1

What is small cell lung cancer?

Small cell lung cancer (SCLC) is defined as a malignant neuroendocrine epithelial pulmonary tumour consisting of small cells, with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin and absent or inconspicuous nucleoli (Figure 1).

Small cells can be round, oval and spindle-shaped.

SCLC was historically known as oat cell carcinoma.

Macroscopically, SCLC are soft, friable, white-tan tumours that can be extensively necrotic.

Histologically, SCLC is positive for neuroendocrine markers (such as chromogranin and CD56) and thyroid transcription factor-1 (TTF-1) in 90% of patients.

2

What are the differences between SCLC and non-small cell lung cancer?

Non-small cell lung cancer (NSCLC) represents any epithelial tumour without small cells and includes adenocarcinoma, squamous cell carcinoma and large cell tumours.

SCLC is more likely to:

a)

be centrally located;

b)

be associated with paraneoplastic syndromes;

c)

exhibit aggressive behaviour, rapid growth and spread rapidly to distant sites;

d)

be exquisitely chemo- and radio-sensitive;

e)

contain small cells with scant cytoplasm.

3

What is the epidemiology of SCLC?

SCLC represents 15% of all newly diagnosed lung cancers in Europe and the USA.

As with other forms of lung cancer, most cases occur between 35-75 years with a peak incidence at age 55-65 years.

SCLC has a male preponderance.

4

What are the risk factors for developing SCLC?

Tobacco use – which is the predominant cause of SCLC, with 98% of patients having a smoking history.

Uranium mining.

Exposure to radon gas.

5

What is a paraneoplastic syndrome?

A paraneoplastic syndrome represents a disorder triggered by the non-metastatic effects of a malignant tumour, caused by the direct release of hormone peptides by the tumour.

6

Which paraneoplastic syndromes are associated with SCLC?

Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) – which occurs in 10-45% of patients with SCLC.

Cushing’s syndrome – which occurs in 2-5% of patients with SCLC and is caused by excessive adrenocorticotropic hormone (ACTH) production.

Lambert-Eaton myasthenic syndrome (LEMS) – which occurs in 3% of patients with SCLC.

7

What are the clinical features of SCLC?

Bronchial obstruction caused by the central location of the tumour, leading to:

a)

dyspnoea;

b)

haemoptysis;

c)

cough;

d)

wheeze;

e)

pneumonia.

Constitutional symptoms:

a)

weight loss;

b)

fatigue.

Compression of local structures:

a)

facial and upper limb swelling due to superior vena cava obstruction;

b)

stridor due to tracheal obstruction;

c)

dysphagia due to oesophageal obstruction;

d)

hoarse voice due to recurrent laryngeal nerve involvement;

e)

dyspnoea due to phrenic nerve involvement (causing diaphragmatic paralysis).

Metastatic symptoms:

a)

cerebral – dizziness, headaches, nausea and vomiting or neurological deficits;

b)

bone – bone pain (pathological fractures);

c)

spinal cord – neurological deficits (cord compromise);

d)

hepatic – abdominal pain, jaundice.

Paraneoplastic syndromes.

8

What blood tests are used in the investigation of a patient with SCLC?

Although radiology and histology are the mainstay in the diagnosis of SCLC, some blood tests can be used to detect metastatic or paraneoplastic disease.

Full blood count (FBC) – pancytopaenia may indicate the presence of bone marrow involvement.

Urea & electrolytes (U&Es):

a)

serum sodium levels – hyponatraemia may indicate the presence of SIADH;

b)

serum potassium levels – hypokalaemia may indicate the presence of Cushing’s syndrome.

Liver function tests (LFTs) – which may be abnormal in the presence of hepatic metastases.

Serum calcium and alkaline phosphatase (ALP) levels – which may be raised in the presence of bone metastases.

9

What are the radiological features of SCLC (Figure 2)?

Chest radiograph (CXR) – which may demonstrate the presence of:

a)

primary tumour – hilar, mediastinal or parenchymal mass;

b)

lymph node involvement – hilar enlargement;

c)

metastatic disease – deposits in the ipsilateral or contralateral lung;

d)

pleural effusion;

e)

obstructive pneumonia or atelectasis.