Cancer Basics

This page contains a collection of what we call "cancer basics". These began life as short articles published in our regular newsletter "Progress". Following a number of email requests for information, we decided that a collection specially designed for the website would help people looking for general information. They are designed to be simple, straightforward and written in layman's terms. It is our hope that you find the information useful and informative. The short articles are not intended to be exhaustive in nature but are designed as a starting point should you wish to know more about any given topic. More information can be found in our document library. We would be delighted to receive your feedback on these short articles. If you have any comments on them, please email us ataicr@aicr.org.uk
Cancer Basics

What is cancer? All living things - ourselves included - are made up of cells. Cells are microscopic packages of living material and we have billions of them. They come in many different types: liver cells, brain cells, blood cells and so on. In the normal adult, cells only grow and divide slowly and under very tight control to make sure that

the number of cells in each tissue stays the same. Cancer begins when one cells changes and starts growing and dividing rapidly and out of control. This one cells divides to give two cells, then four, eight and so on until they form growing mass of cancer cells called a tumour.

What do malignant and benign mean? In some tumours, the cells stay in the same place and as the tumour stops growing before it gets very large often because it simply runs out space to grow. These are called benign tumours and they are not normally dangerous. We all have benign tumours, such as moles and warts. However, in other tumours the cells are able to invade the surrounding tissue and spread into nearby organs where they can cause serious and, eventually, fatal damage. These are called malignant tumours.

What is metastasis? In many malignant tumours, as the cells spread, they come across blood vessels. If they actually spread into the blood vessel, they get carried around the body and eventually get stuck in a smaller blood vessel in another part of the body. Here they begin to divide

and grow again eventually forming a new tumour. These are called secondary tumours or metastases. This process of cancers spreading around the body is called metastasis.

Do genes cause cancer? Every cell carries a set of coded instructions for every activity or function that it can perform. Different genes are active in different cells, which is why a brain cell carries out many different activities from muscle cell. Genes also carry the coded instructions for basic functions of the cell such as the way cells grow and divide. The growth and division of normal cells is tightly controlled by the activity of certain genes. However, when these genes are faulty or when they mechanisms controlling the activity of these genes is damaged, it can cause the growth and division of the cells to go out of control - in other words, the become cancerous. Genes themselves do not cause cancer. When they function normally, genes prevent cancer. However, it is when some genes become damaged that they can malfunction and cause cancer.

Can you inherit cancer?

Cancer itself cannot be inherited, but some people do inherit a higher risk of getting cancer. This is because they inherit, from their parents, a slightly damaged version of one of the genes involved in controlling cell division. On its own, this damaged gene is not enough to make cells cancerous. Normally, two or three different genes have to be damaged before a cell will become cancerous. That is why so very few of the billions of cells in our body ever become cancerous. However, if someone starts out with every cell in their body carrying damage in one of these genes, the chance of a cell getting the other types of gene damage and becoming cancerous is much higher. Some of these inherited damaged genes have been identified, such as BRCA1 and BRCA2 which increase the risk of getting breast cancer by five to seven times.

Do tumours need a blood supply? A tumour usually starts with a single cancerous cell that begins growing and dividing. The resulting mass of cancer cells soon gets large enough to need a new blood supply to provide oxygen and nutrients and to remove waste products. Without a blood supply, the cells in the middle of the tumour will die off. In fact, tumours without a blood supply are unable to grow

more that about one millimetre across. As soon as they start growing, tumours release small, hormonelike molecules that cause nearby blood vessels to start growing towards the tumour until they actually form a new branch supplying the tumour with blood.
http://www.aicr.org.uk/CancerBasics.stm

Benign White Cell Disorders: Reactive Lymphadenopathy REACTIVE LYMPHOID HYPERPLASIA is the benign and reversible enlargement of lymphoid tissue secondary to antigen stimulus. The lymph node response to stimuli varies. Follicles can increase in size and number; sinuses can enlarge and fill with histiocytes, or the architecture can be diffusely effaced by sheets of lymphocytes, a few immunoblasts and macrophages. In some cases there is a mixture of follicular, sinus and diffuse patterns. Each of these morphologically recognizable patterns is associated with certain antigenic stimuli, thus the morphologic type of lymphadenopathy may offer clues as to the etiology of the lymphadenopathy. FOLLICULAR HYPERPLASIA is characterized by enlargement of lymph nodes by hyperplasia of follicular (germinal) centers. At right, note the variablilty in the size of the follicles and the presence of mantle zones in the reactive node.

In FOLLICULAR HYPERPLASIA, the hyperplastic germinal center contains a normal mixture of varibly sized lymphocytes, plasma cells, and macrophages, as well as a few dendritic reticular cells. No one lymphocyte type predominates as in lymphoma.

In SINUS HYPERPLASIA the sinuses become distended and filled with histiocyte/macrophages and some plasma cells.

In DIFFUSE HYPERPLASIA the lymph node architecture is diffusely effaced by sheets of small lymphocytes, and a few scattered

immunoblasts and macrophages.

MIXED HYPERPLASIA is a combination of follicular, sinus and diffuse patterns of hyperplasia.

Morphologic patterns of reactive lymphoid hyperplasia and their associated disorders. FOLLICULAR rheumatoid arthritis

giant lymph node hyperplasia (Castleman's disease) AIDS (persistent generalized lymphadenopathy)* idiopathic (most common)

SINUS sinus histiocytosis with massive lymphadenopathy

lymphangiogram effect

* increasingly frequent, 1 differential malignant lymphoma, especially

ML,large cell Morphologic patterns of reactive lymphoid hyperplasia and their associated disorders. DIFFUSE post-vaccinial lymphadenitis

anticonvulsant therapy viral lymphadenitis dermatopathic lymphadenopathy

MIXED infectious mononucleosis

toxoplasmosis cat scratch disease tuberculosis

In addition to the aforementioned hyperplasias other diseases, i.e., histiocytosis X and metastatic carcinoma can involve lymph nodes causing a reactive hyperplasia or mimic a hyperplasia (Histiocytosis X in the sinuses of a lymph node) and thus need to be carefully ruled out on microscopic exam. Reactive follicular hyperplasia may closely resemble some follicular lymphomas and some diffuse interfollicular viral infections mimic diffuse lymphoma. Whenever a malignant diagnosis is being considered benign reactive disorders must be ruled out by an experienced pathologist. This is the final page of the Benign White Cell Disorders. The next page

begins the Leukemia section.

http://www.med-ed.virginia.edu/courses/path/innes/wcd/reactive.cfm

Chronic granulomatous disease

On this page: Description Genetic changes Inheritance Diagnosis Additional information Other names Glossary definitions

Reviewed August 2012

What is chronic granulomatous disease?

Chronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and fungi. Individuals with chronic granulomatous disease have recurrent bacterial and fungal infections. People with this condition often have areas of inflammation (granulomas) in various tissues that can be damaging to those tissues. The features of chronic granulomatous disease usually first appear in childhood, although some individuals do not show symptoms until later in life. People with chronic granulomatous disease typically have at least one serious bacterial or fungal infection every 3 to 4 years. The lungs are the most frequent area of infection; pneumonia is a common feature of this condition. Individuals with chronic granulomatous disease are susceptible to a condition called mulch pneumonitis, which causes fever and shortness of breath after exposure to decaying organic materials such as mulch, hay, or dead leaves. Exposure to these organic materials and the numerous fungi involved in their decomposition causes people with chronic granulomatous disease to develop fungal infections in their lungs. Other common areas of infection in people with chronic granulomatous disease include the skin, liver, and lymph nodes.

Inflammation can occur in many different areas of the body in people with chronic granulomatous disease. Most commonly, granulomas occur in the gastrointestinal tract and the genitourinary tract. In many cases the intestinal wall is inflamed, causing a form of inflammatory bowel disease that can lead to stomach pain, diarrhea, nausea, and vomiting. Other common areas of inflammation in people with chronic granulomatous disease include the stomach, colon, and rectum, as well as the mouth and throat. Additionally, granulomas within the gastrointestinal tract can lead to tissue breakdown and pus production (abscesses). Inflammation in the stomach can prevent food from passing through to the intestines (gastric outlet obstruction), leading to an inability to digest food. These digestive problems cause vomiting after eating and weight loss. In the genitourinary tract, inflammation can occur in the kidneys, bladder, and genitalia. Inflammation of the lymph nodes (lymphadenitis) and bone marrow (osteomyelitis), which both produce immune cells, can lead to further impairment of the immune system. Rarely, people with chronic granulomatous disease develop autoimmune disorders such as myasthenia gravis, which causes muscle weakness, and juvenile rheumatoid arthritis, which causes joint pain and swelling. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Repeated episodes of infection and inflammation reduce the life expectancy of individuals with chronic granulomatous disease; however, with treatment, most affected individuals live into mid- to late adulthood.

How common is chronic granulomatous disease?

Chronic granulomatous disease is estimated to occur in 1 in 200,000 to 250,000 people worldwide.

What genes are related to chronic granulomatous disease?

Mutations in the CYBA, CYBB, NCF1, NCF2, or NCF4 gene can cause chronic granulomatous disease. There are five types of this condition that are distinguished by the gene that is involved. The proteins produced from the affected genes are parts (subunits) of an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Specifically, NADPH oxidase is primarily active in immune system cells called phagocytes. These cells catch and destroy foreign invaders such as bacteria and fungi. Within phagocytes, NADPH oxidase is involved in the production of a toxic molecule called superoxide. Superoxide is used to generate other toxic substances, which play a role in killing foreign invaders and preventing them from reproducing in the body and causing illness. NADPH oxidase is also thought to regulate the activity of immune cells called neutrophils. These cells

play a role in adjusting the inflammatory response to optimize healing and reduce injury to the body. Mutations in the CYBA, CYBB, NCF1, NCF2, and NCF4 genes result in the production of proteins with little or no function or the production of no protein at all. Mutations in the genes that cause chronic granulomatous disease that prevent the production of any functional protein are designated "0". For example, mutations in the CYBB gene that lead to no functional beta subunit are designated CYBB0. Mutations that lead to a reduction of the amount of protein produced are designated "", for example, CYBB-. Without any one of its subunit proteins, NADPH oxidase cannot assemble or function properly. As a result, phagocytes are unable to kill foreign invaders and neutrophil activity is not regulated. A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation. Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown. Read more about the CYBA, CYBB, NCF1, NCF2, and NCF4 genes.

How do people inherit chronic granulomatous disease?

When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. The CYBB gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Rarely, females with one altered copy of the CYBB gene have mild symptoms of chronic granulomatous disease, such as an increased frequency of bacterial or fungal infections. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Men and women are affected by autosomal recessive conditions equally.
http://ghr.nlm.nih.gov/condition/chronic-granulomatous-disease#definition