With the improvement of living standards and the emphasis on health, the rapid development of imaging technology and the widespread implementation of health checkups, the detection of asymptomatic intrapulmonary nodular lesions has increased significantly.
Currently, chest X-ray and CT examinations are the most common means of diagnosing lung diseases. According to statistics, the sensitivity of small nodular lesions in the lung is poor in conventional chest X-ray, with a detection rate of only 0.2%, while the detection rate in high-resolution CT reaches 40%-60%, which is much higher than that of X-ray examination. Because CT has high resolution and is a cross-sectional image, it can avoid the obstruction of ribs, spine, heart and diaphragm and clearly observe the lung tissue, so CT has the advantage that X-rays cannot match, therefore, CT examination is recommended for most of the chest examinations.
SPN is a common and difficult disease to identify, and its diagnosis and treatment has always been a clinical challenge because of its complex etiology, lack of specificity in clinical manifestations, and difficulty in diagnosis, and easy misdiagnosis and omission. Once SPN is detected, in addition to systemic examination and medical history questioning, such as previous history of pneumonia, diabetes, tuberculosis and tumor, it also involves several clinical departments, such as respiratory medicine, radiology, thoracic surgery and pathology, but the main thing is to observe its imaging manifestations.
I. Imaging manifestations of SPN
1.Nodule size and number
The solid, single, round, well-defined lesions in the lung, >3.0 cm, are called masses, while opaque nodules <3.0 cm are customarily referred to as "isolated nodules in the lung". With the continuous progress of diagnostic techniques, nodules with a diameter of 1-1.5 cm are now called small nodules, and those smaller than 0.5 cm are called small nodules of the emblem.
There is a relationship between the size of intrapulmonary lesions and the degree of benignity and malignancy. Some data reported more than 2000 cases of tiny nodules less than 4 mm, none of which were malignant. Literature data on lung cancer screening point out that the possibility of malignancy of nodules >2.0 cm is 64%~80%, 1.1-2.0 cm is 33%~64%, 0.5~1.0 cm is 6%~28%, and <0.5 cm is 0~1%. If there is a history of tumor, the presence of multiple SPNs should be considered as a possible metastatic tumor. In addition, if there is an aggregation of tiny nodules, two or more <10 mm, separate lesions from each other, in nodular or clustered form, it suggests a high possibility of infectious lesions.
2.Nodule growth rate
The growth rate of benign and malignant SPN is obviously different due to different growth characteristics. After SPN is found, the first step should be to follow up the presence of previous chest X-rays or CT films, which can be of great help in the differential diagnosis. If the lesion has been seen on imaging 1 to 2 years ago, a comparison with the current size remains the same or shrinks suggesting a high likelihood of benign and vice versa for malignancy. Some patients say that they had previous examinations but lost them or threw them away when they moved, which is a pity. Therefore, we hope to keep the previous examination data as health records.
Progressive progression is a characteristic of malignant tumors with exponential growth rate, and the doubling time (VDT) is mainly determined by the histological type and blood supply of the tumor. A retrospective study analyzed the VDT of tumors; 33% were 100 days, 40% were 100-400 days, and 27% were greater than 400 days. In general, the possibility of malignancy was to be suspected at a VDT of 30 to 400 days; infectious lesions had a VDT of less than 1 month; granulomatous lesions and mismatched tumors had a VDT of greater than 18 months; and nodules that did not show growth for more than 2 years were considered highly probable as benign lesions. In another study, VDT ranged from 42 to 1486 days for carcinoma in situ, fine bronchoalveolar carcinoma (BAC), but 120 to 402 days for invasive adenocarcinoma.
However, tumors without growth for several years are still observed clinically, mostly in carcinoma in situ or precancerous lesions with atypical adenomatous hyperplasia (AAH), which are mostly purely ground glass-like or semi-solid lesions, so VDT still needs to be combined with imaging features.
3.Nodule morphology
Nodule morphology is an important parameter for judging benign and malignant lesions. Most nodules are round or round-like, but some are oval, flat or tubular in shape. In patients with lung cancer, although the tumor occupies an area at the beginning of growth, the internal structure is sparse and gradually dense as the tumor grows, which constitutes a special morphological feature, in the shape of bud or mulberry. Due to the burrs of different lengths at the edges and pleural traction pulling around, it can also form insect-like such as partial elongated caterpillars, scleractinia with tentacles, flying bird-like or even butterfly-like, and mucinous adenocarcinoma has a button-like manifestation. Most benign lesions are round or round-like in shape.
The same study also found that the ratio of maximum transverse diameter/vertical diameter is more relevant in determining benign lesions. A ratio >1.78 is more likely to be a benign lesion, i.e., tubular and flattened lesions are more likely to be benign. In other words, if the ratio is small, i.e., round or round-like lesions tend to be more malignant. If subpleural lesions, solid predominantly, morphologically polymorphic, or tubular or flat, the sensitivity and specificity of the diagnosis of benign nodules are 61% and 100%, respectively.
4.Nodule margin
The imaging features of malignant SPN are often lobulated and occur due to uneven growth of intra-tumor cells. In addition, fine burr is a characteristic manifestation of lung cancer. The literature reports that 33% to 100% of malignant nodes are lobulated and burred, but 50% of them are not lobulated and burred. Benign nodules may also be lobulated, but they are shallow, without burrs, and have neat and smooth margins. Radiolucent changes are seen in inflammatory lesions, which can sometimes be confused with burrs, but are generally longer, not lobulated, and have blurred borders. About 1/3 of malignant SPN may also have smooth margins and are commonly seen in metastatic tumors. A pathomorphologic and imaging-based study reported that 24% of polygonal nodules are benign lesions, especially lesions immediately adjacent to the pleura, showing straight lines on the immediate pleural surface and concave surfaces on the remaining surfaces, mostly due to shrinkage or fibrosis of the lesions to form concave surfaces.
5.Nodular density
The density of SPN was also found to be extremely meaningful for the diagnosis of benign and malignant lesions by three-dimensional reconstruction with high-resolution CT (HRCT). Based on the density of SPN in the lung, they can be classified into 3 categories: pure ground glass nodules, partially ground glass nodules and solid nodules. The nature of these three types of nodules varies.
In 1993, Remy-Jardin et al. and Engeler et al. proposed the concept of pulmonary ground (gross) glass-like density (GGO) and its diagnostic significance, and in 1996, the American Board of Nomenclature defined ground glass-like density as a faint dense shadow on HRCT in which bronchial structures or pulmonary vessels can still be seen. In recent years, the research around GGO in related departments, such as respiratory department, thoracic surgery, imaging department and pathology department, has become a hot spot. With the popularization of CT, the wide application of HRCT and the low-dose CT screening for lung cancer in recent years, the detection of GGO has gradually increased, and they may represent malignant tumors, such as BAC and adenocarcinoma; or precancerous lesions, such as AAH; or benign lesions, including focal interstitial fibrosis or mechanized pneumonia, inflammation and hemorrhage.
(1) Pure frosted glass nodules: The frosted glass-like component is a uniform frosted shadow, and sometimes small vacuolar signs are seen. Usually such frosted glass nodules progress very slowly, or remain unchanged for several years, or only show gradual denseness. Frosted glass-like nodules increase the likelihood of malignancy, and the literature reports that 19% of noncalcified lesions with a nonsubstantial component are mostly frosted glass or partially frosted glass-like, 34% of which are malignant. Pure ground glass-like lesions are mostly small in size, uniform in density, and burrs are less common than parenchymal lesions. The pathological basis is mostly alveolar cell carcinoma, microinvasive carcinoma or precancerous lesion AAH. AAH is a typical pure ground glass nodule on CT, which is pathologically confined with clear borders. The diameter of AAH is usually 5 mm or less, rarely >10 mm. AAH can be followed up for 2-3 years without significant changes, but it has a tendency to develop into BAC or adenocarcinoma. bac or small adenocarcinoma will keep increasing in size and appear pleural depression and traction. When the diagnosis is not clear by cytology or biopsy, the growth rate and volume of the nodule can also suggest malignancy. Therefore, during the follow-up period of non-substantial pure ground glass nodules, once a parenchymal lesion appears and the nodule is enhanced by CT-enhanced scan or some microvascular signs are found at the edge of the nodule, the follow-up should be stopped immediately and surgical resection should be performed to avoid delaying the diagnosis and treatment of early lung cancer.
(2) Partially ground glass nodule: it may be accompanied by vacuolar sign, bronchography sign or micronodules, in which the solid component is often invasive adenocarcinoma. ＜The solid component of <5 mm is more commonly seen as microinvasive adenocarcinoma or as volvulus growth type with good prognosis. In mixed ground glass nodules, the smaller the solid component accounts for the volume, the less invasive the histologic component of the pathology. Mixed ground glass is morphologically more pleomorphic than ground glass-like nodules and solid nodules, and its morphology can be punctate, lobulated or accompanied by bubble sign, vacuole sign, or even solid part with fibrous contraction and longer burrs like acanthosis, which cannot be easily distinguished from benign lesions.
(3) Solid nodules: due to the small size of the lesion, it is difficult to puncture for clear pathology, and the false-negative rate of diagnosis is significantly higher with positron emission tomography (PET/CT) for lesions <8 mm, so observation of any progression during follow-up and combining with imaging features is the main basis for clinical decision on whether to open the chest for exploration. It is worth noting that the pathological type of malignant solid nodules is mostly invasive adenocarcinoma with predominantly glandular follicular, papillary and solid subtypes. Squamous carcinoma is rarely seen in small nodal lesions even in solid nodules. 107 SPNs were analyzed and none of them were squamous carcinoma.
6.Internal structure
1. Calcified spots: the imaging feature of benign lesions is calcification. It has been reported in the literature that dense and uniform calcifications indicate benign lesions. In lung cancer screening studies, 14% of the micronodules had calcifications with CT values >164 Hu or similar to rib density by visual comparison. Because enhanced CT injection of contrast increases the density of small lesions, density analysis needs to be performed with plain CT. Typical calcifications in benign lesions are laminar, central and popcorn-like. Laminar and central-type calcifications are more common in inflammatory granulomas, and popcorn-like calcifications are typical of malignant nodules. However, it is worth noting that 15% of malignant nodules also have calcifications.
2. Bronchography sign, vacuolation sign, cavity: found in a controlled study of CT and pathologic tissue. Malignant features usually include bronchiectasis, vacuolation and cavitation lesions, with at least one of these present in 80% of malignant lesions. The vacuolar sign was present in 50% of in situ carcinomas and BAC. Unlike the bronchogram sign, the latter is a branched, inflated image. The vacuolar sign may be a feature of adenocarcinoma and histologically corresponds to a markedly dilated air-containing fine bronchus or a tumor-associated cystic structure. In contrast, cavitation is caused by ischemic necrosis and is less common in carcinoma in situ or small invasive adenocarcinoma.
3. Adipose tissue: Another characteristic of benign lesions is the presence of fatty density inside the lesion. For example, a CT value of -40Hu to -120Hu in the central region is a characteristic of a misshapen tumor.
Second, what should I do if SPN is found?
Many people start to suspect whether they have lung cancer when SPN is found in the CT report, but in reality, benign SPN lesions account for 50% to 65% and malignant tumors account for 35% to 50%. Benign SPN include inflammatory granuloma, malignant tumor, sclerosing hemangioma, lung abscess, fungal disease, tuberculosis bulb, limited fibrosis and limited chronic inflammation, precancerous lesions and AAH, etc.; malignant ones are mainly primary lung cancer and metastatic lung cancer. Therefore, for the discovery of SPN, there is no need to be overly nervous or paralyzed, but should actively consult respiratory, radiology and thoracic surgeons to receive formal further examination and timely treatment.
1.People with high risk of tumor: The following groups of people are at high risk of tumor and should be actively further examined when SPN is found and surgically removed if necessary.
(1) Long-term smokers, those who have smoked for more than 20 years and more than 20 cigarettes per day, or those who have long-term passive smoking.
(2) Those who are over 40 years old with chest pain, dry cough, unexplained sputum blood, wasting and weight loss.
(3) Those with a family history of tumor or their own history of tumor.
(4) Those with SPN > 1.0cm with lobar, burr or ground glass-like, pleural depression changes; or those with recent SPN with significant enlargement and thickening.
2, the general population, such as those who cannot confirm the diagnosis, immediately perform thin-layer scanning HRCT as well as image three-dimensional reconstruction to further observe its size, morphology, margin, density, structure and relationship with the surrounding.
(1) Close follow-up observation by CT: The frequency and duration of follow-up depends on the size of the nodule. Since malignancy of single SPN in lungs larger than 1.0 cm in diameter accounts for more than half of the cases, one should try to determine the benignity and malignancy of nodules by multiple methods. In contrast, tiny nodules less than 5 mm are more than 90% benign if there is no history of tumor. Therefore, the SPN below 5mm should be reviewed by CT every 6 months, 5-10mm every 3 months, and 10mm every 1-2 months. If there is no change on review, the review can be extended to 1 year, 6 months and 3 months, respectively. If SPN is found to be unchanged for 2 years, it is more likely to be benign, but continued follow-up is required.
(2) Diagnostic tests, such as PET/CT, percutaneous lung biopsy, and transbronchoscopic lung biopsy
The sensitivity and specificity of PET/CT depend on the size of the lesion, and are 94% and 83% for substantial nodules of 1 to 3 cm. However, the false-negative rate is much higher for SPN <1.0 cm, such as carcinoma in situ, carcinoid tumor, and mucinous adenocarcinoma; false positives are common in fungal diseases, such as Cryptococcus novelis and podocytic histoplasmosis, and other diseases such as inflammation, tuberculosis, nodular disease, and rheumatic nodules may also show positive results. Therefore, multiple factors should be integrated and analyzed, including other clinical imaging diagnoses. For larger SPN, if pathological or cytological diagnosis cannot be obtained, PET/CT examination with elevated SUV and delayed SUV increase of 30% has the value of diagnosing malignant lesions.
②Puncture biopsy: The positive rate of CT-guided fine-needle aspiration (FNAB) is between 60% and 90%, depending on the size and location of the nodule. Its main complication is pneumothorax, mostly in patients with small lesions, deeply located lesions or emphysema, and about 5% of those requiring drainage after puncture. Transbronchoscopy-guided lung biopsy (TBLB) has a diagnostic rate of 10% to 50%, and about 33% of peripheral lesions <20 mm can be diagnosed. If bronchial air contrast signs are shown in CT, especially those leading to the lesion, the positive rate of TBLB can reach 70%. Endobronchial ultrasound biopsy (E-BUS) and CT imaging with magnetic avionics combined with tracheoscopy are also very helpful for the diagnosis of SPN.
③Other tests including blood tumor marker (TM) measurement, blood TB infection T-cell spot test (T-SPOT), and sputum exfoliative cell examination are also helpful for differential diagnosis.
④Surgery: When the possibility of malignant lesion is expected to be greater than 60% to 70% and other examination methods cannot give a clear diagnosis, surgical intervention is needed to clarify the diagnosis and further treatment. The surgery can be wedge resection or segmental lung resection, and an intraoperative ice-cold section is required. If the ice-cold section is considered benign, only a wedge or segmental resection is performed; if the lesion is malignant, the operation is then expanded and systemic lymph node dissection is performed. Most of these SPN are early-stage lung cancers with good postoperative prognosis without chemotherapy and radiation therapy, with a 5-year survival rate of more than 90%. Television thoracoscopic surgery is increasingly used for the surgical treatment of intrapulmonary SPN due to less injury and fewer postoperative complications.