Asbestos lung cancer C34.9

Synonyms

Occupational bronchial cancer; occupational bronchial carcinoma; occupational lung carcinoma; asbestos-related bronchial cancer; asbestos-related bronchial carcinoma; asbestos-related lung carcinoma;

First author

The first two cases of occupational cancer in asbestos workers were described by M. Nordmann in 1938. As a result, the first protective measures were taken in Germany during World War 2 (Büttner 2004).

Asbestos lung cancer is a malignant disease of the lung caused by exposure to asbestos. The disease is a notifiable occupational disease (Herold 2022).

The following classifications are available under lung carcinoma:

- Macroscopic classification according to location and spread.

- Degree of differentiation

- TNM- classification lung carcinoma UICC 2017 (8th edition)

- Lymph node status

- metastases

- Stage classification

- Classification in small cell lung cancer (SCLC):

- Regression grades

Lung carcinoma is the most common cause of cancer death in men, and is 2nd in women (after breast carcinoma). Occupational carcinogens cause approximately 5% of all lung cancers, with asbestos being the most common trigger at >90% (Herold 2022).

Barone- Adesi et al (2016) estimate the number of lung carcinomas triggered by asbestos exposure to be much higher than the number of mesotheliomas caused by asbestos.

After asbestos exposure, the risk of developing lung cancer is 20-fold higher in nonsmokers and 50-fold higher in smokers compared to people without asbestos exposure (Haustein 2008). If there is also an interaction with PAH (artificial mineral fibers), the probability of developing lung cancer is at least 50% (Herold 2022).

In Germany, asbestos-induced malignancies (see "Asbestos-related diseases") are the most common occupational cancer.

Due to the long latency period (15-50 years), diseases are expected to peak around 2020 (Herold 2022).According to the Guideline Program (2018), the rate of asbestos-triggered carcinomas has remained approximately constant since 1995, at about 700 cases per year.

Workers in cement plants and shipyards are particularly at risk, as are workers who handle insulating materials (Thomas 2010) or are involved in asbestos mining or processing. However, other groups are also at risk, such as those who wash clothes that have come into contact with asbestos (Nowak 2018), painters, electricians, those exposed to asbestos through road surfacing or playground materials, etc. (Kasper 2015).

Indirect exposures such as washing work clothes are not eligible for recognition because they are not occupational exposures (Nowak 2018).

Because the latency period for asbestos-related lung cancer is very long, asbestos-associated lung cancers have only been observed since 1975. At that time, there were only 15 proven cases. Then, in the following years, there was a rapid increase in the numbers (Ukena 2018).

Although the neoplastic effects of asbestos have been known since the mid-1930s, asbestos itself was used medically until the second half of the 20th century, e.g., in spontaneous pneumothorax or it was applied preoperatively to the pleural space to make it stick together (Ulmer 1976).

Asbestos-related lung carcinoma is caused by inhaled asbestos dust consisting of various silicates such as amosite, anthophyllite, chrysotile, crocidolite, etc. (see also types of asbestos), which have a fiber width of less than 3 µg in diameter and a length of more than 10 µg. Only with these size ratios do the fibers succeed in penetrating the alveoli on the one hand, and on the other hand their removal by macrophages is significantly more difficult due to their size (Piper 2007).

In a study by Klebe et al. (2020), it was demonstrated that asbestosis is not a prerequisite for asbestos-related lung carcinoma; likewise, pleural plaques do not increase the risk (Harber 2020).

After inhalation of dusts containing asbestos fibers, they are deposited in the peripheral airways and alveoli. From there, they enter the parenchyma of the lung up to the area of the pleura. There they can be visualized by scanning electron microscopy as protruding fiber ends consisting of phagocytosing cells (Matthys 2009).

In the further course, a chronic inflammatory and fibrosing process with fibroblast proliferation and macrophage activation occurs. Edema with histiocytic and giant cell reaction occurs in the terminal bronchial area, followed by interstitial collagen fiber proliferation. This spreads to the septa and alveoli, resulting in progressive fibrosis of the alveoli, alveolar ducts, and bronchioli. However, the elastic structures are typically preserved in the process (Kraus 2020).

Chronic damage to the epithelium leads to cell dysplasia and metaplasia and even the development of carcinoma (Ludwig 2020).

The latency period between exposure and the onset of lung cancer is a minimum of 15-19 years (Kasper 2015) and a maximum of 60 years (Matthys 2009).

In the early stage of the disease there are usually no symptoms.

Only as the disease progresses do symptoms appear:

• Cough
• chest pain
• dyspnea

and as late symptoms:

• Hemoptysis
• Phrenic paralysis
• Pleural exudate
• recurrent paresis
• Influence congestion (V. caca- superior- syndrome)
• First manifestation by metastasis with initially unknown primary tumor (so-called CUP- syndrome = cancer of unknown primary site)

(Herold 2022)

• Dysphagia (with obstruction of the esophagus)
• Anorexia
• general weakness
• Night sweats
• fever (Kasper 2015)

In the rarely occurring bronchoalveolar adenocarcinoma occurs:

• Irritable cough with mucopurulent watery sputum (Herold 2022).

Typical of Pancoast syndrome - a peripheral lung tumor located near the apex (Harvey 2012) - are:

• Horner's symptom complex due to infiltration of the stellate ganglion (Ludwig 2020) with
  • Ptosis
  • Miosis
  • Enophthalmos
• Intercostal neuralgia
• Bone destruction of the 1st rib and/or 1st BWK.
• Arm pain due to plexus neuralgia
• Swelling of the arm due to lymphatic or venous congestion (Herold 2022)

In small cell carcinoma, the following paraneoplastic symptoms may occur:

• paraneoplastic neuropathies and myopathies such as:
  • Lambert- Eaton syndrome with difficult stair climbing due to myasthenia-like weakness of the proximal limb muscles, ptosis, and double vision
  • paraneoplastic cerebellar degeneration
  • Polymyositis
  • dermatomyositis
  • neurological disorders (Herold 2022)
• paraneoplastic endocrinopathies such as:
  • Cushing's syndrome: This results from ectopic ACTH production and is the most common paraneoplastic disorder.
  • Hypoglycemia: Insulin-like growth factor II (IGF- II) is produced.
  • Tumor hypercalcemia due to ectopic production of peptides related to parathyroid hormone, so-called PTHrP
  • syndrome of inadequate ADH secretion
  • hypertrophic pulmonary osteoarthropathy ( Pierre-Marie-Bamberger syndrome):
  • Clock glass nails
  • drumstick fingers (in 0-20% [Ukena 2018]).
  • joint pain in hands, ankles, knees
• Thrombocytosis

This is found in about 1/3 of patients, often combined with a tendency to thrombosis (Herold 2022).

Dermatological symptoms

The following paraneoplastic symptoms/diseases may also occur in association with lung carcinoma:

• Erythema multiforme
• Erythema gyratum repens
• Exfoliative dermatitis
• Erythroderma
• Necrolytic migratory erythema
• Sweet syndrome
• Acanthosis nigricans
• Tylosis
• Pruritus and urticaria (Ukena 2018).

Metastases

In metastases, in addition to the above symptoms, there may be:

• Brain metastases:
  • Nausea
  • Vomiting
  • Headache
  • seizures
  • neurological deficits
• Bone metastases:
  • pain
  • pathological fractures
  • signs of spinal cord compression
  • cytopenia of blood cells
  • leukoerythroblastosis
• Liver metastases:
  • pain in the right upper abdomen
  • Hepatomegaly
  • Liver dysfunction or bile duct obstruction rarely occurs
• Adrenal metastases (common):
  • rarely pain (Kasper 2015)

The diagnosis of lung carcinoma includes - in addition to a detailed medical and occupational history, especially with regard to asbestos - the (imaging) examinations and laboratory findings mentioned below.

Physical examination:

- possibly enlarged lymph nodes (especially in the supraclavicular fossa)

- signs of upper influence congestion

- Evidence of anemia (Ludwig 2020)

To exclude distant metastases should be done:

- Sonography (especially of the liver)

- bone scintigraphy

- CT or MRI of the brain

- Bone marrow aspiration (to exclude M1 status in small cell lung cancer [Meyer 2020])

- PET (positron emission tomography)

[Herold 2022)

The Karnofsky index (Ukena 2018) is used to assess exercise capacity and general condition.

X-ray thorax

• Round focus:
• There is no decrease in transparency that cannot be caused by lung carcinoma.
• Mediastinal widening
• Atelectasis
• Pleural effusion (Ukena 2018).
• Signs of chronic pneumonia (in bronchoalveolar adenocarcinoma [Herold 2022]).
• In the presence of asbestosis, one finds:
• Pleural plaques: Pleural plaques with thickening or calcification of the parietal pleura are visible on radiographs - especially along the lower lung fields, cardiac border and diaphragm (Kasper 2015).
• The changes usually occur bilaterally, but not symmetrically (Kraus 2020)

The following factors are particularly suspicious for carcinoma:

• anamnestically known exposure to asbestos
• increase in size of the round focus (compared to previous images)
• spicules radiating into the lung parenchyma
• absence of calcification (Herold 2022)

In bronchoalveolar adenocarcinoma:

• Signs of chronic pneumonia (Herold 2022)

Computed tomography / spiral CT with 3D images / HRCT

CT, always contrast-enhanced, should be performed before bronchoscopy in order to target it. However, to establish the diagnosis of a solitary round focus, the morphological signs in CT are usually not sufficient, because although the sensitivity is very high, the specificity is only low (Ukena 2018).

In HRCT may be present:

• Pleural plaques:
  • predominant involvement of the lateral and diaphragmatic pleura.
  • Calcifications
  • occurring bilaterally (Herold 2022).
• Asbestosis:

Changes in the subpleural curve lines parallel to the surface with a length of 5 - 10 mm (Kasper 2015).

MRI

MRI is the most effective method for imaging brain metastases. It is equally used for imaging tumors in the superior sulcus (Kasper 2015).

MRI with contrast medium administration is also suitable for staging lung carcinoma - just like CT - or is even more suitable due to the higher soft tissue contrast (Ukena 2018).

PET- CT

PET- CT represents the most sensitive method in cases of previously unknown primarius or possible metastases (Herold 2022). For more details, see lung carcinoma.

Sonography

Both abdominal sonography and thoracic sonography should be used.

Abdominal sonography is particularly important with regard to any liver metastases, while thoracic sonography (TTUS) may reveal evidence of pleural effusion and allows puncture of tumors close to the chest wall (Ukena 2018).

Preoperative pulmonary function diagnostics

Pulmonary function should be assessed even before invasive diagnostic testing, as poor pulmonary function represents functional inoperability.

• Prerequisites for a pneumectomy are:
  • FEV1 > 2.0 l (80 % target)
  • Diffusion capacity (DLCO) > 60 % target
• Prerequisites for lobectomy are:
  • FEV1 > 1.5 l
  • Diffusion capacity (DLCO) > 60 % target (Herold 2022)

If values are poor, additional diagnostics of spirometry, pulmonary function scintigraphy, and blood gases are recommended.

• Spiroergometry:
  • low risk at oxygen uptake of > 20 ml / kg / min
  • medium risk at 16 - 20 ml / kg / min
  • high risk at 10 - 15 ml / kg / min
  • Inoperability even for lobectomy at < 10 ml / kg / min
• postoperative pulmonary function:

In addition, the lung function to be expected postoperatively should be calculated (Herold 2022). This can be done with the following formula:

Postoperative FEV1 in liters = preoperative FEV1 x (100 - percentage of lung perfusion of the portion to be resected relative to total perfusion).

(Herold 2022)

In the presence of asbestosis, pulmonary function typically shows:

• restrictive ventilation disorder
• Decrease of lung volume (especially FVC and TLC [Kraus 2020])
• decrease of diffusion capacity
• mild airway obstruction due to peribronchial fibrosis possible (Kasper 2015)
• arterial hypoxemia
• decreased oxygen uptake
• FEV1 / FVC (the function of the large airways) is typically well preserved (Kraus 2020)

Biopsies

Biopsies can be obtained by several techniques:

• 1. bronchoscopy

Bronchoscopy can be used to confirm the diagnosis biopsy-histologically. Identification of cancerous tissue can be improved by auto-fluorescence bronchoscopy (LIFE = Lung Imaging Fluorescence Endoscopy).

(Herold 2022)

• 2. EBUS

During endobronchial ultrasound (EBUS), mediastinal lymph nodes can be secured by fine needle biopsy (Herold 2022).

• 3. transthoracic puncture

This is used for peripheral round lesions > 2 cm by CT- or sonography-guided puncture (Herold 2022).

• 4. video-assisted thoracoscopy (VATS).
• 5. mediastinoscopy
• 6. Diagnostic thoracotomy (Herold 2022)

- CSF puncture

In patients with signs of spinal cord compression, such as weakness, paralysis urinary retention, etc., CSF sampling should be performed in addition to CT or MRI. Likewise in patients with symptoms of leptomeningitis (Kasper 2015).

- Bone marrowaspiration

This is indicated to exclude M1 status in small cell lung carcinoma (Meyer 2020).

For further investigations, see lung carcinoma.

Small cell carcinoma:

• In Lambert- Eaton syndrome:
  • Antibodies against VGCC (voltage gated calcium channel [Herold 2022])
• In paraneoplastic cerebellar degeneration:
  • Anti-Yo antibodies
  • Anti- Hu antibodies (found in about 15% [Herold 2022])
• Thrombocytosis (occurs in about 1/3 of patients and increases the risk of thrombosis [Herold 2022])
• ACTH elevated
• BG daily profile
• PTHrP (peptide related to parathyroid hormone)
• ADH (sometimes decreased)
• LDL (a steadily increasing level is associated with a poor prognosis)
• Tumor marker

These are not important in asbestos lung carcinoma, either in terms of diagnosis or follow-up (Herold 2022), as both sensitivity and specificity are too low (Ukena 2018).

• Hyponatremia

This can occur in the context of SIADH (syndrome of inadequate ADH- secretion) (Herold 2022).

• Leukoerythroblastosis (in bone metastases).
• Blood cell cytopenia (may be increased in liver metastases).
• Liver function values (increased in liver metastases).

(Kasper 2015)

• paraneoplastic endocrinopathies in SCLC with:
  • Hypoglycemia
  • Hypercalcemia
  • ACTH elevation
  • Disturbance of ADH - secretion (inadequate secretion)

(Herold 2022)

In lung cancer due to asbestos exposure, all known histological tumor forms occur (Kasper 2015) such as:

• small cell lung cancer = SCLC.

SCLC occurs in about 15% of all lung cancers (Herold 2022).

The cells are small and contain little cytoplasm. the nuclear chromatin is finely granulated, the cell borders are blurred, there are absent or inconspicuous nucleoli and a strikingly high mitotic count (Kasper 2015)

• Non-small cell lung cancer = NSCLC (the most common type, accounting for 80%). These include:
  • Squamous cell carcinoma (approximately 35%). This is morphologically identical to extrapulmonary squamous cell carcinoma (Kasper 2015).
  • Adenocarcinoma (approx. 40 %). In this case, glandular differentiation or production of mucin is often found (Kasper 2015).
  • Large cell lung carcinoma (approx. 10 %).
  • Adenosquamous carcinoma
  • Bronchial gland tumor
  • Carcinoid tumor
  • Sarcomatoid carcinoma (Herold 2022).

In every 3rd lung carcinoma, different histological proportions are found in the same tumor. Therefore, the percentages of the individual histological types often differ (Herold 2022).

For subsequent treatment, it is important to differentiate between small cell and non-small cell carcinoma, as their treatment is fundamentally different (Ukena 2018).

• Asbestosis:

In case of an additionally existing asbestosis, non-granulomatous fibrosis of the lung with acinar involvement and concomitant chronic inflammatory changes are found (Kraus 2020).

• Immunophenotyping

If a neuroendocrine lung tumor is detected, the diagnosis should be confirmed by immunohistochemistry (Ukena 2018).

• Lung carcinoma of other genesis
• Metastases of other primary tumors (Kraus 2020)

see also lung carcinoma

Metastasis of bronchial carcinomas occurs early to regional lymph nodes, then hematogenously to the liver, brain, adrenal glands, and skeleton (especially frequently to the spine). In small cell carcinoma, hematogenous spread is found very early, often at diagnosis (Herold 2022).

The therapy corresponds to the usual treatment of lung carcinoma (see d.).

Prognosis is determined by:

- tumor stage

- immunological type (patients with low lymphocyte count and negative skin test of delayed type have a particularly poor prognosis)

- histological type

- age and sex (women have a higher 5-year survival rate)

- general condition of the patient (Herold 2022)

- Weight loss of >10% of body weight is a prognostically unfavorable sign (Kasper 2015).

According to a 2013 Robert Koch Institute study, the 5-year relative survival rate was 21% in women and 16% in men, and the 10-year relative survival rate was 16% in women and 12% in men (Niehoff 2017).

Patients with Pancoast tumors have a 5-year survival rate of > 50% after appropriate therapy (Kasper 2015).

In 2013, 29,560 men and 15,524 women died of lung cancer in Germany (Ukena 2018).

• Primary prevention:

In Germany, both the manufacture and use of asbestos have been banned since the Hazardous Substances Ordinance of 1993 came into force - with the exception of its use as diaphragms for chlorine potassium electrolysis (Büttner 2004), EU-wide only since 2005 (Herold 2022).

As of 2019, asbestos is banned in 66 countries or regions of the world (Huang 2021).

It is also important to comply with the occupational health and safety measures required by law in case of occupational exposure (Ukena 2018).

• Secondary prevention:

Secondary prevention is for unavoidable exposure. Since materials containing asbestos are still present in many buildings today, demolition, renovation and maintenance of asbestos are now legally regulated by the Official Journal of the European Union, EU Directive 2009/148/EC on the protection of workers at work from asbestos. The Official Journal contains detailed information on dust control measures, wearing of special protective work suits, use of fine dust filters and regular occupational medical examinations (Büttner 2004).

Persons exposed to asbestos should be closely monitored by:

- sputum cytology with DNA cytometry for reliable detection of tumor cells

- Low-dose spiral CT with 0.2 - 1.0 mSv (tumor detection from a size of 2 mm diameter)

(Herold 2022)

• Follow-up

The intervals between follow-up examinations should depend on the individual case. They are usually days or weeks. Here, imaging techniques should be used in addition to physical examination, as well as laboratory analyses. However, routine bronchoscopy is not indicated (Meyer 2020).

Asbestos was included in the Occupational Diseases Ordinance in 1943. In 1973, the International Agency for Research on Cancer (IARC) classified asbestos as a human carcinogen (Guideline Program 2018).

In 1987, the International Agency for Research on Cancer (IARC) classified asbestos as a Class I carcinogen (Huang 2021).

In 1992, lung cancer was recognized as an occupational disease after 25 fiber years of asbestos exposure(Kraus 2020). The term "fiber years" is used to estimate tumor risk. One understands a fiber year = 1 x 10 to the power of 6 fibers / m³ x 1 year.

The risk of lung cancer, for example, doubles after 25 fiber years (Herold 2022).

The latency period between exposure and the onset of lung cancer is at least 15 - 19 years (Kasper 2015) to a maximum of 60 years (Matthys 2009). The higher the exposure was, the greater the risk of disease (Kasper 2015).

When the cumulative dose of asbestos fiber dust plus PAH (polycyclic aromatic hydrocarbons) combine, there is a 50% chance of lung cancer (Herold 2022)

According to CAP (College of American Pathologist) / NIOSH (National Institute of Occupational Safety and Health), only the detection of one asbestos body is required in the histological section. If this is not possible in the case of typical interstitial fibrosis or lung carcinoma, more sensitive methods such as lung dust analysis (LSA) should be performed. If light microscopic detection is not possible, electron microscopy is recommended (Kraus 2020).

For recognition as an occupational disease caused by asbestos, evidence of the so-called "bridge symptoms" is required. These are:

- in conjunction with asbestosis

or

- in connection with disease of the pleura caused by asbestos

or

- Evidence of exposure to a cumulative dose of asbestos dust for at least 25 years in the workplace (Herold 2022).

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