Thorax: first published as 10.1136/thx.26.1.6 on 1 January 1971. Downloaded from Thorax (1971), 26, 6. Diffuse malignant pleural mesothelioma and asbestos exposure F. WHITWELL and RACHEL M. RAWCLIFFE ))roadgreen Hospital, Liverpool; Aintree Hospital, Liverpool; and St. Catherine's Hospital, Birkenhead Pleural mesothelioma has been diagnosed in 52 patients in three hospitals on Merseyside between 1955 and 1970, 60% being diagnosed from operation specimens and the rest from postmortem tissues. Necropsies eventually held on nearly half the operation cases confirmed the diagnosis, giving a necropsy rate of 70% for the series. The morbid anatomy conformed to earlier descrip- tions except that widespread metastases were much commoner than has usually been described. Histological findings agreed with previous accounts of the tumour, except that, in our hands, special acid mucopolysaccharide staining was less reliable than Southgate's mucicarmine, which was of value in differential diagnosis. Association with asbestos was confirmed from industrial histories in 80% of cases, the commonest industries involved being shipbuilding and repairing in men and sackware repairing in women. Lungs of industrial mesothelioma cases showed basal asbestosis in 17% and excessive asbestos bodies in almost all the rest. Quantitative comparison of asbestos bodies in lung smears from mesothelioma cases compared with lung smears from other counts in the mesothelioma cases. The first Merseyside adults showed much higher interval from copyright. exposure to asbestos until appearance of mesothelioma ranged between 13 and 63 years, with a mean of 42 years. We think the incidence of mesothelioma will continue to rise with the increased use of asbestos until about 40 years after adequate protective measures have been taken. The recent reinstatement of diffuse malignant cases (Elmes, McCaughey, and Wade, 1965). In http://thorax.bmj.com/ pleural mesothelioma as a legitimate neoplasm 1964 Owen reported 17 cases of mesothelioma on dates mainly from the papers of Godwin in 1957 Merseyside with an asbestos link in 82% of cases, and McCaughey in 1958. However, the con- and in 1968 Harries analysed the trades at risk in troversy as to whether these pleural tumours are the Royal Naval dockyards. primary or almost always secondary might have These investigations have been largely retro- remained a nice academic exercise but for the spective, often involving much environmentaI work of Wagner, Sleggs, and Marchand who in and occupational research made after the patients' 1960 reported an association of pleural meso- deaths, and also hampered by an inadequacy of thelioma with asbestos exposure. They described preserved specimens, particularly lung tissue, on September 25, 2021 by guest. Protected 33 pleural mesotheliomas associated with asbestos making assessment of the asbestos association very exposure in Cape Province, the exposure being difficult, which may as a result have been under- more frequently environmental than occupa- estimated. The present paper is a prospective tional. continuation of the Merseyside series reported by Since then there have been many studies link- Owen in 1964, when he described cases occurring ing both pleural and peritoneal mesotheliomas between 1955 and 1963 in what was also largely with asbestos. In the United Kingdom the largest a retrospective study. series of cases published have occurred in East London, usually in people working in or living THE SUBJECTS STUDIED near asbestos factories (Enticknap and Smither, 1964; Hourihane, 1964; Newhouse and Thomp- Fifty-two cases have been examined, comprising 14 of son, 1965), and other accounts have described the 17 cases described by Owen (1964) and 38 addi- cases occurring in the major shipbuilding areas. tional cases which have occurred between 1963 and The Belfast cases described by McCaughey in 1970. The three cases of the earlier series not included 1958 were reviewed in 1965 with further cases are one which was a peritoneal tumour, one for which added, showing asbestos exposure in 32 out of 42 there were no histological sections, and one (his case 6 Thorax: first published as 10.1136/thx.26.1.6 on 1 January 1971. Downloaded from Diffuse malignant pleural mesothelioma and asbestos exposure 7 14) for which the records and slides have been lost. pulmonary oedema is present. The beaker is left at All but one patient, who was in the earlier series, room temperature for a day, when the contents are have been patients in Broadgreen Hospital or Aintree transferred to a conical centrifuge tube. After spin- Hospital, Liverpool, or in St. Catherine's Hospital, ning the tube the supematant is discarded and smears Birkenhead. These three hospitals admit the majority of the deposit are spread on a microscope slide. The of Merseyside pleural mesotheliomas, because patients dried smear is mounted in balsam and examined with are referred to the Regional Thoracic Surgical Centres a 2/3 in objective. Quick identification of asbestos at Broadgreen and Aintree Hospitals, while St. bodies can be aided by staining with Perls' stain, but Catherine's Hospital is the district hospital for most the intense blue staining sometimes makes it difficult of those who work in Birkenhead shipyards. Though to differentiate true from pseudo asbestos bodies, as all the cases were diagnosed in these hospitals a few the centre of the body becomes obscured, so un- died in other hospitals where necropsies were some- stained smears are preferred. times performed. Tumour tissue and necropsy reports This method of preparing smears can be used quite were available for study in these cases, though some- satisfactorily with lungs which have been fixed for times no lung tissue was examined microscopically. several years. HISTOLOGICAL EXAMINATION IN NECROPSY CASES DIAGNOSIS The following routine has been adopted in the three The diagnosis has always been made from histo- hospitals for the last 24 cases, being performed by logical findings, obtained during the patients' lives ourselves in 18 cases. in 60%, of cases and at necropsy examination in the rest. THE TUMOUR Several tissue blocks from the primary was it to make a definite and its direct extensions, and blocks from any secon- Only rarely possible daries, were examined microscopically in each case. diagnosis from a needle biopsy specimen, and Sections were stained routinely with haematoxylin and most tissues were obtained at thoracotomy when eosin, and alcian blue. In pleural biopsy, pleurectomy, decortication, and Southgate's mucicarmine, copyright. the earlier cases, in order to demonstrate hyaluronic occasionally pleuro-pneumonectomy was per- acid (Wagner, Munday, and Harington, 1962), Hale's formed. The same staining methods were used colloidal iron, alcian blue, Southgate's mucicarmine, with operation specimens as with the postmortem and periodic acid Schiff were used on hyaluronidase- tissues. Positive diagnosis was made in 30 patients, treated and untreated sections, but the method was confirmed eventually at necropsy in 14 cases. abandoned as the results were inconclusive, possibly Eleven patients have died without necropsy http://thorax.bmj.com/ due to formol-saline fixation. studies, and five are still alive who have been THE LUNGS The lungs were examined for fine fibrosis, diagnosed in the last three years. It was possible honeycomb areas, and scarred areas. Blocks were to find asbestos bodies in only four of these examined from any such areas but also from the surgical specimens, which usually showed just bases of a lower lobe when the lung tissue looked narrow rims of subpleural alveoli, or consisted normal. In addition 20 ,u thick unstained sections from only of parietal pleura. In 22 cases the diagnosis the base of a lower lobe were examined for asbestos was first confirmed at necropsy, though often it bodies. had been suspected clinically for months or even on September 25, 2021 by guest. Protected years. In seven of these cases there had been LUNG JUICE SMEARS Asbestos bodies are more negative pleural needle biopsies. readily demonstrated by examining smears of lung juice than by examining lung sections. The same method of lung juice preparation was used through- HISTOLOGICAL FEATURES out this study and also in a series of 200 consecutive adult necropsies at Broadgreen Hospital in 1966-7. The wide range of microscopical features re- The method is not as searching as many that have ported by many writers and well described and been described but seems to have about the same illustrated by Godwin (1957), McCaughey (1958), sensitivity as the techniques used by Roberts (1967) in and Hourihane (1964) were present in this series. Glasgow, and Ashcroft (1968) on Tyneside. It does Though some admixture of types was found in provide a comparison of the lung asbestos body con- most cases, the tumours were predominantly of tent of the urban population of Merseyside with that one form in over half the cases. They were classi- of the mesothelioma patients. fied as follows: At necropsy a basal segment of lower lobe is removed and cut into several pieces, which are Tubulo-papillary 20 cases squeezed hard over a beaker, into which the fluid Sarcomatous 11 cases collects. Enough water is added to the juice to haemo- Undifferentiated polygonal 3 cases lyse the red cells, though this is unnecessary when Mixed 18 cases Thorax: first published as 10.1136/thx.26.1.6 on 1 January 1971. Downloaded from 8 F. Whitwell and Rachel M. Rawcliffe Tumour giant-cells were sometimes present in 4. Dilated acini often contain and may be dis- the sarcomatous, polygonal, and mixed types. tended by branching papillary fronds of tumour cells, which arise from acinar lining cells and TUBULO-PAPILLARY TYPE These tumours can often cover a fine connective tissue core (Fig. 2). This only with difficulty be differentiated from feature is also seen in secondary ovarian carci- secondary adenocarcinomas, particularly those noma but otherwise suggests a mesothelioma. originating from primaries in the lung, prostate, 5. Where tumour has invaded lung or lymph stomach, breast, and ovary.