Pulmonary nodule is defined as a well-defined, opaque, single or multiple pulmonary nodule with a diameter of 3 cm, completely surrounded by air-containing lung tissue, without pulmonary atelectasis, hilar enlargement, or pleural effusion. Pulmonary nodules can be classified as solid or subsolid nodules based on whether they completely obscure the lung parenchyma on CT, and the latter can be subdivided into purely ground glass nodules and partially solid nodules.
Pulmonary nodules ≤8 mm are defined as subcentimeter nodules according to the size of the nodule, which is defined as 8mm. A lesion >3 cm in diameter is defined as a lungmass rather than a nodule, which is usually malignant according to previous studies. When CT reveals benign features such as benign calcified foci (in the form of diffuse, central, thin or popcorn-like calcifications), intra-nodular fatty hypodensities (e.g., malformations) or arteriovenous malformations, the nodule density may be observed with or without follow-up to avoid unnecessary examination!
I. Imaging evaluation
The detection rate of CT for pulmonary nodules is 40% to 60%, and chest CT is the main basis for determining the characteristics of pulmonary nodules (including nodule size, border features and density).
When the presence of a pulmonary nodule is determined on chest CT, the same area of the patient’s previous CT images needs to be reexamined. Information on the size and characteristics of the nodule is important for determining benignity and malignancy and for formulating subsequent treatment plans. The results of the study showed that subcentimeter nodules were less malignant, regardless of whether they were solid or subsolid nodules. Lung nodules with burrs or irregular borders were 5 times more likely to be malignant than those with smooth borders; pulmonary nodules with pleural depression signs were 1 times more likely to be malignant; vascular signs and lobar forms increased the probability of malignancy by 70% and 10%, respectively.
II. Clinical management strategies
Currently, there are 3 basic management strategies for patients with pulmonary nodules based on the type of nodule, the classification of malignancy probability (very low: <5%; low-moderate: 5%-65%; {degree: >65%), lung cancer risk factors and potential surgical risks (including preoperative cardiovascular and pulmonary function assessment, postoperative complications, etc.): (1) surgical treatment; (2) non-surgical biopsy; and (3) serial CT follow-up.
There is no doubt that surgical treatment is the gold standard for a definitive diagnosis. For pulmonary nodules with a high probability of malignancy (>65%), the recommended management strategy is surgery, unless the patient is a contraindication to surgery or cannot tolerate it. Surgical treatment consists of televised thoracoscopic surgery (VATS), open chest, and mediastinoscopy. Thoracoscopic wedge resection is the method of choice for diagnosing highly malignant pulmonary nodules, and results of a large clinical study showed that the complication rate of lung segment or lobectomy under VATS (26%) was significantly lower than that of open-chest surgical treatment (35%).
Non-surgical biopsy, as an invasive test, is often used to clarify the diagnosis of benign or malignant with potential risks, and is indicated for a definitive diagnosis of pulmonary nodules with a moderate probability of malignancy (10% to 60%), or when patients require definitive preoperative evidence of malignancy, especially in patients with high anticipated surgical complications. The main non-surgical biopsies include CT-guided percutaneous transluminal needle aspiration biopsy (TTNB), bronchoscopy combined with endobronchial ultrasound (EBUS), electromagnetic navigation bronchoscopy (ENB) and virtual bronchoscopic navigation (VBN).
All CT surveillance follow-up observations should be performed with a thin-layer, low-dose, non-enhanced CT scan. Compared to surgical treatment and non-surgical biopsy, CT
The advantages of surveillance are that it avoids unnecessary invasive testing of benign lesions and that the indications for surveillance include: (1) pulmonary nodules with a low (<5%) or low (30%-40%) probability of malignancy; (2) contraindications to surgical treatment or non-surgical biopsy; and (3) intolerance to surgical treatment or non-surgical biopsy.
Monitoring of lesion volume changes is recommended during follow-up, and lung nodules with stable lesion volume for 2 years are indicative of benign lesions.
Clinical management pathway
In 2013, the ACCP published the 3rd edition of its clinical management pathway guidelines for solitary or multiple pulmonary nodules, which are summarized below, depending on the size and nature of the nodule.
1. 3=8 mm diameter solid pulmonary nodules: For solid pulmonary nodules that are more than 8 mm in diameter, the first step is for the clinician to determine the patient’s surgical risk, the probability of malignancy of the nodule, and the PET scan.
Although some physicians still use clinical experience, the Mayo Clinic model is the most widely used method of estimation.
This model calculates the probability of malignancy of pulmonary nodules based on 6 independent risk factors (age, history of smoking, history of extrathoracic neoplasia, nodule diameter, burr sign and nodule localization) based on the formula: probability of malignancy = ex/(1+ex), X=-6.8272+(0.039Ix age)+(0.7917x history of smoking)+(1.3388X history of neoplasia)+(0.1274X nodule diameter)+(1.0407X nodule diameter) (1.0407X burr sign) + (0.7838X localization).
If the probability of malignancy is low (<5%) or if the probability of malignancy is low to moderate (5% to 65%) but the patient is at high risk for surgery, strict periodic follow-up with CT scans at 3-6, 9-12, and 18-24 months after the initial examination is recommended.
For low to moderate (5% to 65%) and highly malignant (>65%) probable pulmonary nodules that can tolerate surgery, surgical treatment, non-surgical biopsy and CT monitoring may be an option after evaluation of metabolism and staging using PET scan.
For highly malignant probable pulmonary nodules that cannot tolerate surgery, chemotherapy, radiotherapy, radiotherapy and radiofrequency ablation are feasible after PET evaluation.
2. Solid pulmonary nodules <8 mm in diameter: As shown in Figure 2, the 2013 ACCP 3rd edition guidelines and the 2005 Fleischner
The 2013 ACCP 3rd edition guidelines are consistent with the 2005 Fleischner Society guidelines for follow-up of small solid nodules, which determine the duration and interval of CT surveillance based on lung cancer risk factors such as lung nodule size, patient age, and smoking history.
Subsolid lung nodules: Detterbeck and Homer concluded that pure ground-glass lung nodules ≤10 mm in diameter are usually confirmed as atypical adenomatous hyperplasia (AAH) or adenocarcinoma in situ (AIS), whereas pure ground-glass nodules >10 mm in diameter are considered to be atypical.
Pure ground-glass nodules >10 mm in diameter are more likely to be invasive adenocarcinoma (IA). If the solid portion of a partially solid nodule exceeds 50% of the total nodule volume, or if the existing pure ground glass nodule is more likely to be invasive (IA).
If the solid portion of a partially solid nodule exceeds 50% of the total nodule volume, or if an existing purely ground glass nodule develops into a partially solid nodule, malignancy is highly suspected.
The 2013 ACCP recommends the following management pathway for subsolid pulmonary nodules: (1) For pure ground-glass nodules ≤5 mm in diameter, follow-up is usually not required. For pure ground-glass nodules 5-10 mm in diameter, CT should be reviewed once a year for 3 years. For pure ground-glass lung nodules >10 mm in diameter, repeat CT 3 months after the initial CT examination.
If the lesion persists, non-surgical biopsy or surgical treatment is recommended unless the patient cannot tolerate surgery.
(2) For partially solid pulmonary nodules with a diameter of 8mm, CT scans should be performed at 3, 12, and 24 months after the first examination for strict periodic follow-up, and then I CT scan every year for the next 3 years. non-surgical biopsy or surgical treatment should be performed as soon as an enlargement of the solid portion is detected during follow-up. For partially solid pulmonary nodules >8 mm in diameter, CT should be repeated 3 months after the first tear, and if the lesion persists, PET scan, non-surgical biopsy, and surgical treatment should be actively managed. For subsolid pulmonary nodules >15 mm in diameter, no follow-up CT is required and active management is performed directly. 4.
4. Multiple lung nodules: For patients with confirmed or highly suspected lung cancer, CT scans usually reveal multiple lung nodules. The 2013 ACCP recommends that for multiple pulmonary nodules, each individual nodule should be treated with caution and further evaluated with a PET scan, rather than arbitrarily assuming that the additional nodules are metastases or benign lesions. Management of multiple pulmonary nodules is challenging and requires a combination of systems, and should be treated aggressively unless metastatic foci are confirmed.
Summary and outlook
Clinicians should provide effective and cost-effective management pathways for patients with pulmonary nodules based on guideline principles and adequate information about potential risks and benefits.