Laboratory tests
General laboratory tests
Patients need routine laboratory tests prior to treatment to understand their general condition and suitability for appropriate treatment measures.
Blood workup
Liver function, renal function, and other biochemical and immunological tests as needed
Coagulation tests
Serological tumor markers
Coagulation tests
Serological tumor markers
Commonly used markers for primary lung cancer recommended by the American Committee on Clinical Biochemistry and the European Expert Group on Tumor Markers are carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratinfragment (NSE), and cytokeratin-fragment (NSE). cytokeratinfragment (CYFRA21-1) and pro-gastrin-releasing peptide (ProGRP), as well as squamous cell carcinoma antigen (SCCAg). The combination of the above tumor markers can improve their sensitivity and specificity in clinical applications.
Adjunctive diagnosis
The tumor markers associated with lung cancer can be tested as needed for clinical diagnosis, to aid in the diagnosis and differential diagnosis, and to understand the possible pathological types of lung cancer.
① SCLC: NSE and ProGRP are ideal indicators to assist in the diagnosis of SCLC.
② NSCLC: Elevated levels of CEA, SCC and CYFRA21-1 in the serum of patients can help in the diagnosis of NSLCL. It is generally believed that SCC and CYFRA21-1 have a high specificity for squamous lung cancer. The combination of NSE, CYFRA21-1, ProGRP, CEA, and SCCAg can improve the accuracy of differentiating SCLC from NSCLC.
CautionsThe results of tumor marker assays are closely related to the assay used, and direct comparison of the results obtained by different assays is not appropriate. If the assay is changed during treatment observation, it must be measured simultaneously and in parallel using the original assay to avoid incorrect medical interpretations.
② Each laboratory should study the test method used to establish an appropriate reference interval.
③Unqualified specimens such as hemolysis, coagulation, and insufficient blood volume can affect the results of coagulation function, NSE and other tumor markers, and even liver and kidney indicators.
The specimens should be sent for examination as soon as possible after collection, and prolonged storage of the specimens may affect the results of tumor markers such as ProGRP and other laboratory indices.
Imaging
Imaging methods for lung cancer include X-ray chest radiographs, CT, MRI, ultrasound, nuclear imaging, PET, and other methods. They are mainly used for diagnosis and differential diagnosis, staging and restaging of lung cancer, assessment of surgical resectability, efficacy monitoring and prognosis assessment. Imaging is the best method for non-invasive detection and evaluation of tumors, and imaging information enables clinicians to be more certain about the prognosis of tumors and to make treatment decisions. In the diagnosis and treatment of lung cancer, one or more imaging methods should be selected reasonably and effectively according to different examination purposes.
Chest radiography
In China, frontal and lateral chest X-rays are often the basic imaging methods to detect lung lesions in primary hospitals, but they have limited diagnostic value for early lung cancer.
Chest CT examination
Chest CT is the most important and commonly used imaging method for lung cancer diagnosis, staging, efficacy evaluation, and post-treatment follow-up. CT can reveal imaging information that is difficult to detect on X-ray chest radiographs, which can effectively detect early lung cancer and further verify the location and extent of lesion involvement. For patients with initial diagnosis of lung cancer, CT scan of the chest should include both adrenal glands. For lesions in the chest that are difficult to diagnose qualitatively, CT-guided percutaneous lung aspiration biopsy can be used to obtain cytologic or histologic diagnosis.
Traditional imaging staging of lung cancer is based on the location of lung cancer into central, peripheral, and site-specific types. Central lung cancer occurs in the main bronchi and in the lobar and segmental bronchi and often causes secondary obstructive changes. Peripheral lung cancer occurs in the distal part of the segmental bronchus. Site-specific lung cancers such as supraglottic sulcus tumors.
Central lung cancer
Most central lung cancers are squamous, small cell carcinomas, but more recently, adenocarcinoma has also become a central lung cancer. Early central lung cancer presents with limited bronchial wall thickening, wall irregularities, luminal narrowing, and intrabronchial striations or punctate (axial) hyperintensities in the pulmonary arteries, usually without obstructive changes. The imaging manifestation can sometimes be mainly obstructive pneumonia, and the inflammation dissipates after anti-inflammatory treatment, but it is still necessary to pay attention to whether the proximal bronchial wall is thickened. In the middle and late stage of central lung cancer, central mass and obstructive changes are the main manifestations. The obstructive changes first become obstructive emphysema, and then further develop into obstructive pneumonia and pulmonary atelectasis. The proximal end of the obstructed lung often protrudes due to the tumor, forming a transverse “S” sign. Bronchial inflations may be seen on CT in cases of incomplete bronchial obstruction. Enhanced CT often reveals dilated, mucus-filled bronchi. CT thin-section (1-1.25 mm reconstruction layer thickness) and multiplanar reformation (MPR) are valuable in the preoperative evaluation of central lung cancer and should be routinely used. If there is no contraindication, enhanced scanning should be performed. In central lung cancer with atelectasis, MRI is helpful to distinguish the tumor from the atelectasis, and the signal of the atelectasis is higher than that of the tumor in T2WI, and the enhancement of the atelectasis is higher than that of the tumor in T1WI.
Peripheral type lung cancerA confined lesion in the lung ≤1 cm in diameter is usually referred to as a small nodule, a confined lesion of 1 cm <3 cm in diameter is referred to as a nodule, and a diameter >3 cm is referred to as a mass. When analyzing the imaging presentation, the size, morphology, density, internal structure, tumor-lung interface and volume doubling time of the nodule or mass are the most important diagnostic indications. When observing the characteristics of nodules/masses, thin layer CT (layer thickness 1-1.25 mm) should be routinely applied and MPR can be used to observe the morphology of nodules in all directions, which helps in qualitative diagnosis. For solid nodules, the differential diagnosis can be made by selecting enhancement scans, dual-phase enhancement scans and dynamic enhancement scans, depending on the situation. For subsolid nodules in the lungs, especially pure ground glass nodules, it is recommended to use only thin layer plain scan.
a. Size and morphology: Typical peripheral lung cancer is mostly round, oval or irregular in shape, and mostly lobulated. With the gradual popularization of physical examination, there are more and more early stage lung cancers with imaging manifestations of small lung nodules and pulmonary nodules. At this time, the diagnosis is relatively easy based on the contour and marginal features of the mass.
b.Density
CT plain scan: It can be divided into solid nodules, partially solid nodules and pure ground glass nodules (the latter two are collectively called ground glass nodules or sub-solid nodules) according to whether the nodules cover the lung parenchyma or not. Pure ground glass nodules are purely ground glass-like densities, which are tumors growing along the alveolar architecture without obscuring the lung parenchyma, with peripheral pulmonary vascular penetration visible within the lesion; solid nodules completely obscure the lung parenchyma without ground glass-like density components; and partially solid nodules have both components. Persistent ground glass nodules are most often associated with atypical adenomatous hyperplasia, adenocarcinoma in situ, microinvasive adenocarcinoma, and invasive adenocarcinoma, depending on size and density. Lung cancers presenting as ground glass nodules have a tendency to be multiple, and preoperative thin-section CT of the whole lung should be carefully observed to facilitate the determination of treatment options.
Enhancement scans: Enhancement CT scans are compared with plain scans, with an increase of 15 to 20 HU as the threshold for differentiating benign and malignant lesions. Double-phase enhancement scans and dynamic enhancement scans can be selected to further assist in the diagnosis when peripheral nodules are difficult to diagnose.
c. Internal structure
Bronchial inflatable signs and vacuoles: can be seen in lung cancer, inflammatory lung lesions or lymphoma, but lung cancer is more common. Thin-layer CT is better and often coexists with the vacuolation sign. Image post-processing techniques such as MPR can help show oblique bronchial inflation signs. Vacuoles are generally small cavities of about 1 mm in size and are commonly found in adenocarcinoma, accounting for about 20% to 25% of cases, often multiple, some of which may be axial phases of inflated bronchioles, or residual air-containing alveoli that have not been filled with tumor.
Calcification: The probability of finding calcification in nodules is much higher on thin-section CT than on conventional CT. Calcification can be found in approximately 6% to 10% of lung cancers, and is more likely to be malignant if it is located in the center of the nodule/mass in a reticular pattern, diffuse small peppery endpoints, or indeterminate shape. High spatial resolution algorithms can produce edge enhancement artifacts, which can easily outline high density at the nodal edges and can be mistaken for calcifications; applying standard algorithms or soft tissue reconstruction algorithms can avoid such artifacts.
Cavities and cavities: Cavities are generally considered to be formed after the bronchial drainage of necrotic material and can be 1-10 cm in size, either centrally or eccentrically. The cavity wall is mostly 0.5-3 cm, and the thick-walled cavity and the uneven inner wall support the diagnosis of lung cancer. The cystic cavity is usually considered to be partly a carcinoma occurring in the wall of a pulmonary blister or cyst, and partly due to the formation of a living valve effect within the tumor.
Pulmonary solid change: The tumor grows and infiltrates along the alveolar wall and has not completely destroyed the alveolar septum, but thickens the alveolar wall or there is secretion in the adjacent alveoli, and some of the alveoli still contain air, forming pulmonary solid change, which is also called pneumonia type change. On enhancement scan, enhanced blood vessels can be seen in the solid lung tissue, which is called angiographic sign on CT image. It can be seen in mucinous adenocarcinoma of the lung, as well as in obstructive and infectious pneumonia, lymphoma, pulmonary infarction, and pulmonary edema.
d. Tumor-pulmonary interface: A linear shadow extending from the nodule edge to the periphery and a slightly thicker burr-like change near the nodule end, mostly seen in lung cancer. Usually the thickness of the nodule is less than 2 mm, and the thickness of the nodule is less than 2 mm, which is called fine burr. The pathologic basis for burr formation is tumor invasion of adjacent lobular septa, peri-tumor lung parenchymal fibrosis, and/or inflammatory cell infiltration.
e. Adjacent structures
Pleural changes: Pleural indentation is a thin linear or striated hyperdense shadow from the nodule or mass to the pleura, sometimes with a flared periphery, and localized pleural indentation is seen in the gross lesion. It is mainly caused by the contraction of the scar caused by the fibroblastic reaction within the mass that pulls the local pleura, which may be filled with fluid or extra pleural fat, most commonly in pulmonary adenocarcinoma. If the above linear changes are thick or irregular, the possibility of tumor infiltration along the pleura should be considered.
Satellite lesions: adenocarcinoma of the lung is the most common, often appearing as nodules or small patches, and are considered to be stage T3 if they are located in the same lobe as the main lesion, or stage T4 if they are located in the same lung. Benign lesions, especially tuberculosis, can also be seen as satellite lesions.
f. Tumor volume doubling time: Tumor volume doubling time refers to the time required for the tumor volume to increase by a factor of 1 (diameter increase of about 26), which is one of the important indicators to determine the benignity and malignancy. The growth rate of different pathological types of lung cancer varies significantly, and the doubling time varies greatly, generally >30 days, <400 days, squamous carcinoma 800 days. Three-dimensional volumetric measurements make it easier to accurately compare changes in nodule volume and determine the time to multiplication.
Supra-pulmonary sulcus tumor
CT can show apical lung lesions, distinguish masses from pleural thickening, and show bone destruction, extent of chest wall invasion, and whether the tumor is invading the cervical root. The use of enhanced CT-MPR and maximum density projection is important, with the latter being used primarily to show whether large vessels, such as the subclavian artery, are invaded. MRI has good soft tissue resolution and can show anatomic detail of the superior thoracic orifice and brachial plexus, which is better than CT for determining the extent of tumor invasion and bone marrow invasion.
Differential diagnosis of lung cancer imaging
a. Differential diagnosis of bronchial obstructive lesions: The causes of bronchial obstructive lesions can be divided into the following categories.
Neoplastic: including central lung cancer, benign tumors in the bronchial lumen such as malignant tumors and papillomas, inflammatory myofibroblastic tumors, and in a few cases metastases and lymphomas can cause bronchial obstructive changes.
Infectious: tuberculosis, nodular disease, right middle lung syndrome, etc. Other: foreign body, bronchiectasis, pulmonary amyloidosis, etc.
a1 Central lung cancer: as previously described.
a2 Nodules: intrapulmonary manifestations are more likely to involve one or more segments than the whole lobe. Sometimes disseminated lesions are seen in different lobes of the lung or contralaterally. If the entire lobe is caseous, the lobe may be enlarged and the interlobular fissures may be expanded and cavities may be present. Obstructive changes due to lung cancer are usually obstruction of the entire distal segment or lobe or atelectasis (or inflammation).
Tuberculous bronchial lesions may cause distorted bronchial stenosis or irregular bronchial dilatation and inflation without proximal masses, which is an important differentiator from lung cancer. It is more difficult to differentiate from lung cancer when there is a narrowing of the bronchial lumen.
The lymph nodes in the hilum or mediastinum that are enlarged due to tuberculosis are not clearly related to the lymphatic drainage area and may have calcification or circumferential enhancement. The metastatic lymph nodes of lung cancer are related to the distribution of the drainage area. Circumferential enhancement of lymph node margins is occasionally seen in metastases of squamous carcinoma, but rarely in adenocarcinoma and small cell carcinoma.
a3 Bronchial luminal tumors: Benign bronchial luminal tumors are rare, but pulmonary malformations, papillomas, and neurogenic tumors can cause obstructive changes to varying degrees. When soft tissue density masses or nodules in the bronchial cavity are associated with pulmonary atelectasis without mediastinal or hilar lymph node enlargement, it is difficult to distinguish benign and malignant tumors by imaging, but benign tumors are very rare and are mostly diagnosed as central lung cancer before surgery. Thin-layer CT of intraluminal bronchial malformation tumors can mostly detect fatty density and calcified foci, which are relatively easy to identify.
In addition, inflammatory myofibroblastoma located in the bronchial lumen may be associated with obstructive pneumonia and pulmonary atelectasis and is a low-grade malignant mesenchymal tumor.
a4 Endobronchial foreign bodies: A history of foreign body aspiration and recurrent fixed site infections support the diagnosis of foreign body with obstructive changes. a diagnosis is easier on CT if fatty density foci (lipid aspiration) or high density foci (aspiration of bone) are found in the bronchial lumen.
b. Differential diagnosis of isolated pulmonary nodules/masses: The causes of isolated pulmonary nodules/masses are as follows.
Neoplastic: malignant tumors include peripheral lung cancer, solitary lung metastases, malignant lymphoma, and malignant mesenchymal lung tumors; benign tumors include mismatched tumors and sclerosing pneumocytoma.
Infectious inflammatory lesions: tuberculosis bulb, spherical pneumonia, lung abscess, mechanized pneumonia, fungal infections.
Developmental abnormalities: bronchial/pulmonary cysts, pulmonary isolation disease, arteriovenous fistula. Other: spherical pulmonary atelectasis.
b1 Peripheral lung cancer: as previously described.
b2 Tuberculosis spheres: Tuberculosis spheres are often located in the posterior segment of the upper or dorsal segment of the lower lobe, but not infrequently occur in atypical locations. They are usually round or round-like in shape and may be regular or irregular, often with a flat, angular contour. Due to its inflammatory nature, it may have long haptic or cord-like margins, and the adjacent pleura is often thickened and adherent, which is different from the burr and pleural invagination of lung cancer due to fibrogenic reaction or infiltration of cancer cells along the lobular septa, but sometimes it is also extremely difficult to distinguish. Calcifications and cavities are not uncommon, and the walls of tuberculous cavities are thin and smooth, which is different from the nodular thickening of cavities caused by necrosis in lung cancer, and fluid is rarely seen in the cavities. Tuberculous cavities can also be crescent-shaped or have a bizarre ring-over-ring shape. Patches of satellite lesions are often seen around the nodules (masses). In some cases, draining bronchi may be seen. Enhancement scans are more characteristic and may be non-enhancing or circumferential, with the thickness of circumferential enhancement depending on the amount of granulation tissue surrounding the nodule.
b3 Pulmonary malformation tumor: smooth or shallowly lobulated peripheral nodules that may have calcification, typically popcorn-shaped. Thin-section CT of the fatty component of the tumor is helpful in confirming the diagnosis. Enhancement scans do not show significant enhancement. Chondromatous malformations can be lobulated without calcification or fatty components and sometimes need to be differentiated from peripheral lung cancer.
b4 Sclerosing pneumocytoma: It appears as a round or oval shaped well-defined mass or nodule on X-ray chest radiographs, as if outlined with a pen. b4 Sclerosing pneumocytoma has uniform density on CT scan, sometimes with small hypodense areas and coarse punctate calcifications, and occasionally cystic changes. b4 Sclerosing pneumocytoma has moderate to marked enhancement on CT enhancement. For round, ovoid and well-defined masses or nodules with early enhancement, a time-lapse scan should be performed. The lesion may sometimes have mild obstructive changes distal to the lesion. Involvement of hilar and mediastinal lymph nodes is rare and does not affect the prognosis.
b5 Spherical pneumonia, lung abscess, and mechanized pneumonia: Mostly occur in the dorsal and basal segments of the lower lobes of both lungs, located in the periphery of the lung, near the pleura, and may be square, flattened, or triangular in shape, with multiplanar reconstruction showing irregular lesions, whereas lung cancer is more uniformly spherical in all directions. In acute inflammation, the central area is high density, the surrounding area is low density, and the edges are blurred; in the case of abscess formation, a more regular low-density necrotic area may appear in the center of the lesion; in the case of small cavity formation, the cavity wall is more regular. The adjacent pleura is reactive thickened and more extensive. After effective anti-infective treatment, the lesion usually shrinks significantly.
b6 Fungal infection: the typical presentation is a nodular foci with well-defined margins visible in thick- or thin-walled cavities with air crescent sign, and the Aspergillus balls within them are movable on changing body scans. Vascular invasive Aspergillosis presents early as focal pulmonary solid lesions with blurred margins or ground glass density, and late can present as cavernous nodules with air crescent sign, i.e., Aspergillus globules. Chronic necrotizing aspergillosis may present as solid, large cavernous lesions with an irregular lining. It may be associated with hilar and mediastinal lymph node enlargement, pleural effusion, and pleural thickening.
b7 Pulmonary isolation disease: imaging is very important in the diagnosis of pulmonary isolation disease, and the diagnosis can be established in most cases. It is mostly located in the posterior or inner basal segments of the lower lobes, more on the left than on the right. The intralobar type mainly presents as a uniformly dense mass, round, ovoid, or triangular or polygonal in a few cases, with clear borders and CT values similar to those of muscle in those with uniform density; those with bronchial communication show inhomogeneous density and cystic changes within, with intracapsular density close to water and regular clear borders, with gas sometimes seen within the capsule, and fluid levels seen if there is concomitant infection, which may change in the short term. The lung lobes appear as hyperdense shadows adjacent to the posterior mediastinum or diaphragm, with clear margins and uniform density, rarely with cystic changes. Computed tomography angiography is superior for the visualization of abnormal arteries and internal structures, allowing multiple views of abnormal supply arteries from the thoracic aorta, abdominal aorta, or other rare arteries and draining veins.
b8 Bronchial/pulmonary cysts: those located in the middle mediastinum near the trachea or hilum are more typical and are not difficult to diagnose. Those located in the periphery of the lung mostly present as round or round-like, well-defined, smooth, and rarely lobulated. It is not uncommon to see higher densities, and in a few cases, the density may be higher than that of soft tissue.
However, there is no enhancement on enhancement scan. There may be calcification in the cyst wall. Cysts occurring in fine bronchi may be lobulated, with uneven margins, and even small vacuoles may be seen within them, which may be difficult to differentiate from lung cancer.
b9 Pulmonary arteriovenous fistula: Pulmonary arteriovenous fistula is a congenital abnormality of vascular development and is more common in young females. CT shows one or more round or oval nodules with round or curved calcifications, and enhanced scans usually show thickened blood supply arteries and draining veins.
b10 Spherical atelectasis: Spherical atelectasis is a specific type of atelectasis caused by localized pleural adhesions that limit lung expansion after resolution of pleurisy and effusion. CT scans may show curved or distorted vascular and bronchial shadowing towards the center of the mass, like a snail or comet tail, with thickening of the adjacent pleura, reduced lung volume in the lesion, and compensatory emphysema in the surrounding lung tissue.
b11 Solitary pulmonary metastases: Most images show round or slightly lobulated nodules with clear margins and uniform or heterogeneous densities, but a few may show irregular margins with burrs. The clear, well-defined margins need to be differentiated from benign pulmonary lesions such as sarcoidosis and malignant tumors, and those with irregular margins need to be differentiated from second primary lung cancer.
MRI examination
MRI can be used selectively in the chest to determine whether the chest wall or mediastinum is invaded; to show the relationship between supraglottic sulcus tumors and brachial plexus nerves and vessels; to distinguish hilar masses from atelectasis and obstructive pneumonia; to observe the invasion of the mediastinum and hilar vessels and lymph node enlargement in patients for whom iodine contrast is contraindicated; and to distinguish fibrosis from tumor recurrence after radiotherapy. MRI is particularly useful for determining whether there are metastases in the brain and spinal cord, and brain-enhanced MRI should be used as a routine preoperative staging test for lung cancer. MRI is highly sensitive and specific for metastases in the bone marrow cavity and can be used according to clinical needs.
PET examination
PET is the best method for diagnosis, staging and restaging, efficacy evaluation, and prognosis assessment of lung cancer. According to the NCCN Clinical Practice Guidelines in Oncology, the American College of Chest Physicians Clinical Practice Guidelines, and national expert consensus, PET is recommended for the following conditions when available: ①Diagnosis and differential diagnosis of isolated lung nodules (solid nodules ≥8 mm, persistent partially solid nodules with internal solid component ≥ 6 mm)
(2) pre-treatment staging of lung cancer, PET has better diagnostic efficacy for lymph node metastasis and extrathoracic metastasis (except brain metastasis); (3) lung cancer radiotherapy localization and target area sketch; (4) adjuvant identification of post-operative scar and tumor recurrence that cannot be judged by conventional CT, such as increased PET uptake, requiring biopsy confirmation; (5) adjuvant identification of post-radiotherapy fibrosis and tumor residual/recurrence that cannot be judged by conventional CT, such as PET uptake, requiring biopsy confirmation (6) To assist in evaluating the efficacy of lung cancer (especially molecularly targeted therapy), the recommended criteria for evaluating the efficacy of PET solid tumors (Table 1).
Table 1 PET efficacy evaluation criteria for solid tumors (2009)
Ultrasound examination
Ultrasound is not usually able to visualize intra-lung lesions due to gas in the lungs and obscuration of the ribs and sternum, so ultrasound in lung cancer patients should be used mainly for observation of lymph nodes in the supraclavicular region, liver, adrenal glands, kidneys, and other sites and organ metastases to provide information for tumor staging. Ultrasound can also be used for examination of pleural and pericardial effusion and localization before fluid extraction. Ultrasound-guided aspiration can be used to obtain specimens for histological examination of subpleural lung tumors, supraclavicular lymph nodes, and metastases from parenchymal organs. The diagnosis of lung cancer is based on clinical manifestations and various ancillary tests. The diagnosis of lung cancer, especially peripheral lung cancer, is difficult to distinguish from some pulmonary nodular lesions and some chronic inflammatory lesions, so the diagnosis of lung cancer requires various biopsies or punctures to obtain pathological or cytological evidence.
(6) Bone nuclide scan: a routine examination for determining bone metastasis of lung cancer. When bone scan suggests suspicious metastasis, MRI, CT or PET will be performed to verify the suspicious area; preoperative PET examination can replace bone scan.
Endoscopy and other examinations
Bronchoscopy and ultrasound bronchial aspiration biopsy
Bronchoscopy is valuable for localizing the tumor and obtaining a histologic diagnosis. In central lung cancer, bronchoscopy can directly visualize the lesion, and more than 95 can obtain a definitive pathologic diagnosis by cytologic brushings and histologic biopsy. Ultrasound bronchoscopy can also be used to perform puncture biopsies of the hilar and mediastinal lymph nodes adjacent to the bronchi for qualitative diagnosis of lung cancer and staging of mediastinal lymph nodes. A variety of navigation techniques are available for peripheral lung cancer biopsy.
Mediastinoscopy
With standard and expanded mediastinoscopy, 2R, 2L, 4R, 4L, 5, 6, 7, and 10 zone lymph nodes can be obtained for the qualitative diagnosis of lung cancer and regional lymph node staging, which used to be the gold standard for evaluating mediastinal lymph node metastases. Due to the need for general anesthesia for mediastinoscopy and the maturation of trans-ultrasound bronchoscopy and esophagoscopic aspiration biopsy techniques, the use of mediastinoscopy in the diagnosis and staging of lung cancer has tended to decrease.
Thoracoscopic or open lung biopsy
For lung lesions detected by imaging, for which a definitive histologic and cytologic diagnosis cannot be obtained despite sputum cytology, bronchoscopy, and various methods of puncture and biopsy, and for which lung cancer is highly suspected clinically or cannot be excluded after short-term observation, thoracoscopy or even open lung biopsy is one of the methods for qualitative diagnosis of lung cancer.
Sputum exfoliative cytology examination
Sputum exfoliative cytology is simple, noninvasive, and easily accepted by patients, and is one of the simple and effective methods for the qualitative diagnosis of lung cancer, and can also be used as a screening tool for people at high risk for lung cancer. The positive rate of sputum exfoliative cytology depends on the method of sputum specimen collection, the method of cytology smear preparation, the diagnostic level of cytologists, and the location and pathological type of the tumor.
Supra-pulmonary sulcus tumor
CT can show apical lung lesions, distinguish masses from pleural thickening, and show bone destruction, extent of chest wall invasion, and whether the tumor is invading the cervical root. The use of enhanced CT-MPR and maximum density projection is important, with the latter being used primarily to show whether large vessels, such as the subclavian artery, are invaded. MRI has good soft tissue resolution and can show anatomic detail of the superior thoracic orifice and brachial plexus, which is better than CT for determining the extent of tumor invasion and bone marrow invasion.
Differential diagnosis of lung cancer imaging
a. Differential diagnosis of bronchial obstructive lesions: The causes of bronchial obstructive lesions can be divided into the following categories.
Neoplastic: including central lung cancer, benign tumors in the bronchial lumen such as malignant tumors and papillomas, inflammatory myofibroblastic tumors, and in a few cases metastases and lymphomas can cause bronchial obstructive changes.
Infectious: tuberculosis, nodular disease, right middle lung syndrome, etc. Other: foreign body, bronchiectasis, pulmonary amyloidosis, etc.
a1 Central lung cancer: as previously described.
a2 Nodules: intrapulmonary manifestations are more likely to involve one or more segments than the whole lobe. Sometimes disseminated lesions are seen in different lobes of the lung or contralaterally. If the entire lobe is caseous, the lobe may be enlarged and the interlobular fissures may be expanded and cavities may be present. Obstructive changes due to lung cancer are usually obstruction of the entire distal segment or lobe or atelectasis (or inflammation).
Tuberculous bronchial lesions may cause distorted bronchial stenosis or irregular bronchial dilatation and inflation without proximal masses, which is an important differentiator from lung cancer. It is more difficult to differentiate from lung cancer when there is a narrowing of the bronchial lumen.
The lymph nodes in the hilum or mediastinum that are enlarged due to tuberculosis are not clearly related to the lymphatic drainage area and may have calcification or circumferential enhancement. The metastatic lymph nodes of lung cancer are related to the distribution of the drainage area. Circumferential enhancement of lymph node margins is occasionally seen in metastases of squamous carcinoma, but rarely in adenocarcinoma and small cell carcinoma.
a3 Bronchial luminal tumors: Benign bronchial luminal tumors are rare, but pulmonary malformations, papillomas, and neurogenic tumors can cause obstructive changes to varying degrees. When soft tissue density masses or nodules in the bronchial cavity are associated with pulmonary atelectasis without mediastinal or hilar lymph node enlargement, it is difficult to distinguish benign and malignant tumors by imaging, but benign tumors are very rare and are mostly diagnosed as central lung cancer before surgery. Thin-layer CT of intraluminal bronchial malformation tumors can mostly detect fatty density and calcified foci, which are relatively easy to identify.
In addition, inflammatory myofibroblastoma located in the bronchial lumen may be associated with obstructive pneumonia and pulmonary atelectasis and is a low-grade malignant mesenchymal tumor.
a4 Endobronchial foreign bodies: A history of foreign body aspiration and recurrent fixed site infections support the diagnosis of foreign body with obstructive changes. a diagnosis is easier on CT if fatty density foci (lipid aspiration) or high density foci (aspiration of bone) are found in the bronchial lumen.
b. Differential diagnosis of isolated pulmonary nodules/masses: The causes of isolated pulmonary nodules/masses are as follows.
Neoplastic: malignant tumors include peripheral lung cancer, solitary lung metastases, malignant lymphoma, and malignant mesenchymal lung tumors; benign tumors include mismatched tumors and sclerosing pneumocytoma.
Infectious inflammatory lesions: tuberculosis bulb, spherical pneumonia, lung abscess, mechanized pneumonia, fungal infections.
Developmental abnormalities: bronchial/pulmonary cysts, pulmonary isolation disease, arteriovenous fistula. Other: spherical pulmonary atelectasis.
b1 Peripheral lung cancer: as previously described.
b2 Tuberculosis spheres: Tuberculosis spheres are often located in the posterior segment of the upper or dorsal segment of the lower lobe, but not infrequently occur in atypical locations. They are usually round or round-like in shape and may be regular or irregular, often with a flat, angular contour. Due to its inflammatory nature, it may have long haptic or cord-like margins, and the adjacent pleura is often thickened and adherent, which is different from the burr and pleural invagination of lung cancer due to fibrogenic reaction or infiltration of cancer cells along the lobular septa, but sometimes it is also extremely difficult to distinguish. Calcifications and cavities are not uncommon, and the walls of tuberculous cavities are thin and smooth, which is different from the nodular thickening of cavities caused by necrosis in lung cancer, and fluid is rarely seen in the cavities. Tuberculous cavities can also be crescent-shaped or have a bizarre ring-over-ring shape. Patches of satellite lesions are often seen around the nodules (masses). In some cases, draining bronchi may be seen. Enhancement scans are more characteristic and may be non-enhancing or circumferential, with the thickness of circumferential enhancement depending on the amount of granulation tissue surrounding the nodule.
b3 Pulmonary malformation tumor: smooth or shallowly lobulated peripheral nodules that may have calcification, typically popcorn-shaped. Thin-section CT of the fatty component of the tumor is helpful in confirming the diagnosis. Enhancement scans do not show significant enhancement. Chondromatous malformations can be lobulated without calcification or fatty components and sometimes need to be differentiated from peripheral lung cancer.
b4 Sclerosing pneumocytoma: It appears as a round or oval shaped well-defined mass or nodule on X-ray chest radiographs, as if outlined with a pen. b4 Sclerosing pneumocytoma has uniform density on CT scan, sometimes with small hypodense areas and coarse punctate calcifications, and occasionally cystic changes. b4 Sclerosing pneumocytoma has moderate to marked enhancement on CT enhancement. For round, ovoid and well-defined masses or nodules with early enhancement, a time-lapse scan should be performed. The lesion may sometimes have mild obstructive changes distal to the lesion. Involvement of hilar and mediastinal lymph nodes is rare and does not affect the prognosis.
b5 Spherical pneumonia, lung abscess, and mechanized pneumonia: Mostly occur in the dorsal and basal segments of the lower lobes of both lungs, located in the periphery of the lung, near the pleura, and may be square, flattened, or triangular in shape, with multiplanar reconstruction showing irregular lesions, whereas lung cancer is more uniformly spherical in all directions. In acute inflammation, the central area is high density, the surrounding area is low density, and the edges are blurred; in the case of abscess formation, a more regular low-density necrotic area may appear in the center of the lesion; in the case of small cavity formation, the cavity wall is more regular. The adjacent pleura is reactive thickened and more extensive. After effective anti-infective treatment, the lesion usually shrinks significantly.
b6 Fungal infection: the typical presentation is a nodular foci with well-defined margins visible in thick- or thin-walled cavities with air crescent sign, and the Aspergillus balls within them are movable on changing body scans. Vascular invasive Aspergillosis presents early as focal pulmonary solid lesions with blurred margins or ground glass density, and late can present as cavernous nodules with air crescent sign, i.e., Aspergillus globules. Chronic necrotizing aspergillosis may present as solid, large cavernous lesions with an irregular lining. It may be associated with hilar and mediastinal lymph node enlargement, pleural effusion, and pleural thickening.
b7 Pulmonary isolation disease: imaging is very important in the diagnosis of pulmonary isolation disease, and the diagnosis can be established in most cases. It is mostly located in the posterior or inner basal segments of the lower lobes, more on the left than on the right. The intralobar type mainly presents as a uniformly dense mass, round, ovoid, or triangular or polygonal in a few cases, with clear borders and CT values similar to those of muscle in those with uniform density; those with bronchial communication show inhomogeneous density and cystic changes within, with intracapsular density close to water and regular clear borders, with gas sometimes seen within the capsule, and fluid levels seen if there is concomitant infection, which may change in the short term. The lung lobes appear as hyperdense shadows adjacent to the posterior mediastinum or diaphragm, with clear margins and uniform density, rarely with cystic changes. Computed tomography angiography is superior for the visualization of abnormal arteries and internal structures, allowing multiple views of abnormal supply arteries from the thoracic aorta, abdominal aorta, or other rare arteries and draining veins.
b8 Bronchial/pulmonary cysts: those located in the middle mediastinum near the trachea or hilum are more typical and are not difficult to diagnose. Those located in the periphery of the lung mostly present as round or round-like, well-defined, smooth, and rarely lobulated. It is not uncommon to see higher densities, and in a few cases, the density may be higher than that of soft tissue.
However, there is no enhancement on enhancement scan. There may be calcification in the cyst wall. Cysts occurring in fine bronchi may be lobulated, with uneven margins, and even small vacuoles may be seen within them, which may be difficult to differentiate from lung cancer.
b9 Pulmonary arteriovenous fistula: Pulmonary arteriovenous fistula is a congenital abnormality of vascular development and is more common in young females. CT shows one or more round or oval nodules with round or curved calcifications, and enhanced scans usually show thickened blood supply arteries and draining veins.
b10 Spherical atelectasis: Spherical atelectasis is a specific type of atelectasis caused by localized pleural adhesions that limit lung expansion after resolution of pleurisy and effusion. CT scans may show curved or distorted vascular and bronchial shadowing towards the center of the mass, like a snail or comet tail, with thickening of the adjacent pleura, reduced lung volume in the lesion, and compensatory emphysema in the surrounding lung tissue.
b11 Solitary pulmonary metastases: Most images show round or slightly lobulated nodules with clear margins and uniform or heterogeneous densities, but a few may show irregular margins with burrs. The clear, well-defined margins need to be differentiated from benign pulmonary lesions such as sarcoidosis and malignant tumors, and those with irregular margins need to be differentiated from second primary lung cancer.
MRI examination
MRI can be used selectively in the chest to determine whether the chest wall or mediastinum is invaded; to show the relationship between supraglottic sulcus tumors and brachial plexus nerves and vessels; to distinguish hilar masses from atelectasis and obstructive pneumonia; to observe the invasion of the mediastinum and hilar vessels and lymph node enlargement in patients for whom iodine contrast is contraindicated; and to distinguish fibrosis from tumor recurrence after radiotherapy. MRI is particularly useful for determining whether there are metastases in the brain and spinal cord, and brain-enhanced MRI should be used as a routine preoperative staging test for lung cancer. MRI is highly sensitive and specific for metastases in the bone marrow cavity and can be used according to clinical needs.
PET examination
PET is the best method for diagnosis, staging and restaging, efficacy evaluation, and prognosis assessment of lung cancer. According to the NCCN Clinical Practice Guidelines in Oncology, the American College of Chest Physicians Clinical Practice Guidelines, and national expert consensus, PET is recommended for the following conditions when available: ①Diagnosis and differential diagnosis of isolated lung nodules (solid nodules ≥8 mm, persistent partially solid nodules with internal solid component ≥ 6 mm)
(2) pre-treatment staging of lung cancer, PET has better diagnostic efficacy for lymph node metastasis and extrathoracic metastasis (except brain metastasis); (3) lung cancer radiotherapy localization and target area sketch; (4) adjuvant identification of post-operative scar and tumor recurrence that cannot be judged by conventional CT, such as increased PET uptake, requiring biopsy confirmation; (5) adjuvant identification of post-radiotherapy fibrosis and tumor residual/recurrence that cannot be judged by conventional CT, such as PET uptake, requiring biopsy confirmation (6) To assist in evaluating the efficacy of lung cancer (especially molecularly targeted therapy), the recommended criteria for evaluating the efficacy of PET solid tumors (Table 1).
Table 1 PET efficacy evaluation criteria for solid tumors (2009)
Ultrasound examination
Ultrasound is not usually able to visualize intra-lung lesions due to gas in the lungs and obscuration of the ribs and sternum, so ultrasound in lung cancer patients should be used mainly for observation of lymph nodes in the supraclavicular region, liver, adrenal glands, kidneys, and other sites and organ metastases to provide information for tumor staging. Ultrasound can also be used for examination of pleural and pericardial effusion and localization before fluid extraction. Ultrasound-guided aspiration can be used to obtain specimens for histological examination of subpleural lung tumors, supraclavicular lymph nodes, and metastases from parenchymal organs. The diagnosis of lung cancer is based on clinical manifestations and various ancillary tests. The diagnosis of lung cancer, especially peripheral lung cancer, is difficult to distinguish from some pulmonary nodular lesions and some chronic inflammatory lesions, so the diagnosis of lung cancer requires various biopsies or punctures to obtain pathological or cytological evidence.
(6) Bone nuclide scan: a routine examination for determining bone metastasis of lung cancer. When bone scan suggests suspicious metastasis, MRI, CT or PET will be performed to verify the suspicious area; preoperative PET examination can replace bone scan.
Endoscopy and other examinations
Bronchoscopy and ultrasound bronchial aspiration biopsy
Bronchoscopy is valuable for localizing the tumor and obtaining a histologic diagnosis. In central lung cancer, bronchoscopy can directly visualize the lesion, and more than 95 can obtain a definitive pathologic diagnosis by cytologic brushings and histologic biopsy. Ultrasound bronchoscopy can also be used to perform puncture biopsies of the hilar and mediastinal lymph nodes adjacent to the bronchi for qualitative diagnosis of lung cancer and staging of mediastinal lymph nodes. A variety of navigation techniques are available for peripheral lung cancer biopsy.
Mediastinoscopy
With standard and expanded mediastinoscopy, 2R, 2L, 4R, 4L, 5, 6, 7, and 10 zone lymph nodes can be obtained for the qualitative diagnosis of lung cancer and regional lymph node staging, which used to be the gold standard for evaluating mediastinal lymph node metastases. Due to the need for general anesthesia for mediastinoscopy and the maturation of trans-ultrasound bronchoscopy and esophagoscopic aspiration biopsy techniques, the use of mediastinoscopy in the diagnosis and staging of lung cancer has tended to decrease.
Thoracoscopic or open lung biopsy
For lung lesions detected by imaging, for which a definitive histologic and cytologic diagnosis cannot be obtained despite sputum cytology, bronchoscopy, and various methods of puncture and biopsy, and for which lung cancer is highly suspected clinically or cannot be excluded after short-term observation, thoracoscopy or even open lung biopsy is one of the methods for qualitative diagnosis of lung cancer.
Sputum exfoliative cytology examination
Sputum exfoliative cytology is simple, noninvasive, and easily accepted by patients, and is one of the simple and effective methods for the qualitative diagnosis of lung cancer, and can also be used as a screening tool for people at high risk for lung cancer. The positive rate of sputum exfoliative cytology depends on the method of sputum specimen collection, the method of cytology smear preparation, the diagnostic level of cytologists, and the location and pathological type of the tumor.