Diagnosis of lung cancer
Lung cancer mostly occurs in the epithelial cells of bronchial mucosa and its glands at all levels, which is also called bronchopulmonary cancer. In the past half century, the incidence and mortality rate of lung cancer in the world have been increasing, and the mortality rate of lung cancer in western industrialized countries and regions such as the United Kingdom, the United States, France, the Netherlands, Sweden and Germany ranks first among malignant tumors.
Lung cancer is generally divided into small cell undifferentiated carcinoma (SCLC) and non-small cell lung cancer (NSCLC), the latter including lung squamous epithelial cell carcinoma, adenocarcinoma, large cell carcinoma, etc. Fine bronchoalveolar cell carcinoma is a subtype of lung adenocarcinoma.
I. Clinical manifestations of lung cancer
The clinical manifestations of lung cancer are closely related to the location, size, whether the cancer invades adjacent organs and whether there is metastasis. These clinical manifestations can be divided into four categories.
1. Symptoms caused by the primary tumor.
Cough, hemoptysis, wheezing, shortness of breath, weight loss, fever, etc.
2. Symptoms caused by local extension of tumor.
(1) Invasion of phrenic nerve, causing ipsilateral diaphragm paralysis.
(2) Invasion of the recurrent laryngeal nerve, causing vocal cord paralysis.
(3) compression of superior vena cava, causing edema of face and neck and superior vena cava obstruction syndrome due to anger of upper chest veins.
(4) Invasion of the pleura, which can cause pleural effusion.
(5) Invasion of the mediastinum by cancer and involvement of the esophagus, which can cause dysphagia.
(6) lung cancer at the top of the upper lobe, also called Pancoast tumor or supraglottic sulcus tumor, can invade and compress organs or tissues located in the upper thoracic opening, producing chest pain, jugular vein or upper limb vein anger, edema, arm pain and upper limb movement disorder, ipsilateral upper eyelid drooping, pupil narrowing, eye sunken, facial sweating and other cervical sympathetic syndrome (Horner syndrome).
3.Symptoms caused by distant metastasis of cancer.
(1) When metastasis to brain, neurological symptoms such as headache, vomiting, vertigo, diplopia, ataxia, cerebral nerve palsy, weakness of one limb or even hemiplegia may occur, and in severe cases, symptoms of intracranial hypertension may appear.
(2) Local pain and pressure when metastasizing to the bones, especially the ribs, vertebrae and pelvis.
(3) Anorexia, pain in the liver, hepatomegaly, jaundice and ascites when metastasis to the liver.
(4) supraclavicular lymph nodes are often the site of lung cancer metastasis.
(5) In case of subcutaneous metastasis, subcutaneous nodes can be palpated.
4. Extra-pulmonary manifestations caused by cancer.
In a few cases of lung cancer, due to endocrine substances produced by the tumor, non-metastatic systemic symptoms are presented clinically: such as osteoarthritis syndrome, Cushing’s syndrome (Cushing), myasthenia gravis, male breast enlargement, multiple muscle neuralgia and other extra-pulmonary symptoms.
II. Diagnosis of lung cancer
The main sources of diagnostic information of lung cancer are medical history and chest X-ray. If there are early local symptoms in medical history, it will arouse the suspicion of tumor; chest X-ray can clarify the location of lesion and show its influence on surrounding tissue structure. And pathological basis is generally needed to confirm the diagnosis of lung cancer. The diagnosis of lung cancer requires not only qualitative diagnosis, but also staging diagnosis to facilitate the selection of treatment and prognosis. There are various examination methods to diagnose lung cancer, including imaging examination, pathological examination and cancer marker examination, etc.
1.Imaging examination
Imaging examination can detect lesions and some specific manifestations can suggest the diagnosis of lung cancer, which is also the main basis of lung cancer staging, but generally does not have qualitative diagnostic value.
X-ray fluoroscopy or chest radiography
is the main means to diagnose lung cancer. Central type lung cancer may have no abnormal X-ray signs in early stage. When the cancer obstructs the bronchus, obstructive pneumonia or pulmonary atelectasis may appear. On tomographic X-ray, it may show the shadow of the mass protruding into the bronchial lumen, irregularity, thickening or narrowing of the lumen or obstruction. Peripheral type lung cancer X-ray often shows nodular shadow or block shadow around the lung field, often showing small lobes or cut marks, emitting thin and short burrs. Diffuse type of fine bronchoalveolar cell carcinoma shows infiltrative lesions with blurred contours, ranging from widespread small nodules and patches to fusion into a large shadow, resembling pneumonia.
Computed tomography (CT) scan
It can show thin section image, with higher resolution than conventional chest X-ray, and can reflect finer structures or small nodules of lesions; avoid overlapping of lesions and normal tissues, and can detect early lung cancer in hidden areas of general X-ray examination (such as apical lung, supra-diaphragm, paraspinal, posterior heart, mediastinum, etc.); enhanced scan is more valuable to clarify whether there are metastases in hilar and mediastinal lymph nodes; CT scan of abdomen and head is beneficial to detect metastases CT scan of the abdomen and head is useful for detecting metastases.
Magnetic resonance imaging (MRI)
The advantage of MRI is that it is easy to distinguish mediastinum, hilar vessels from masses and lymph nodes, and multifaceted imaging can better determine the extent of tumor and vascular involvement. However, it is not as effective as CT for parenchymal lung lesions.
Fluorodeoxyglucose positron emission computed tomography (FDG-PET)
It is an imaging technique that has been used more and more widely for lung cancer diagnosis in recent years. Unlike traditional imaging techniques, it reflects the metabolic changes of lesions and therefore has certain qualitative diagnostic value. It has a sensitivity of more than 90% and specificity of 80%-90%, and can make corresponding clinical judgment on hilar and mediastinal lymph node metastasis and distant metastasis outside the chest, so it is an important method for clinical staging before lung cancer treatment. Gupta et al. reported that among 168 mediastinal lymph nodes in 54 patients, the sensitivity, specificity and accuracy of FDG-PET in diagnosing lymph node metastases were 96%, 93% and 94%, respectively, which were significantly higher than those of CT (68%, 65% and 66%). Hicks et al. compared the staging of 153 lung cancer patients before and after PET imaging and found that PET imaging combined with conventional staging changed the staging of 43% of patients (33% had higher staging and 10% had lower staging), and 35% of patients had a change in treatment plan. However, the diagnosis of lung tumors with PET has false negatives for tumors with lower metabolism, especially alveolar cell carcinoma; it also has many false positive results for lesions such as inflammation of the lung and tuberculosis.
2.Pathological examination
Confirmation of lung cancer diagnosis mainly relies on histological and cytological examination, and many clinical auxiliary examination means are for collecting lung cancer specimens. Cytological specimens mainly come from sputum, plasma cavity effusion, trans-fibrinoscopic brush examination and fine needle aspiration specimens from various parts. Histological specimens can be obtained from biopsies such as fibrinoscopy, thoracoscopy, mediastinoscopic biopsy and percutaneous mass aspiration. With the development of science and technology, immunochemical techniques and molecular biology techniques are gradually applied in lung cancer diagnosis, but they are not yet mainstream in clinical practice, and their specimen collection methods are roughly the same as pathological examination.
Sputum exfoliative cell examination
This method is simple, non-invasive and economical, and it is the most commonly used method to diagnose lung cancer, even for the screening of high-risk groups of lung cancer, and can detect some early lung cancers. The positive rate of sputum exfoliative cytology examination is 60% to 70%, but its diagnostic value is affected by more factors, including the quality of sputum collection, the experience and technical level of the examiner, and the location of the lesion. Therefore, it is important to ask patients to cough up sputum from deep; multiple submissions can improve the positive rate of the test and the reliability of the results.
Plasmapheresis and pleural biopsy
About 1/2 of lung cancer patients will have pleural effusion during the course of the disease, and most of them are caused by metastasis of tumor in the pleural cavity, so thoracentesis for exfoliative cell examination is a common method to confirm the diagnosis of such patients, and the operation is relatively simple and safe. The detection of cancer cells in pleural fluid has a confirmatory value, but the detection rate is low (about 50%), and the positive rate can be increased to 90% after 3 consecutive examinations. The positive detection rate can be significantly increased after hypotonic treatment of hemorrhagic pleural fluid.
Pleural biopsy with pleural biopsy needle can further improve the rate of lung cancer diagnosis, and histopathological examination is more favorable to tumor typing than exfoliative cell examination; the chance of clarifying other diseases such as tuberculosis through pleural biopsy is greatly increased, which also helps to exclude lung cancer diagnosis. Therefore, pleural biopsy is feasible for patients who cannot be diagnosed clearly by simple thoracentesis.
Bronchoscopy
Bronchoscopy is one of the most important tools for clinical diagnosis of lung cancer. Biopsy can be performed under direct vision (TBB) for lesions that can be visualized, and biopsy can be performed under fluoroscopic guidance (TBLB) for peripheral lesions. Fibrinoscopy has a very high diagnostic rate for central lung cancer and a confirmatory rate of about 70% for peripheral lung cancer. In addition to biopsy, brushing of the lesion, lavage recovery and cough specimens sent for exfoliative cytology after examination can also improve the diagnostic rate.
Fluorescence ciliary microscopy, which has been used clinically in recent years, can make the mucosa with cancerous lesions and atypical hyperplasia emit special fluorescence, which makes the biopsy site more targeted and improves the positive biopsy rate and early lung cancer diagnosis. For enlarged lymph nodes in the hilum or mediastinum suspected to have metastasis, fine needle aspiration or biopsy can be performed via fibronectomy.
Percutaneous thoracic lesion puncture
Percutaneous puncture can be performed on the lung, chest wall and even mediastinal masses. There are two types of puncture needles for thoracic lesion puncture: aspiration needle and cutting needle, the former is used for cytological examination with negative pressure, while the latter is used to cut small sections of tissue for histopathological examination. In recent years, due to the development of exfoliative cytology and immunohistochemistry techniques, fine needle aspiration has been more widely used because of its advantages of being less invasive and safer. Especially for lesions close to important organs such as large blood vessels or multivessel lesions, fine needle aspiration is appropriate. However, the diagnostic sensitivity of fine needle aspiration is lower than that of cutting biopsy needles. The most commonly used lesion-guiding measures for percutaneous thoracic lesion puncture are X-ray fluoroscopy, CT, and ultrasound.
The sensitivity and specificity of percutaneous pulmonary puncture varies depending on the case selected, the difference in the means of puncture, and the technical proficiency of the operator. the sensitivity and specificity of CT-guided puncture are higher than those of other guidance methods, with a sensitivity of 67% to 97.4%, a specificity of 90% to 100%, and a diagnostic accuracy of 67% to 98.5%.
Thoracoscopy
In recent years, thoracoscopy, especially video imaging assisted thoracic surgery (VATS), has been gradually applied to clearly visualize and biopsy lesions in pulmonary nodules or pleural effusions that cannot be diagnosed by conventional methods, using the micro-invasive advantages of thoracoscopy. VATS can also partially replace mediastinoscopy to observe the mediastinal lymphatic status and biopsy can be more clearly staged, which has a good prospect of application.
Mediastinoscopy
Mediastinoscopy through a cervical or parasternal incision is an accurate method to determine whether the mediastinal lymph nodes are metastatic. For mediastinal lymph nodes larger than 1 cm on imaging, mediastinoscopy has special significance. Nowadays, mediastinoscopy is replaced by CT, ultrasound or fine needle aspiration guided by tracheoscopy in many cases, but it is still necessary when those tests cannot make a definite diagnosis. Mediastinoscopy is of particular value in staging lung cancer and in the selection of surgical treatment.
Other
Lung cancer tends to metastasize to ipsilateral supraclavicular lymph nodes, and lymph node metastasis or subcutaneous metastatic nodes from other sites are not uncommon. Of course, surgical biopsy of the lesion may also be performed as appropriate. If the nature of the lung mass is not clearly defined by multiple methods of examination and short-term exploratory treatment, and the possibility of lung cancer cannot be ruled out, a thoracotomy should be performed if the patient’s general condition permits. In addition, it is reported that about 1/5 of small cell lung cancer patients will have extensive bone marrow metastasis, so bone marrow aspiration is feasible for those who suspect small cell lung cancer.
3.Cancer marker examination
Serum cancer markers that are more valuable for the diagnosis of non-small cell lung cancer include carcinoembryonic antigen (CEA), squamous carcinoma-associated antigen (SCC), cytokeratin 19 fragment (CYFRA21-1), etc. Neuron-specific enolase (NSE) is more valuable for the diagnosis of small cell lung cancer. However, the overall sensitivity of these cancer markers is not high enough for the diagnosis of lung cancer, and they are often significantly increased when the tumor load is heavy, which limits their clinical value for early diagnosis. Combined testing of multiple cancer markers can partially compensate for their shortcomings, and the diagnostic value of pleural fluid cancer markers is sometimes higher than that of serum tests.