Document 95D3ye8qRp4zEQKz4rzZ2jnq

FILE NAME: Neighborhood Exposures (NE) DATE: 1974 DOC#: NE021 DOCUMENT DESCRIPTION: Medical Journal Article - Mesothelioma Register 1967-68 ~ British Journal o f industrial Medicine, 1974, 31, 91-104 4 ;^ 3 ^ ti lStr.t Mesothelioma Register 1967-68 il on M O R R I S G R E E N B E R G and T. A. LLO Y D D A V I E S Employment Medical Advisory Service, Department of Employment, 1-13 Chepstow Place, London W2 \ iry 'lai 73. ty. me Greenberg, M ., and Lloyd Davies, T. A. (1974). British Journal o f Industrial Medicine, 31, .ial 91-104. Mesothelioma Register 1967-68. A register of mesothelioma cases is maintained by the Department of Employment, Medical Services Division (now Employment Medical the Advisory Service). This paper describes an investigation of 413 notifications to the Register in 1967-68 from England and Wales and Scotland. Cases were regarded as 'definite' when histological confirmation of diagnosis had been obtained, either by hospital pathologists, or by the U1CC Panel of Pathologists, to whom pathological material was submitted whenever possible. Two .hundred and forty-six cases -ep were accepted as `definite' and 76 cases were regarded as `definitely not' mesothelioma. The remainder were classified as `undecided' or `insufficient pathological material*. Thirty-five of the 76 cases definitely not mesothelioma had nevertheless been so described on death certifi cates. The investigation carried out covers clinical aspects, survival, and evidence of exposure to asbestos. Twelve per cent of definite mesotheliomata were of peritoneal origin. The age range was 21 to 87 years, but, in general, mesothelioma occurred at an earlier age than `carcinoma of bronchus and lung* or `all malignant tumours* in the Registrar General's statis tical mortality tables. Concomitant asbestosis and the finding of asbestos bodies or pleural plaques occurred as am frequently in those cases classified as definitely not mesothelioma as in confirmed the Occupational exposure to asbestos was found in 68% of definite cases, apparently signifi cantly more frequently than in those definitely not mesothelioma, but there was observer bias. The interval between first exposure and death from mesothelioma exceeded 23 years in 83 % of cases but was only three and a half years in one case. The duration of exposure varied io widely: in 12% of cases it was under five years. The type of asbestos could be ascertained in fts. so few cases that it was impossible to assess the role of croddolite in aetiology. There were 38 )-X deDfineiftienictaesems eisnowthheilciohmnaotahisshtoorwyeodf manayrkeexdpocsluursetetroinagsbienstaorseacsouwldhebree otbhtearieneids.substantial lip industrial use of asbestos. Whether this should be interpreted as evidence of causation or an HU effect of heightened awareness in these areas cannot be deduced from this study. Evidence is quoted suggesting that the observed annual incidence of approximately 120 definite mesothe- ats Homata in England, Scotland, and Wales may considerably understate the true prevalence. am 1 Diffuse or malignant mesothelioma of the pleura and Marchand, I960)'gave impetus to the enquiry. For Peritoneum, although rare, has been sought for some years the Pneumoconiosis Unit of the Medical ^teasingly in the past decade. The reported associa- Research Council had recorded cases of mesothe- oo with asbestos exposure (Wagner, Sleggs, and lioma reported to them. By 1966 a register of some 91 SSJ.W ! '*>. - t e} . p i <'. 91 M orris Greenberg and T. A . L loyd D avits I 200 cases which had bees diagnosed in Britain in the previous 15 years, with histological confirmation of diagnosis, was in their possession with the help of information resulting from an enquiry (Smither, Gilson, and Wagner, 1962). In that year the register was handed over to the Medical Branch of HM Factory Inspectorate (now Employment Medical Advisory Service, Department of Employment). The objects of the register were stated in.the Senior Medical Inspector's Advisory Panel Memorandum (1968): i to record the annual number of deaths from mesothelioma of the pleura or peritoneum associated with asbestos exposure; ii to ascertain trends in the prevalence rates; ill to discover, if possible, tumours occurring without any exposure to known or suspected occupational causes; iv to provide part of the evidence on which pre ventive measures should be based. This paper presents the results of investigations into cases notified to the register from England and Wales and from Scotland for the period 1 January 1967 to 31 December 1968. Preliminary results have been published elsewhere (Lloyd Davies, 1970) and the present report relates to information available to May 1972. Plan of inrestigatloa The Registrars General for England and Wales and for Scotland forwarded copies of (a) death certifi cates which included a diagnosis of mesothelioma of pleura or peritoneum and (A) Cancer Bureaux registrations with a diagnosis of malignant mesothe lioma. Pneumoconiosis Medical Panels also notified cases of mesothelioma which were subject to claims for benefit under the National Insurance Acts or otherwise came to their notice. Information about other cases was received from chest physicians, surgeons, pathologists, and coroners. The majority of cases were notified from two or more sources. The Central Ethical Committee of the British Medical Association agreed that tracing of cases by medical advisers should take place only after the prior approval of.the patient's medical attendant. In the event, approval was given in ail cases. Where possible histological slides or blocks of histological material were obtained: these were submitted to the Union International contre le Cancer (UICC) Panel of Pathologists (see Appendix). Diagnostic criteria A definitive diagnosis was made only when histo logical proof was available. Borrowed material was referred to the UTCC Panel of Pathologists together with an abstract of occupational and clinical histories and of necropsy findings. The histological jaj histochemical features of mesothdiai tumours has been discussed by UICC panel pathologists (Wagner Munday, and Harington, 1962; Hourihane, l$6<! McCaughey, 1965; Whitwefi and Rawcliffe, 197j) and the criteria employed by the UICC panel to derive a consensus opinion appears in the Appendix. Where material could not be borrowed the reports of consultant pathologists were examined. Where several pathologists gave varying opinions on i section and it was not possible to refer material to' the UICC panel, the majority derision was talco. The occupational history was often sought after the histological diagnosis had been made by the non- panel pathologists. Diagnoses made by these pathologists were allocated to the following groups: *Definite', where in the view of the pathologist, based on adequate histological material supported by the gross appearance at thoracotomy, lapar- otomyornecropsy,mesotheliomawas the diagnosis of election. `Undecided', where the material examined and other features while compatible with a diagnosis of mesothelioma did not permit the pathologist to make a firm diagnosis (this corresponds to the category `undecided' finally employed by UICC pathologists). 'Insufficient histological material', where the pathologist was dissatisfied with the material, or where neither histological nor necropsy material were ever examined. 'Definitely not', where a definite alternative diagnosis was made by the pathologist. When tumour was present in both thorax and abdomen the site stated in the analysis is that given by the pathologist as the primary site. Where the death certificate differed from the necropsy report, the latter was accepted. . Asbestos exposure history Where possible living subjects were interviewed, but for deceased subjects the relatives were interviewed in the first instance. Occupational histories were also sought from coroners and from former employes and workmates. The initial classification was made by the investigating medical adviser who may or may not have been aware of the interim diagnosis and was rarely aware of the final diagnosis. The final classification was made by a second medical adviser in consultation with the first, and often this took place before the final diagnosis had been received. Occupational exposure .. Occupational exposure to asbestos was defined as follows: 'z.'- 'D efinite', where the job involved fun-rime or intermittent handling of asbestos or asbestos- M esotheliom a register 1967-68 93 le histological and belial tumours have ithologists (Wagner, ; Hourihane, 1964; nd Rawcliffe, 1971) the UICC panel to ars in the Appendix, orrowed the reports e examined. Where ing opinions on a to refer material to decision was taken, 'tea sought after the made by the noni made by these te following groups: of the pathologist, 1material supported horacotomy, laparmawas the diagnosis trial examined and s with a diagnosis of . the pathologist to rresponds to the .ployed by UICC ferial', where the ith the material, or r necropsy material definite alternative thologist. both thorax and naiysis is that given try site. Where the he necropsy report, tistory ire interviewed, but is were interviewed 1histories were also t former employers >ification was made 'viser who may or e interim diagnosis diagnosis. The final md medical adviser nd often this took iad been received. stos was defined as ved full-time or -tos o r asbestos- coataining compounds, or where the subject worked in an atmosphere contaminated by asbes tos dust. 'Possible', where the job description was too imprecise to be certain, but there was a strong suspicion of exposure to asbestos. 'None', where, after exhaustive enquiry, no 1 occupational exposure could be presumed. 'Unknown', where adequate industrial details were not forthcoming. If possible the duration of exposure was recorded and the length of time before death that exposure ceased. The duration in intermittent exposures is presented as a cumulative figure. i Domestic exposure Domestic exposure was considered as positive when a history that members of a subject's family had come, home visibly contaminated by asbestos was obtained. 3 Hobby exposure I Hobby exposure was recorded in several house holders or smallholders who gave a history of. sawing asbestos sheeting for the construction of outhouses, garages, and chicken houses. Neighbourhood exposure Neighbourhood exposure was recorded when sub jects lived within one mile of an asbestos factory or shipyard using asbestos but had no occupational exposure. 'Other evidence of asbestos exposure Asbestos exposure was presumed in cases showing evidence of asbestosis (either on chest radiograph or at necropsy) and in those in whom asbestos bodies or fibres had been demonstrated by light microscopy in sputum, lung sections, or fluid expressed from the cut surface of the lung. The reported finding of pleural plaques at operation or necropsy, or evidence of plaques on the chest radiograph, was regarded as suggestive of asbestos exposure. ,, Results For the years 1967 and 1968, a total of 413 cases was reported to the mesothelioma register. Of these, 168 were first notified by death certificate as having died in those years and a further 166 were notified in life and died during this period. Seventy-nine subjects notified survived the period of study. Death certificates were the most important source of notification comprising 53-5% of all notifications in 1967 and 77-8% in 1968. In the absence of death certifications, further notifications were received from cancer bureaux, 45 (26-5%) in 1967 and 33 (13-6%) in 1968. Further groups of cases were reported exclusively by other sources (physicians, surgeons, and pathologists), 31 (18.-2%) in 1967 and 18 (7-4%) in 1968. Three other cases otherwise unreported were reported in each year by the Pneumoconiosis Medical Panels. A total of 170 notifications were made in 1967 and 243 in 1968. Pathological diagnosis In Table 1 the notifications are shown categorized according to the criteria of diagnosis. The correla tion between histological diagnosis and the diagnosis given on the death certificate was weak. Of the 246 cases accepted as `definite', only 186 were so des cribed on death certificates. On the other hand, of 76 cases `definitely not mesothelioma' death had been attributed to mesothelioma on the death TABLE 1 Notifications to M esothelioma R egister analysed by D iagnostic C riteria and Site op T umour UICC Panel Other pathologists Total AU eases Site of tumour Pleura Peritoneum Pleura Peritoneum Pleura Peritoneum Definite US') >13* 16j Ml rm MJ 216 30 246 Diagnostic category1 Undecided Insufficient material 1 <J 26-j 2- Jf 2* 40 6 46 121 r 13 u 32) ,,OJr 32 44 I 43 Definitely not 231 U 7J 421 *) 63 11 76 Total 167 28 198 20 363 48 413 'See texc for definition 94 Morris Greenberg and T. A. Lloyd Davies certificates in 35 instances. The pathological diagnoses in these 35 cases were: Carcinoma of bronchus........................... 11 Carcinoma, origin unstated . . .. 10 Secondary adenocarcinoma (primary unstated) ..................................... 3 Not mesothelioma (no other diagnosis) 4 M y e lo m a to s is ..................................... 1 Transitional carcinoma of bladder .. 1 Adenocarcinoma of thyroid .. .. 1 Retroperitoneal fibroma or chordoma 1 Asbcstosis and tuberculosis . . .. 1 Severe anaemia secondary to peptic ulcer 1 Malignant m e la n o m a ......................... 1 As the concordance of diagnoses between the UICC pathology panel and other pathologists was higher than 74% and the characteristics of the two groups are so similar for distribution of age at death (Fig. 1), tumour site, sex (Table 2), and survival (Figs 2 to 4), they can be treated as one. In this study #rperitoneal tumour represented 12-2% of all a, firmed mesotheliomas (Table 2). This compares reponed proportions by five authors with a range rf 3-7% (of 30 cases) to 72-7% (of 22 cases) (Table 3), From Table 2 it can be seen that the distribution cf cases between the sites was similar in the groups confirmed by UICC pathologists and by otho pathologists. -:y; Sex distribution Table 2 shows that the ratio of mesothelioma in n^s and women for both UICC and other pathology was about 5:1, which is similar to that for t | malignant neoplasms of the respiratory systoa (Registrar Genc.ul, 1970). The sex difference & carcinoma of the bronchus in general is thought in part to be due to difference in smoking habin (Hammond, 1966) but tobacco is not known to play a role in the aetiology of mesothelioma. IT it is assumed that mesothelioma is related to asbestos TABLE 2 246 `D efinite' M esotheliomas analysed by Sex and Site of T umour Pathologists UICC Panel........................ Other patnolocisu .. A l l ................................... Site o f tumour Pleural Peritoneal Pleural Peritoneal Pleural Peritoneal Males (3 o f ail mesothtiial tumours) 96 14 (12 8 32 SI 10 (10-932 177 24 (12032 ,, Females ( 3 o f all mso thlial tumours) 22 2 (8-3 30 17 4 (19-032 39 6 (13-330 Total ns 16 (11-930 98 14 (12-530 216 30 (12-230 TABLE 3 Prevalence of Peritoneal M esothelioma reported by Various A uthors Authors McEwen et at. (1970) Ashcroft and Heppleston (1970) .. Selikolf el al. (1970) Thomson ( 1 9 7 0 ) ........................ Newhouse et al. (1972) Present study ........................ All mesotheliomas 80 23 22 17 11 49 246 Peritoneal mesotheliomas only Ctotal) 3 (3-730 3 03-030 16 (72-732 3 07-632 5 (45-430 30 (61-230 30 02-230 Comment 73 males and 7 females; 2 males described as `both sites' (Scotland) Tyneside Male insulation workers (USA) Cape Town Females (London) Males Cram the same factory EaglftOtf Wilts and Scotland I-!* ; o f ail con. his compares with >rs with a range of I cases) (Table 3>. the distribution of lar in the groups ts and by other sothelioma in men other pathologists tr to that for all espiratory system sex difference in nerai is thought in n smoking habits not known to play othelioma. If it is 'elated to asbestos a -- Total 113 16 98 14 216 i 30 (11-9 70 (12-570 (12-2*0 exposure it would be necessary tp know the numbers i of men and women at risk over the past 50 years in order to assess the relative susceptibility of the sexes to mesothelioma. TABLE 4 N otifications to M esothelioma R egister ANALYSED BY ASBESTOS EX POSURE Age at death The distribution of age at death of confirmed cases is presented in Fig. 1: there is no significant dif ference between cases diagnosed by the two groups of pathologists (mean age: UICC, 59-4 0-9; other pathologists, 60-2 1-3). For comparison the age distributions for all malignant neoplasms and for carcinoma of the bronchus and lung (Registrar General, 1970) are also shown. The mean age at death from mesothelioma is significantly younger (r < 0-05) than that for bronchial carcinoma and all neoplasms'. This may be due in part or in whole either to the greater chance of identifying occupa tional cancers within the working age compared with the retired or to earlier death from mesothe lioma associated with occupational exposure to a carcinogen. Exposure to asbestos In Table 4 it can be seen that of 24fi confirmed cases ' 167 (68%) had definite occupational exposure to asbestos and a further 29 were possibly exposed, either at work or at home. There were, however, Asbestos exposure history Definite occupational exposure Possible occupational exposure Neighbourhood, domestic nr bobby .. N o n e ........................ Not obtained .. No. o f definite mesotheliomas h'o. undecided, inadequate materai, or definitealternatile diagnoses 167 63 16 17 13 10 38 57 12 20 still 38 (15%) for whom careful enquiry failed to elicit any exposure whatever. In the remaining notifications (`undecided', `inadequate material', `definite alternative diagnosis') nearly one third were without apparent exposure, and those with definite occupational history formed only 38 % of the total. The differences between these groups are significant (p < 0-001) but may be affected by bias towards HORS Comment . 7 females: 2 males `both sites' (Scottasti) on workers (USA) ndoa) :he same factory les and Scotland 1967-68 to. 1. Age distributions it death. l - f .- l^ .i^ i - - - '- ,! . 1L.', >V--. 1 1' iIl h w u i leAwi.id .W l 96 M orris Greenberg and T. A . L loyd Davies underdiagnosis in areas without large-scale asbestos industry, or to bias on the part of the interviewers who might have been more assiduous in pursuing an asbestos association history in cases of definitive mesothelioma. Ideally it would have been desirable to conceal from interviewers the diagnosis in individual cases, but on account of limited manpower the interviewer may have been responsible for identify ing cases and arranging for confirmation of diagnosis. On the other hand, the number of notifications which were not subsequently fully confirmed but had TABLE 5 Industry or Job T itle in 167 `D efinite' M esotheliomas w it h D efinite O ccupational E xposure to Asbestos Industry nr jab Ship worker................................................ Asbestos factory w o rk e r......................... Insulation worker (not marine) .. Boiler house worker (not marine) Chemical w o rk e r..................................... Docker ................................................ Welding rod manufacture Building w o r k e r .................................... Electrician................................................ Sack deaner/repairer Welder/plater ..................................... Battery boa manufacture Electricity generating industry .. Gas worker .................................... Railway coach/locomotive builder Motor mechanic Refuse work Number of mesotheliomas 7 39 13 4 4 3 3 3 3 2 2 2 2 1 1 ' m -.x!$ known asbestos exposure may have been the rest* over-diagnosis because of die well-known 3 of mesothelioma with this occupational W cija Z - introducing a bias in the opposite direcdos. ' v* The individual occupations of confirmed " with industrial exposure are shown in Table 5. - degree of risk associated with these occupaia* cannot be computed because the populatfe* " exposed, over a period of 30 years, is unknown t* -cannot even be guessed. Table 6 lists those subjects with mcsotheGoo, where a history of exposure to asbestos, not oceup*. tional in origin, was obtained. Of those jubjea with neighbourhood exposure, the first four In* near the same asbestos factory in a district w ta chest physicians have a high awareness of theiioma. The final four subjects listed had exposn that might be considered minimal and commoi experience. In cases notified to the register by the Regianr General for England and Wales a control group tb established (from 1 January 1968). the next den* registration matched for age and sex but not fa area being notified to the register for comparison* occupation. It was found, however, that as a v s * mesothelioma were more commonly referred to coroners than were other subjects the job description was frequently qualified to indicate asbestos a- posure; for example, `plumber' or `fitter1was further categorized as `shipyard*, whereas no such qualifies.. tion appeared in the controls. Even `housewife* and "widow' were recorded as occupations with the disease attributed to asbestos exposure. Ethical considerations prevented the interviewing ' of control subjects (or their relatives) though it is \ 1 1: - '^ TABLE 6 N on-occu? attonal Asbestos E xposure H istories obtained in C ases of Mesothelioma Case number EW S7/70 EW 43/174 EW 3/38 EW 8/86 S 8/71 S $8/31 S 68/23 EW 7/82 EW 67/113 EW 68/19 EW 68/83 EW 68/190 EW 68/186 EW 68/80 Duration o f exposure 23 years 14 years 3 years 22 years Unknown 13 yean 30 yean Unknown 14 yean Unknown 17 yean 40 yean 2 yean Unknown 4 yean 4 3 years 1 day Nature o f exposure Resident within yards of an asbestos factory; at school nearby Resident close to an asbestos factory; probably went to school nearby; both parents worked in asbestos factory Worked next door to asbestos factory ' Resident H miles from same asbestos factory Hobby: reiining aad refitting clutches and brakes Resident 200 yards from an asbestos factory Resident < J mile from a shipyard Resident < j mile from a shipyard Resident ) mile from an asbestos using factory Resident < J rails from an abestos factory Resident < I mil* from asbestos factory ' Resident < 1 mile from an asbestos factory Husband worked an asbestos factory Lived in a house largely composed of asbestos cement sheeting Worked on and Imd adjacent to chicken farm composed of asbestos cement buildings Intermittent exposure to brother's overalls contaminated with asbeetar Sawing up ashesUMcement sheets to construct two sheds y have been the result of J well-known association / cupational history thus I xjsite direction. | as of confirmed cases ) shown in Table 5. The I rith these occupations ause the population years, is unknown and :ts with mesothelioma a asbestos, not occupaed. Of those subjects e, the first four lived >ry in a district where t awareness of meso:ts listed had exposures tinimai and common tister by the Registrar ss a control group was 1968), the next death I and sex but not for iter for comparison of vever, that as cases of immonly referred to cts the job description "'"^dicate asbestos ex- j r `fitter' was further eas no such quaiificaEven `housewife' and ccupations with the exposure. need the interviewing elatives) though it is SOTHELIOMA LH CC senei nik.f nntholoailis fig. 2. Definite mesotheliomas with definiteoccupational asbestos exposure: survival after first exposure. recognized that this would have been desirable (McEwen, Finlayson, Mair, and Gibson, 1970). Figures 2,3 and 4 illustrate time relationships with known asbestos exposure. In 85% of cases death occurred more than 25 years after first exposure, although the shortest period was three and a half years and the longest 53 years. There was no significant difference in the distributions of years of no. 3. Definite mesotheliomas with definite occupa tional asbestos exposure: survival after last exposure. ool nearby it to school nearby; it sheeting osed of asbestoa ted with asbestos `I TABLE 7 T ype of Asbestos involved in O ccupational Asbestos E xposure Asbestos type to which exposed occupationally r ------------------------------ ------------------------ - -- Crocidoiite only ............................................... Crocidoiite and other asbestos Mixed asbestos without crocidoiite Definite mesothelioma 4 117 167 Bhtohfical diagnosis Undecided and insufficient material \ 0 o g 2 25 36 Definitely not mesothelioma 1 1 1 7 2 15 27 98 M orris Greenberg and T. A . LLoyd Davies usas1 Number of s e t QtK^f jflthQiQQnM Number o f cates small proportion of subjects. Of the 50 subjems `definite mesotheliomas', where the types of ash to which they were exposed were known, 45 been exposed to croddolite. Of the group c subjects diagnosed as 'definitely not mesothefi. in which types of asbestos to which they had exposed were known, eight had been expose croddolite. There is no significant difference between 1 two groups. In four cases of definite mesotheli no exposure was known other than to chrysotii history of exposure to talc was obtained in s subjects with definite mesothelioma*, but si them had also been exposed to asbestos. It waj possible to identify the nature of the talc to w they had been exposed. f ig . 4. Definite^ pleural mesothelioma: duration of occupational exposure to asbestos. survival after first exposure in the two groups (mean age: UICC, 37-4 years; other pathologists, 38-4 years). The interval between last handling asbestos and death was under one year in about 40% cases but varied up to 52 years (one case)! The duration of exposure was more widely spread, ranging from three weeks to over 50 years. Twelve per cent of cases had been exposed for under five years. The man with only three weeks' exposure died over half a century later. Table 7 summarizes information regarding the type of asbestos, but this could be obtained in only a Other evidence of asbestos exposure It is apparent that a history of occupational expo to asbestos is frequently associated with the pres of asbestosis, asbestos fibre bodies, asbestos fibn pleural plaques observed at necropsy or radio! cally (Table 8). Ashcroft and Heppleston (I stress the importance of phase contrast micro and electron microscopy in searching for asbe in tissues. The presence of pleural plaques does always indicate asbestos exposure (Rous Studeny, 1970). It is not possible, however observe a significant difference of asbestos expo between subjects with definite pleural mesotheiio and those subsequently categorized as definitely pleural mesothelioma. In four `definite pieural mesotheliomas' corrob tive evidence of asbestos exposure was found in absence of occupational exposure histories. Of tl subjected to `hobby' or `domestic' exposure cases) none showed corroborative features. Of tl with `neighbourhood' exposure (eight cases), had asbestos bodies. TABLE 8 C orroborative E vidence of Asbestos E xposure1 related to Occupational Exposure H istory N otifications to M esothelioma R egister (Pleural T umours only) Occupational asbestos exposure history Definite Possible None ascertainable .. Definite pleural mesothelioma Corroborative evidence No corroboratile evidence Not reported 100 (6933 8 (50 *0 4 (1353 24 (1630 4 (25 V3 18 (36 y j (isy.) 4 (25*,3 10 (3153 Definitely not pleural mesothelioma Corroborative evidence No corroborative evidence Not reporten 19 (73 33 0 (-) 0 (-) 3 (1230 3 (6033 6 (33 33 4 (1533 2 (4033 12 (6733 'Asbestosis, asbestos bodies, asbestos fibres or pleural plaques the 50 subjects with the types of asbestos ere known, 45 had )f the group of i; not mesothelioma' hich they had been id been exposed to < Geographical distribution Merseyside, Clydeside, Tyneside, the South East 1 Tables 9a and 9b show the distribution and rate/ Lancashire conurbation, and Greater London had million per year of mesothelioma notifications and an incidence of mesothelioma markedly greater than diagnoses in England and Wales and in Scotland. the national rate with deficits in the remainder of The Registrar General's standard regions are these regions. They have in common the presence of employed for England and Wales. Gydeside includes heavy asbestos-using industries. Dunbartonshire, Renfrewshire, Greenock, Glasgow, The geographical distributions of cases, and of Hamilton, and Motherwell The distributions are by cases with occupational exposure, are shown in ence between these finite mesothelioma han to chrysotile. A s obtained in seven .-liomas, but six of asbestos. It was not of the talc to which no means related to population density. South western England, with a population of 3 652 thousands, had a total of 22 definite cases (a rate of 2-97 cases/million per year) yet Plymouth, with a population of 250 000,1 had 13 cases, all with histories of occupational exposure to asbestos. The remainder of the region, with nearly 3 million population, produced nine mesotheliomas of which Figures 5 and 6. Discussion The recognition of diffuse mesothelioma depends on awareness and acceptance of the tumour as a pathological entity. The macroscopic appearance of a typical mesothelioma, resulting from its propensity only four had a history of occupational exposure to to infiltrate serosal membranes, is best characterized ure asbestos (a rate of 1-5 cases/million per year). by the well-developed pleural mesothelioma with xupational exposure 'Assuming that Plymouth hospitals serve a population of permeation of visceral and parietal surfaces by a ed with the presence twice that number, the rate would be 25 cases/million per continuous layer of tumour. However, metastatic es, asbestos fibres or J ;ear. tumour in the pleura, usually from a primary adeno- cropsy or radiologi- Heppleston (1973) T A B L E 9 (a) contrast microscopy trching for asbestos /'""'ral plaques does not Geographical D istribution of N umbers and D ates of N otifications and Confirmations of M eso thelioma 1967-68 jsure (Rous and ssible, however, to of asbestos exposure eurai mesotheliomas ized as definitely not Region1 967 population (millions) Notifications to Register 1967-66 No. Rate/ million Definite mesothetiomasf 196746 No. Ratei million year heiiomas' corroborajre was found in the re histories. Of those lestic" exposure (six ve features. Of those e (eight cases), two Greater London Rest of SE England SE Lancashire conurbation Mersevside conurbation Rest of NW England .. Tyneside................................... Rest of N England 7-9 Ill 7-03 9-3 40 204 2-3 21 4-20 1-4 33 11-79 2-9 13 2-24 0-8 14 8-75 2-5 13 2-60 38 3-67 18 0-97 16 3-20 23 8-93 8 1-38 9 3-63 9 1-80 W Yorkshire conurbation Rest of Yorks 4 Humberside 1-7 17 3-00 12 3-53 30 5 0-83 3 0-50 osure H istory and y) tirai mesothelioma J ralive nee \ \ ;> '3 Not reported 4 (13 %) 2 (to*;) 12 (67%) N Wales ........................ 0-8 SE Wales................................... 1-9 E Anglia.............................................. 1-6 Clydeside* ....................... 1-7 Rest of Scotland 3-3 SW England ................................... 3-7 E Midlands ....................... 3-3 W Midlands conurbation . . 2-4 Rest of W Midlands .. 2-6 England, Wales 4 Scotland .. 33-6 3 1-88 14 3-68 6 188 43 12-63 IS 2-37 30 4-03 9 1-36 II 2-29 11 2-12 412* 3-84 'Standard regions of Registrar General England St Wales, except Clydeside 'Dunbartonshire, Renfrewshire, Greenock, Glasgow, Hamilton. Motherwell One subject who died in Australia not included 3 1-81 10 2-63 3 0-94 28 1-24 6 0-86 22 2-97 3 0-43 6 1-23 6 1-13 243 2-29 100 M arris Greenberg and T. A . L lo yd Davies TABLE 9(b) G eographical D istribution o f M esotheliomas associated w ith Occupational Asbestos Exposure and th e Proportion of T hese Cases to all Cases of Mesothelioma Region1 Greater London ...................................................................... Rest of SE E n g la n d ........................................................... SE Lancashire co n u rb a tio n ........................................................... Merseyside conurbation ........................................................... Rest of NW E ngland...................................................................... Tyneside ................................................................................. Rest of N E n g l a n d ...................................................................... W Yorkshire c o n u r b a tio n .......................................................... Rest of Yorks St Humberside ............................................... N Wales........................ ........................................................... 5E Wales ........................ .................................... E Anglia .. .. .. Clydeside1 ................................................................................. Rest of Scotland .................................... ......................... SW E n g l a n d ................................................................................ E Midlands ........................ ............................................... W Midlands conurbation .. Rest of W M id la n d s................................... ......................... England, Wales St S co tlan d .......................................................... Mesotheliomas with definire occupational aebesto. exposure No. Percentage of all mesotheliomas 29 50 12 7 13 81 22 83 3 100 3 89 6 67 11 92 2 67 l 33 6 60 -- -- 22 79 3 50 13 32 1 33 4 67 1 17 167 . 68 'Standard regions of Registrar General England & Wales, except Clydeside 'Dunbartonshire. Renfrewshire. Greenock. Glasgow, Hamilton, Motherwell carcinoma, can produce widespread sheet-like growth resembling lace diffuse pleural mesothelioma. Histologically the cellular and intercellular charac teristics can be highly equivocal. The UICC patholo gists' panel criteria for reaching a decision were modified in the course of the survey (see Appendix) and have not finally been decided (McCaughey and Oldham, 1974). Willis (1952) cautioned against accepting the diagnosis of mesothelioma until, by careful search, an alternative primary neoplasm had been excluded. In a series of 3 771 necropsies Cameron, Litton, and Lyon (1961) found a prevalence ofprimary carcinoma multiplex of 1-2%. In the present series there were three with additional primary neoplasms in the 246 `definite' cases (one with carcinoma of the stomach, another with carcinoma of the bronchus, and the third with myelogenous leukaemia). This represents a prevalence of carcinoma `multiplex of 1*2 %. Sections referred to the UICC pathologists had previously been'studied by other pathologists who had not necessarily made a diagnosis of mesothe lioma. In 182 cases where adequate histolog material had been studied by UICC patholoj they made a diagnosis of mesothelioma in 134 (74 were undecided in 10%, and made an altema diagnosis on 30 occasions(16%).Theconcordanc diagnosis between UICC and other pathologist greater in view of the fact that a number of secti were referred to the UICC panelists for a sea opinion when the other pathologists had said condition was not mesothelioma but an asbe occupation history had been obtained by clinicians. In those cases with adequate histological mates not referred to the UICC panel (186 cases) pathological diagnosis of definite mesothelioma ' made in 112 (60%). The submission of sections to the UICC pa varied in different pans of the country. In Gres London 77 out of 111 cases were referred (69 compared with only 12 out of 61 cases in Scotl. (20%). The number of cases diagnosed is unlikely to If the two opinions lead to a blank entry above ha the specimen should be sent to the two otiereaders and a combined diagnosis made on the baaj of four readings. There are many possibilities fmm' four readings but the combined diagnosis should follow the majority if there is a clear one and other wise be undecided. The following rule Is sufficient to determine all cases of four readings: score a definite as 1 point, probable as J, possible as 0, not as - I ; then add up the four scores and if the total is greater than or equal to 1J the diagnosis is Definite, between --1 and + 1 inclusive it is Undecided, less than or equal to - 1 is Not a mesothelioma. The UICC Panel of Pathologists and diagnostic criteria A British panel of pathologists specializing in the diagnosis o f msothlial tumours was formed unofficially in 1963 and consisted of Dr. K. F. W. Hinson, Dr. F. Whitwell, Professor W. F. E. McCaughey, and Dr. J. C. Wagner. From 1963 to 1967 all cases were examined by all members of the panel and a majority opinion was arrived at. Subsequently the panel was constituted as a UICC panel. From 1967 panellists decided whether the diagnosis was definitely mesothelioma, definitely not mesothelioma or whether there was insufficient histological material, only referring material to another member or members of the panel in case of doubt. After mid-1968 the policy was adopted that all cases referred to the panel should be seen by at least two members and that if there was a difference of opinion a third opinion should be sought. In mid-1971 the following protocol was designed for combined panel diagnosis. Two opinions are necessary for diagnosis and these two opinions should be combined as below: The Mesothelioma Register, which in 1967 and 1968 recorded cases from all available sources, hat since continued with notifications of deceased caw only. The following table gives details o f notification (subject to confirmation) for the years up to 1971, figures for the years 1967 and 1968 being included on a similar basis for comparison. N otifications to the Mesothelioma R egisth (D eath C ases) 1967-71 Sources o f notification Death certificate Cancer Registry1 Industrial injury data* Other Total 1967 966 1969 1970 1971 91 189 126 165 124 3 28 20 ti 11 ' 3 3 6 3 30 13 i 5 3. 163 233 157 184 131 `Not so certified at death `Not on death certificate or c - registration In the short period studied it is not possible to observe a significant trend. The large number of cases notified in 1968 may have resulted from the publicity and vigilance generated by the survey. If the impression of a falling off in notifications is coofirmed then whether this will be due to a change ia the prevalence of the disease or to a change io vigilance will require to be evaluated. First opinion Second opinion Dfinit Probable Possible Not Definite mesothelioma Definite Definite --p -- Probable mesothelioma Definite Undecided Undecided -- Possible mesothelioma -- Undecided Undecided Not Not a mesothelioma -- Not Not