Document b5g4kZMRboae1DkyYz2rkbDB3

t-Zd-2 4 . ... _ Sputum cytopathological findings in former asbestos workers S. Donald Greenberg, MD; George A. Hurst, MD; William T. Matlage, MD; Charles S. Christianson, MD; Irby J. Hurst, MD; Linda C. Mabry, CT Cigarette smoking asbestos workers con stitute a high-risk group for the potential development of lung cancer. The Tyler Asbestos Workers Program was begun in July 1974 to examine 890 former asbes tos workers, approximately 90% of whom are cigarette smokers. As of April 1975, 456 former workers had been studied by sputum cytopathology; 217 (48%) were found to have mild squamous epithelial atypias, 20 (4%) severe atypias, and 1 (0.3%) malignant cells of a squamous carcinoma. Sputum cytopathology has been found to be an excellent, simple, noninvasive, painless, and inexpensive means of early detection of premalignant and malignant lesions of the lungs. One-third (33%) of these former as bestos workers had ferruginous bodies in their sputum. The ferruginous bodies were most numerous in aerosol-induced sputa specimens and could be readily identified by the routine Papanicolaou stain. Introduction The Tyler Asbestos Workers Program has been developed for former asbestos workers in order to provide them the most up-to-date care for the early detection and treatment of pulmonary diseases, par ticularly carcinoma. Approximately 90% of these men are also cigarette smokers, and this along with their previous occupa tional asbestos exposure renders them 90 times more likely than the general popu lation to develop carcinoma of the lung.12 The cohort for the program is composed From the Department of Pathology, Baylor College of Medicine, and the East Texas Chest Hospital, Tyler, Texas. Supported in part by Contract No. l-CN-45-66 of the National Cancer Institute, Division of Cancer Control and Rehabilitation to the Texas Chest Foundation. of 890 former amosite asbestos workers, most of whom still live within a 150-mile radius of Tyler, Texas. The plant operated between 1954 and 1972. The program began in July 1974, and is ongoing. Each former worker is scheduled for a complete interview, physical examination, and lab oratory diagnostic studies including com plete blood count and urinalysis, roent genogram of the chest, electrocardiogram, spirometry, and sputum cytopathology which serves as the heart of the program. Through April 1975, 1,184 sputum speci mens from 456 workers had been studied and the results serve as the basis of this report. Material and Methods Sputum is collected by both aerosol inhalation during the initial clinic visit and early morning cough at home. All sputa are collected directly into 60% alcohol which serves as an instant fixative. Three sequential early morning home-col lected sputa are mailed to the cytopatho logy laboratory and pooled into one. Spu tum induction is carried out by transoral inhalation of a few breaths of an ultrasonic aerosol mist of 8% solution of sodium chloride in water. After inhaling as few as three to five breaths, the patient yields an adequate specimen which is collected directly into 60% alcohol in the sputum container. The sputum specimens are poured into a Petri dish and the cytotechnologist, using curettes, selects out portions of cellular aggregates, debris, and particulate matter and transfers them onto four prelabeled microscopic slides which have been coated with a thin layer of albumin. The cellular material is spread thinly and evenly over the slide by a sec ond slide which is not albumin coated. The Voluma 72, January, 1976 ( 1 I ABS-010584 Asbestos workers' sputa * i slides to be stained are then placed in 95% ethyl alcohol, in a Coplin jar and subsequently stained in the routine man ner by the Papanicolaou technique. The remainder of the specimen is utilized for preparation of a cell block. The sediment for the cell block is placed into a tissue embedding bag, passed through the rou tine tissue fixatives, and embedded in paraffin. The paraffin blocks of the sedi ment are sectioned and stained with hema toxylin and eosin and Prussian blue for iron. Screening of the Papanicolaou-stain ed sputum smears averages five to seven minutes per slide. Black ink dots are placed by atypical cells and green ink dots by ferruginous bodies. The total number of ferruginous bodies per specimen (four slides) is reported as follows: few, 1 to 14; moderate, 15 to 29; and many, more than 30. For quality control, the cytopathology slides of 10% of all negative sputa specimens are rescreened. The sputa specimens are reported as unsatisfactory (saliva), no atypia, mild atypia, severe atypia, and positive for carcinoma. Free alveolar macrophages must be identified in order for the speci men to be considered adequate; other wise it is presumed to be unsatisfactory. Mild atypias include squamous metaplasia and mild dysplasias. Severe atypias in clude moderate and severe dysplasias. The term "dysplasia" is used to imply dyskaryosis. The squamous metaplasia and the dysplasias are thought to be re versible atypias of the bronchial epitheli um. "Positive for carcinoma" includes both carcinoma in situ and invasive carci noma. We are applying this nomenclature of descriptive terminology to represent the progression of epithelial atypias from the mildest change of simple squamous metaplasia to the development of frank squamous carcinoma. Results Ferruginous bodies have been found in the sputa of approximately one-third of the former asbestos workers. Less than 1. Photomicrograph of sputum showing a dumbbell shaped ferruginous body. Note the adjacent cluster of free alveolar macrophages. Papanicolaou stain. X260. 2. Photomicrograph of sputum showing a lance shaped ferruginous body. Papanicolaou stain, X260. 40 TEXAS MEDICINE 4I ABS-(t)10585 ft 1 % of those tested have failed to produce satisfactory specimens. Thus far, only one former worker has been found to have cells positive for squamous carcinoma in his sputa. He was a 76-year-old Cau casian man who had worked in the as bestos plant from 1954 to 1961. He was also a chronic cigarette smoker of 180 pack years.* Initial sputum examination disclosed both ferruginous bodies (Figs 1, 2) and malignant cells of squamous carcinoma (Fig 3). A roentgenogram of the chest showed reticular infiltrates con sistent with interstitial fibrosis in the low er lobes of both lungs; however, no local izing lesion was seen. Fiberoptic bron choscopy revealed an ulcerating lesion of the bronchus intermedius which, by brush ing, washing, and biopsy, was positive for squamous carcinoma (Fig 4). Media stinoscopy and other routine laboratory studies showed no metastasis, and a right exploratory thoracotomy was performed. When visceral pleural metastases were dis- Three packs of cigarettes/day/50 years. covered, the carcinoma was considered to be unresectable and the operation was - terminated. The patient refused both radi ation therapy and chemotherapy, and died of probable ventricular fibrillation six months after diagnosis. Necropsy re vealed the squamous cell carcinoma of the bronchus intermedius (Fig 5) with metastases to right bronchial lymph nodes, right visceral pleura, and pericardium. Asbestosis with interstitial fibrosis was present in both lower lobes of the lungs (Figs 6, 7) and centrilobular emphysema was present in the upper lobes. Twenty former workers (4%) have had sputa with severe epithelial atypias, and 48% have had mild atypias, the majority of which are squamous metaplasia. In the group of former workers whose sputa has yielded ferruginous bodies, the aerosol method of sputum specimen in duction has provided for more frequent recovery of the bodies than spontaneous sputa alone. Also, by our methods of quantitation, the aerosol-induced sputa specimens contain a larger number of 3. Photomicrograph of sputum revealing two large malignant cells of squamous carcinoma. Papani colaou stain, X 260. 4. Photomicrograph of the tissue preparation of the bronchial biopsy. Note nest of malignant cells of squamous carcinoma. Hematoxylin and eosin stain, X145. Voluma 72, January, 1976 Asbestos workers' sputa 5. Gross photograph of a coronal section of the right lung. Note the irregular white squamous carcinoma (arrow) involving the bronchus intermedius. 6. Gross photograph of coronal section of right lung. There is diffuse interstitial fibrosis of the lower lobe (arrow). 1 ferruginous bodies.'This appears to be ^gyen more significant when one considers thattfie aerosol-induced specimen is a single specimen, while the spontaneous specimen is a pool of three. The sputa specimens with severe epithelial atypias were equally distributed between aerosolinduced and spontaneous specimens. Discussion While the first cases of pulmonary fibrosis caused by asbestos inhalation were report ed in 1929,3 and the first case of lung cancer associated with asbestos in 1935,4 it was not until 19682 that epidemiologic studies established the role of asbestos in the development of lung cancer in ciga rette smoking asbestos workers. The Tyler asbestos plant was in opera tion between 1954 and 1972, employing 890 men who processed amosite asbestos mined in South Africa. For many years, sputum cytopathology has been known to be a useful clinical laboratory means of early detection and diagnosis of lung cancer, yielding positive results in up to 80% of cases.3 Only re cently, however, has the role of fiberoptic bronchoscopy been established in the localization of superficial endobronchial carcinomas.* Serial roentgenograms of the chest will not permit truly early detection of lung cancer because such a cancer must grow and double for more than five years before it becomes large enough to be seen by the radiologist.7 Thus far, in the Tyler Asbestos Workers Program, only one of 456 former workers has had a sputum cytopathologic diag nosis of squamous carcinoma. Although the roentgenogram of this man's chest showed no localizing lesion, the cancer found by fiberoptic bronchoscopy in the bronchus intermedius had already metas tasized to the visceral pleura and was nonresectable for cure. Twenty of these 456 former workers have severe atypia of epithelial cells in their sputa. Close clinical and cytologic follow-up of these 20 patients is presently in progress. As the program continues, all 890 former workers will be examined and reexamined TEXAS MEDICINE routinely at six-month intervals or more often depending upon cytopathologic and clinical findings in each case. As yet, no statistical correlations can be made between the association of fer ruginous bodies (Fig 8) and atypical epithelial cells in the sputa, but in the future, as more data are gained, this will be of great interest. Even now, one can state that the finding of ferruginous bodies in such numbers indicates significant as bestos exposure, because from 1972 to 1975, not one such body had been found in similar cytopathologic examinations of 12,000 sputa specimens from the general public in the Cytopathology Laboratory of the Harris County Hospital District, Hous ton, Texas. Conclusion Sputum cytopathology is an excellent, simple, noninvasive, painless, and inex pensive means for early detection of ma lignant and premalignant lesions of the lung, and no special techniques are neces sary for the identification of ferruginous bodies. 7. Photomicrograph of tisane preparation from right lower lobe of lung showing a deeply stained fer ruginous body with associated free alveolar macro phages and fibroblasts. Prussian blue stain, X170. References 1. Selitoff, IJ, Churg J, Hammond EC: Asbestos ex posure and neoplasia. JAMA 188:22*26, 1964. 2. Selitoff IJ, Hammond EC, Churg J: Asbestos ex posure, smoking and neoplasia. JAMA 204:106-112, 1968. 3. Cooke WE: Fibrosis of the lungs due to the in halation of asbestos. Br Med J 2:578-580, 1929. 4. Lynch KM, Smith WA: Pulmonary ssbestosis: car cinoma of lung in asbestos-silicosis. Am J Cancer 24:56-64, 1935. 5. Russell WO, Neidhardt HW, Mountain CF, et al: Cytodiagnosis of lung cancer. A report of a four-year laboratory, clinical, and statistical study with a review of the literature on lung cancer and pulmonary cytology. Acta CytoJ 7:1-44, 1963. 6. Manats-Estrella P, Fry WA: Cytologic diagnosis of lung lesions by bronchial brushing. Ann Clin Lab $d 3:289-295. 1973. 7. Fontana RS: The Philadelphia Pulmonary Neo plasm Research Project JAMA 225:1373-1374, 1973. Dr. Greenberg, Director of Cytopathology, De partment of Pathology, Baylor College of Medi cine, Texas Medical Center, Houston, Texas 77025. Drs. G. A. Hurst, Matlage, Christianson, I. J. Hurst, and Ms. Mabry. Tyler Asbestos Workers Program, East Texas Chest Hospital, Box 2003, Tyler, Texas 75701. 8. Artists sketch of a club-shaped ferruginous body with associated free alveolar macrophages. Volume 72, January, 1976 ABS-010588 Lead health hazards from smelter emissions The El Paso City County Health Depart where climatic conditions such as aridity, ment began an investigation of a large low wind velocity, and frequent thermal custom smelter in its city in December 1971 in preparation for a court case filed inversions minimize opportunities for pol lutant dispersion. Studies of human lead by the city for violations of Texas rules absorption in such areas as described and regulations governing air pollution. might illustrate further the potential The smelter has been in operation since health hazard posed by particulate lead 1887, producing lead, copper, and zinc and its role and route of absorption from from over 800,000 metric tons of ore the environment. concentrates shipped to this central loca In our studies, first we determined lead tion. During the investigation, it was de concentrations in particulate matter col termined that the smelter had emitted lected with high-volume samplers 1,012 metric tons of lead, as well as 508 metric tons of zinc, 11 metric tons of throughout El Paso from 1969 through 1971. After consulting with appropriate cadmium, and 1 metric ton of arsenic authorities concerning the measured lead from its stacks into the surrounding at mosphere from 1969 through 1971.12 levels in the ambient air, we then pro ceeded to determine blood lead levels in a The emission of particulate lead into sample of persons living throughout El atmosphere has been of concern not only in El Paso but throughout the United Paso. Results of this initial study caused us concern and thus began an extensive States, where it is estimated that 166,000 study of exposure of these people to lead metric tons of particulate lead alone is in dust, soil, paint, food, water, and pot emitted into the atmosphere each year.3 tery. Our purpose was to ascertain the The principal source of this emission is prevalence and severity of lead absorp from the automobile, and this has led to a growing realization that this source may tion in this locale, and to evaluate the role of particulate lead in lead uptake (Fig 1). be a widespread and potentially important source of lead absorption among chil dren.4-5'282'31 Chronic ingestion and in Background halation of particulate lead from contami El Paso is located in the extreme western nated dust, soil, and air may account in part of Texas alongside the Rio Grande part for the higher mean blood lead levels River adjoining Ciudad Juarez,Chihua of urban as compared to rural children,4 hua, Mexico. According to the 1970 and may account for the increased lead United States census, it has a population levels seen in children living near busy of 322,261. roadways.* The topography of the area is moun While automobiles may be the major tainous with the City of El Paso separated source of lead-bearing particulate mat by the Franklin Mountains and the Juarez ter, stationary sources such as smelters Mountains to the south in Mexico. The can create environmental concentrations area is semidesert and arid to the extent of lead which should be closely watched that rainfall supports only limited vegeta and monitored. High levels of lead concen tion (10 to 25 cm of rainfall per year).11 trations in the vicinity of stationary Winds are moderate (annual average 13.5 44 sources710 are particularly possible km per hour)12 but a fine, gritty dust be- TEXAS MEDICINE ABS-010589