In the presence of a suspected lung cancer, it is necessary to go through an appropriate diagnostic process that provides a careful diagnosis of the lung cancer based on cytology and/or histology (typing) as well as a careful assessment of the disease’s extent (staging).
Lung cancers are divided into benign and malignant. Malignant lung cancers are divided into two main groups, small cell carcinomas (small-cell lung cancer-SCLC), which are about 15-20%, and non-small cell carcinomas (non-small-cell lung cancer-NSCLC) that are about 70%. NSCLC are further divided into three histological types, adenocarcinomas (50%), squamous cell or epidermoid (30%) and large cell cancers (10%).
Histological classification of lung cancers.
Benign
a)Papilloma
b)Adenoma
Malignant invasive
- Small cell lung cancer (SCLC) (20%)
- Non-small cell lung cancer (NSCLC) (70%)
Squamous cell or epidermoid
- Adenocarcinoma (acinar, papillary, bronchi-alveolar carcinoma)
- Large cell carcinoma
- Mixed
Other (10%)
- Adeno-squamous carcinoma
- Elements with pleomorphic carcinoma, sarcomatoid
- Carcinoid tumour
- Undifferentiated tumours
The lung squamous cell carcinoma
Epidermoid or squamous cell carcinoma develops from the bronchi and tends to grow within the bronchial tree, closing it, as well as outside and toward the lung tissue. In about 25% of metastasized lung cancer, this lung cancer can metastasize at the level of the adrenal glands and liver and more frequently to the hilar lymph nodes, mediastinum, pleura and the contra-lateral lung. However in 20-25% of cases lung metastases occur in the peripheral site evolving from the glands of the lung parenchyma. This site is usually that of adenocarcinomas, but it can also be the venue of lung metastases arising from primary cancers of other organs (pancreas, kidney, breast and large intestine), whose diagnosis can be made through the patient's clinical history and histology examination. Metastasized lung cancer is with high frequency (70-80%) to the mediastinal lymph nodes, the adrenal glands, liver, bones and brain.
Small cell lung cancer
Small cell lung cancer (SCLC) at the time of diagnosis is often scattered and tends to metastasize to regional lymph nodes, bone marrow, liver, adrenal gland and brain. Currently the incidence of small cell lung cancer is gradually declining (15%) in Europe.
Staging of lung cancer
The stage classification of lung cancer follows the TNM system (where the symbol T refers to the primary tumour, N refers to the lymph nodes involved and M refers to the presence of distant metastases).
T1 ≤ 3 cm
T1a ≤ 2 cm
T1b> 2 cm, ≤ 3 cm
T2 main bronchus ≤ 2cm from the hull, invasion of the visceral pleura, partial atelectasis
T2a> 3cm, 5cm ≤
T2B> 5 cm, 7 cm ≤
T3> 7 cm; chest wall, diaphragm, pericardium, mediastinal pleura, main bronchus <2 cm from the hull, complete atelectasis; one or more separate nodules in the same lobe
T4 mediastinum, heart, great vessels, hull, trachea, esophagus, vertebral bodies, one or more separate nodules in one different homo-lateral lobe
N1 homo-lateral peri-bronchial, homo-lateral hilar
N2 Homo-lateral mediastinum; subcarinal homo-lateral
N3 mediastinum and contra-lateral hilar, scalenic or supraclavicular
M1 Distant metastasis
M1a one or more nodules separated in a contra-lateral lobe; pleural nodules or malignant pleural or pericardial effusion
M1b Distant metastasis
The only true primary prevention (risk factor reduction) is to quit smoking and reduce environmental exposure to known carcinogens. Here are some important steps to take :
- support prevention programmes in schools that can be repeated over the course of the study period;
- carefully observe smoking bans in public places;
- protect yourself in high-risk workplaces because some environments can be a source of exposure to chemical or physical carcinogens, that may increase the incidence of lung cancer. In this regard, occupational exposure to asbestos involves a fivefold increase of the risk of lung cancer, and this risk becomes 50 times higher for those who are also smokers.
Secondary prevention (early detection of diseases already in progress) includes early diagnosis and treatment of pre-neoplastic lesions, or population screening, which in the case of lung cancer has unfortunately not shown great efficacy. Various studies for population screening have been carried out using chest X-ray, CT and sputum cytology. The results showed an increase in the percentage of lung cancer that is still resectable in the patients screened, but we do not know if this would reduce mortality in the whole population. The latest studies with spiral CT would seem to indicate an improvement of early diagnosis with an impact on survival, but the results of large randomised trials in progress are still pending. Other biological and genetic methods that seem promising are under investigation but they still need large-scale prospective studies. Tertiary prevention is the therapeutic treatment of lung cancer.
The symptoms of lung cancer strictly depend on the anatomical location of the disease, the level of aggressiveness and the type of growth. Sometimes the diagnosis of lung cancer is random.
The following lung cancer symptoms may cause the physician to suspect lung cancer:
- persistent cough
- dyspnea
- chest pain
- haemoptysis (coughing producing blood)
- dysphonia (voice alteration).
It is not easy for the doctor or the patient to attribute the symptoms to lung cancer, because they are mostly symptoms of other diseases that are quite common in smokers. That’s why the risk of delayed diagnosis is tangible in subjects with chronic bronchitis or emphysema.
Lung metastases are usually diagnosed randomly during follow-up visits after treatment of the primary cancer. It is rare for a lung metastasis to have symptoms. In this case the most frequent symptoms of lung cancer are cough, weight loss, and haemoptysis (emission of blood with cough).
Study for the early diagnosis of lung cancer
In 2000, the European Institute of Oncology (IEO) undertook a scientific study called C.O.SMO.S. (Continuous Observation of Smoking Subjects) enrolling 1,000 smoking volunteers in the year 2000. In 2004, the study was expanded by involving 500 more smoking volunteers.
The study demonstrated the efficacy of computer tomography at low-dose radiation (CT) in the diagnosis of the majority of lung cancers at a curable stage. The COSMOS study has shown the possibility of associating spiral CT with a specific blood test that detects the presence of molecules (Micro RNA - tumour markers) indicating the presence of lung cancer. This line of research is active at IEO, it is part of the COSMOS 2 project and will lead to results in a few years’ time. The latest studies with spiral CT would seem to indicate an improvement of early diagnosis of lung cancer with an impact on survival, but the results of large randomised trials in progress are still pending.
The first rule to prevent lung cancer is therefore not to smoke or not to be exposed to cigarette smoke, but the Mediterranean diet appears to be associated with a lower risk of lung cancer among heavy smokers.
People who consume a diet rich in fruits and vegetables, with olive oil as the principal source of fat, moderate consumption of wine and a low consumption of red meat tend to get sick less. The Mediterranean diet has long been recognised as being responsible for a better state of general health, longer survival and a reduced risk of cancer attributable to the content of fatty acids and antioxidants (polyphenolic compounds, carotenoids, tocopherols), found mainly in fruits, vegetables and olive oil. This positive effect is probably not due to individual nutrients, but the arrangement of all components interacting with each other and playing a positive effect in our body.
High consumption of red meat and processed meat have been associated with an increased probability of getting cancer. There is an increased risk among people who have high consumption of beef and offal, but not for high consumption of pork and poultry meat. The exact mechanism is not clear, it may be related to fat content but also to the presence of carcinogenic substances (N-nitroso compounds, heterocyclic amines and polycyclic aromatic hydrocarbons) and iron which can act as a pro-oxidant causing cell damage.
To prevent lung cancer, it is helpful to follow a healthy and balanced diet that includes regular consumption of fruit and vegetables rich in carotenoids such as tomatoes, carrots, sweet and spicy peppers, pumpkin, apricots, aromatic herbs. Taking large doses of vitamins in the form of potentially harmful supplements should be avoided. It is also helpful to be active by doing regular physical activity.
Diagnostic and therapeutic procedures for lung cancer and for diseases of the respiratory system
Interventional Pneumology
Interventional Pneumology is a new branch of pneumology that uses minimally invasive techniques for diagnosis and treatment of patients suffering from respiratory problems and for the diagnosis of lung cancer. IEO offers an interventional pulmonology outpatient clinic for patients who require a preliminary evaluation before procedures are performed. The IEO interventional pneumology programme started in 2010 and is able to provide a diagnostic and therapeutic service at the forefront of pulmonary medicine. The IEO interventional pneumology service annually performs more than 700 operational bronchoscopy procedures for the diagnosis and treatment of lung cancer patients. The interventional pulmonologists work in the Thoracic Surgery Division and collaborate with many specialists (radiation oncologists, medical oncologists and other surgical specialties) for the diagnosis and treatment of lung cancers.
EBUS-TBNA (trans-bronchial ultrasound)
EBUS (Endo-bronchial Ultrasound) is a minimally invasive new bronchoscopy technologythat allows the respiratory specialist to visualise the central structures of the mediastinum and peripheral lung parenchyma, otherwise not accessible with traditional bronchoscopy, using an ultrasound probe.
EBUS is used in many cases of lung cancer for evaluation of the mediastinal lymph nodes (mediastinal staging), diagnosis of peripheral lung nodules, mediastinal lymph nodes enlarged and affected by other diseases, for the diagnosis of benign pulmonary and mediastinal diseases, thymomas, tuberculosis and sarcoidosis.
The procedure does not require general anaesthesia (not requiring intubation) and runs under sedation by the anaesthetist, ensuring patient comfort and safety.
EBUS significantly increases the diagnostic accuracy of transbronchial biopsies under fluoroscopic guidance and transbronchial needle aspiration.
EBUS-TBNA bronchoscopies are performed in collaboration with a pathologist in the endoscopy room who can provide immediate evaluation of the sample material (ROSE: Rapid on-site cytologic Evaluation). EBUS-TBNA is an excellent method for obtaining new biopsies in cancer patients for the detection of cancerous genetic mutations that may lead to targeted therapies with biologics.
Rigid bronchoscopy
Rigid bronchoscopy is performed with a rigid bronchoscope under general anaesthesia. It allows the major airways (trachea and main bronchi) obstructed by intra-luminal lung cancer to be recanalised, thereby restoring patency. The lesions are removed mechanically or by laser therapy. In patients with intra-luminal lesions that cannot be completely recanalised and in those with distortion of the trachea-bronchial tree due to extrinsic compression, prostheses (endo-bronchial stents) can also be positioned for palliative purposes.
Pleural medical inspection
Pleuroscopy is a minimally invasive technique that allows exploration of the pleural cavity through a thoracic access performed under local anaesthesia and sedation. This procedure has diagnostic and therapeutic purposes in diseases of the pleura (malignant and benign).
Various studies for lung cancer screening have been carried out using chest X-ray, CT and sputum cytology. The results showed an increase in the percentage of lung cancer that was still resectable in the patients screened, but we do not know if this would affect the reduction of mortality in the whole population.
Chest Computed Tomography (TC)
Chest Computed Tomography (CT) scans provide definition of the extent of the lung cancer, detection of enlarged lymph nodes in the hilar-mediastinal areas, infiltration of the chest wall, pleural effusion and other pulmonary nodules.
CT scan of the brain and the abdomen
The CT scan of the brain and the abdomen completes staging, highlighting the presence of liver adrenal and brain metastases from lung cancer.
Positron Emission Tomography (PET)
A lung positron emission tomography (PET) scan is an important imaging modality in lung cancer patients. It uses a radioactive substance (called a tracer) to look for disease in the lungs such as lung cancer and distant metastases.
The fine needle aspiration/trans-thoracic biopsy
CT or bronchoscopy-guided fine needle aspiration/transthoracic biopsy are the examinations of choice for typing the lung cancer. In addition, transbronchial ultrasonography (EBUS) can be performed using bronchoscopy, allowing evaluation of the mediastinal lymph nodes, which is essential for the appropriate choice of therapeutic procedure for lung cancer.
Micro-RNAs and molecular diagnosis
Various studies show that lung cancer cells and the cells defending the body from the tumour itself release specific gene fragments (miRNA, microRNA), circulating long before the more advanced imaging tool today available (low-dose CAT) is able to detect the nodule. Via a simple blood test, fundamental information can be obtained for an in-depth diagnosis and for orientating the treatment of lung cancer, which in most cases, if discovered promptly, is a curable disease.
Serum miRNA can accurately identify patients with non-small cell lung cancer at an early stage in asymptomatic subjects. They can distinguish between benign and malignant lesions. They are abundant and stable in serum and have a simple clinic application. MicroRNA can represent a cheaper, simpler and immediately applicable screening platform for lung cancer than spiral CT.