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cancer : causes of cancer, growth of tumour, effect of tumour, cause of death in malignant disease

cancer/tumour/neoplasm|causes of cancer|growth of tumour |spread of tumour|effect of tumour|cause of death in malignant disease

cancer/tumour/neoplasm

A tumour or neoplasm or cancer (literally meaning ‘new growth’) is a mass of tissue that grows faster than normal in an uncoordinated manner and continues to grow after the initial stimulus has ceased.
Process of cancer cell development


Tumours are classified as benign or malignant although a clear distinction is not always possible. Benign tumours only rarely change their character and become malignant. Tumours, whether malignant or benign, may be classified according to their tissue of origin, e.g. adeno- (glandular) or, sarco- (connective tissue); the latter may be further distinguished e.g. myo- (muscle), osteo- (bone).

Malignant tumours are further classified according to their origins; for example, a carcinoma, the commonest form of malignancy, originates from epithelial tissue and a sarcoma arises from connective tissue. Hence, an adenoma is a benign tumour of glandular tissue but an adenocarcinoma is a malignant tumour of the epithelial component of glands; a benign bone tumour is an osteoma, a malignant bone tumour an osteosarcoma.

Causes of neoplasms/cancer

There are more than 200 different types of cancer, but all are caused by mutations within the cell’s genetic material. Some mutations are spontaneous, i.e. happen by chance during cell division, others are related to exposure to a mutagenic agent (a carcinogen) and a small proportion are inherited. 

Advancing knowledge in the area has led to the identification of many specific genes/chromosome mutations associated directly with particular cancers. Cell growth is regulated by genes that inhibit cell growth (tumour suppressor genes) and genes that stimulate cell growth (proto-oncogenes). One important tumour suppressor gene, p53, is thought to be defective in 50–60% of cancers. A proto-oncogene that becomes abnormally activated and allows uncontrolled cell growth can also cause
cancers and is then referred to as an oncogene.

Carcinogens

These cause malignant changes in cells by irreversibly damaging a cell’s DNA. It is impossible to specify a maximum ‘safe dose’ of a carcinogen. A small dose may initiate change but this may not be enough to cause malignancy unless there are repeated doses over time that have a cumulative effect. In addition, there are widely varying latent periods between exposure and signs of malignancy.

Chemical carcinogens
Examples include:
• cigarette smoke, which is the main risk factor for lung (bronchial) cancer.
• aniline dyes, which predispose to bladder cancer.
• asbestos, which is associated with pleural mesothelioma.

Ionising radiation
Exposure to ionizing radiation including X-rays, radioactive isotopes, environmental radiation and ultraviolet rays in sunlight may cause malignant changes in some cells and kill others. Cells are affected during mitosis so those normally undergoing frequent division are most susceptible. These labile tissues include skin, mucous membrane, bone marrow, reticular tissue and gametes in the ovaries and testes. For example, repeated episodes of sunburn (caused by exposure to ultraviolet rays in sunlight) predispose to development of skin cancer.

Oncogenic viruses
Some viruses cause malignant changes. Such viruses enter cells and incorporate their DNA or RNA into the host cell’s genetic material, which causes mutation. The mutant cells may be malignant. Examples include-hepatitis B virus, which can cause liver cancer and human papilloma virus (HPV), which is associated with cervical cancer.

Host factors
Individual characteristics can influence susceptibility to tumours. Some are outwith individual control e.g. race, increasing age and inherited (genetic) factors. Others can be modified and are referred to as lifestyle factors; these include eating a healthy balanced diet, cigarette smoking, taking sufficient exercise and avoiding obesity. Making healthy lifestyle choices where possible is important as these factors are thought to be involved in the development of nearly half of all malignant tumours.

Growth of tumours

Normally cells divide in an orderly manner. Neoplastic cells have escaped from the normal controls and multiply in a disorderly and uncontrolled manner forming a tumour. Blood vessels grow with the proliferating cells, providing them with a good supply of oxygen and nutrients that promotes their growth. In some malignant tumours the blood supply does not keep pace with growth and ischaemia (lack of blood supply) leads to tumour cell death. If the tumour is near the body surface, this may result in skin ulceration and infection. In deeper tissues there is fibrosis; e.g. retraction of the nipple in breast cancer is due to the shrinkage of fibrous tissue in a necrotic tumour.

spread of tumours

Most benign tumours are contained within a fibrous capsule derived partly from the surrounding tissues and partly from the tumour. They neither invade local tissues nor spread to other parts of the body, even when they are not encapsulated.

Malignant tumours are not encapsulated. They spread locally by growing into and infiltrating nearby tissue (known as invasion). Tumour fragments may spread to other parts of the body in blood or lymph. Some of the spreading tumour cells may be recognized as ‘non-self’ and phagocytosed by macrophages or destroyed by defense cells of the immune system, e.g. cytotoxic T-cells and natural killer cells. Others may escape detection and lodge in tissues away from the primary site and grow into secondary tumours (metastases). Metastases are often multiple.

The likely prognosis may by assessed using staging, a process that assesses the size and spread of the tumour. A commonly used example is the TMN system where T is tumour size, N indicates affected regional lymph nodes and M identifies metastatic sites. For most tumours, large size and extensive spread suggest a poorer prognosis.

Local spread 

Benign tumours enlarge and may cause pressure damage to local structures but they do not spread to other parts of the body.
Benign or malignant tumours may:
• damage nerves, causing pain and loss of nerve control of other tissues and organs supplied by the damaged nerves
• compress adjacent structures causing e.g. ischaemia (lack of blood), necrosis (death of tissue), blockage of ducts, organ dysfunction or displacement, or pain due to pressure on nerves.

Additionally, malignant tumours invade surrounding tissues and may also erode blood and lymph vessel walls, causing spread of tumour cells to distant parts of the body.

Body cavities spread

This occurs when a tumour penetrates the wall of a cavity. The peritoneal cavity is most frequently involved. If, for example, a malignant tumour in an abdominal organ invades the visceral peritoneum, tumour cells may metastasize to folds of peritoneum or any abdominal or pelvic organ. Where there is less scope for the movement of fragments within a cavity, the tumour tends to bind layers of tissue together, e.g. a pleural tumour binds the visceral and parietal layers together, limiting expansion of the lung.

Lymphatic spread

This occurs when malignant tumours invade nearby lymph vessels. Groups of tumour cells break off and are carried to lymph nodes where they lodge and may grow into secondary tumours. There may be further spread through the lymphatic system and to blood because lymph drains into the subclavian veins.

Blood spread 

This occurs when a malignant tumour erodes the walls of a blood vessel. A thrombus (blood clot) may form at the site and emboli consisting of fragments of tumour and blood clot enter the bloodstream. These emboli block small blood vessels, causing infarcts (areas of dead tissue) and development of metastatic tumours. Phagocytosis of tumour cells in the emboli is unlikely to occur because these are protected by the blood clot. Single tumour cells can also lodge in the capillaries of other body organs.

Division and subsequent growth of secondary tumours, or metastases, may then occur. The sites of blood-spread metastases depend on the location of the original tumour and the anatomy of the circulatory system in the area. The most common sites of these metastases are bone, the lungs, the brain and the liver.

Effects of tumours

Pressure effects

Both benign and malignant tumours may compress and damage adjacent structures, especially if in a confined space. The effects depend on the site of the tumour but are most marked in areas where there is little space for expansion, e.g. inside the skull, under the periosteum of bones, in bony sinuses and respiratory passages. Compression of adjacent structures may cause ischaemia, necrosis, blockage of ducts, organ dysfunction or displacement, pain due to invasion of nerves or pressure on cell dysplasia is an important factor

 Well-differentiated benign tumours are more likely to secrete hormones than markedly dysplastic malignant tumours. High levels of hormones are found in the bloodstream as secretion occurs in the absence of the normal stimulus and homeostatic control mechanism. Some malignant tumours produce uncharacteristic hormones, e.g. some lung tumours produce insulin. Endocrine glands may be destroyed by invading tumours, causing hormone deficiency.

Cachexia

This is the severe weight loss accompanied by progressive weakness, loss of appetite, wasting and anaemia that is usually associated with advanced metastatic cancer. The severity is usually indicative of the stage of the disease. The causes are not clear.

Causes of death in malignant disease

Infection

Acute infection is a common cause of death when superimposed on advanced malignancy. Predisposition to infection is increased by prolonged immobility or bed rest, and by depression of the immune system by cytotoxic drugs and radiotherapy or radioactive isotopes used in treatment. The most common infections are pneumonia, septicaemia, peritonitis and pyelonephritis.

Organ failure

A tumour may destroy so much healthy tissue that an organ cannot function. Severe damage to vital organs, such as lungs, brain, liver and kidneys, are common causes of death.

Carcinomatosis

This is the presence of widespread metastatic disease and is usually associated with cachexia. Increasingly severe physiological and biochemical disruption follows causing death.

Hemorrhage

This occurs when a tumour grows into and ruptures the wall of a vein or artery. The most common sites are the gastrointestinal tract, brain, lungs and the peritoneal cavity.






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