QuestionSBA
QuestionChoice
An ABG would help determine if this patient has type one or type two respiratory failure; however, it would not provide an underlying diagnosis
32690
c
Arterial blood gas (ABG)
QuestionChoice
Spirometry would be useful in diagnosing the difference between different patterns of lung disease (restrictive vs obstructive patterns) and, therefore would be of use if you were concerned about smoking-associated diseases such as chronic obstructive pulmonary disease (COPD). Whilst COPD can occasionally lead to SIADH, it is more important to rule out cancer. Changes due to COPD would also be evident on a CT chest
32689
b
Spirometry
QuestionChoice
A number of lung diseases can cause SIADH. Serum ACE is a test for sarcoidosis. In this case, the significant smoking history, weight loss and lack of other features makes lung cancer more likely favouring a CT Chest as the most useful investigation
32692
e
Serum ACE
QuestionChoice
Paired urine and serum osmolalities are useful in determining whether this is a renal or other cause for hyponatraemia. In healthy individuals, if serum osmolality is low, urine osmolality should also be low as the kidneys should be working hard to retain solute. In SIADH, the excess of ADH results in water retention, but not solute retention. As a result, concentrated urine, which is relatively high in sodium is produced, despite low serum sodium. Whilst paired osmolalities would be useful in the workup of this patient; they are unlikely to provide a definitive diagnosis
32691
d
Paired urine and serum osmolalities
QuestionChoice
This patient is a smoker with weight loss and euvolaemic hyponatraemia, which should raise the concern of syndrome of inappropriate antidiuretic hormone secretion (SIADH) from a small cell lung cancer. The gold standard investigation for this would be a CT chest
32688
a
CT Chest
Concept
Chapter
# Summary

Lung cancers are divided into two main subtypes: small cell and non-small cell, with small cell lung cancers being more aggressive and incurable. Types of non-small cell lung cancer include squamous cell and adenocarcinomas, with several rarer subtypes. Most cases of lung cancer are linked to smoking. Lung cancers may present with chest symptoms such as cough, breathlessness or haemoptysis, systemic symptoms of weight loss and anorexia or symptoms of metastatic disease such as bone pain or seizures. Chest X-ray is the initial investigation of choice, followed by CT chest and a biopsy. Staging scans are done after diagnosis to help plan treatment. Management can be curative or palliative depending on the stage of the cancer, the subtype and the patient’s overall health. It may include chemotherapy, radiotherapy, immunotherapy, targeted therapies to specific mutations and surgery. 


# Definition

Lung cancer refers to a primary malignancy arising from the lung parenchyma or the bronchi. Cancers are classified as small cell (SCLC) or non-small cell (NSCLC), with 80% being non-small cell. The main histological subtypes of NSCLC are squamous cell cancers and adenocarcinomas.

# Epidemiology

Lung cancer makes up the largest proportion of cancer deaths of any tumour type, with nearly 35,000 deaths per year in the UK (21% of all cancer deaths). It is the second most common cancer in both males and females (after prostate and breast respectively). 

Incidence is strongly related to age, with the highest rates in people aged over 75 years old. Although non-smokers can also get lung cancer, 86% of cases are linked to smoking and so the majority of cases are felt to be preventable.

# Aetiology

Risk factors for lung cancer include:

- Tobacco smoking (e.g. cigarettes, pipes, cigars)
- Passive smoke exposure
- Occupational exposures (e.g. beryllium, cadmium, arsenic, asbestos, silica)
- Radon exposure
- Family history of lung cancer
- Radiation to the chest (e.g. in lymphoma treatment)
- Air pollution
- Immunosuppression (e.g. HIV, medications)
- Increasing age

# Classification

Lung cancers are classified by the cell of origin of the malignancy. Small cell cancers come from neuroendocrine cells of the lung. Non-small cell cancers are split into adenocarcinomas (coming from alveolar type 2 epithelial cells), squamous cell carcinomas (coming from basal epithelial cells) and large cell carcinomas (which come from a variety of epithelial cells). There are also rarer subtypes of lung cancer such as sarcomatoid or salivary gland-type lung cancers which come under the NSCLC umbrella.

Staging is also an important way to classify lung cancers depending on how advanced they are. TNM (tumour, node, metastasis) staging is used to describe how large the tumour is and where it has spread to. This can then be used to classify lung cancers into stage 1 to 4, where stage 1 is localised and small (under 4cm), stages 2 and 3 are locally advanced and stage 4 is metastatic. 

# Signs and symptoms

**Symptoms include:**

- Persistent cough
- Haemoptysis
- Dyspnoea especially on exertion
- Chest pain
- Weight loss
- Recurrent chest infections, or infections resistant to treatment
- Anorexia

**Signs include:**

- Cachexia
- Finger clubbing
- Lymphadenopathy (supraclavicular or persistent cervical)
- If there is lung collapse due to an obstructing tumour - absent breath sounds, trachea deviated towards side of collapse
- If there is a malignant pleural effusion - stony dull on percussion, decreased breath sounds over affected area

**Other signs and symptoms related to paraneoplastic presentations of lung cancer:**

- **Cushing syndrome** - usually SCLC producing ectopic ACTH, presents with dorsal cervical fat pads, truncal obesity, hypertension, striae and proximal muscle weakness
- **Syndrome of inappropriate ADH secretion (SIADH)** - usually SCLC, present with symptoms of hyponatraemia e.g. fatigue, nausea, weakness, confusion or seizures
- **Lambert-Eaton myasthenic syndrome (LEMS)** - usually SCLC, due to autoantibodies to presynaptic calcium channels at the neuromuscular junction develop proximal muscle weakness that improves with repeated movement, as well as autonomic effects such as dry mouth, lightheadedness, constipation, urinary symptoms and erectile dysfunction
- **Humoral hypercalcaemia of malignancy** - usually squamous cell carcinomas (SCC) that release parathyroid hormone-related protein (PTHrP) that mimics PTH and causes hypercalcaemia, leading to symptoms of bone pain, constipation, anorexia, abdominal pain, excessive thirst and confusion
- **Hypertrophic pulmonary osteoarthropathy** - usually adenocarcinomas which cause a periosteal reaction of bones, resulting in clubbing and arthritis especially affecting wrists and ankles

# Differential diagnosis

- Lung metastases from another primary cancer (e.g. breast or colorectal cancer)
- Mesothelioma (cancer of the pleura, strongly related to asbestos exposure)
- Tuberculosis 
- Bronchiectasis

# Investigations

In primary care, patients should be referred on a 2 week wait pathway in the following situations:

- Aged 40+ with unexplained haemoptysis
- Chest X-ray findings suspicious for lung cancer

Urgent chest X-rays (to be done within 2 weeks) should be done for patients aged 40+ who have one of these symptoms and have ever smoked (or two symptoms if they are never smokers):

- Cough
- Fatigue
- Shortness of breath
- Chest pain
- Weight loss
- Anorexia

An urgent chest X-ray should be considered in patients aged 40+ with any of:

- Persistent/recurrent chest infection
- Finger clubbing
- Supraclavicular or persistent cervical lymphadenopathy
- Thrombocytosis
- Chest signs consistent with lung cancer (e.g. reduced breath sounds, dullness to percussion)

Chest X-ray findings include:

- Lung mass (may be rounded or spiculated, squamous cell carcinomas may cavitate)
- Consolidation (where there is infection downstream of the tumour obstructing an airway)
- Bulky hilum (especially squamous cell carcinomas which often arise centrally)
- Lobar collapse (due to bronchial obstruction, especially squamous cell carcinomas)
- Pleural effusion

[lightgallery]

Other initial investigations include:

- **Sputum cytology** - low sensitivity but may be of use in patients who decline or cannot have a biopsy
- **Diagnostic thoracocentesis** - i.e. a pleural tap; if a pleural effusion is present this should be done and the fluid sent for cytology as well as cell count, microscopy, culture, glucose, LDG and protein (to determine whether it is a transudate or exudate)
- **Blood tests** - including FBC for anaemia and thrombocytosis, U&Es for hyponatraemia and baseline renal function, LFTs for baseline liver function (may be deranged in liver metastases), bone profile for hypercalcaemia, CRP for superadded infection, clotting if interventions planned
- **CT chest with contrast** - should be done after chest X-ray to better characterise any lesion seen and investigate for local spread
- **Biopsy** - to confirm the diagnosis and subtype of cancer, may be done percutaneously for peripheral tumours or via bronchoscopy for central masses

Once a lung cancer is diagnosed, further investigations may include:

- **Spirometry** - to assess lung function to determine if a patient is suitable for surgical intervention
- **CT chest abdomen and pelvis** - to stage the cancer (determine if there are any metastases)
- **PET-CT scan** - a more sensitive way to stage the cancer and look for local or distant spread
- **CT or MRI head** - may be done as part of staging investigations if curative treatment is planned, or if there are symptoms suspicious of intracranial metastases 

# Management 

**Conservative:**

- **Holistic support** and an **MDT approach** (e.g. clinical nurse specialist involvement, palliative care input for troubling symptoms or end of life care, signpost to support e.g. Macmillan groups)
- **Smoking cessation**
- Discussions around **advance care planning** where appropriate

**Medical**

- **Chemotherapy** is first line in most cases of small cell lung cancer and stage 3 or 4 non-small cell lung cancer - this is with palliative intent (i.e. not aiming to cure the disease but to prolong life and improve symptoms). It is also offered to some patients prior to (neoadjuvant) or after (adjuvant) curative surgery.
- **Immunotherapy** is also used especially in advanced non-small cell lung cancer; this includes medications such as pembrolizumab or atezolizumab (again with palliative intent).
- Other **targeted therapies** exist for patients with specific mutations, e.g. erlotinib for patients with advanced non-small cell lung cancers with EGFR-TK mutations.
- **Radiotherapy** may be curative (for example in early non-small cell lung cancer) or palliative - it is often combined with chemotherapy or other treatment modalities.
- **Supportive therapies** include analgesia, oxygen if hypoxic and opioid treatment for breathlessness.

**Surgical**

- **Lobectomy** is the standard curative therapy for early stage lung cancers (which can be open or thoracoscopic in approach).
- Some small tumours can be removed with a **wedge resection.**
- More extensive surgery such as a **pneumonectomy** (removal of a lung) may be required depending on the size and location of the tumour, however patients need to have adequate FEV1 on pre-operative spirometry to be appropriate for surgery (over 2L for a pneumonectomy).
- All patients undergoing surgery should also have **mediastinal and hilar lymph nodes sampled** (to look for metastases) or **resected** (removed) to reduce the chances of recurrence.

# Complications

**Common sites of metastatic spread include:**

- Lymph nodes
- Liver - this can cause significant pain due to stretching of the liver capsule
- Brain - may cause nausea and vomiting, headaches, seizures, personality changes, sensory or motor symptoms, dysphasia or cerebellar symptoms, depending on where in the brain is affected
- Bones - mostly osteolytic metastases, can cause bony pain and pathological fractures; there is a risk of metastatic spinal cord compression with vertebral metastases
- Adrenal glands - may cause flank pain and adrenal insufficiency
- The contralateral lung or elsewhere in the ipsilateral lung

**Local complications include:**

- Horner’s syndrome - due to an apical (Pancoast) tumour, causes ipsilateral anhidrosis, miosis and partial ptosis
- Superior vena cava obstruction (SCVO) - lung cancer is the commonest cause of SCVO, causing symptoms of breathlessness, dizziness, headache and swelling of the face, neck and arms. This is a medical emergency due to the risk of airway obstruction.
- Malignant pleural effusion
- Hoarse voice - secondary to invasion of left recurrent laryngeal nerve
- Persistent lower respiratory tract infection due to obstructing tumour
- Raised hemidiaphragm secondary to invasion of phrenic nerve
- Brachial plexus injury secondary to tumour invasion from a Pancoast tumour

# Prognosis

Overall prognosis is poor, with an average 5 year survival rate of 17%. This is lower for small cell lung cancer and for metastatic cancers, both of which have around a 5% 5 year survival. Small cell lung cancers are aggressive and are usually metastatic at the time of presentation, hence curative treatment is not possible

In early stage cancers survival is better, with 70% of patients with stage 1 NSCLC undergoing curative surgery surviving 5 years from diagnosis.

# NICE Guidelines

[Lung cancer: diagnosis and management](https://www.nice.org.uk/guidance/ng122)

[NICE CKS - recognition and referral of lung and pleural cancers](https://cks.nice.org.uk/topics/lung-pleural-cancers-recognition-referral/)

# References

[Radiopaedia - lung cancer](https://radiopaedia.org/articles/lung-cancer-3?lang=gb)

[Patient UK - lung cancer](https://patient.info/doctor/lung-cancer-pro)

[Cancer Research UK - lung cancer statistics](https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer)
213
Picture
A chest x-ray of an individual with a left sided lung cancer.
1027
Lung cancer.jpeg
images/3qgbltgx1665036171692.jpg
images/3qgbltgx1665036171692_256.jpg
images/3qgbltgx1665036171692_512.jpg
FggKB4A391dzfIiZdVVoiHd0BwAAAAAA
2659
Lung cancer
Topic
20
Respiratory Physiology
6538
A 67-year-old male smoker is noted to be hyponatraemic at 128 on routine bloods done at his general practice. All other bloods are normal. He is euvolaemic, and physical examination is normal. He also discloses that he has had some weight loss recently. He has no past medical history. He is a smoker with a 30 year pack history.

Which of the following investigations is most likely to provide a diagnosis?
a