Lung Cancer

Aetiology

  • Inhalation of carcinogens:
    • SMOKING
    • Asbestos - chrysotile fibres most common and account for majority of cases, crocidolite (amphibole) is the most dangerous type due to straight structure
    • Pollution

Pathophysiology

Small cell lung cancer (SCLC) - 25%

  • Rapidly progressive disease - early metastases
  • Worst prognosis of all types of lung cancer
  • Central tumour
  • Associated with ectopic ACTH secretion → Cushing’s
  • Associated with SIADH → hyponatremia

Non small-cell lung cancer

Adenocarcinoma - 35%
  • Type most likely to be found in non-smokers
  • Type most closely linked with asbestos
  • Peripheral tumour
Squamous cell carcinoma - 30%
  • Most common type in smokers
  • Central tumour
  • Local spread common
  • Ectopic PTHrP release → hypercalcaemia
Large cell carcinoma - 10%
  • Second-worst survival prognosis - early metastases
  • Peripheral tumour

Paraneoplastic syndromes - non-endocrine, nonmetastatic complication

  • Lambert-Eaton syndrome: disorder of neuromuscular transmission causing muscle weakness, depressed tendon reflexes etc.
  • Thrombophlebitis: blood clot formation
  • Anaemia
  • Hypertrophic pulmonary osteoarthropathy (HPOA): joint stiffness, severe pain in wrists and ankles

Common sites of metastases from a primary lung cancer

  • Brain
  • Liver
  • Adrenal
  • Bone

Clinical presentation

General symptoms

  • Cough 3 weeks +
  • Dyspnoea - due to airway obstruction
  • Haemoptysis - due to erosion of a blood vessel by the tumour
  • Chest or shoulder pain - pleuritic chest pain indicates invasion of the pleura
  • Unexplained weight loss
  • Unexplained tiredness/lack of energy

Symptoms associated with invasion of the mediastinum + compression of structures

  • Pancoast’s tumour: tumour in the lung apex infiltrates the brachial plexus causing Horner’s syndrome: miosis, ptosis and anhidrosis
  • Recurrent laryngeal nerve - hoarse voice
  • Pericardium - breathlessness, AF, pericardial effusion
  • Oesophagus - dysphagia
  • SVC - puffy eyelids, headache, distension of the jugular veins and veins on the chest (anastomoses)

Signs

  • Stridor
  • Clubbing
  • Enlarged liver
  • Lymphadenopathy
  • Tracheal deviation
  • Involvement of the pleura may cause pleural rub and stony dull percussion
  • Recurrent pneumonia - tumours which block the bronchi can stop the mucosillary escalator from functioning

Investigations

Bloods

  • FBC
  • Coagulation screen
  • ↓ Na+, ↑Ca2+ indicates malignancy

CXR

  • Peripheral tumours (adenocarcinoma and large cell carcinoma) arise beyond the hilum and are rarely visible on CXR
  • Central tumours (squamous cell carcinoma and SCLC) arise at/close to the hilum; they are indicated by hilar enlargement and distal collapse/consolidation

Biopsy

  • Bronchoscopy and biopsy for central tumours
  • CT guided biopsy for peripheral tumours
  • Aspiration of lymph nodes and pleural fluid

Other imaging

  • CT thorax - used to stage (tumour size, metastases, local invasion, lymph node involvement)
  • PET scan - metastases
  • USS - pleural effusion, movement of diaphragm, subphrenic abscess

Management

SCLC

  • Chemotherapy +/- radiotherapy

NSCLC

  • Peripheral tumours (large cell, adenocarcinoma) with no metastases can be excised
  • Chemotherapy +/- radiotherapy

Palliative measures

  • Chemo/radiotherapy
  • Stenting
  • Analgesia, antiemetics

Targeted treatments

  • Based on tumour markers e.g. TTF in adenocarcinoma, nuclear antigen p63 and HMW cytokeratins in squamous cell carcinoma → allows more targeted chemotherapy regiments to be developed
  • EGRF gene in adenocarcinoma → tyrosine kinase inhibitors
  • Some NSCLCs express PD-L1 which inactivates cytotoxic immune response - targeted therapy can inhibit this effect and enhance immune killing of the tumour