Definition

 • A malignant epithelial tumour arising in the lung.

 Epidemiology

 • One of the most common and deadly cancers with nearly 2 million deaths annually. • Most present in patients aged over 60 years.

 Aetiology

 • About 80% of cases are directly attributable to smoking.

 Classification

 • Adenocarcinoma (40%).

 • Squamous cell carcinoma (20%).

 • Small cell carcinoma (15%).

 • A number of rare subtypes make up the remainder.

 Carcinogenesis

 • Similar to other carcinomas, lung carcinomas are likely to arise from a precursor phase of epithelial dysplasia, representing neoplastic transformation of lung epithelium without invasion.

 • Adenomatous dysplasia/adenocarcinoma in situ precedes adenocarcinoma.

 • Squamous dysplasia/ squamous carcinoma in situ precedes squamous cell carcinoma.

 Genetic mutations

 • Adenocarcinoma: Gain of function mutations in receptor tyrosine kinase genes such as EGFR, ALK, ROS, and MET.

 • Squamous cell carcinoma: Loss of function mutations in tumour suppressor genes such as TP53 and CDKN2A.

 • Small cell carcinoma: Inactivation of TP53 and RB; amplification of MyC family.

Presentation

 • Symptoms related to local growth of the tumour include progressive breathlessness, cough, chest pain, hoarseness, or loss of voice, haemoptysis, weight loss, and recurrent pneumonia.

 • Abdominal pain, bony pain, and neurological symptoms may occur from metastases.

 • A small proportion of small cell carcinomas present with paraneoplastic syndromes or the superior vena cava syndrome.

 Macroscopy

 • A firm white/ grey tumour mass within the lung.

 • yellow consolidation may be seen in the lung parenchyma distal to large proximal tumours due to an obstructive pneumonia (Fig.1).

 • Pleural puckering may be seen overlying peripheral tumours that have infiltrated the pleura.

 • Metastatic tumour deposits may be seen in hilar lymph nodes.

Fig.1 A central lung carcinoma. note how the lung tissue distal to the tumour shows flecks of yellow consolidation due to an obstructive pneumonia. the tumour was found to be a squamous cell carcinoma when examined microscopically. Reproduced with permission from Clinical Pathology (Oxford Core texts), Carton, James, Daly, Richard, and Ramani, Pramila, Oxford University Press (2006), p.131, Figure 7.13.

Histopathology

 • Adenocarcinoma: malignant epithelial tumour showing glandular differentiation and/ or mucin production.

 • Squamous cell carcinoma: malignant epithelial tumour showing keratinization and/ or intercellular bridges.

 • Small cell carcinoma: high grade neuroendocrine carcinoma composed of small cells with scant cytoplasm, ill- defined cell borders, finely granular chromatin, and absent nucleoli. Mitotic activity is high and necrosis is often extensive.

Immunohistochemistry

 • the main histological types of lung carcinomas show differing patterns of immunohistochemistry which can aid in diagnosis.

 • Adenocarcinoma: p63/ p40 negative; TTF1 positive.

 • Squamous cell carcinoma: p63/ p40 positive; TTF1 negative. • Small cell carcinoma: neuroendocrine marker (CD56, chromogranin, synaptophysin) positive; TTF1 positive.

 Prognosis

 • Poor with 5- year survival rates of ~10% in most countries.