Pathology of lung cancer

There are four main types of lung cancer based on the histological appearance of the cancer cells:

• small cell carcinoma (20% of cases) [1]
• large cell carcinoma (10% of cases) [1]
• squamous cell carcinoma (25% of cases) [1]
• adenocarcinoma (30% of cases) [1]

Collectively, the latter three types are referred to as non-small cell lung cancer.

Non-small cell lung cancers generally grow and spread more slowly than small cell cancers, which grow rapidly and are highly metastatic and so invade other body organs quickly [1] .

The development of lung cancer is not the result of a sudden, transforming event in the bronchial epithelium. Rather, it is a multi-step process involving sequential genetic and cellular changes, predominantly in recessive oncogenes. Although the particular cell of origin is unclear, there is evidence that tumours tend to develop from a common stem cell.

Development of lung cancer

Chronic exposure to harmful substances is thought to cause bronchial mucosal cells to undergo changes. The injury elicits a compensatory and inflammatory response. Mucosal basal cells respond by proliferating to generate mucus-secreting goblet cells, and columnar epithelial cells are replaced by stratified squamous epithelium (metaplasia). Cellular atypia and increased mitotic activity which leads to mucosal dysplasia signals the development of neoplasia. Pre-invasive lesions are defined as morphological changes within the basal mucosa that are not invasive carcinomas but that may represent the initiation of carcinogenesis.

Growth and spread of lung cancer

An In situ carcinoma is defined as neoplasia that has not penetrated the basement membrane of the mucosa. The first signs of invasive cancer are invasion of the basement membrane and infiltration of malignant cells into the underlying connective tissues and blood vessels. The process can take between 10 and 20 years or longer to develop.

Direct spread

Local spread of bronchial carcinoma destroys lung tissue and reduces ventilation capacity. The pleura and ribs may also be directly involved.

Carcinoma in the apex of the lungs can erode ribs and involve the lower part of the brachial nerve plexus, causing severe pain in the shoulder and down the inner surface of the arm.

Bronchial carcinoma can:

• invade the phrenic nerve, paralysing the diaphragm
• invade the oesophagus producing progressive dysphagia
• invade the pericardium, leading to pericardial effusion/malignant dysrhythmias.

Metastasis

Metastasis can occur by three main routes:

• spread into body cavities
• invasion of lymphatic vessels
• haematogenous spread

The lymphatic channels of the lungs are a common route for the spread of bronchial carcinoma. This leads to lymphangitis carcinomatosa and severe dyspnoea. There is frequent involvement of the lymph nodes of the lung, mediastinum, axillae and neck. Organs with a rich blood supply, such as the liver, are often affected. Secondary tumours are also common in the brain and adrenal gland.

Metastasis from other primary tumours, such as renal carcimomas, often become established in the lungs. This usually represents a significant deterioration that is usually treated with palliative rather than curative chemotherapy.

Non-metastatic extrapulmonary manifestations of lung cancer

Certain types of bronchial carcinoma are often associated with symptoms at distant sites, in the absence of metastases. This is thought to be either chemically or hormonally mediated, and can cause problems such as elevated calcium or cortisol.

1. Americ an Thoracic Society/European Respiratory Society. Pretreatment evaluation of non-small cell lung cancer. Am J Respir Crit Med 1997;156:320-32