38. Lung tumours

1. Definition

• Lung tumour → benign or malignant neoplasm of the lung parenchyma or airways
• Lung cancer (bronchogenic carcinoma) → malignant epithelial tumour arising from the bronchial or alveolar epithelium
• Solitary pulmonary nodule (SPN) → single round opacity ≤ 3 cm surrounded by lung; > 3 cm → mass

2. Epidemiology

• Lung cancer → most common cause of cancer death in the UK and worldwide (1.8 million deaths in 2020)
• Rising incidence in women → about 25% of cancer deaths in women
• Age 50–70 years at diagnosis; most present at an advanced stage
• Benign tumours → under 5% of lung tumours

3. Aetiology and risk factors

• Cigarette smoking → about 85% of cases; risk rises with pack-years; passive smoking
• Radon → second most important cause
• Occupational → asbestos (synergistic with smoking), arsenic, chromium, nickel, polycyclic hydrocarbons, coal tar
• Previous chest radiotherapy (Hodgkin's lymphoma, breast cancer)
• Air pollution
• Pulmonary fibrosis, chronic obstructive pulmonary disease (COPD)
• Family history; never-smoker adenocarcinoma → EGFR, ALK mutations, women, Asian origin

4. Pathogenesis

1. Carcinogens injure the bronchial epithelium
2. Squamous metaplasia → dysplasia → carcinoma in situ → invasive carcinoma
3. Spread:
   • Local → bronchus, pleura, chest wall, mediastinum, nerves
   • Lymphatic → hilar → mediastinal → supraclavicular nodes
   • Blood → brain, bone, liver, adrenal glands, other lung
4. Bone metastases → osteolytic
5. Adenocarcinoma → spreads early, often to the brain

5. Classification

Benign tumours

• Hamartoma → most common benign lung tumour; cartilage, fat, epithelium; "popcorn" calcification
• Others → lipoma, leiomyoma, chondroma, papilloma, haemangioma

Low-grade malignant

• Carcinoid tumour → neuroendocrine, from Kulchitsky cells; 1–2% of lung cancers:
  • Typical → indolent; 5-year survival about 90%
  • Atypical → intermediate grade; more nodal spread
  • Central, endobronchial ("cherry red" polyp); young adults; carcinoid syndrome rare
• Salivary gland-type → adenoid cystic carcinoma, mucoepidermoid carcinoma

Lung cancer (World Health Organization)

• Non-small cell lung cancer (NSCLC) → about 80–85%:
  • Adenocarcinoma → 30–50%; most common type; peripheral (75%); non-smokers and women; early metastasis
  • Squamous cell carcinoma → 20–30%; central (two-thirds); smokers; cavitation; hypercalcaemia; late metastasis
  • Large cell carcinoma → about 10–15%; peripheral; poor prognosis
• Small cell lung cancer (SCLC) → about 15–20%:
  • Neuroendocrine, central, aggressive
  • Early spread to mediastinal nodes, brain, bone marrow
  • Paraneoplastic syndromes
  • Limited stage (one hemithorax, one radiotherapy field) or extensive stage

Secondary tumours

• Lung metastases → from colorectal cancer, kidney, breast, sarcoma, germ cell tumours, melanoma

TNM staging (8th edition, key points)

• T1 ≤ 3 cm (T1a ≤ 1, T1b 1–2, T1c 2–3 cm)
• T2 > 3–5 cm, main bronchus, visceral pleura, atelectasis
• T3 > 5–7 cm, chest wall, phrenic nerve, parietal pericardium, separate nodule same lobe
• T4 > 7 cm, mediastinum, heart, great vessels, trachea, carina, oesophagus, vertebra, recurrent laryngeal nerve, diaphragm, nodule in another ipsilateral lobe
• N1 → ipsilateral hilar; N2 → ipsilateral mediastinal or subcarinal; N3 → contralateral or supraclavicular
• M1a → malignant pleural or pericardial effusion, contralateral lung nodule; M1b → single extrathoracic metastasis; M1c → multiple

6. Clinical picture

Symptoms

• Cough, change in a chronic cough
• Haemoptysis
• Dyspnoea, wheeze, stridor
• Chest pain → pleural or chest wall invasion
• Recurrent or non-resolving pneumonia
• Weight loss > 5%, anorexia
• Local invasion:
  • Hoarseness → left recurrent laryngeal nerve
  • Raised hemidiaphragm → phrenic nerve
  • Dysphagia → oesophagus
  • Pleural effusion, pericardial effusion
• Superior vena cava (SVC) obstruction → swelling of face and arms, distended neck and chest veins
• Pancoast tumour (superior sulcus) → shoulder and arm pain (C8–T1), Horner's syndrome, small hand muscle wasting
• Metastatic → headache, seizures, bone pain, jaundice

Signs

• Finger clubbing, hypertrophic pulmonary osteoarthropathy
• Supraclavicular or cervical lymph nodes
• Signs of effusion or collapse
• Cachexia

Paraneoplastic syndromes

• SCLC → syndrome of inappropriate antidiuretic hormone (SIADH), ectopic adrenocorticotropic hormone (Cushing's), Lambert-Eaton myasthenic syndrome
• Squamous cell → hypercalcaemia (parathyroid hormone-related peptide)
• Adenocarcinoma → migratory thrombophlebitis (Trousseau's sign)

7. Diagnosis

• Aim → diagnosis and staging within 6–12 weeks of first suspicion

Laboratory

• Full blood count, calcium, sodium, liver function tests
• Sputum cytology → central squamous tumours
• Pleural fluid cytology
• Molecular tests on tissue → EGFR, ALK, ROS1, KRAS, PD-L1

Imaging

• Chest X-ray → mass, collapse, effusion, widened mediastinum
• CT chest and upper abdomen with contrast → T stage, nodes, liver, adrenals
• PET-CT → nodal and distant staging before radical treatment
• MRI brain → stage II–III before radical treatment, or symptoms
• MRI → Pancoast tumour, chest wall invasion

Tissue and nodal staging

• Bronchoscopy → central tumours; before any lung resection
• Endobronchial ultrasound (EBUS) with transbronchial needle aspiration → mediastinal nodes
• Mediastinoscopy → stations 2, 4, 7
• CT-guided percutaneous biopsy → peripheral lesions
• Biopsy of supraclavicular node → N3, stage at once

SPN

• Benign features → complete or "popcorn" calcification, stable for 2 years on CT
• Malignant features → spiculated edge, size > 8 mm, growth, upper lobe, smoker
• Management → CT surveillance, PET-CT, biopsy, or diagnostic wedge resection

Fitness for surgery

• Spirometry and transfer factor (DLCO)
• Predicted postoperative FEV1 and DLCO > 40% → acceptable risk
• Borderline → cardiopulmonary exercise testing; VO₂ max > 15 mL/kg/min favours resection
• Cardiac assessment, performance status

8. Differential diagnosis

• Pneumonia, lung abscess
• Tuberculosis, fungal infection (aspergilloma)
• Hamartoma, granuloma
• Hydatid cyst
• Metastasis
• Lymphoma, mediastinal mass
• Pulmonary infarction, organising pneumonia → mass that persists 6–8 weeks is resected to exclude cancer

9. Treatment

• Decided by lung cancer MDT; based on stage, histology, mutations, fitness

Surgical

• Indications → NSCLC stage I–II and selected stage IIIA; typical carcinoid; small peripheral SCLC (T1–2 N0)
• Principles:
  • Lobectomy → standard operation, with mediastinal node dissection or sampling
  • Pneumonectomy → central tumours not removable by lobectomy
  • Sleeve lobectomy → central tumour, spares lung
  • Segmentectomy or wedge → small peripheral tumours (≤ 2 cm) or poor lung function
  • Clear margins (R0), no spillage, frozen section of the bronchial margin
  • Approach → VATS or robotic lobectomy, or thoracotomy
• Operative mortality → lobectomy about 2%, pneumonectomy about 6%
• Contraindications → N3, M1 (except selected single metastasis), malignant effusion, SVC invasion, poor lung function
• Carcinoid → lobectomy or sleeve resection with nodal dissection
• Lung metastases → metastasectomy if primary controlled, all lesions removable, no other metastases, enough lung reserve

Conservative

• Stage I unfit for surgery → stereotactic ablative radiotherapy (SABR)
• Adjuvant chemotherapy (cisplatin-based) → resected stage II–IIIA
• Adjuvant osimertinib → resected EGFR-mutant NSCLC; immunotherapy → selected patients
• Stage III unresectable → concurrent chemoradiotherapy, then durvalumab
• Stage IV → targeted therapy (EGFR, ALK inhibitors), immunotherapy (pembrolizumab), chemotherapy, palliative radiotherapy
• SCLC → chemotherapy (platinum + etoposide) ± radiotherapy; prophylactic cranial irradiation if response
• Palliation:
  • SVC obstruction → stent, steroids, radiotherapy
  • Airway obstruction → endobronchial stent, laser, debulking
  • Malignant effusion → drainage, talc pleurodesis, indwelling pleural catheter
  • Bone pain → radiotherapy

10. Complications

Of disease

• Haemoptysis, airway obstruction, post-obstructive pneumonia, lung abscess
• SVC obstruction
• Malignant pleural and pericardial effusion
• Spinal cord compression, hypercalcaemia, SIADH

Of surgery

• Prolonged air leak (> 5 days)
• Atelectasis, pneumonia, respiratory failure
• Atrial fibrillation
• Bronchopleural fistula → after pneumonectomy, especially right
• Empyema
• Haemorrhage
• Recurrent laryngeal or phrenic nerve injury
• Chylothorax
• Post-thoracotomy pain

11. Prognosis

• 5-year survival by stage → I about 75% (IA1 92%), II about 40–55%, III under 30%, IV near 0–10%
• SCLC → 5-year survival about 5%
• Typical carcinoid → about 90% at 5 years