Lung Cancer 2: Clinical features

Lung cancer is the 3rd most common cancer in the UK with 3 in 4 cases being diagnosed at a late stage. It has a poor prognosis with just 10% of patients surviving for 5 years or more after diagnosis and is the leading cause of all cancer-related deaths. Both incidence and mortality increase exponentially with age, with 75-92 being the most vulnerable group.

Lung cancer survival rates have improved marginally over the past 10 years compared to other cancer types such as prostate (which has seen massive improvements in survival rates). This highlights the need for new therapeutic approaches for lung cancer in order to improve the currently low survival rates.

Treatment modalities include surgery, radiotherapy, chemotherapy or targeted drug therapy acting on specific mutated genes (identified on a case by case basis).  The management of lung cancer patients depends on many confounding factors such as the characteristics of the malignancy (e.g. type,  size, location, presence of metastasis) and is discussed at Multi-Disciplinary Team (MDT) meetings attended by a variety of medical specialists such as radiologists, surgeons, histopathologists, oncologists and respiratory physicians.

Learning objectives Part 1 of 8

  1. Appreciate the difference between malignant and benign lung tumours
  2. Appreciate the severity of lung cancer in terms of incidence and prognosis
  3. Recall the main types of lung cancer
  4. Describe the main presenting symptoms and clinical signs of lung cancer
  5. Outline the paraneoplastic effects of lung cancer
  6. Describe the metastatic effects of lung cancer
  7. Appreciate the main clinical features of mesothelioma: symptoms/signs, risk factors, prognosis

Lung cancer types: summary Part 2 of 8

There are many types of lung cancers but for the purposes of this tutorial we will focus on the 3 most prevalent: lung adenocarcinoma, small cell carcinoma, squamous cell carcinoma. These are grouped into two main categories: Small Cell Lung Cancer (SMLC) and Non-Small Cell Lung Cancer (NSCLC).

 

Risk factors Part 3 of 8

 

Cigarette smoking

Strong correlation between cigarette smoking and lung cancer. One of the most important, reversible risk factors.

Smokers’ sputum contains a larger number of dysplastic cells compared to non-smokers’ sputum.

The number of abnormal cells correlates in proportion to the number of cigarettes smoked daily.

Important to ask whether a patient ‘has ever smoked’ when taking a clinical history and quantify this in pack-years (20 cigarettes per day for 1 year = 1 pack-year)

 

 

Occupational hazards

 

Inhalation of carcinogenic dusts:

  • Asbestos
  • Latent period of  20-40 years between asbestos         exposure and disease presentation
  • Other carcinogenic dusts: Nickel, chromates, mustard gas, arsenic, coal-tar

Radioactive gases

  • e.g, radon, uranium
 

Pulmonary fibrosis

 

Some peripheral lung cancers, such as lung adenocarcinoma, frequently arise in areas of pre-existing fibrous scars in the lung.

The ‘scar cancer’ hypothesis has been challenged but it is worth noting that there is an increased number of lung adenocarcinomas being reported in patients with a past medical history of pulmonary fibrosis.

Presentation: symptoms and signs Part 4 of 8

Symptoms are those identified and reported by the patient (e.g. difficulty breathing, chest pain) whereas clinical signs are those identified by a healthcare professional upon history taking and clinical examination (e.g. ‘pleuritic’ nature of chest pain, finger clubbing, reduced air entry on auscultation) or clinical investigations (e.g. right upper lobe opacity on a chest X-ray).

Common presenting signs/symptoms of lung cancer:

  • Chronic cough (>4 weeks)
  • Unintentional weight loss
  • Pleuritic chest pain (sharp in nature, worse on inspiration)
  • Increased sputum production
  • Haemoptysis
  • Malaise
  • Fever
  • Associated paraneoplastic manifestations (see later)

Paraneoplastic effects of lung cancer Part 5 of 8

  • These are due to hormones ectopically and inappropriately secreted by some types of lung cancer
  • They are NOT metastatic effects
  • Small cell carcinoma can secrete ACTH, ADH
  • Squamous cell carcinoma can secrete PTHrP

Raised ACTH:

–> adrenal hyperplasia

–> increased cortisol secretion

–> Cushing’s syndrome

Raised ADH

Also referred to as ‘Syndrome of Inappropriate ADH secretion’ (SIADH)

–> water retention

–> dilutional hyponatraemia

Raised PTHrP

–> stimulates increased osteoclastic activity

–> increased bone resorption

–> hypercalcaemia

Emergency conditions associated with lung cancer:

  • Spinal cord compression: can lead to permanent neurological paralysis. Requires early discussion with neurosurgeons for consideration of surgical decompression.
  • Superior vena cava (SVC) involvement: can lead to massive haemoptysis

Metastatic effects of lung cancer Part 6 of 8

Lung cancer commonly metastasizes to:

  • Lymph nodes
  • Bone
  • Brain
  • Liver
  • Adrenal glands

Local spread of lung cancer to nearby structures can cause further clinical features beyond the initial, presenting symptoms and signs. Below we outline a list of anatomical structures that can be involved by local lung cancer metastasis and the effect this might have on the patient.

Anatomical structure involved Effect
Pleural membranes Haemorrhagic effusion
Pericardium Pericardial effusion
Blood vessels Haemoptysis
Superior Vena Cava obstruction Dilated collateral veins on the chest wall
Recurrent laryngeal nerve Hoarse voice
Phrenic nerve Dyspnoea due to paralysis of the hemidiaphragm
Pancoast tumour Apical lung tumour compressing the brachial plexus giving rise to sensory and motor disturbances (reduced sensation in the T1 dermatome, weak grip). Also causing Horner’s syndrome (a triad of ptosis, miosis, hemifacial anhidrosis) due to compression of the Stellate ganglion of the cervical sympathetic chain.

Mesothelioma Part 7 of 8

Mesothelioma is a malignant neoplasm derived from mesothelial cells.

Mesothelial cells line body cavities and the most common site of malignant mesothelioma is the lung pleura. Both the visceral and parietal pleural membranes can be affected.

Mesothelioma has the ability to infiltrate adjacent structures (e.g. pericardium, chest wall) thus exemplifying malignant potential.

Most patients present with chest pain and dyspnoea. Unlike lung cancer where chest pain is pleuritic in nature (sharp character, worse on inspiration), chest pain secondary to mesothelioma is usually dull in nature due to chest wall invasion.

Diagnosis can be achieved through cytology (examination of pleural fluid) or histopathological analysis (of pleural biopsy).

Unfortunately, mesothelioma is incurable and has a very poor prognosis. Malignant mesothelioma is closely linked to asbestos exposure with a 20-40 year latent period between exposure and disease presentation.

Asbestos is a substance resistant to electricity, chemicals, sound and heat thus making it a popular material between 1950-80s for commercial use such as boiler and steam pipe manufacturing.

There are 4 main lung pathologies closely associated with asbestos exposure:

  • Malignant mesothelioma
  • Pleural plaques
  • Diffuse pleural fibrosis
  • Reactive pleural effusions

Examining each condition in detail is beyond the scope of this tutorial. Nevertheless it is important to appreciate the impact of asbestos exposure on health and therefore remember to ask patients when taking history on possible asbestos exposure during their working lives.

On lung malignancies:

  • Malignancies in the lung are not always primary. Very frequently they are metastases from a distant, primary cancer source such as colorectal carcinoma or breast cancer that has spread to the lung.
  • Secondary metastatic spread to the lungs is very common.

Beyond malignancies: Benign lung tumours

  • Despite the rarity of benign lung tumours it is important not to forget this possibility. Not all tumours in the lung are malignancies.

Beyond lung neoplasia:

  • Similarly, not all lung lesions represent neoplastic changes. An example of non-neoplastic lung lesions is mycobacterium tuberculosis infection.