Lung Cancer
Related Subjects:
| Bronchogenic Lung Cancer
| Hypercalcaemia
| Oncological Emergencies
| Malignant Hyperparathyroidism due to PTHrP
| Lambert-Eaton Syndrome (LEMS)
| Superior Vena Caval Obstruction (SVCO)
| SIADH
| Ectopic ACTH – Cushing's Syndrome
🌬️ Lung cancer is the leading cause of cancer death worldwide.
It is divided into Small Cell Lung Cancer (SCLC) (~20%) and Non-Small Cell Lung Cancer (NSCLC) (~80%).
🚬 90% of cases are linked to smoking, though occupational and genetic factors also play a role.
📈 >40,000 new cases are diagnosed in the UK annually, with rising incidence in women due to changing smoking trends.
🧬 Aetiology & Risk Factors
- 🚬 Smoking – the dominant risk factor, esp. for squamous cell and SCLC.
- 🏭 Occupational exposures: asbestos, radon gas, silica, nickel, chromium, arsenic.
- 🌡️ Underlying lung disease: COPD, pulmonary fibrosis, TB scars.
- 🧪 Genetic mutations: EGFR, ALK, KRAS, PD-L1 expression influence prognosis and therapy.
🔬 Histological Types
- Small Cell Lung Cancer (SCLC) (~20–30%)
- Central, aggressive, rapid doubling time.
- Almost always metastatic at diagnosis.
- ⚠️ Strongly linked to paraneoplastic syndromes.
- 💊 Chemo ± radiotherapy mainstay; surgery rarely used.
- Non-Small Cell Lung Cancer (NSCLC) (~80%), subtypes:
- Adenocarcinoma 🌿 – peripheral, most common subtype, better prognosis, seen in smokers & non-smokers.
- Squamous Cell Carcinoma 🔥 – central, strongly smoking-related, often cavitates, can secrete PTHrP → hypercalcaemia.
- Large Cell Carcinoma ⚡ – peripheral, poorly differentiated, aggressive.
🩺 Clinical Presentation
- Local: cough, haemoptysis, chest pain, recurrent pneumonia, dyspnoea.
- Regional: hoarseness (recurrent laryngeal nerve), SVCO, Pancoast tumour (Horner’s, shoulder pain, arm weakness).
- Systemic: weight loss, fatigue, anorexia.
- Paraneoplastic: hormonal or immune-mediated effects (see below).
🧪 Paraneoplastic Syndromes in Lung Cancer
|
|
| Syndrome |
Mechanism |
Associated Type |
Clinical Features |
| SIADH 💧 |
ADH secretion |
SCLC |
Hyponatraemia → confusion, seizures, coma |
| Cushing’s Syndrome 🌙 |
ACTH secretion |
SCLC |
Hypertension, central obesity, skin changes, muscle weakness |
| Hypercalcaemia ☀️ |
PTHrP secretion |
Squamous NSCLC |
Thirst, polyuria, constipation, confusion |
| Lambert-Eaton Myasthenic Syndrome ⚡ |
Autoantibodies against presynaptic Ca²⁺ channels |
SCLC |
Proximal muscle weakness, autonomic dysfunction, improves with activity |
| Hypertrophic Pulmonary Osteoarthropathy (HPOA) 🦴 |
Unknown (possibly VEGF/PDGF) |
Adenocarcinoma |
Clubbing, painful periostitis |
🔎 Investigations
- 🩸 Bloods: FBC, U&E, calcium, LFTs.
- 📷 Imaging: CXR → CT chest/abdomen ± PET-CT for staging.
- 🔬 Tissue: bronchoscopy, EBUS, CT-guided biopsy, mediastinoscopy.
- 🧪 Molecular: EGFR, ALK, PD-L1 testing for targeted therapy planning.
📊 Staging (NSCLC – Simplified)
- Stage I: Local tumour, no nodal disease.
- Stage II: Ipsilateral hilar nodes.
- Stage III: Mediastinal or contralateral nodes/local invasion.
- Stage IV: Distant metastases or malignant effusion.
🛠️ Management
- NSCLC:
- Stage I–IIIA → Surgery (lobectomy preferred) ± adjuvant chemo/RT.
- Stage IIIB–IV → Chemo, immunotherapy, targeted therapy ± palliative RT.
- SCLC: Almost always systemic at diagnosis → chemo ± radiotherapy; prophylactic cranial irradiation in responders.
- 💡 All patients discussed in MDT (oncology, thoracic surgery, pulmonology, radiology, palliative care).
⚖️ Comparison Table – SCLC vs NSCLC
| Feature |
SCLC |
NSCLC |
| Prevalence |
~20% |
~80% |
| Growth |
Very rapid, early spread |
Slower, variable |
| Location |
Central |
Central (squamous) or peripheral (adeno) |
| Paraneoplastic |
Very common (SIADH, ACTH, LEMS) |
Less common (PTHrP → hypercalcaemia, HPOA) |
| Prognosis |
Poor, median survival months without treatment |
Stage- and subtype-dependent, potentially curable |
| Treatment |
Chemo ± RT, no surgery |
Surgery (if early) ± chemo/RT/targeted therapy |
🚀 Newer Advances
- 📈 Screening: Low-dose CT in high-risk smokers (early detection).
- 🎯 Targeted therapy: EGFR inhibitors (gefitinib, osimertinib), ALK inhibitors (crizotinib), ROS1 inhibitors.
- 🛡️ Immunotherapy: Checkpoint inhibitors (pembrolizumab, nivolumab) for advanced NSCLC with PD-L1 positivity.
📚 Exam Pearls
- 🚬 90% of lung cancers in smokers/ex-smokers.
- ⚠️ SCLC → paraneoplastic syndromes (SIADH, Cushing’s, LEMS).
- 🌿 Adenocarcinoma = peripheral; 🔥 Squamous = central, may cavitate.
- 🩺 NSCLC Stage I–IIIA → surgery mainstay; Stage IV → systemic therapy only.
- 👩⚕️ MDT discussion is essential before definitive treatment.
Cases - Lung Cancer
- Case 1 - Central squamous cell carcinoma 🚬: A 67-year-old man with a 50-pack-year smoking history presents with cough, haemoptysis, and weight loss. Exam: clubbing, enlarged cervical lymph nodes. CXR: hilar mass. Biopsy: keratin pearls. Diagnosis: central squamous cell carcinoma. Managed with surgical resection if operable, plus chemo-radiotherapy.
- Case 2 - Small cell lung cancer (SCLC) ⚡: A 62-year-old man presents with cough, facial swelling, and shortness of breath. Exam: raised JVP, facial plethora, dilated chest wall veins (SVC obstruction). Biopsy: small blue cells, neuroendocrine markers. Diagnosis: small cell lung cancer with superior vena cava obstruction. Managed with urgent chemo-radiotherapy; not usually surgical.
- Case 3 - Adenocarcinoma (peripheral) 🌿: A 58-year-old non-smoking woman presents with persistent cough and pleuritic chest pain. CXR: peripheral mass in right lower lobe. Biopsy: adenocarcinoma. Diagnosis: peripheral adenocarcinoma of the lung. Managed with lobectomy + adjuvant chemotherapy.
- Case 4 - Paraneoplastic syndrome 🔬: A 55-year-old man presents with confusion, nausea, and muscle cramps. Bloods: Na⁺ 118 mmol/L. Exam: euvolaemic, no oedema. CXR: left hilar mass. Biopsy: small cell lung carcinoma. Diagnosis: SCLC with SIADH (paraneoplastic hyponatraemia). Managed with fluid restriction, chemotherapy, and tolvaptan if resistant.
- Case 5 - Pancoast tumour (apical) 💪: A 60-year-old man presents with shoulder pain radiating down his arm, hand muscle wasting, and ptosis/miosis on the left side. CXR: apical lung mass. MRI: invasion of brachial plexus. Diagnosis: Pancoast tumour (likely NSCLC) with Horner’s syndrome. Managed with combined chemo-radiotherapy and surgical resection if feasible.
Teaching Point 🩺: Lung cancer types:
- NSCLC: squamous (central, smoking), adenocarcinoma (peripheral, more in non-smokers), large-cell.
- SCLC: aggressive, central, early mets, paraneoplastic syndromes.
Red flags: haemoptysis, persistent cough, unexplained weight loss, clubbing, paraneoplastic features.
Investigations: CXR, CT chest, bronchoscopy/biopsy, staging (TNM).
Management: NSCLC → surgery ± chemo; SCLC → chemo-radiotherapy, usually not surgical.
