SOLITARY PULMONARY NODULES Early diagnosis of solitary pulmonary nodules Chunhua Xu1,2*, Keke Hao1,2*, Yong Song3, Like Yu1,2, Zhibo Hou1,2, Ping Zhan1,2 1
Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, China; 2Nanjing Clinical Center of Respiratory Diseases, Nanjing 210029, China; 3Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210029, China
ABSTRACT
KEYWORDS
Early detection of solitary pulmonary nodules (SPNs) and early treatment are of great importance. However, patients with early SPNs always do not present with any symptoms or signs, only to demonstrate SPNs in radiology findings. So it is very critical to improve the ability to identify the SPNs, and with the development of sorts of diagnostic modalities, the accuracy in the evaluation of the SPNs has improved greatly. In this paper, the diagnostic methods and techniques of SPNs are reviewed. Solitary pulmonary nodules (SPNs); early; diagnosis
J Thorac Dis 2013;5(6):830-840. doi: 10.3978/j.issn.2072-1439.2013.11.19
With the development of equipment and technology, solitary pulmonary nodules (SPNs) are being increasingly detected year by year. The reported detection rate of SPNs is about 8-51% (1). The differentiation between benign and malignant nodules, and the management thereof, has thus become the main focus of interest and challenge in clinical research nowadays. The goal is to rapidly identify the nature of a pulmonary nodule, making early detection and treatment possible, and in turn avoid unnecessary invasive examination or open-chest surgery for benign lesions. Based on the clinical experience regarding the diagnosis and treatment of SPNs in the past decade in our department, we presented the techniques and advancement in the early diagnosis of SPNs in recent years in this study, as follows.
Overview of the early diagnosis
(Figure 1). Despite a variety of causes, SPNs are common in granulomatous diseases and lung cancer, and not often seen in carcinoid tumors or a single lung metastasis of other tumors. It is rare in hamartomas and pulmonary arteriovenous malformations (Figure 2). Risk factors of lung cancer in SPNs When a pulmonary nodule is detected, the probability of malignancy should be evaluated first. The clinical evaluation includes a review of medical history and examination of physical sign. Clinical risk factors indicating a high probability of malignancy include the size of nodule, age, history of tumor, COPD, smoking history, and history of asbestos exposure (See Table 1) (4).
Definition and etiology of SPNs
Common non-invasive examination of SPNs
A SPN is an isolated, single lesion in a round or oval shape with a diameter of ≤3 cm in lung parenchyma, surrounded entirely by gas-containing lung tissue. Such lesions are not accompanied by lung atelectasis, hilar enlargement or pleural effusion (2,3)
Commonly used non-invasive tests of SPNs include: sputum cell biology techniques, blood biomarker detection and imaging.
*
Xu Chunhua and Hao Keke contributed equally to this work and should be
considered as co-first authors. Corresponding to: Like Yu. Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing Clinical Center of Respiratory Diseases, 215 Guangzhou Road, Nanjing 210029, China. Email: [email protected]. Submitted Nov 04, 2013. Accepted for publication Nov 22, 2013. Available at www.jthoracdis.com ISSN: 2072-1439 © Pioneer Bioscience Publishing Company. All rights reserved.
Sputum cell biology techniques Sputum cytology is a non-invasive and simple cytological test, with a sensitivity of 28-80% for early diagnosis of lung cancer. Due to certain restrictions, however, the positive rate in the diagnosis of SPNs is not high. In recent years, thin liquid based cytology has been introduced, but it still can not meet the clinical demands. The detection of DNA ploidy changes in sputum cytology can help increase the early diagnosis rate of malignant pulmonary nodules. Detection of biomarkers These mainly include a number of tumor markers, such as
831
Journal of Thoracic Disease, Vol 5, No 6 December 2013
A
B
C
D
greatly improved the detection rate and qualitative accuracy in the diagnosis of pulmonary nodules (Figure 4); (III) positron emission computed tomography (PET): PET/CT combines PET that reflects the metabolic capacity of a tumor and CT that shows the organizational structure in a high-resolution way. It has a sensitivity of 97% and a specificity of 85% to SPNs, and is recognized as the optimal non-invasive means of differentiating benign SPNs from malignant ones (7). According to most studies, the maximum standardized uptake value (SUVmax) of 2.5 is used as a diagnostic threshold, in which a SUVmax of ≥2.5 is suggestive of malignancy (Figure 5); Malignancies with a SUVmax of ≤2.5 are often bronchioloalveolar carcinoma and metastatic carcinoid tumors. For SPNs ≤1 cm in diameter, a SUVmax of ≥2.5 is not highly accurate in the diagnosis of malignancy. False positive results can occur in granulomatous inflammation, fungal infections, tuberculosis, or other active inflammation.
Imaging characteristics and assessment of probability of malignancy Imaging parameters used to assess the risk of pulmonary nodules include the nodule size, margin characteristics, density, and peripheral signs. Size Figure 1. A and B are nodules; C and D the masses.
carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (Cyfra21-1), carbohydrate antigen (CA125), lung cancer-associated antigens, vascular endothelial growth factors, proliferating cell nuclear antigens and epidermal growth factor receptors, which have attracted a wide range of interests. Detecting a single marker is of limited value in the diagnosis of malignant lesions, and the combined use of multiple markers is thus preferred. It has been reported (5) that malignant SPNs have significantly elevated tumor marker values compared with benign SPNs. In cases with SPNs, serum CEA and Cyfra21-1 are highly sensitive indicators of lung cancer, and the combination of both is helpful in differentiating the benign and malignant lesions. Imaging techniques (I) Chest radiographs (CR) are commonly used in chest examination. Most patients are often found to have SPNs through this method. According to foreign reports, the examination pulmonar y nodules rate on CR is about 0.09-0.2% (6) (Figure 3); (II) computed tomography (CT) is currently considered the most sensitive imaging examination of lung nodules. In particular, the introduction of multi-slice CT has
Generally, small nodules tend to be benign, while larger ones are more likely malignant (Figure 6). The probability of malignancy is less than 1% in nodules
Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, China; 2Nanjing Clinical Center of Respiratory Diseases, Nanjing 210029, China; 3Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210029, China
ABSTRACT
KEYWORDS
Early detection of solitary pulmonary nodules (SPNs) and early treatment are of great importance. However, patients with early SPNs always do not present with any symptoms or signs, only to demonstrate SPNs in radiology findings. So it is very critical to improve the ability to identify the SPNs, and with the development of sorts of diagnostic modalities, the accuracy in the evaluation of the SPNs has improved greatly. In this paper, the diagnostic methods and techniques of SPNs are reviewed. Solitary pulmonary nodules (SPNs); early; diagnosis
J Thorac Dis 2013;5(6):830-840. doi: 10.3978/j.issn.2072-1439.2013.11.19
With the development of equipment and technology, solitary pulmonary nodules (SPNs) are being increasingly detected year by year. The reported detection rate of SPNs is about 8-51% (1). The differentiation between benign and malignant nodules, and the management thereof, has thus become the main focus of interest and challenge in clinical research nowadays. The goal is to rapidly identify the nature of a pulmonary nodule, making early detection and treatment possible, and in turn avoid unnecessary invasive examination or open-chest surgery for benign lesions. Based on the clinical experience regarding the diagnosis and treatment of SPNs in the past decade in our department, we presented the techniques and advancement in the early diagnosis of SPNs in recent years in this study, as follows.
Overview of the early diagnosis
(Figure 1). Despite a variety of causes, SPNs are common in granulomatous diseases and lung cancer, and not often seen in carcinoid tumors or a single lung metastasis of other tumors. It is rare in hamartomas and pulmonary arteriovenous malformations (Figure 2). Risk factors of lung cancer in SPNs When a pulmonary nodule is detected, the probability of malignancy should be evaluated first. The clinical evaluation includes a review of medical history and examination of physical sign. Clinical risk factors indicating a high probability of malignancy include the size of nodule, age, history of tumor, COPD, smoking history, and history of asbestos exposure (See Table 1) (4).
Definition and etiology of SPNs
Common non-invasive examination of SPNs
A SPN is an isolated, single lesion in a round or oval shape with a diameter of ≤3 cm in lung parenchyma, surrounded entirely by gas-containing lung tissue. Such lesions are not accompanied by lung atelectasis, hilar enlargement or pleural effusion (2,3)
Commonly used non-invasive tests of SPNs include: sputum cell biology techniques, blood biomarker detection and imaging.
*
Xu Chunhua and Hao Keke contributed equally to this work and should be
considered as co-first authors. Corresponding to: Like Yu. Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing Clinical Center of Respiratory Diseases, 215 Guangzhou Road, Nanjing 210029, China. Email: [email protected]. Submitted Nov 04, 2013. Accepted for publication Nov 22, 2013. Available at www.jthoracdis.com ISSN: 2072-1439 © Pioneer Bioscience Publishing Company. All rights reserved.
Sputum cell biology techniques Sputum cytology is a non-invasive and simple cytological test, with a sensitivity of 28-80% for early diagnosis of lung cancer. Due to certain restrictions, however, the positive rate in the diagnosis of SPNs is not high. In recent years, thin liquid based cytology has been introduced, but it still can not meet the clinical demands. The detection of DNA ploidy changes in sputum cytology can help increase the early diagnosis rate of malignant pulmonary nodules. Detection of biomarkers These mainly include a number of tumor markers, such as
831
Journal of Thoracic Disease, Vol 5, No 6 December 2013
A
B
C
D
greatly improved the detection rate and qualitative accuracy in the diagnosis of pulmonary nodules (Figure 4); (III) positron emission computed tomography (PET): PET/CT combines PET that reflects the metabolic capacity of a tumor and CT that shows the organizational structure in a high-resolution way. It has a sensitivity of 97% and a specificity of 85% to SPNs, and is recognized as the optimal non-invasive means of differentiating benign SPNs from malignant ones (7). According to most studies, the maximum standardized uptake value (SUVmax) of 2.5 is used as a diagnostic threshold, in which a SUVmax of ≥2.5 is suggestive of malignancy (Figure 5); Malignancies with a SUVmax of ≤2.5 are often bronchioloalveolar carcinoma and metastatic carcinoid tumors. For SPNs ≤1 cm in diameter, a SUVmax of ≥2.5 is not highly accurate in the diagnosis of malignancy. False positive results can occur in granulomatous inflammation, fungal infections, tuberculosis, or other active inflammation.
Imaging characteristics and assessment of probability of malignancy Imaging parameters used to assess the risk of pulmonary nodules include the nodule size, margin characteristics, density, and peripheral signs. Size Figure 1. A and B are nodules; C and D the masses.
carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (Cyfra21-1), carbohydrate antigen (CA125), lung cancer-associated antigens, vascular endothelial growth factors, proliferating cell nuclear antigens and epidermal growth factor receptors, which have attracted a wide range of interests. Detecting a single marker is of limited value in the diagnosis of malignant lesions, and the combined use of multiple markers is thus preferred. It has been reported (5) that malignant SPNs have significantly elevated tumor marker values compared with benign SPNs. In cases with SPNs, serum CEA and Cyfra21-1 are highly sensitive indicators of lung cancer, and the combination of both is helpful in differentiating the benign and malignant lesions. Imaging techniques (I) Chest radiographs (CR) are commonly used in chest examination. Most patients are often found to have SPNs through this method. According to foreign reports, the examination pulmonar y nodules rate on CR is about 0.09-0.2% (6) (Figure 3); (II) computed tomography (CT) is currently considered the most sensitive imaging examination of lung nodules. In particular, the introduction of multi-slice CT has
Generally, small nodules tend to be benign, while larger ones are more likely malignant (Figure 6). The probability of malignancy is less than 1% in nodules
