Carcinoma of the lung
Maior ask factors for the development of lung cancer are:
- cigarette smoking
- occupational h~s, e.g, inhalahon of asbestos and other dusts, radioactive gsses
- pulmonary fibrosis.
features Weight loss, cough and haemoptysis are common presenting features. Weight loss is often severe and may be due to humoral factors from the tumour.Dyspnoea and chest pain are also common;the latter is often pleuritic and due to obstructive changes. Patients may present with, or ultimately develop, metastases; common sites include lymph nodes, bone, brain, liver and adrenals. Paraneoplastic effects are common and are due to ectopic hormones:ACTH and ADH from small cell lung carcinomas,PTH from squamous cell carcinomas. Finger-clubbing and hypertrophic pulmonary osteoarthropathy are common.
Most tumours arise from bronchi close to the hilum; usually an upper lobe or main bronchus is involved. Ulceration is common,so the sputum may be bloodstained and contain malignant cells which can be detected cytologically. Distally, the lung may be consolidated with foamy macrophages,the usual result of proximal bronchial obstruction.
Some adenocarcinomas may arise peripherally. Small peripheral tumours are most amenable to surgery if detected before the development of metastases.
There are four major types of lung cancer,classified according to their appearance on light microscopy; their approximate incidences are:
- squamous cell carcinoma (SqCC): 20-30%
- small cell lung carcinoma (SCLC) (including oat cell carcinoma) and bronchial carcinoids: 15-20%
- adenocarcinoma (AC): 30-40%
- large cell undifferentiated carcinoma (LCUC):10-15%.
The lung cancers are discussed below according to this classification, but it should be noted that LCUC probably represents a group of squamous and adenocarcinomas that are too poorly differentiated to categorise as such by light microscopy. In fact. using electron microscopy it can be seen that many SqCC and AC are mixtures,composed of glandular and squamous cells;sometimes,a few cells with neuro-endocrine granules characteristic of SCLC are also seen, This is not entirely surprising as it is now thought that all lung cancers arise from a primitive stem cell that gives rise to the numerous varied cells seen in the mature respiratory tree.
Squamous cell carcinoma
This is the type of lung cancer most closely associated with cigarette smoking.The tumours are tumours are almost always hilar, and are thought to arise from squamous metaplasia through grades of dysplasia.There is often haemorrhage and necrosis with cavitation.Tumours may be well, moderately or poorly differentiated.SqCC tends to metastasise locally to hilar lymph nodes;distant metastases are a later feature.
Smaa cell lung carrmomas
Also known as 'oat eell' carcinoma because the small nuclei are thought to resemble oat grains, SCLC usually arise in an hilar bronchus. Unlike SqCC, they metastasise very early, producing widespread bulky secondary deposits. Sometimes, the primary tumour can be small and difficult to find. The histology is of a highly cellular tumour composed of small cells with hyperchromatic nuclei and indistinct nucleoli. The cells are very delicate and the chromatin may appear smudged, Electron microscopy shows a few dense core secretory granules in the cytoplasm suggesting that the tumour oroginates from bronchial endocrine or APUD cells. Similar granules are seen in cells of bronchial carcinoid tumoors, although in far greater numbers. It is for this reason that SCLC and bronchial carcinoid are thought to represent types of bronchial neuro-endocrine carcinoma; SCLC is aggressive and highly malignant, while bronchial carcinoid is slowgrowing and of low-grade malignancy. An intermediate type of bronchial neuro-endocrine carcinoma is also recognised which has some features of SCLC and some of bronchial carcinoid. Bronchial carcinoids are either central or peripheral, and may have a partial capsule. Histologically,they show packets or trabeculae of round cells with bland regular nuclei.
These are usually peripheral. There is a significant association with diffuse pulmonary fibrosis and honeycomb lung, especially if due to asbestosis. There is a suspicion that AC may arise in discrete areas of scarring such as old infarcts or fibrotic tuberculous foci, but it is also likely that the scar is a product of the adenocarcinoma. Two growth patterns are seen. A discrete nodule in the periphery with pleural tethering is the more common.A few cases, however, show multifocal and bilateral diffuse tumour, so-called bronchiolo-alveolar cell carcinoma. In the latter case, the tumour cells creep along alveolar walls. It is not clear whether the multifocal nature of the disease is due to multiple pulmonary tumours or spread by the movement of air or through intrapulmonary lymphatics. Against the latter explanation is the fact that hilar lymph nodes are often uninvolved. Adenocarcinomas arise from glandular cells, such as mucous goblet cells, Clara cells and type 11 pneumocytes. The histology may,therefore, be of a mucus-secreting AC, forming glands and tubules, or of an AC without significant mucus production. A premalignant stage of pulmonary adenosis is recognised.