Investigating the solitary pulmonary noduleBMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e2759 (Published 19 April 2012) Cite this as: BMJ 2012;344:e2759
- William McNulty, specialist registrar1,
- Giles Cox, consultant respiratory physician1,
- Iain Au-Yong, consultant radiologist2
- 1Department of Respiratory Medicine, King’s Mill Hospital, Sutton-in-Ashfield NG17 4JL
- 2Department of Radiology, King’s Mill Hospital, Sutton-in-Ashfield NG17 4JL
- Correspondence to: I Au-Yong
- Accepted 20 March 2012
Certain chest radiograph appearances, including a solitary pulmonary nodule, raise suspicion of cancer and require prompt referral for further investigation
Both radiological and clinical factors influence the probability of malignancy in a solitary pulmonary nodule
Computed tomography will help to make the diagnosis, stage the disease, and guide which investigation should be performed to obtain a histological diagnosis
Positron emission tomography has high sensitivity for detecting malignant disease and, if available, should be offered to all patients suitable for radical therapy to ensure accurate staging
Small nodules have a lower risk of malignancy and may be observed for change over an interval period
An 81 year old man presented to the emergency department with a one week history of fever, cough, and right sided chest pain. He had had a myocardial infarction in 2004 but was otherwise well. He had a 50 pack-year smoking history. Clinical examination was unremarkable. His chest x ray showed a left mid-zone nodule (fig 1⇓). He was treated for a lower respiratory tract infection and referred to the lung cancer clinic with two week wait for an appointment.
Chest x ray
The chest x ray is often the first investigation where a solitary pulmonary nodule is detected. A solitary pulmonary nodule is a rounded opacity, well or poorly defined, measuring up to 3 cm in diameter.1 They may represent early lung cancer, and prompt detection and treatment may improve clinical outcome. However, some nodules are benign, and determining which require further investigation may be difficult. Some common differential diagnoses are listed in box 1.2 3
Chest x rays are readily available and have a low radiation dose. They may help identify features of the nodule that can give an indication of the cause. Larger nodules, ill defined edges, and those growing over time are more likely to be malignant.4 However, a chest x ray is less sensitive at identifying these features than computed tomography. In addition most nodules are visible only once they reach 1 cm in size and hence can be easily missed.5 Peripheral nodules or those lying close to or behind other structures may be obscured from view.6 It has been estimated that 19% of patients with lung cancer diagnosed have solitary pulmonary nodules visible when previous chest x rays are retrospectively reviewed.7 False positives may occur from misinterpretation of composite shadows, vascular structures, skin lesions, and rib abnormalities.8 Comparison with previous radiographs is important as lesions that are stable over two years are unlikely to be malignant.9 Other appearances such as lobar collapse, non-resolving consolidation, and pleural effusions may be due to underlying lung cancer and require further investigation.
What should be the next investigation?
When a solitary pulmonary nodule is discovered the first step should be to make an assessment of the probability of lung cancer based on factors such as age and smoking history. The patient’s fitness and preferences for treatment also need to be taken into account. This will guide the next investigations and how the patient should be followed up. Both clinical factors and the radiological features of the nodule affect the probability of malignancy.4 These have been combined into risk assessment tools to enable a calculation for an individual patient. The table⇓ lists these characteristics and their associated likelihood ratios.
Computed tomography of the lower neck, chest, and upper abdomen is performed to allow precise characterisation of the nodule and stage malignant disease. Computed tomography is highly sensitive for nodule detection10 and may identify nodules as small as 2 mm in diameter.11 It allows better characterisation of features that may suggest malignancy or identify benign features such as certain patterns of calcification or fat density material seen in hamartomas.12 Computed tomography is widely available and well tolerated, although patients have to be able to lie flat. Its drawbacks include the substantial radiation dose of approximately 7 mSv (compared with 0.02 mSv for a chest x ray).13 Intravenous contrast is precluded in patients with contrast allergy or pre-existing renal impairment, which reduces the information obtainable from the scan.
Staging of malignant disease is achieved by assessing the size and location of the tumour, nodal involvement, and identifying metastatic disease. However computed tomography can less reliably determine whether mediastinal lymph nodes are involved than positron emission tomography.14
Positron emission tomography
Positron emission tomography may help determine whether a nodule is malignant or benign and is indicated when considering a patient for radical treatment.15 It combines computed tomography with the administration of radiolabelled glucose which is taken up by metabolically active tissues. The sensitivity for detection of malignant nodules is 96% with a specificity of 88%.16 Positron emission tomography also has a high sensitivity for detecting metastatic disease and can determine with more certainty whether mediastinal lymph nodes are infiltrated by tumour.14 This allows more accurate staging and ensures that radical treatment is carried out in appropriate patients.
Its limitations include false positives from uptake of radiolabelled glucose in inflammatory lesions such as pneumonia or granulomas from old tuberculosis or sarcoid. The brain also appears “hot,” which limits the ability to detect cerebral metastases. Small lesions below 1 cm may be below resolution and yet could represent an early tumour or metastasis. Likewise “cold” lesions with little metabolic activity may still be low grade tumours, and if these are not biopsied follow-up computed tomography is usually recommended. Positron emission tomography is a limited and expensive resource that involves a prolonged scan time and high radiation dose.
There are several techniques which can be used to obtain a tissue diagnosis in those with suspected lung cancer. Current guidelines recommend biopsying the area which provides the most staging information and is least risky to the patient.15 Where less invasive techniques fail then options include surgical resection of nodules and mediastinoscopy to sample lymph nodes.
Bronchoscopy and endobronchial ultrasound
Flexible bronchoscopy allows examination of the central airways and biopsy of central lesions to obtain histology. It is usually performed by respiratory physicians or thoracic surgeons. The diagnostic yield for solitary pulmonary nodules is poor,17 although emerging techniques such as radial endobronchial ultrasound and navigational bronchoscopy allow better access to peripheral lesions,18 19 but these are not yet in widespread use. Although “blind” transbronchial needle aspiration of enlarged subcarinal lymphadenopathy is possible, it is limited in the staging information it can give. Endobronchial ultrasound allows real-time imaging and guided transbronchial needle aspiration of multiple mediastinal nodal stations and peribronchial tumours. A meta-analysis has shown a sensitivity of 88% and specificity of 100% for staging mediastinal disease.20 Guidance from the National Institute for Health and Clinical Excellence (NICE) gives recommendations on its use in staging disease and biopsying paratracheal or peribronchial tumours.15
Transthoracic needle biopsy
Transthoracic needle biopsy under computed tomographic or ultrasound guidance is often the only available approach in patients with a solitary pulmonary nodule where no metastases have been found. The sensitivity of transthoracic biopsy for detecting malignant lesions is estimated at 86% and specificity as high as 98.8%.21
Complications include pneumothorax: although the rates vary widely depending on whether x ray or computed tomography is used for detection. A recent large study found that only 6.6% of patients required chest tube drainage.22 Bleeding was seen in just 1% of cases.22 There is also a risk of inadequate sampling, and the procedure may need to be repeated. Before performing a biopsy, lung function should be measured and clotting should be checked. An FEV1 of >35% of predicted is preferred to avoid respiratory compromise from pneumothorax.23 Anticoagulants and antiplatelet agents such as clopidogrel should be stopped, although aspirin may be continued.
Small nodule pathway
Computed tomography is the modality of choice for following up smaller indeterminate lesions whether detected on chest x ray or computed tomography. Smaller lesions are difficult to investigate as they are below the resolution of positron emission tomography and difficult to biopsy. The Fleischner Society guidelines suggest radiological follow-up of nodules at various intervals depending on size and risk factors for malignancy. Where nodules increase in size further investigation is indicated, with consideration of biopsy or positron emission tomography.24 Stable nodules should be followed for up to two years. This approach offers a balance between timely identification of malignancies against the burden of scans, radiation exposure, and complications from procedures.
Computed tomography revealed a 17 mm peripheral nodule staged as T1aN0M0. The patient was counselled regarding treatment options and was initially keen to know a diagnosis and consider surgery. The nodule was biopsied percutaneously under computed tomographic guidance, complicated by a small pneumothorax that did not require intervention (fig 2⇓). The histology showed a squamous cell carcinoma. Positron emission tomography was performed with a view to surgery and demonstrated a metabolically active nodule (fig 3⇓) with low grade uptake in a 6 mm subcarinal lymph node but no other evidence of metastases. The possibility of spread to lymph nodes was discussed, and endobronchial ultrasound or mediastinoscopy was offered. At this point the patient did not want to pursue surgical intervention as he felt the impact of treatment on quality of life in the short term would outweigh its benefits. The final radiological staging was T1aNxM0.
An alternative approach following the new NICE guidance would be to offer positron emission tomography before consideration of biopsy. If any positive nodes are identified then these can be sampled to obtain both a histological diagnosis and accurate staging in a single test.
The patient remains well and asymptomatic at more than 12 months from diagnosis.
National Institute for Health and Clinical Excellence The diagnosis and treatment of lung cancer. NICE clinical guideline CG121. http://guidance.nice.org.uk/CG121
Baldwin DR, White B, Schmidt-Hansen M, Champion AR, Melder AM. Diagnosis and treatment of lung cancer: summary of updated NICE guidance. BMJ 2011;342:d2110.
Cite this as: BMJ 2012;344:e2759
This series provides an update on the best use of different imaging methods for common or important clinical presentations. The series advisers are Fergus Gleeson, consultant radiologist, Churchill Hospital, Oxford, and Kamini Patel, consultant radiologist, Homerton University Hospital, London. To suggest a topic for this series, please email us at email@example.com.
Contributors: All authors planned, wrote, and revised this review article. IA-Y is the guarantor.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent obtained.