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21st February 2025
Lung cancer
Pathology
Lung cancer is one of the most common cancers in the world and one of the leading causes of cancer deaths.
The most important clinical distinction is between small cell and non-small cell lung cancers, as this defines the management approach.
Table 1 Histological subtypes of lung cancer
| Histological subtype | Key facts | |||
| Small cell lung cancer (SCLC) | Aggressive, fast-growing; most strongly associated with smoking | |||
| Non-small cell lung cancer (NSCLC) | Adenocarcinoma | Most common; arises peripherally | ||
| Squamous cell carcinoma (SCC) | Involves central airways | |||
| Large cell carcinoma | Arises centrally; diagnosis of exclusion (no features of other subtypes) | Other | Neuroendocrine tumours (NET) | Including large cell neuroendocrine carcinoma and well-differentiated NETs (carcinoid tumours) |
| Rarer subtypes | E.g. salivary gland type tumours, lung sarcoma, lung lymphoma | |||
Presentation of lung cancer
Lung cancer is often picked up at an asymptomatic stage via imaging; symptoms can indicate advanced disease. The most common presenting symptoms are cough, haemoptysis, dyspnoea and chest pain. Signs on imaging include lung nodules, hilar enlargement, lobar collapse and pleural effusions.
The NICE suspected cancer referral guidelines for lung cancer are as follows:
| Two week wait referral | Urgent CXR | Consider urgent CXR |
|---|---|---|
| CXR suspicious for lung cancer
OR Age ≥40 with unexplained haemoptysis |
Age ≥40 with 2 of these features, or smoking history with 1 feature:
Cough Fatigue Dyspnoea Chest pain Weight loss Appetite loss |
Age ≥40 and any of the following:
Persistent/recurrent chest infection Finger clubbing Supraclavicular or persistent cervical lymphadenopathy Chest signs consistent with lung cancer Thrombocytosis |
Table 2 NICE guidelines for suspected lung cancer
Complications of lung cancer
Metastases
Common sites to which lung cancers metastasise include the brain, bones, liver and adrenals.
Paraneoplastic syndromes
Paraneoplastic syndromes are frequently seen in lung cancer, especially in association with small cell lung cancer.
| Syndrome | Features | Associated cancer |
|---|---|---|
| SIADH | Euvolaemic hyponatraemia. Improves with treatment of the cancer. | SCLC |
| Lambert-Eaton myasthenic syndrome (LEMS) | Neuromuscular junction disorder similar to myasthenia gravis. Limb weakness is predominant, and characteristically improves with exercise. Autonomic involvement is also common. Antibodies against the voltage-gated calcium channel present. | SCLC |
| Other neurological syndromes | E.g. cerebellar ataxia, sensory neuropathy, limbic encephalitis, encephalomyelitis, autonomic neuropathy, opsomyoclonus. | SCLC |
| Hypertrophic pulmonary osteoarthropathy (HPO) | Painful symmetrical arthropathy and long bone pain secondary to periosteal proliferation. Clubbing of fingers and toes. | Adenocarcinoma |
| Hypercalcaemia | Most commonly caused by tumour secretion of parathyroid hormone-related peptide (PHTrP). In PTHrP-driven hypercalcaemia, you would also expect suppressed serum PTH and low phosphate. | SCC > others |
| Carcinoid syndrome | Flushing, shortness of breath, wheeze, tachycardia, diarrhoea. | NET |
Table 3 Paraneoplastic syndromes associated with lung cancer
Horner’s syndrome
Pancoast tumours (tumours in the lung apex) can involve the sympathetic chain, leading to Horner’s syndrome: ipsilateral ptosis, miosis and anhidrosis.
Superior vena cava obstruction (SVCO)
Lung cancer is the most common malignancy to cause SVCO.
Lymphangitis carcinomatosa
Lymphangitis carcinomatosa is the infiltration of cancer cells into the lymphatic system, leading to inflammation. Pulmonary lymphangitis carcinomatosa is rare but important as it can cause severe symptoms and is associated with a poor prognosis (around half of patients will die within two months of first developing symptoms). Symptoms include shortness of breath and a dry cough. Imaging findings may be similar to those of interstitial lung disease. Lymphangitis is most commonly associated with lung, breast and gastrointestinal cancers.
The most effective treatment is treatment of the underlying cancer. Steroids may be trialled for symptom control.
Management of lung cancer
Management of NSCLC
Treatment algorithms for non-small cell lung cancers are becoming increasingly complex, with choice of treatment depending on various factors including tumour stage, patient fitness and tumour molecular characteristics.
| Curative treatment | Palliative treatment |
|---|---|
| Stage I-IIIA lung cancers are potentially curable, and so patients should be assessed for fitness for surgery.
Lung function testing is an important part of this assessment. Radical chemoradiotherapy may be an option for those not suitable for surgery. In rare cases a stage IIIB tumour is downstaged with treatment to become resectable and therefore curable. |
Stage IIIB, IIIC and IV lung cancers are generally considered unsuitable for radical treatment. The presence of distant metastasis makes a tumour stage IV.
Systemic treatment may be offered, such as chemotherapy, immunotherapy and tyrosine kinase inhibitors. Tumour molecular characteristics are important in treatment decisions at this stage. |
Table 4 Overview of treatment of NSCLC
Prognosis varies significantly depending on the stage of disease, with 5 year survival rates of 67% for stage IA disease down to 1% for stage IV disease.
Management of SCLC
Small cell lung cancer can be broadly divided into limited and extensive stages, which define treatment options.
| Limited-stage SCLC | Extensive-stage SCLC | |
|---|---|---|
| Definition | Confined to ipsilateral haemothorax | Disease beyond ipsilateral haemothorax |
| Approach | Curative treatment may be considered | Treatment is palliative |
| Treatment options | Generally treated with concurrent chemoradiotherapy (typically etoposide + cisplatin/carboplatin).
Surgical resection with adjuvant chemotherapy ± radiotherapy is possible but infrequent. |
Generally treated with chemotherapy alone (again using etoposide + cisplatin/carboplatin).
Radiotherapy may be used for symptom management. |
Table 5 Overview of treatment of SCLC
SCLC often responds well to chemotherapy initially, but overall prognosis is poor, with a 5 year survival of <5% for extensive-stage and 12-24% for limited-stage disease.
Supportive management
Breathlessness is a common problematic symptom in lung cancer. Options for treating breathlessness include low-dose opiates, breathing control techniques and palliative oxygen therapy.
Chest drains and pleurodesis can be helpful in management of symptoms related to pleural effusions.
Radiotherapy can be effective in management of symptoms such as haemoptysis and chest pain.
References
- National Institute for Health and Care Excellence. Suspected cancer: recognition and referral [Internet]. NICE. 2015 [cited 2022 Jan 31]. Available from: https://www.nice.org.uk/guidance/ng12
- National Institute for Health and Care Excellence. Lung cancer: diagnosis and management [Internet]. NICE. 2019 [cited 2022 Jan 31]. Available from: https://www.nice.org.uk/guidance/ng122
- Heist RS. Small cell lung cancer [Internet]. BMJ Best Practice. 2018 [cited 2022 Jan 31]. Available from: https://bestpractice.bmj.com/topics/en-gb/1081
- Baldwin DR, Popat S. Non-small cell lung cancer [Internet]. BMJ Best Practice. 2020 [cited 2022 Jan 31]. Available from: https://bestpractice.bmj.com/topics/en-gb/1082
- Klimek M. Pulmonary lymphangitis carcinomatosis: systematic review and meta-analysis of case reports, 1970-2018. Postgraduate Medicine. 2019 Apr 5;131(5):309–18.
- Anwar A, Jafri F, Ashraf S, Jafri MAS, Fanucchi M. Paraneoplastic syndromes in lung cancer and their management. Annals of Translational Medicine. 2019 Aug;7(15):359–9.
- Midthun D. Clinical manifestations of lung cancer [Internet]. Lilenbaum R, Vora S, editors. www.uptodate.com. 2021 [cited 2022 Jan 31]. Available from: https://www.uptodate.com/contents/clinical-manifestations-of-lung-cancer
- Tazelaar H. Pathology of lung malignancies [Internet]. Nicholson A, Lilenbaum R, Vora S, editors. www.uptodate.com. 2021 [cited 2022 Jan 31]. Available from: https://www.uptodate.com/contents/pathology-of-lung-malignancies
- Longmore M, Wilkinson I, Baldwin A, Wallin E. Oxford Handbook of Clinical Medicine [Internet]. Oxford Medicine Online. Oxford University Press; 2014 [cited 2022 Jan 31]. Available from: https://oxfordmedicine.com/view/10.1093/med/9780199609628.001.0001/med-9780199609628
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