1. Lung Cancer

1.1 Introduction

• Definition
  • Malignant disease of the lungs includes primary lung cancer, lung metastases, and mesothelioma.
  • Primary lung cancer (arising from respiratory epithelium) is broadly classified as small-cell lung cancer (SCLC) or non–small-cell lung cancer (NSCLC).
  • NSCLC is subdivided into adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma.
• Significance
  • One of the most common cancers globally and a leading cause of cancer death.
  • About 90% of cases are associated with smoking.

1.2 Epidemiology

• Incidence
  • Lung cancer accounts for 13% of all new cancer diagnoses worldwide and remains the leading cause of cancer mortality.
  • 60% die within 1 year of diagnosis; ~90% eventually die from the disease.
• Age and Gender
  • Incidence peaks at 80–84 years; ~87% diagnosed after age 60.
  • Historically higher in men but increasing rates in women who smoke.

1.3 Aetiology

• Cigarette Smoking
  • 9 out of 10 lung cancer cases in smokers. The risk correlates with quantity (pack-years) and duration. Risk remains elevated after quitting but is lower than in ongoing smokers.
• Other Risk Factors
  • Passive smoking
  • Radon gas
  • Asbestos
  • Family history of lung cancer
  • Exposure to chemicals (coal products, diesel exhaust, arsenic, etc.)

1.4 Pathogenesis

• Genetic Susceptibility plus carcinogen exposure.
• Oncogene Activation (e.g. K-ras, EGFR), tumour suppressor gene inactivation (p53).
• NSCLC with EGFR mutations may respond to targeted anti-EGFR therapies (e.g. erlotinib).

1.5 Classification of Primary Lung Cancer

1. Small-Cell Lung Cancer (SCLC)
   • Accounts for ~20% of lung cancers.
   • Rapidly growing, arises commonly from the central bronchi.
   • Usually metastasised by diagnosis (liver, brain, bones, adrenals).
   • Often associated with paraneoplastic syndromes (SIADH, ACTH).
2. Non–Small-Cell Lung Cancer (NSCLC)
   • About 80% of cases; subtypes are:
     1. Adenocarcinoma (40%): Usually peripheral; most common type in non-smokers.
     2. Squamous Cell Carcinoma (30%): Usually central, associated with haemoptysis, cavitation, hypercalcaemia.
     3. Large-Cell Carcinoma (10–15%): Poorly differentiated, often peripheral.
   • May be amenable to surgical resection or radical radiotherapy if localised.

1.6 Clinical Features

• Common Presentations
  • Cough (up to 80%).
  • Haemoptysis (70%).
  • Dyspnoea (60%).
  • Chest pain (40%).
  • Weight loss, anorexia, malaise.
  • Slowly resolving or recurrent pneumonia; hoarse voice if recurrent laryngeal nerve is involved.
• Local Invasion
  • Pancoast’s tumour (apical tumour) → Horner’s syndrome, brachial plexus involvement.
  • SVC obstruction → distended neck veins, upper limb oedema, raised JVP.
  • Phrenic nerve palsy → elevated hemidiaphragm.
• Paraneoplastic Syndromes
  • Small cell: SIADH (hyponatraemia), ectopic ACTH (Cushing’s syndrome), neurological syndromes (Lambert–Eaton).
  • Squamous cell: PTHrP → hypercalcaemia.
  • Any type: Cachexia, Trousseau’s syndrome (hypercoagulability).
• Metastases
  • Common sites: liver, bones, adrenals, brain, kidneys, contralateral lung, pleura.
  • Symptoms vary: e.g. bone pain, confusion, focal neurology.

1.7 Diagnostic Approach

1. Chest X-Ray
   • May show nodules, masses, consolidation, hilar enlargement, collapse, pleural effusion.
   • Detectable lesion size usually >1 cm.
2. CT and PET Scans
   • Chest and upper abdomen CT to evaluate tumour size/location, hilar/mediastinal lymphadenopathy, distant metastases.
   • PET-CT for staging and searching for occult metastases.
3. Biopsy/Cytology
   • Sputum cytology: non-invasive but less sensitive.
   • Bronchoscopy ± endobronchial ultrasound for central/proximal lesions and mediastinal nodes.
   • Percutaneous needle biopsy for peripheral lesions or accessible lymph nodes.
   • Thoracocentesis if pleural effusion.
   • Mediastinoscopy or thoracoscopic biopsy if needed.
4. Blood Tests
   • FBC (anaemia), U&E and bone profile (SIADH, hypercalcaemia), LFTs (liver involvement), clotting.
5. Pulmonary Function Tests
   • Evaluate resectability or radical radiotherapy tolerance.
   • Typically done if curative therapy is considered.
6. MRI or CT Brain
   • If neurological symptoms suggest possible metastases.

1.8 Staging

Non–Small-Cell Lung Cancer

• TNM classification – key points:
  • T: tumour size/extent (T1–4).
  • N: nodal involvement (N0–3).
  • M: metastases (M0–1).
  • Stages I–IV combine T, N, and M.
• 5-year survival depends on stage: ~35% in stage I, dropping to single digits in stage III, and <1% in stage IV.

Small-Cell Lung Cancer

• Traditionally staged as:
  1. Limited disease: Confined to one hemithorax, encompassed in a single radiotherapy portal.
  2. Extensive disease: Spread beyond one hemithorax (including contralateral lung, distant metastases).

1.9 Management

1. Surgery (NSCLC)
   • Potentially curative for localised stage I/II or selected stage III disease.
   • Types: lobectomy, pneumonectomy, or parenchymal-sparing wedge resection if borderline fitness.
   • Patient must have adequate lung function and performance status.
2. Radiotherapy
   • Curative intent: radical external beam radiotherapy or stereotactic ablative radiotherapy for inoperable localised NSCLC.
   • Palliative: lower dose for symptomatic relief (haemoptysis, bone pain, SVC obstruction, brain metastases).
3. Chemotherapy
   • NSCLC: platinum-based regimens (cisplatin, carboplatin) plus additional agents (gemcitabine, vinorelbine).
     • Targeted therapies for tumours with EGFR or ALK mutations, or PD-L1 expression (immunotherapy).
   • SCLC: usually extensive at presentation, responds well to chemo but frequently relapses (commonly cisplatin-based).
4. Other Treatments
   • Endobronchial therapies (stenting, cryotherapy, laser) relieve obstruction.
   • Pleural effusion: drainage, pleurodesis, or indwelling pleural catheter.
   • Prophylactic cranial irradiation in SCLC to reduce brain mets.
5. Palliative Care
   • Essential for advanced disease to control pain, dyspnoea, anxiety, etc.
   • Address nutrition, psychosocial support, and managing paraneoplastic complications.

1.10 Prognosis

• Overall, 5-year survival remains low (often <5%).
• Non–Small-Cell Lung Cancer
  • Stage I 5-year survival ~35%; stage IV <1%.
  • Comorbidities (e.g. COPD) and poor performance status worsen survival.
• Small-Cell Lung Cancer
  • Mean survival from diagnosis ~6 weeks without treatment.
  • Treatment can produce dramatic tumour shrinkage, but relapses are common.

2. Mesothelioma

2.1 Epidemiology

• Definition
  • Mesotheliomas are malignancies of mesothelial cells, most commonly affecting the pleura (less often peritoneum, pericardium, or testes).
  • Pleural mesothelioma is by far the most frequent form.
• Global Incidence
  • Incidence varies widely depending on asbestos usage patterns.
  • There is a long latent period (often 20–45 years) between exposure and the development of disease.
• Prognosis
  • Typically poor; median survival ranges between 8–14 months from diagnosis.

2.2 Aetiology

• Asbestos Exposure
  • The principal carcinogen linked to mesothelioma.
  • Occupations with asbestos exposure: mining, dock/ship/rail work, building and insulation trades, etc.
  • Even minimal or single-episode exposure can raise the risk (e.g. household contacts).
• Genetic Changes
  • Monosomy of chromosome 22 is found in ~40% of cases; associated with loss of tumour suppressor gene function.

2.3 Pathogenesis & Histology

• Main Histological Subtypes
  • Sarcomatous
  • Epithelial
  • Mixed (sarcomatous–epithelial)
• Tumour Growth
  • Begins as malignant plaques, usually at the lower chest.
  • Plaques coalesce into a sheet of tumour, potentially involving the diaphragm, lung surfaces, chest wall, and mediastinum.
  • Distant metastases occur but often present with few or no specific symptoms.

2.4 Clinical Features

• Presentation
  • Dyspnoea, typically from a pleural effusion.
  • Chest pain: often severe and difficult to manage.
  • Systemic symptoms: fatigue, night sweats, weight loss, anorexia.
  • History of asbestos exposure (may be decades prior).
• Complications
  • Local invasion: can affect brachial plexus, ribs, pericardium, mediastinum, oesophagus, or SVC.
  • Metastases to contralateral lung or distant organs can occur but are usually asymptomatic initially.

2.5 Diagnosis

1. Imaging
   • Chest X-Ray: may show pleural thickening or plaques, pleural effusion, and reduced lung volume on the affected side.
   • CT Scan: typically reveals circumferential nodular or irregular pleural thickening, effusion, and possible tumour extension.
2. Pleural Fluid
   • Often exudative with high protein but rarely diagnostic by cytology (malignant cells are infrequent).
3. Pleural Biopsy
   • Thoracoscopic or radiologically guided biopsy is essential for definitive histology.
   • Repeat biopsies may be needed if initial samples are inconclusive.
4. Staging
   • Four stages, from localised disease (stage 1) to extensive thoracic invasion (stage 3) or widespread metastases (stage 4).

2.6 Management

1. Surgery
   • Pleurectomy ± lung resection (e.g. extrapleural pneumonectomy) is considered in selected early-stage disease with good performance status.
   • Operative mortality can be high and complete resection is often difficult.
2. Radiotherapy
   • Largely palliative to reduce chest wall pain or tumour mass.
   • Does not significantly improve survival.
3. Chemotherapy
   • Generally poor responses, though certain regimens (e.g. platinum-based therapy) can offer a modest survival benefit.
   • Trials are ongoing to find better combinations.
4. Supportive Measures
   • Indwelling pleural catheter or repeated thoracocentesis to manage symptomatic effusions.
   • Analgesia for pain control.

2.7 Prognosis

• Adverse prognostic factors include: advanced stage, non-epithelial histology, severe chest pain, weight loss, male gender, older age, poor performance status, and high inflammatory markers.
• Median Survival is about 8–14 months from diagnosis.

3. Lung Metastasis

3.1 Introduction

• Definition
  • The lungs are a frequent site of metastatic spread for various intra- or extrathoracic malignancies, due to extensive lymphatic and vascular networks.
  • Common primary tumours that metastasise to the lung include colon, breast, renal, bladder and lungcancers, as well as melanoma.

3.2 Epidemiology

• Incidence
  • Up to 50% of patients with a malignancy develop lung metastases at some stage, indicating advanced disease (stage 4).
  • The presence of pulmonary metastases significantly worsens prognosis.

3.3 Patterns of Metastasis

1. Intrapulmonary Nodules
   • Characteristically round ‘cannonball’ lesions of varying sizes.
   • Some primaries (e.g. squamous cell or renal cell carcinoma) can produce cavitating metastases.
   • Many are incidentally found on staging scans, often asymptomatic initially.
   • Symptoms: cough, haemoptysis, chest pain, dyspnoea.
2. Pleural Effusions
   • Caused by pleural metastases leading to exudative fluid accumulation.
   • Patients may have breathlessness and dullness on percussion.
3. Mediastinal Lymphadenopathy
   • Often asymptomatic, discovered on chest X-ray or CT/PET.
   • Massively enlarged nodes occur in lymphoma.
4. Lymphangitis Carcinomatosis
   • Diffuse infiltration of malignant cells along pulmonary lymphatics → progressive dyspnoea, reticular nodular patterns on imaging.
   • Markedly reduced transfer factor.

3.4 Aetiology and Risk Factors

• Primary Tumour Types
  • Lung, colorectal, breast, bladder, renal, melanoma are frequent.
• Disease Stage
  • Lung metastases typically denote advanced (stage 4) disease.

3.5 Clinical Features

• Common Presentations
  • Frequently asymptomatic and discovered on routine staging or follow-up scans.
  • Respiratory symptoms: new cough, change in character of existing cough, haemoptysis, dyspnoea, chest pain.
  • Systemic: weight loss, fatigue, decreased appetite.
  • Signs of advanced disease: pleural effusion, SVC obstruction (if mediastinal involvement), or paraneoplastic phenomena (depending on the primary).

3.6 Diagnostic Approach

1. Imaging
   • Chest X-ray: solitary/multiple nodules, masses, cavitation, or pleural effusion.
   • CT or PET-CT: better definition of nodules, lymphadenopathy, pleural lesions, or lymphangitis carcinomatosis.
2. Biopsy/Cytology
   • Percutaneous needle biopsy of a peripheral lung lesion.
   • Pleural fluid aspiration to confirm malignant effusion.
   • Histology or cytology helps confirm metastatic origin vs. a new primary lung cancer.
3. Assessment of Primary Cancer
   • Correlate with known malignant disease history.
   • If no known primary, additional investigations (e.g. colonoscopy for possible colorectal primary) may be needed.
4. Blood Tests
   • Similar to evaluating a primary tumour: FBC, LFTs, bone profile, tumour markers if relevant to the known or suspected primary.

3.7 Management

• Influenced by the Primary Tumour
  • Breast or prostate may respond to hormonal therapy.
  • Colorectal or lung primaries might benefit from chemotherapy, targeted therapies, or immunotherapy.
  • Bone metastases can cause hypercalcaemia or fractures (palliative radiotherapy, bisphosphonates).
• Local Interventions
  • Surgery: rare but feasible for limited oligometastatic disease (particularly if the primary is controlled).
  • Radiotherapy or ablative therapies (e.g. radiofrequency ablation) may be considered for one/few metastases.
  • Pleural effusions: repeated drainage, pleurodesis, or indwelling pleural catheter.
• Supportive & Palliative Care
  • Symptom-based: analgesia for chest pain, management of breathlessness, psychosocial support, end-of-life care if needed.

3.8 Prognosis

• Generally poor, since lung involvement signifies stage 4 disease.
• Prognosis differs according to the nature of the primary tumour, burden of metastatic disease, and overall performance status.

4. Carcinoid and Other Lung Tumours

4.1 Epidemiology

• Carcinoid Tumours
  • Rare, constituting < 3% of all lung cancers.
  • Typically originate from neurosecretory cells in the bronchial mucosa (often in major bronchi).
  • Usually grow slowly and can recur locally after excision, but rarely metastasise.
• Adenoid Cystic Carcinoma
  • A benign salivary gland tumour that can involve the bronchial tree.
• Hamartoma
  • A benign peripheral tumour composed of well-differentiated tissue, often found incidentally.

4.2 Aetiology

• Carcinoid Tumours
  • Arise from bronchial neurosecretory (Kulchitsky) cells, producing hormones (ACTH, serotonin, bradykinin).
  • Unrelated to smoking.
• Adenoid Cystic Carcinoma
  • Affects the salivary gland tissue in the bronchial tree.
• Hamartoma
  • Consists of disorganised but mature tissue elements (e.g. cartilage, fat), typically benign.

4.3 Risk Factors

• Carcinoid Tumours
  • Incidence is not related to smoking, differing from the majority of lung tumours.
• Adenoid Cystic Carcinoma and Hamartoma
  • No specific modifiable risk factors highlighted; appear sporadically.

4.4 Clinical Features

1. Carcinoid Tumours
   • Bronchial Obstruction: Cough, haemoptysis, recurrent infection (distal to obstruction), or lobar collapse on imaging.
   • Paraneoplastic Syndromes: Hormone secretion (ACTH → Cushing’s syndrome; serotonin → carcinoid syndrome of flushing & diarrhoea).
   • Slow Growth: Local invasion, possible recurrence post-excision, rarely metastatic.
2. Adenoid Cystic Carcinoma
   • Similar obstructive symptoms: cough, recurrent infections.
   • Typically grows slowly along the airways.
3. Hamartomas
   • Often asymptomatic and discovered incidentally on chest X-ray or CT.
   • Rarely cause airway obstruction or systemic symptoms.

Clinical Caveat: Slowly progressive obstruction from a benign endobronchial tumour may be mistaken for asthma if imaging initially appears normal.

4.5 Diagnosis

• Imaging
  • Chest X-Ray may show a localised mass, lobar collapse, or distal consolidation.
  • CT defines tumour extent, helps exclude other pathologies, and aids staging if malignant potential is suspected.
• Bronchoscopy
  • Enables visualisation and biopsy, especially in tumours of major bronchi (carcinoid, adenoid cystic carcinoma).
• Biopsy/Histology
  • Essential for definitive diagnosis and differentiation (e.g. from endobronchial malignancies like NSCLC).
• Laboratory Findings
  • In carcinoid, paraneoplastic markers possible (e.g. elevated ACTH).
  • Serotonin release in carcinoid may cause flushing, diarrhoea (carcinoid syndrome) if metastatic to or beyond the liver.

4.6 Management

• Surgical Resection
  • Best option for carcinoid tumours if anatomically operable; can be curative in most cases.
  • Adenoid cystic carcinomas also treated surgically if feasible.
  • Hamartomas generally observed unless symptomatic or suspicious of malignancy.
• Medical Therapy
  • Somatostatin Analogues (e.g. Octreotide) to reduce carcinoid syndrome symptoms (flushing, diarrhoea).
  • Chemotherapy may be used if inoperable or metastasised, though carcinoids usually have limited metastatic potential.
• Prognosis
  • Carcinoid: Typically good if localised and fully resected; recurrences can occur, but metastases are rare.
  • Adenoid Cystic Carcinoma: Slow growing, can locally invade airways.
  • Hamartomas: Benign, rarely require intervention.