 % 66-1 (33-9)* 10-7 10-7 12-5 404 Table 3 Peritoneal mesothelioma (n = 112) Lilis, Ribak, Suzuki, Penner, Bernstein, and Selikoff Table 5 Pleural mesothelioma (n = 72) Pleuralfibrosis* Right Left Circumscribed Diffuse No % No % Circumscribed Diffuse No % No % 32 28-6 13 11-6 Includes pleura face on. 35 31-2 20 17-9 calcifications were not radiologically detected in 67 cases (59-8%); they were bilaterally present in 27 (24* 1 %) and in more cases, 14 (12*5%) on the left than on the right, four (3*6%). PLEURAL MESOTHELIOMA Seventy two cases of pleural mesothelioma had chest x ray films satisfactory for interpreting nonmalignant pleural and parenchymal changes, either on the hemithorax opposite to the tumour (in 60 cases) or on the full chest x ray film that had preceded the development of mesothelioma by several years. The malignant mesothelioma had developed on the right side in 43 (59-7%) cases and on the left in 27 (37*5%); in two cases the primary site remained unidentified (table 5). The contralateral site was inter preted in 35 cases of right pleural mesothelioma and in 25 cases of left mesothelioma, whereas the full chest * ray film was read in eight cases of right and two of left mesothelioma (table 5). In 14 cases (19*7%) there was absence of radio logically detectable non-malignant abnormalities (table 6). Parenchymal changes only (small irregular or rounded opacities) were found in 18 (25-4%) cases, a higher proportion than that of cases with peritoneal mesothelioma (12*5%). Pleural fibrosis only was present in 12 (16*9%) cases of pleural mesothelioma, whereas an association between parenchymal and pleural fibrosis was the most frequent occurrence in 27 (38%) cases. Small parenchymal opacities, mostly irregular but Location of tumour Hemithorax No % Right Left Side unindentified 43 59-7 27 37-5 2 2-8 Interpretation of chest x rayfilms ofpleural mesotheliomafor non-malignant pulmonary and pleural abnormalities Contralateral Full chest x ray film (preceding malignant mesothelioma) Right pleural Left pleural mesothelioma mesothelioma 35 25 82 also rounded, indicating interstitial pulmonary fibrosis, were detected in 45 (62-5%) cases with pleu ral mesothelioma. The profusion of small opacities was 1/0-1/2 in 35 (48-6%) and 2/1-2/3 in 10 (13*9%) cases. As with peritoneal mesothelioma, the predom inant type of small irregular opacities was s (in 62-7% of cases) followed by t in 21 (35*6% of cases). The prevalence of tangential fibrosis (tables 7 and 8) approached 50% for both the right and left hemi thorax (somewhat higher than in peritoneal meso thelioma). Diffuse pleural fibrosis was much less frequent (25% of all cases of pleural fibrosis) than circumscribed pleural fibrosis (table 9). Pleural fibrosis face on was again found relatively often in 16 (22-2%) cases. Pleural diaphragmatic plaques were found with a much lower prevalence (45*8%) than in the cases of peritoneal mesothelioma where it was 65*2%. There is a strong possibility that the unilateral chest x ray film interpretation for non-malignant radiological changes had a significant influence on this lower prevalence of diaphragmatic plaques detected in pleural as compared with peritoneal meso thelioma. Blunting of the costophrenic angle was found with similar frequency (18-1 % of cases). Pleural calcifications were found with a higher Table 6 Pleural mesothelioma (n = 72) Table 4 Peritoneal mesothelioma No % No Diaphragmatic pleural plaques: None Bilateral Left Right Costophrenic angle blunted: Right Left ,, 39 35 20 18 112 21 22 % 34-8 31-2 17-9 16-1 1000 18-7 19-6 Non-malignant radiological abnormalities: None 14 Parenchymal changes (small irregular opacities) only 18* Pleural fibrosis only 12 Parenchymal and pleural fibrosis 27 19-7 25-4* 16-9 38 0 Interstitial pulmonaryfibrosis (small irregular opacities): Profusion category: 0/0-0/1 27 37-5 1/0-1/2 35 48-6 2/1-3/4 10 13-9 One chest x ray film was unreadable for parenchymal changes. Non-malignant chest x ray changes in patients with mesothelioma in a large cohort ofasbestos insulation workers ' 405 Table 7 Pleural mesothelioma (n = 72) Chest x ray interpretations for pleural abnormalities Right hemithorax (left tumour) (n = 25) Pleural fibrosis (tangential) 8 Pleural fibrosis face on 3 Pleural diaphragmatic plaques 10 Costophrenic angle 5 * Bilateral pleural fibrosis present. Left hemithorax (right tumour) (n = 35) 17 11 15 3 Total chest x ray (preceding tumour) (n = 12) 7(3)* 2(2)* 8(5)* 5(1)* Total No 32 16 33 13 % (444) (22-2) (45-8) (181) prevalence (20%) on the right hemithorax (in the case of left mesothelioma) and on the left (34-3%) hemi thorax (in the case of right mesothelioma) than was the case with peritoneal mesothelioma, where the cor responding prevalences were 3-6 and 12*5%. There were, nevertheless, an additional 24* 1% of cases of peritoneal mesothelioma with bilateral pleural calcifications. In 46 of the 184 cases (21 pleural, 25 peritoneal) lung tissue was available for histopathology assess ment of interstitial fibrosis. Whereas in 20 (43*5%) of the 46 the radiological interpretation was negative Table 8 Pleural mesothelioma (n = 72) Pleuralfibrosis: tangential Right No Left No Extent 1 2 3 Width A B C Total 5(2)* 7(3)* KO)* 6(2)* 4(3)* 3(0)* 13 6(1)* 13(1)* 3(3)* 7(2)* 12(2)* 3(D* 22 *Cases in which full chest x ray films preceding the malignant pleural mesothelioma were available (total number = 12). (small opacities 0/0 in 8, 0/1 in 12 cases), histopathological evidence of interstitial fibrosis was present in all. Discussion and conclusions The relations between both pleural fibrosis and radio logically detectable interstitial fibrosis with the type of mesothelioma--pleural or peritoneal--were tested by using chi-square statistics. Pleural changes were found in 76% of the cases of peritoneal mesothelioma and in only 55% of cases of pleural mesothelioma (X2 = 8-74; p = 0 003). Therefore, there seemed to be an association between type of mesothelioma and pleural fibrosis, with cases of peritoneal meso thelioma having a greater frequency of pleural changes. Nevertheless, this apparent higher preva lence of pleural fibrosis among the cases of peritoneal mesothelioma might be, at least in part, due to the fact that in most cases of pleural mesothelioma nonmalignant changes were interpreted in one hemi thorax only. With regard to parenchymal changes, no association with type of mesothelioma, peritoneal or pleural, was found (x2 = 0 058; p = ns). As was shown by the comparison of radiological parenchymal abnormalities and histopathological changes, the absence of radiologically detectable small opacities on the chest x ray film does not exclude the existence of interstitial pulmonary fibrosis in cases of mesothelioma among insulation workers. Table 9 Pleural mesothelioma (n = 72) Pleuralfibrosis: circumscribed and diffuse Right hemithorax (left tumour) (n = 25) Pleural fibrosis circumscribed Pleural fibrosis diffuse 6 3 * Bilateral pleural fibrosis was present. Left hemithorax (right tumour) (n = 35) 15 2 Total chest x ray (preceding tumour) (n = 12) 6(1)* 4(0)* Total No 27 9 406 Similar findings have recently been reported in cases of lung cancer from the same cohort.8 The possibility still exists that mesothelioma due to past exposure to asbestos might occur in the absence of interstitial pulmonary fibrosis in subjects with lower levels of asbestos exposure than that which characterised insulation work in the past. The findings in this study of cases of mesothelioma from the cohort of asbestos insulation workers cannot be extrapolated to lower levels of exposure that are known to have resulted in cases of mesothelioma among, for example, family contacts of workers exposed to asbestos.9 References 1 Selikoff IJ, Hammond EC, Seidman H. Mortality experience of insulation workers in the United States and Canada, Lilis, Ribak, Suzuki, Penner, Bernstein, and Selikoff 1943-1976. Annals NY Acad Sci 1979;330:91-116. 2 Anderson HA, Lilis R, Daum SM, Selikoff IJ. Asbestosis among household contacts of asbestos factory workers. Annals NY Acad Sci 1979;330:387-400. 3 Vianna NJ, Polan AK. Non-occupational asbestos exposure and malignant mesotheliomas in females. Lancet 1978;i: 1061-3. 4 Newhouse ML, Thompson H. Mesothelioma of pleura and peri toneum following exposure to asbestos in the London Area. Br J Ind Med 1965;22:261-9. 5 Newhouse ML. Asbestos in the workplace and the community. Ann Occup Hyg 1973;16:97-102. 6 Ribak J, Lilis R, Suzuki Y, Penner L, Selikoff IJ. Malignant mesothelioma--clinical characteristics. Br J Ind Med(in press). 7 International Labour Office. Guidelines for use of ILO Inter national Classification of Radiographs of Pneumoconioses. Rev 80. Geneva; ILO, 1980. (Occupational Safety Health Series No 22.) 8 Kipen HM, Lilis R, Suzuki Y, Valciukas JA, Selikoff IJ. Radio logic and histopathologic evaluation of pulmonary fibrosis in asbestos insulation workers with lung cancer. Br J Ind Med (in press). 9 Anderson HA, Lilis R, Daum SM, Fischbein AS, Selikoff IJ. Household contact asbestos neoplastic risk. Annals NY Acad Sci 1976;271:311-23. Correspondence and editorials The British Journal of Industrial Medicine wel comes correspondence relating to any of the material appearing in the journal. Results from preliminary or small scale studies may also be published in the correspondence column if this seems appropriate. Letters should be not more than 500 words in length and contain a minimum of references. Tables and figures should be kept to an absolute minimum. Letters are accepted on the understanding that they may be subject to editorial revision and shortening. The journal now also publishes editorials which are normally specially commissioned. The Editor welcomes suggestions regarding suitable topics; those wishing to submit an editorial, how ever, should do so only after discussion with the Editor.