Asbestos-related lung cancers: A retrospective clinical and pathological study

Introduction

Occupational lung cancer generates high mortality and is the most common cancer compensated in France (1). In 1997, the Helsinski criteria for identifying individuals with a high risk of asbestos exposure at work were accepted (2). Older studies found inconsistent results regarding the lobe of origin and histology of asbestos-related lung cancer (ARLC) (3). Some studies showed an upper lobe location similar to tobacco-related lung cancer, whereas other investigators found a lower lobe location (4–11). Although adenocarcinoma was found to be the most prevalent in some studies, a recent review of the literature by Nielsen et al (3) showed that there was no difference in location and cell type between ARLC and non-ARLC. They concluded that cell type and location of lung cancer were not useful for differentiating ARLC from other lung cancers. Prognosis of ARLC was not different from that of other lung cancers (3).

Presence of pleural plaques demonstrated a previous asbestos exposure but was not a precancerous condition. Asbestosis argued for high asbestos exposure and was associated with an increased risk of lung cancer (3). All asbestos types were associated with lung cancer (3).

Asbestos-exposed smokers had a higher risk of developing lung cancer compared with asbestos-exposed non-smokers. In fact, smoking was found to be the main risk factor but its interaction with asbestos was not totally clear (3). Some studies showed a multiplicative effect, whereas other studies suggested an additive model (12–15).

The present study investigated the occupational data of patients with compensated lung cancer, their smoking habits and histological subtype of lung cancer. The aim of the present study was also to discuss the criteria for warding occupational cancer compensation.

Patients and methods

After ethics approval was obtained from our institutional review board (CHRU Brest, 2016. CE10), we led a retrospective study based on financially compensated ARLCs identified in occupational disease center between 2003 and 2013. Data on occupational history and smoking habits were collected. Ex-smokers were defined as those who had ceased smoking at the time they consulted in our occupational disease center. Non-smokers were defined as those who had never smoked in their lifetime. Tumor location and histological subtype of lung cancer were noted according to the last pathological data. Patients who had two occupations were recorded separately.

The present study included 146 male patients of whom the majority (90%) were heavy current or former smokers (mean, 30.4 packs/year).

Results

Patient characteristics

In total, 146 male patients with a mean age at diagnosis of 63.2±9.9 years (range, 37–85 years) were included in the present study. Ex-smokers represented 79.5% (116/146) of the cohort, followed by smokers (10.3%, 15/146) and non-smokers (5.5%, 8/146). No data were available for 4.8% (7/146) of the patients. The mean consumption of ex-smokers and smokers was 30.4±16.9 packs/year.

Work-relatedness

Ship repair was the most prevalent occupational industry (69.9%, 102/146), followed by building construction (7.5%, 11/146), and electricity (4.8%, 7/146 (Table I). The most common types of job were maintenance and repair (mechanics, 38 cases), followed by electricity and cable setting (31 cases), welder (27 cases) and boiler-related jobs (7 cases). Thirteen patients had two types of industrial classification in their professional career. Regarding the frequency of asbestos-containing materials, thermal insulation was the most prevalent (64 cases), followed by asbestos dust on equipment (58 cases), seal coating (41 cases), thermal protection workstation (33 cases), and asbestos cement (25 cases) (Table II). The mean duration of asbestos exposure for lung cancer was 28.3±10.1 years, while the mean duration of the latency period was 10.5±8.6 years.

Table I. Distribution of industries and jobs of patients with asbestos-related lung cancers.

Table I.

Distribution of industries and jobs of patients with asbestos-related lung cancers.

Type of exposure	Industrial classification	Job occupation	No. of workers
One type of industrial classification inpatients' professional career
Handling of asbestos-containing products during their job	Building construction	Bricklayer/ carpenter (5) Plumber, sheet metal construction worker (1) Painter (1)	10
	Building construction (two job occupations quoted)	Carpenter and cable setting man (1), Crane operator (demolition waste and brake lining assembler) and maintenance (1) Brake lining assembler/mechanic (1)
Handling of asbestos-containing products during their job	Ship building and repair	Carpenter (11), Mechanic (29), Boiler maker and installer (1),Welder (22), Storekeeper (1), Electricity and cable setting man (24) Maintenance (1), Painter (1) Details not provided (3)	102
	Ship building and repair (two job occupations quoted)	Mechanic and boiler installer (1), Mechanic and carpenter (2), Carpenter and cable settingman (1), Painter and boiler installer (1), Truck driver and installer (2), Installer and storekeeper (1), Coppersmith and mechanic (1)
Handling of asbestos-containing products during their job	Electricity/ gas and steam power	Installer (1), Electricity and cable setting man (4), Boiler installer (1), Mechanic and boiler installer (1), Coppersmith (1)	7
	Transportation services	Maintenance and repairman (1)	1
Using asbestos-containing products in manufacturing process	Manufacturing plastics and rubber materials	Mechanic (2), Electricity and cable setting man (2),Welder (1), Working in co-activity (4)	9
	Details not provided	Details not provided (1), Plumber (1), Welder (2)	4
Two types of industrial classification in patients' professional career
Handling of asbestos-containing products during their job	Building construction and ship building	Bricklayer and boiler installer (1), Maintenance and storekeeper (1), Welder (1), Carpenter and boiler installer (1), Plumber and welder (1)	5
	Building construction and electricity/gas steam power	Mechanic, installer and boiler installer (1)	1
	Building construction and national defense	Electronics (1)	1
	Manufacture of motor vehicles and national defense	Mechanic (brake lining assembler) (1)	1
	Ship building and national defense	Painter (1)	1
	Ship building and water distribution installation	Installer and coppersmith (1)	1
Handling of asbestos-containing products during their job	Ship building andmanufacture of basic iron and steel	Welder, installer and maintenance (1)	1
	Details not provided	Details not provided (2)	2

Table II. Distribution of asbestos-containing materials (no. of times where materials are quoted).

Table II.

Distribution of asbestos-containing materials (no. of times where materials are quoted).

Type of asbestos-containing materials	No. of times where materials are quoted
Thermal insulation	64
Asbestos dust on equipment	58
Seal coating	41
Thermal protection workstation	33
Asbestos cement	25
Individual thermal protection	18
Waste	17
Friction linings	11
Flocking	9
Loose asbestos	3
Asbestos resin	1
Details not provided	5

Tumor localization

The tumor was located in the upper lobe in 61.6% (90/146) of the cases, followed by the lower lobe (21.2%, 31/146), the middle lobe (3.4%, 5/146), and lower and middle lobe associated with 2.1% (3/146). No data were available for 11.6 % of cases (17/146).

Histological cancer type

Adenocarcinoma was the most frequent cancer (45.9%, 67/146), followed by squamous cell carcinoma (38.4%, 56/146), small cell lung carcinoma (4.8%, 7/146), undifferentiated/sarcomatoid carcinoma lacking adenocarcinomatous or squamous differentiation (2.1%, 3/146), and sarcoma (without specification 1.4%, 2/146; dedifferentiated liposarcoma 0.7%, 1/146). One of the undifferentiated sarcomatoid carcinoma arose in the posterior mediastinum without lung tumor. Further pathological analyses reclassified two tumors as lung metastases of an esophageal adenocarcinoma and a primary laryngeal squamous cell carcinoma. There was no histological proof of cancer in 6.8% (10/146) of the cases, diagnosis being only based on radiological data (investigations refused by the patients, non-contributive or prevented by the patients' general condition).

Compensated ARLC

Diagnostic criteria of asbestos-related diseases were established in France in 1950 and 1996 and updated in 2000 (Tables of occupational diseases 30 and 30 bis). The main recognized non-cancerous asbestos- related diseases are asbestosis (Table 30 alinea A) and pleural thickening or pleural plaques (Table 30 alinea B). Recognized asbestos-related cancers are malignant mesothelioma (Table 30 alinea D) and primary lung cancer (Table 30 alinea C if associated with non-cancerous asbestos-related diseases with a requirement of exposition to asbestos for >5 years or Table 30 bis without other asbestos-related diseases but with a requirement of exposition to asbestos for >10 years).

In the present study, the patients represented 52.1% (76/146) and 46.6% (68/146) of compensated lung cancers in Tables 30 and 30 bis, respectively (no data for 2 patients). In addition, 49.3% of patients had pleural plaques (72/146) and 13% had pleural thickening (19/146), while 44.4% of the pleural plaques were located in the costo-vertebral gutters (32/72) and 12.5% on the diaphragm (9/72), 5.6% were located on the anterior wall (4/72) and 5.6% on the posterior wall (4/72). Atelectasis strips were only evident in 2.7% (4/146), asbestosis in 0.7% (1/146) and pleurisy in 4.1% (6/146).

Discussion

To the best of our knowledge, this is the first comprehensive study conducted in France on occupational asbestos exposure and lung carcinoma pathological features. The link between lung cancer and asbestos exposure is sometimes difficult to attest (16). Two criteria for this recognition are used in many countries (Germany, Austria, Belgium, Finland, Norway, Sweden and Switzerland): proved intense exposure (Helsinki criteria or threshold of 25 fibers/ml/year) and/or asbestos-related conditions (asbestosis and/or extensive modification of the pleura) (17). In France, occupational disease tables with specific criteria are used to determine whether or not lung cancer is asbestos-related (Tables 30 and 30 bis) or not. The diagnosis must be based on histological data or, if not available, on the basis of a clinical course and suggestive radiological data (17). Many differences regarding criteria exist between European countries for the recognition of ARLC (Table III) (17).

Table III. European criteria for recognition of ARLC [(adapted from Eurogip. Les maladies professionnelles liées à l'amiante en Europe. 10–43. 1-1-2006). (1,17)].

Table III.

European criteria for recognition of ARLC [(adapted from Eurogip. Les maladies professionnelles liées à l'amiante en Europe. 10–43. 1-1-2006). (1,17)].

Country	Medical criteria	Exposure criteria	Latency
France	Histological examination or on the basis of radiological data and clinical course	10 years (Table 30 bis) or 5 years (Table 30 alinea C) of exposure Limiting list of works	Maximum: 40 years after the end of exposure
Germany	Lung cancer with asbestosis or pleural disease Alternative condition (see exposure criteria)	Exposure of 25 fibers/ml/year (alternative condition to medical criteria)	10 years at least No details provided
Austria	Lung cancer with asbestosis or pleural disease Alternative condition (see exposure criteria)	Exposure of 25 fibers/ml/year (alternative condition to medical criteria)
Belgium	Alternative conditions: Asbestosis or pleural thickening Under optical microscope: 500 asbestos bodies per gram of dry lung tissue or at least 5 asbestos bodies per ml of bronchoalveolar lavage Confirmed by electronic microscopy if doubt Under electron microscope:at least 5 million asbestos fibers longer than 1 µm per gram of dry lung tissue or at least 2 million amphibole fibers longer than 5 µm per gram of dry lung tissue Alternative criteria (see exposure criteria)	Exposure of 25 fibers/ml/year Or limitative list of works Or medical criteria equivalent to exposure above 25 fibers/ml/year	10 years
Denmark	Better microscope diagnosis, otherwise probable diagnosis based on clinical presentation and course of the disease	Helsinski criteria	Details not provided
Spain	Lung cancer with asbestosis. If no asbestosis, diagnosis based on a biopsy, otherwise microscopic examination of the bronchoalveolar lavage	10 years (except for lung cancer with asbestosis)	10–20 years 10 years (if no asbestosis)
Finland	Diagnosis of a neoplasm of lung or bronchi by a pathologist. If asbestosis, automatic recognition	Helsinski criteria (if no asbestosis)
Italy	Radiologic examination (X-ray, CT-scan), blood tests, electrocardiogram, cytological examination	No criteria regarding a minimum duration or intensity of exposure	No details provided
Norway	Histologic examination or on the basis of radiological data and clinical course	Helsinski criteria	15 years
Portugal	X-ray, CT-scan, bronchoscopy, biopsy	Indicative list of works	10 years
Sweden	Diagnosis based on biopsy or cytology and X-ray Lung cancer with asbestosis or exposition criteria	At least 15–20 years or above 10 fibers/ml/year	15 years
Switzerland	Diagnosis based on radiological, histological data or bronchoscopic findings. Recognition if lung cancer with asbestosis or pleural diseases or exposition criteria	25 fibers/ml/year (alternative condition to medical criteria)	No details provided

Shipbuilding and repair are the main industry in Brest, a French port located at the Department of Occupational and Environmental Diseases. The workers most exposed to asbestos were involved in this activity. Approximately 90% of compensated lung cancer patients were current or ex-smokers in the present study. Very few studies described smoking habits in this population (3). A synergistic interaction between asbestos and cigarette smoking is commonly accepted. A review of 23 studies was in favor of a multiplicative interaction (13). However, the multiplicative effect claimed by Hammond et al (12) has never been replicated and the hypothesis of a model somewhere between additive and multiplicative is the most probable (3). In most European countries, smoking is not involved in the recognition procedure of ARLC (17). However, in Denmark, any doubt regarding exposure of asbestos, heavy smoking leads to rejection of the procedure (17). If the patient consumed more than 7 g of tobacco per day or more than 10 packs a year, smoking was taken into account for the compensation of lung and laryngeal cancer. Those considerations also applied to cases of asbestosis if obstructive airways disease or chronic bronchitis was revealed in the past clinical history (17). However, the smoking factor is never retained in cases of mesothelioma or pleural plaques (17).

Adenocarcinoma was the most prevalent histological subtype in the present study (45.9%). Excess of adenocarcinoma in ARLC was shown in some studies (3). Nevertheless, recent well-controlled studies failed to show any significant differences between ARLC and non-ARLC (3). Adenocarcinoma is in fact the most frequent type of lung cancer. According to a recent review of the literature, histology has no significant value in determining whether or not lung cancer can be due to asbestos (3).

Notably, thoracic sarcoma was identified in the present study. To the best of our knowledge, if the link between lung carcinoma and asbestos exposure is well established, this is not true about thoracic sarcoma (6,8–11,18–20). Further investigations also identified two non-primary lung origin carcinomas of esophageal and laryngeal origin in the present study with controversial data regarding the association with asbestos exposure in the literature. In addition, there was no histological proof for 6.8% of the compensated lung cancers, diagnosis being solely based on radiologic data. Metastases of non-ARLC or non-carcinoma tumors cannot be excluded for these cases. In our opinion, histological analysis is a major parameter to evaluate the relationship between asbestos exposure and a lung malignant tumor. It may permit the distinction between a carcinoma of lung origin in which the link with asbestos exposure is well established, and other more doubtful asbestos-related primary or metastatic tumors.

In conclusion, the present results are globally in accordance with other studies on ARLC. Even if the relationship between smoking and asbestos exposure is not clear, the cases reported in the present study strongly argue for the crucial importance of smoking cessation in asbestos-exposed workers.

Thus, histological data have to be considered to evaluate the potent relationship between asbestos exposure and lung malignancy. Indeed, although the relationship between asbestos and lung carcinoma is well established, it is insufficiently proven regarding non-carcinoma type and/or cancer from extra-pulmonary primitive origin, except for mesothelioma.

Acknowledgements

The present study was supported by ‘La Ligue contre le cancer CD29’. We would like to also acknowledge ‘Omnium group’ for financial support and the pathologists of Brest and Local tumor tissue biobank BB-0033-00037 (‘CRB Santé’, CHRU Brest) for their collaboration in the present study.

References