Generality
Among the malignant neoplasms of the lung, non-small cell cancer is the most frequent form, representing about 70% of cases. This tumor originates from epithelial tissues (this is why it is also called carcinoma) that cover the bronchi and the lung parenchyma.
Sometimes, patients with early-stage non-small cell lung cancer (i.e. still small in size) may have no disorder; in these cases, the tumor may be discovered occasionally after performing, for example, a chest x-ray for other medical reasons. In the most advanced stages of the disease, however, shortness of breath (dyspnea), chest tightness and / or blood emission with coughing (haemoftoe or hemoptysis) may occur.
During the course, non-small cell lung cancer can form a mass that obstructs the correct flow of air or can cause pulmonary or bronchial bleeding. In addition, the tumor can metastasize to the mediastinal lymph nodes, adrenals, liver, bones and brain.
The evaluation of non-small cell lung cancer is based on diagnostic imaging tests for chest images (such as radiographic and computed tomography) and histological analysis on samples taken by biopsy, bronchoscopy or thoracoscopic surgery.
Depending on the stage of the disease, treatment may include surgery, chemotherapy and / or radiotherapy.
Histological variants
Non-small cell or non- small cell carcinomas (non-small-cell lung cancer, NSCLC) account for about 70% of malignant lung tumors.
Depending on the type of cells and tissue from which the tumor originates, different forms of disease may occur; non-small cell lung cancer can develop, in fact, from the cells that make up the bronchi, bronchioles and alveoli.
Under the microscope, these tumors can be distinguished in three main histological variants:
- Adenocarcinoma : represents 35-40% of non-small cell lung tumors and can be subdivided, in turn, into an acinar, papillary or bronchioloalveolar carcinoma; it develops at the level of the smaller bronchi, therefore in a more peripheral region than the other histotypes. Adenocarcinoma is the most common lung cancer in non-smokers and is sometimes associated with the presence of pulmonary scars (secondary, for example, to pleurisy or tuberculous infections).
- Squamous cell carcinoma : also called squamous cell carcinoma, spinocellular or epidermoid; represents 25-30% of lung tumors and is born in the medium-large caliber airways, from the transformation of the epithelium that covers the bronchi. This form of lung cancer has the best prognosis.
- Large cell carcinoma : it is the least frequent variant (10-15% of cases); it can appear in different areas of the lung and shows a tendency to grow and spread rather quickly.
Rare, on the other hand, are mixed tumors .
Causes
Non-small cell lung cancer is due to the rapid and uncontrolled growth of some respiratory epithelial cells. This is the result of prolonged exposure to carcinogens, which act by causing multiple mutations . The accumulation of these genetic alterations eventually leads to a neoplastic phenomenon (note: it was calculated that, at the time of clinical diagnosis, 10 to 20 mutations occurred in lung carcinomas).
As in other neoplasms, oncogenes are implicated in the tumor process: they stimulate cell growth (K-ras, c-Myc), cause abnormalities in the transduction of the receptor signal for growth factors (EGFR, HER2 / neu) and inhibit apoptosis (Bcl-2). Furthermore, over time, mutations can occur that inhibit tumor suppressor genes (p53), which contribute to the proliferation of abnormal cells.
Risk factors
- Tobacco smoke. Tobacco smoke is the most important predisposing factor for lung cancer: about 80% of carcinomas occur in smokers. The risk increases according to age (the younger you are, the greater your susceptibility to the disease), the number of cigarettes smoked daily, the duration of this habit, the absence of a filter and the tendency to aspirate smoke. Many of the substances identified in cigarettes are potential carcinogens (including polycyclic aromatic hydrocarbons, nitrosamines, aldehydes and phenol derivatives), that is they are able, over time, to promote the transformation of cells into a tumoral sense. In addition to these components, other harmful substances have been found, such as arsenic, nickel, molds and various additives. The risk of developing non-small cell lung cancer may gradually decrease over the 10-15 years after the cessation of the habit, but it can never be comparable to that of non-smokers. The onset of the tumor can also be favored by passive smoking and, in only a minority of cases, the disease occurs in those who have never smoked.
- Professional risks . Some types of industrial exposure increase the likelihood of developing non-small cell lung cancer. In particular, the risk is higher in the case of exposure to asbestos (or asbestos) and radiation at work, universally recognized as carcinogenic. An increased predisposition to develop the disease is also found among workers exposed to nickel, chromates, coal, nitrogen gases, arsenic, silica and beryllium.
- Air contamination . Air pollution can play a role in the current increase in non-small cell lung cancer incidences. Recently, attention has been focused mainly on air contaminants that can accumulate in closed environments, such as radon, a product of the decay of natural radioactive elements present in soil and rocks, such as radio and uranium.
- Prevented pathological conditions. Some types of non-small cell lung cancer (usually adenocarcinomas) occur near areas of scarring . These can be caused by granulomatous infiltration (tuberculosis), metallic foreign bodies or wounds prior to tumor development. The predisposition may also increase in the presence of pulmonary diseases (such as fibrosis and COPD) and previous radiotherapy treatments (used, for example, for lymphoma). The lung can also be the site of metastases resulting from primitive tumors of other organs (including pancreas, kidney, breast and intestine).
- Familiarity. A positive family history may increase the risk of developing this form of cancer.
Signs and symptoms
Lung carcinomas remain asymptomatic in their initial stages for a long time: this is the reason why they are often diagnosed in an advanced stage or are accidentally detected during tests carried out for other reasons.
The signals that may indicate the presence of a lung tumor include:
- Continuous cough that does not tend to resolve or worsens over time;
- Short and / or breathless breath;
- Sputum, with or without traces of blood;
- Hoarseness (if the laryngeal nerve is involved);
- Difficulty or pain when swallowing (dysphagia);
- Chest pain that increases in the case of a cough or a deep breath;
- Recurrent or persistent fever, usually, not high;
- Unexplained fatigue;
- Unwanted loss of weight and / or loss of appetite;
- Swelling of the face and neck;
- Digital hippocratism (fingers extended to the end);
- Respiratory infections (bronchitis or pneumonia) recurrent.
Possible complications
Non-small cell lung cancer can spread to neighboring structures or cause metastases outside the chest.
Therefore, other symptoms may be present such as:
- Airway obstruction, pleural effusion, superior vena cava syndrome and Pancoast tumor (shoulder or arm pain).
- Abdominal pain, jaundice, gastrointestinal disorders and organ failure caused by liver metastases.
- Neurological disorders resulting from the development of brain metastases, such as behavioral changes, headache, dizziness, confusion, aphasia and coma.
- Bone pain and pathological fractures from bone metastases.
The organs that may be affected by metastasization of non-small cell lung cancer include the liver, brain, adrenal glands, bones, kidneys, pancreas, spleen and skin.
Diagnosis
The diagnosis of non-small cell lung cancer involves, first of all, an accurate history and a complete physical examination .
On the basis of the information collected, the doctor can prescribe further in-depth examinations, such as chest radiography, computed tomography (CT), magnetic resonance imaging and PET (positron emission tomography, alone or in combination with CT).
Diagnosis requires cytopathological confirmation by fine needle biopsy (needle aspiration), bronchoscopy or thoracoscopic surgery. The histological examination of the tissue samples collected in this way allows the detection of cellular lesions typical of non-small cell lung cancer. In some cases, tumor clones can also be found in the patient's sputum.
The evaluation of lung function is instead fundamental in the planning of a possible surgical intervention that foresees the removal of part of the lung.
Treatment
Generally, treatment for non-small cell lung cancer involves the evaluation of the patient's operability, followed by the choice between surgery, chemotherapy and / or radiotherapy. Depending on the type, size, location and stage of the tumor, it is also possible to opt for a multimodal approach.
In the initial stages of the disease, the therapeutic intervention of reference is surgical resection with segmentectomy, lobectomy or pneumonectomy combined with mediastinal lymph node sampling or complete dissection. In these patients, surgery can be decisive. Adjuvant chemotherapy after surgery is now standard practice; this approach reduces the chances that the cancer will recur (recurrence).
In the later stages of non-small cell lung cancer, the therapeutic protocol includes chemotherapy, radiotherapy, surgery or a combination thereof; the sequence and the choice of the treatment depend on the stage of progress of the disease in the patient and on the possible presence of other concomitant pathological conditions.
Locally advanced cases that invade the heart, the large vessels, the mediastinum or the spine are usually subjected to radiotherapy .
In the terminal stages of non-small cell lung cancer, the goal is palliative care for symptom management; when treatment is not possible, chemotherapy and radiotherapy can be used to slow down the progression of the tumor and improve the quality of life.
Prognosis
Despite the progress in treatment, the prognosis of non-small cell lung cancer remains unfortunately poor: only 15% of patients survive for more than 5 years from the time of the clinical finding of the disease.
To improve long-term survival it is necessary to focus attention on early diagnosis, the development of new forms of therapy and interventions to prevent the disease (eg abstention from smoking, adoption of protective devices in the workplace, screening, etc.). .).
Prevention
The prevention of lung cancer undoubtedly involves the cessation of smoking. As for the professional risk factors, it is important to resort to all the protection measures in the workplace that allow you to minimize risks and work safely.
