Lung cancer occurs in the bronchial mucosa epithelium, also known as bronchial cancer. In recent 50 years, many countries have reported a significant increase in the incidence of lung cancer, which has taken the first place among male cancer patients and is also rapidly increasing in women, taking the second or third place among common malignant tumors in women. The etiology of lung cancer is still not completely clear, but a lot of information shows that long-term heavy smoking is an important causative factor of lung cancer. The incidence of squamous and undifferentiated lung cancer is 4 to 10 times higher than that of nonsmokers who smoke more than 40 cigarettes per day for many years. The incidence of lung cancer in urban residents is higher than in rural areas, which may be related to atmospheric pollution and the presence of carcinogenic substances in cigarette smoke. Therefore, non-smoking should be promoted and urban environmental sanitation should be strengthened.
What are the manifestations of lung cancer and how to diagnose it?
I. Clinical manifestations
Almost 2/3 of lung cancer patients are already in advanced stage (stage III or IV) when they are diagnosed. 95% of patients can have clinical examination results, and primary tumor, metastasis, systemic symptoms or tumor concomitant symptoms can be the first symptoms of patients.
The first symptoms caused by primary tumor account for 27%, and the symptoms are related to the site of primary tumor. Central type lung cancer manifests as irritating dry cough, breath-holding, recurrent episodes of pneumonia in the same area, hemoptysis or asthma, symptoms of laryngeal recurrent nerve, phrenic nerve compression or superior vena cava compression syndrome. Peripheral tumors are more commonly associated with chest pain, breath-holding or pleural effusion. Large peripheral type lesions, central necrosis, and cavities eventually present with lung abscess-like manifestations, a common symptom grouping for primary lung cancer.
Distant metastatic lesions cause 32% of the first symptoms. Common distant metastatic sites include: lymph nodes, adrenal glands, liver, bone, lung, brain and chest wall, producing some corresponding symptoms, indicating that lung cancer has reached advanced stage, such as: tumor near the mediastinal surface may invade phrenic nerve, causing ipsilateral diaphragm paralysis, showing elevated position of diaphragm and abnormal breathing movement under fluoroscopy; invade ipsilateral laryngeal recurrent nerve, causing hoarseness and hoarse voice. It can invade and compress the brachial plexus nerve, cervical sympathetic ganglion and subclavian artery, resulting in a series of specific symptoms, such as numbness and pain in the ipsilateral upper limbs, which are gradually increased and hard to tolerate; atrophic changes in muscles and skin, angry and edematous veins in the upper limbs; and cervical sympathetic syndrome, such as ipsilateral ptosis, pupil narrowing, sunken eyes and no sweating on the face.
10-20% of lung cancer patients have tumor-associated syndromes, the most common ones are small cell lung cancer and squamous carcinoma. Common tumor-associated syndromes include: osteoarthrosis of pulmonary origin syndrome (pestle and mortar finger, osteoarthrosis, periosteal hyperplasia, etc.), SIADH (syndrome of abnormal secretion of antidiuretic hormone), hypercalcemia, etc., and Cushing’s syndrome, myasthenia gravis or male breast enlargement. About 16% of patients have neuromuscular symptoms. Some patients have combined skin diseases such as scleroderma and acanthosis nigricans.
The clinical manifestation of lung cancer is closely related to the location, size, whether the cancer is compressing, invading adjacent organs and whether there is metastasis. If the cancer grows in the larger bronchial tubes, irritating cough often appears. The enlarged cancer affects the bronchial drainage and can cause pus sputum when it is secondary to lung infection. Another common symptom is bloody sputum, usually with blood spots or blood in the sputum or intermittent small amount of hemoptysis; some patients have important reference value for diagnosis even if they have bloody sputum once or twice. In some patients, due to large bronchial obstruction caused by tumor, symptoms such as chest tightness, shortness of breath, fever and chest pain may appear.
When advanced lung cancer compresses adjacent organs and tissues or distant metastasis occurs, it can produce.
1. compression or invasion of phrenic nerve, causing ipsilateral diaphragm paralysis.
2. Compression or invasion of the recurrent laryngeal nerve may cause vocal cord paralysis and hoarseness.
3, compression of the superior vena cava may cause anger in the veins of the face, neck, upper extremities and upper chest, subcutaneous tissue edema, and increased venous pressure in the upper extremities.
4.Invasion of pleura can cause pleural effusion, which is mostly hemorrhagic.
5.The cancer invades the mediastinum and presses the esophagus, which may cause difficulty in swallowing.
6.Lung cancer in the upper lobe, also called Pancoast tumor or supraglottic lung tumor, can invade and compress the organs or tissues located in the upper thoracic opening, such as the first rib, supraclavicular artery and vein, brachial plexus nerve, cervical sympathetic nerve, etc., resulting in 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, no facial sweating, etc. Sympathetic nerve syndrome.
In a few cases of lung cancer, due to the endocrine substances produced by the cancer, non-metastatic systemic symptoms may appear clinically, such as osteoarthritis syndrome (pestle and mortar fingers, arthralgia, periosteal hyperplasia, etc.), Cushing’s syndrome, myasthenia gravis, male breast enlargement, multiple muscle neuralgia and other extra-pulmonary symptoms. These symptoms may disappear after resection of lung cancer.
II. Diagnosis
The diagnosis of primary bronchial lung cancer is based on symptoms, signs, x-ray manifestations and sputum cancer cell examination (sputum examination). Different steps should be taken in the diagnostic workup according to different situations.
(A) Negative X-ray and negative sputum examination
1.Anyone without symptoms but with three major high-risk factors (male, age ≥45 years old and smoking >400 cigarettes/year) should undergo 70-100mm fluorescent microscopic x-ray or chest fluoroscopy and sputum cytology examination half-yearly.
2. Anyone with hemoptysis or/and dry choking cough with three major high-risk factors should undergo repeated sputum cytology and be given regular anti-inflammatory therapy at the same time; fiberoptic bronchoscopy (fibronectomy) and televisual fluoroscopy can be considered. If repeated sputum examination or microscopy is still negative, it should be reviewed every two months and adhered to for one year.
(B) Negative X-ray and positive sputum examination
1.Exclude upper respiratory tract and esophageal carcinoma.
2.Perform fibrinoscopy, strive to peer into sub-sub-segments, and if there is suspected local mucosal thickening, roughness or blood stains, brush examination, flushing or puncture of bronchial wall mucosa must be performed in the area to search for cancer cells. If local unevenness or roughness is found, it should be considered for biting biopsy.
3.Conduct TV fluoroscopy and change the body position, focusing on small nodule foci in hidden areas.
4.If no lesion is found by the above examinations, sputum, electron microscopy and fibrinoscopy should still be repeated every two months. CT examination can also be performed, and subdivision can be made at suspicious places. Regular review should be continued for not less than one year.
(C) Positive X-ray and negative sputum examination
1.Patients with segmental or lobar pneumonia or obstructive pneumonia and suspected central lung cancer should undergo fibrinoscopy, including trans-fibrinoscopic biopsy (TBB), or selective bronchography; and repeatedly strengthen sputum examination.
2. Local tomography should be performed for mass or nodal lesions. Transbronchoscopic lung biopsy (TBLB), or percutaneous lung biopsy, or aspiration for cytological diagnosis should be performed if available.
3.Continuous sputum examination should be done at least twelve times.
4.If repeated sputum examination is still negative, and x-ray is highly suspicious of lung cancer, dissection and frozen section biopsy should be performed.
(D) Positive X-ray and positive sputum test
1.Actively make pre-surgical preparation.
2. If regional lymph node enlargement is suspected, frontal and lateral oblique stratification films can be taken. For limited stage small cell lung cancer, CT and lateral tilt stratification film, liver ultrasound, bone isotope scan and bone marrow aspiration into biopsy smear should be routinely used in large hospitals to facilitate the development of treatment plan.
III. Pathological profile
Lung cancer originates from the bronchial mucosa epithelium and those confined to the basement membrane are called carcinoma in situ. The carcinoma can grow into the bronchial lumen or/and adjacent lung tissues, and can spread through lymphatic, hematologic or transbronchial metastasis. The growth rate and metastatic spread of carcinoma are related to the biological characteristics of carcinoma such as histological type and degree of differentiation.
The distribution of lung cancer is more in the right lung than in the left lung, and more in the upper lobe than in the lower lobe. Carcinomas can occur from the main bronchus to the fine bronchus. Lung cancer originating from the main bronchus and lobar bronchus and located close to the hilum is called central lung cancer; lung cancer originating below the bronchus of the lung segment and located in the peripheral part of the lung is called peripheral lung cancer.
(I) Classification Clinically, lung cancer is generally classified into the following four types.
1.Squamous cell carcinoma (also called squamous carcinoma): it is the most common among all types of lung cancer, accounting for about 50%, and most of the patients are above 50 years old, with men accounting for most of them. Most of them originate from the larger bronchi and are often central lung cancer. Although the degree of differentiation of squamous carcinoma varies, it generally has a slow growth rate, a long disease course, and is more sensitive to radiation and chemotherapy. It first metastasizes through lymphatic metastasis, and hematogenous metastasis occurs later.
2.Undifferentiated carcinoma: It is second only to squamous carcinoma in incidence rate, mostly seen in men, with a younger age of onset. It generally originates from larger bronchi and is a central type of lung cancer. It can be divided into oat cell, small round cell and large cell types according to tissue cell morphology, among which oat cell is the most common. Undifferentiated carcinoma is highly malignant, grows rapidly, and has early lymphatic and hematologic metastasis, and is more sensitive to radiation and chemotherapy.
Adenocarcinoma: It originates from the mucosal epithelium of the bronchus, and a few originate from the mucus glands of the large bronchus. The incidence is lower than that of squamous and undifferentiated carcinoma. It occurs at a younger age and is relatively common in women. Most adenocarcinomas originate in the smaller bronchi and are peripheral type lung cancers. There is no obvious clinical symptom in the early stage, but it is often detected during chest x-ray and appears as a round or oval lump, which generally grows slowly but sometimes bloodstream metastasis occurs early, while lymphatic metastasis occurs later.
4.Alveolar cell carcinoma: It originates from bronchial mucosa epithelium and is also called fine bronchial alveolar cell carcinoma or fine bronchial adenocarcinoma. The location is around the lung field. It has the lowest incidence rate among all types of lung cancer and is more common in women. The cancer cells grow along the bronchioles, alveolar ducts and alveolar walls without invading the alveolar septum. Lymphatic and hematogenous metastases occur later, but can spread to other lung lobes or invade the pleura via bronchioles. Alveolar cell carcinoma can be morphologically nodular or diffuse, the former can be a single nodule or multiple nodules; the latter morphology resembles pneumonia. The nodular type with limited lesion scope has better efficacy in surgical resection.
Only early diagnosis and early treatment can achieve better results, therefore, we should widely promote cancer prevention knowledge to the public. For adults over 40 years old, it is advisable to conduct chest X-ray screening once every six months. For those with suspicious symptoms, such as coughing for a long time, blood in sputum and lung shadow, a series of detailed examinations should be conducted to clarify the diagnosis. For nodules ≤5mm found in the screening, they should be reviewed once every 3 months; nodules of 6-10mm should be biopsied by percutaneous puncture, and if biopsy is not possible, CT should be reviewed every 3 months; nodules >1cm should be biopsied.
Lung cancer currently adopts the TNM system clinical staging published by the International Union Against Cancer in 1997, which is only applicable to non-small cell lung cancer. Small cell lung cancer mostly adopts a two-stage system, namely: limited type and extensive type. The limited type is defined as a lesion confined to one side of the chest with or without ipsilateral mediastinal or supraclavicular lymph node metastasis. It accounts for only 26% of small cell lung cancers. Extensive type is defined as a lesion that exceeds the scope of the limited type.
Corresponding to one or more TNM indicators, there are four levels of tumor staging, with stage I having the best prognosis and stage IV the worst.
What tests should be done for lung cancer?
1.Sputum exfoliative cytology examination is simple and easy to perform, but the positive detection rate is only 50%~80%, and there are 1%~2% false positives. This method is suitable for screening in high-risk groups and for confirming the diagnosis of isolated intrapulmonary images or unexplained hemoptysis.
2. Percutaneous lung aspiration cytology is indicated for peripheral lesions and is not suitable for open-chest cases for various reasons, while other methods fail to establish a histological diagnosis. At present, it tends to be combined with CT with a fine needle, which is safer to operate and has fewer complications. The positivity rate is 74%-96% in malignant tumors and 50%-74% in benign tumors. Complications include pneumothorax 20%~35% (about 1/4 of them need to be treated), small amount of hemoptysis 3%, fever 1,3%, air embolism 0,5%, needle tract implant 0,02%. Thoracic surgery is less applied because of the availability of thoracoscopic examination and open-chest exploration.
3.Cytological examination by thoracentesis Patients suspected or diagnosed with lung cancer may have pleural effusion or pleural dissemination metastasis. Cytological analysis of pleural effusion extracted by thoracentesis can clarify the stage, and for some cases, it can also provide a basis for diagnosis. For lung cancer with pleural effusion, bronchopulmonary adenocarcinoma has the highest detection rate, with a positive cytologic diagnosis rate of 40% to 75%. If the cytological analysis of pleural effusion obtained by puncture cannot make a diagnosis, further examination means such as thoracoscopy can be considered.
For patients with lung cancer, routine biopsy of the inaccessible oblique muscle or supraclavicular lymph nodes rarely reveals metastasis, and the diagnostic rate is nearly 90% for patients with palpable supraclavicular lymph nodes. Complications such as pneumothorax and hemorrhage are occasionally seen with biopsy, even if rarely. For cases with palpable lymph nodes in the oblique muscle or supraclavicular, it is now advocated that FNAB (fine needle aspiration biopsy) should be performed while surgical biopsy of lymph nodes is reserved. Routine histology and appropriate immunohistochemical examination can help in the diagnosis of cell typing.
Many kinds of serum tumor markers related to lung cancer have been identified, which may indicate the enhancement of carcinogenic factors or the degree of “detoxification” of certain carcinogens. Serum tumor markers for lung cancer may be valuable indicators for tumor staging and prognostic analysis, and can be used to evaluate the effectiveness of treatment. Tumor marker test results must be integrated with other test results and cannot be used to diagnose cancer alone.
6.Monoclonal antibody scan The use of monoclonal antibodies for census, diagnosis and staging is a current experimental field. The uptake of antibody is also affected by the size and location of the tumor.
(1) X-ray diagnosis is the most common means to diagnose lung cancer, and its positive detection rate can reach over 90%. The early X-ray manifestations of lung cancer include: ① isolated spherical shadow or irregular small infiltration; ② unilateral poor ventilation during deep inspiration under fluoroscopy and mild shift of the mediastinum to the affected side; ③ limited emphysema during expiratory phase; ④ mediastinal oscillation during deep breathing; ⑤ if the lung cancer progresses and blocks a segment or lobe bronchus, the distal part of the blockage will gradually absorb gas and form segmental opacification, and this opacification will form pneumonia or Lung abscess will be formed if this non-distended part is infected. More advanced lung cancer can be seen as a huge mass nodule in the lung field or lung hilum without calcification, lobulated, generally uniform in density, with burrs at the edges, distorted vascular texture around the periphery, and sometimes liquefied in the center, appearing as a thick-walled, eccentric, and uneven interior cavity. The doubling time is short. When the mass blocks the lobe or the common bronchus, lobar or whole lung atelectasis appears, and a large amount of pleural fluid is seen when the pleura is involved, and rib destruction is seen when the chest wall is invaded.
(2) CT examination In the diagnosis and staging of lung cancer, CT examination is the most valuable non-invasive examination means, which can detect the location and cumulative extent of the tumor, and can also roughly distinguish its benign and malignant nature. CT can also clearly show the hilum, mediastinum, chest wall and pleural infiltrates, which can be used for staging of lung cancer. CT abdomen is very helpful to observe whether there are metastases in intra-abdominal organs such as liver, kidney and adrenal gland.
(3) Magnetic resonance imaging (MRI) has certain value in the diagnosis and staging of lung cancer. Its advantage is that it can show the anatomy of the mediastinum in the sagittal and coronal planes, and clearly show the relationship between the central tumor and the surrounding organs and blood vessels without imaging, so as to determine whether the tumor has invaded the blood vessels or compressed and encircled the blood vessels. If the tumor is more than 1/2 of the circumference, it will be difficult to resect; if it is more than 3/4 of the circumference, surgery is not necessary. MRI can also show clearly when the tumor invades soft tissues, and is most valuable for the evaluation of supraglottic sulcus tumor. MRI is similar to CT in the examination of hilar and mediastinal lymph nodes, and can clearly show enlarged lymph nodes, but the specificity is poor.
(4) Bronchoscopy Positive detection rate is 60%~80%, and changes in bronchi of grade 4~5 such as swelling, stenosis, and ulceration can generally be observed, and smear cytology, bite biopsy, and local lavage can be performed. This examination, which is generally safe, has also been reported to be complicated by bleeding after 9% to 29% of biopsies. Caution should be exercised when encountering tumors suspected to be carcinoid and rich in visual blood flow, and it is best to avoid biopsy trauma.
(5) ECT examination ECT bone imaging detects lesions 3-6 months earlier than ordinary X-ray, and can detect bone metastases earlier. If the lesion has reached the middle stage and the decalcification of the bone lesion reaches more than 30%~50% of its content, both X-ray and bone imaging will be positive, if the osteogenic reaction of the lesion is quiescent and the metabolism is not active, the bone imaging will be negative and the X-ray will be positive, the two complement each other and can improve the diagnosis rate.
(6) Mediastinoscopy Mediastinoscopy should be performed under general anesthesia when the lymph nodes in the anterior, paratracheal and inferior ramus (2, 4, 7) groups are enlarged as seen on CT. A transverse incision is made in the superior sternal recess, the anterior soft tissues of the neck are bluntly separated to reach the anterior tracheal space, the anterior tracheal passage is bluntly freed, and a viewing scope is placed to slowly pass behind the innominate artery to observe the enlarged lymph nodes in the paratracheal, tracheobronchial angles and infraluminal areas. Clinical data show that the overall positive rate is 39%, the mortality rate is about 0.04%, and 1.2% have complications such as pneumothorax, laryngeal nerve paralysis, hemorrhage, fever, etc.
(7) PET examination can detect unexpected extrathoracic metastases, which can make the preoperative period more accurate. There is no false-positive rate in cases of extrathoracic metastases, but false-positive findings on PET in intra-mediastinal granulomas or other inflammatory lymphadenopathy need to be confirmed by cytology or biopsy.