How is Lung cancer diagnosed?

Chest X-Ray

Lung Cancer X-ray

A CXR is performed to investigate the appearance of certain symptoms such as cough or breathlessness. If a suspected pulmonary nodule is present, it is necessary to perform a CT scan of the thorax with contrast medium to better investigate its morphological characteristics.

Computerized Axial Tomography of the thorax

In fact, the CT scan of the chest identifies lesions even of small dimensions, and can more precisely (compared to radiograph), discriminate tumor lesions from others (pneumonia, or an inflammatory pathology for example) and evaluates the relationship of the respective lesion with other organs within the chest, such as the heart, large vessels or esophagus.

The CAT also allows the studying of lymph nodes, which if affected, appear more enlarged.

Sometimes, in the presence of a suspected lung tumor, along with the CT scan of the chest, a CT scan of the abdomen and pelvis is also required, to study the abdominal organs and investigate possible extension of the disease out of the lung (at a secondary site, also known as metastasis).

Positron Emission Tomography

In some cases, especially in preparation of a surgical evaluation, the CAT is followed by a PET. PET is a test that uses fludeoxyglucose (a sugar normally used by cancer cells for their growth) as a contrast agent. The more active the cell is, the more sugar is taken up. However, in presence of inflammatory diseases, PET may provide false positive results, whereas for some lung cancer types (i.e. bronchioalveolar carcinoma and neuroendocrine carcinoma), PET may provide false negative results.

The utility of PET lies in the study of disease extension inside and outside the thorax, the involvement of the mediastinal (the anatomical space between the two lungs) lymph nodes, and in distinguishing tumor from the non-malignant tissue (such as in the case of atelectasis, or “collapse” of part of the lung).

Histological and cytological diagnosis

Cytological diagnosis lung cancer

When radiological investigations raise the suspicion of a tumoral disease, it is necessary to perform other investigations, the so-called second-level diagnostic tests. These consist in taking a small portion of the suspected tissue (histological diagnosis), or if this is not possible, some of the cells making up the mass (cytological diagnosis).

The goal in both cases, is to analyze the sample under a microscope to reach a diagnosis, or in other words to understand if what is seen on the CT scan is in fact, a tumor or another pathology. Using staining techniques in lab, we can determine which lung cells gave birth to the tumor. This is the histotype, which then plays a role in our subsequent therapeutic decisions.

The cytological or histological diagnosis can be performed on a sample coming from the primary tumor, on the lymph nodes (if involved) or on distant metastases (if present). The diagnostic methods used to obtain the sample are different and the biopsy site is chosen based on technical considerations, such as which gives the patient the least problems (least invasive).

If the tumor grows inside the airways, like the bronchi, which are tubes carrying air from outside into the lungs, the tumor will be reached using a guide instrument (the bronchoscope) entering these airways. This procedure is called bronchoscopy. Bronchoscopy allows the visualization of airways directly. The tube, inserted through the nose, reaches the bronchi that branch out from the trachea. This is an outpatient procedure and is usually performed following administration of a local anesthetic. It is also sometimes performed following systemic anesthesia.

In addition to bronchial exploration, the procedure allows the collection of liquid and cells present in the airways. A cellular sample may also be obtained using a small brush at the end of the bronchoscope. With a clamp, a tissue sample could be taken (biopsy). Two mediastinal lymph node stations may be reached by the bronchoscope: the subcarinal ones (under the tracheal division) and the paratracheal ones (near the trachea). It is therefore an examination that allows material collection to determine the nature of the disease and evaluates the involvement of mediastinal lymph nodes and thus the extension of the disease.

If the tumor is close to the airways, it can also be reached by the bronchoscope. In this case, the airway is crossed to reach the suspected mass (transbronchial needle biopsy, TBNA). This procedure is performed under radiologic (fluoroscopic) or endoscopic ultrasound (TBNA-EUS) guidance. Endobronchial Ultrasound (EBUS) is a type of bronchoscopy that uses an ultrasound probe to visualize the central and peripheral lung parenchyma. The ultrasound probe significantly increases the diagnostic accuracy of biopsies and transbronchial needle aspiration.

On the other hand, if the lesion is peripheral, or far from the airways, the mass may be sampled by a CT-guided aspiration or CT-guided biopsy. For these peripheral pulmonary lesions, a thin needle is inserted through the thoracic wall (CT guided) to collect single or groups of cells. This procedure can also be performed in an outpatient setting, and it can also be performed for suspected liver or adrenal metastasis.

Rarely, the diagnosis may be done by a surgical biopsy, involving an anesthetic consultation (mediastinoscopy, mediastinotomy, thoracentesis or videothoracoscopy). The cervical mediastinoscopy, extended cervical mediastinoscopy or anterior mediastinoscopy are surgical maneuvers performed under general anesthesia, with the aim to biopsy the mediastinal lymph node stations that are otherwise unreachable by bronchoscopy.

The thoracentesis procedure is done by inserting a needle into the pleural space, to collect the liquid formed between the two pleural sheets covering the lungs. This can assess the presence of metastatic disease in the pleural cavity. In the case of modestly-sized masses, the procedure may also be performed using an ultrasound guide. The video-assisted thoracoscopy (VATS) instead is a surgical procedure that also requires general anesthesia and consists of the insertion of an optic fiber instrument into the chest wall. This allows the visceral and parietal pleura (the bag covering the lungs) to be examined, and to perform pleural biopsies.

The combined effort by a team made up of oncologists, radiologists, radiotherapists, nuclear medicine physicians, thoracic surgeons, pulmonologists and pathologists should analyze the patient’s clinical information and be able to obtain a histological diagnosis, and not only a cytological one. To define a therapeutic strategy, it is necessary to classy the neoplasm molecularly, especially in the presence of a lung adenocarcinoma diagnosis or for non-smoking patients. Furthermore, the development of new immunotherapeutic drugs may require the analysis of the tumor’s immunological profile, which are only obtained from a histological sample.

Genomic Test

The genomic test allows a tumor evaluation from the genetic point of view. The most innovative tests available today can analyze, from a small tumor tissue sample, a large number of genes and possible mutations at the origin of the tumor. This results in an “identikit”, which supports the oncologists in making personalized therapeutic decisions for the patient, depending on the specific tumor characteristics.

Another important therapeutic option are the clinical studies, which in most cases, require sending the histological material to central laboratories to analyze molecular markers. This is useful when it comes to choosing new drugs that are not yet entered into standard clinical practice.

In particular, for non-small cell lung cancer, the discovery of some genetic alterations have allowed the development of targeted therapeutic strategies. To learn more, read the section Genomic test of lung cancer.

Liquid Biopsy

The genomic test is performed on small samples of solid tissue (tissue biopsy) or liquid (liquid biopsy).

The liquid biopsy is performed on a simple blood sample that is analyzed to identify molecular markers. Several national and international groups have developed methods to search for EGFR gene mutations or EML4-ALK gene translocations on blood. These cases are referred to as liquid biopsies, as the genetic analysis is conducted on the plasma.

The Foundation Medicine® liquid biopsy (FoundationOne®Liquid) allows the identification of the four main classes of genomic alterations present in 70 genes associated to the solid tumor and can detect a high microsatellite instability, a parameter used to predict the patient’s response to immunotherapy.

To learn more, read the page about liquid biopsy for lung cancer.

Bone scintigraphy, CT or MRI of the brain with contrast

The third-level diagnostic tests allow an accurate evaluation of the clinical stage (extension of disease inside and outside the chest) and the information obtained is used in the process of choosing the therapeutic strategy. In addition to the abdominal-pelvic CT, normally performed with the chest CT scan, or in the presence of specific symptoms, a bone scan may also be performed. A brain CT or MRI with contrast will also be required.