What Is Lymphoma? Lymphoma Symptoms, Causes and Treatments

Lymphoma is a type of cancer that begins in immune system cells called lymphocytes. Like other cancers, lymphoma occurs when lymphocytes are in a state of uncontrolled cell growth and multiplication.

Lymphocytes are white blood cells that move throughout the body in a fluid called lymph. They are transported by a network of vessels that make up the lymphatic system, part of the immune system. The lymphatic system - whose job it is to fight infections or anything else that threatens the body - is also comprised of lymph nodes that exist throughout the body to filter the lymph that flows through them. The lymph nodes swell and tenderize when a large number of microbial organisms collect inside of them, indicating local infection.

There are two primary types of lymphocytes: B cells and T cells. Both are designed to recognize and destroy infections and abnormal cells. B cells produce proteins that travel throughout the body, attaching themselves to infectious organisms and abnormal cells and alerting the immune system that the pathogen needs to be destroyed. T cells actually kill the pathogens directly and serve a function in regulating the immune system from over- or under-activity.


Lymphoma occurs when lymphocyte B or T cells transform and begin growing and multiplying uncontrollably. Abnormal lymphocytes collect in one or more lymph nodes or in lymph tissues such as the spleen or tonsils, and eventually they form a mass of cells called a tumor. Tumors grow and invade the space of surrounding tissues and organs, depriving them of oxygen and nutrients.

If abnormal lymphocytes travel from one lymph node to the next or to other organs, the cancer can spread or metastasize. Lymphoma development outside of lymphatic tissue is called extranodal disease.

In the United States each year, some 54,000 people are diagnosed with NHL and 7,000 are diagnosed HL. It is the most common type of blood cancer in the US. The European Union sees over 50,000 cases of NHL every year.

How is lymphoma classified?

There are two types of lymphoma: Hodgkin lymphoma (HL, also called Hodgkin's disease) and non-Hodgkin lymphoma (NHL). Both HL and NHL can occur in the same places and have similar symptoms. Their differences are visible at a microscopic level.

Hodgkin lymphoma develops from a specific abnormal lineage of B cells. There are five subtypes of HL. NHL may derive from either abnormal B or T cells, and its 30 subtypes are distinguished by unique genetic markers. The large number of lymphoma subtypes has led to a complicated classification scheme that involves microscopic appearance and well-defined genetic and molecular configurations.

Although several NHL subtypes look similar, they function differently and respond differently to therapies. HL subtypes are microscopically distinct, and classification is based upon the microscopic differences as well as the extent of disease.

What causes lymphoma?

Cancer is ultimately the result of cells that uncontrollably grow and do not die. Normal cells in the body follow an orderly path of growth, division, and death. Programmed cell death is called apoptosis, and when this process breaks down, cancer results. Scientists do not know exactly what causes lymphoma, but they have identified several potential risk factors.

Genetics

Lymphoma can be the result of a genetic predisposition that is inherited from family members. It is possible to be born with certain genetic mutations or a fault in a gene that makes one statistically more likely to develop cancer later in life.

Carcinogens

Carcinogens are a class of substances that are directly responsible for damaging DNA, promoting or aiding cancer. Exposure to certain pesticides, herbicides, and solvents such as benzene has been associated with lymphoma. Similarly, black hair dye has been linked to higher rates of NHL. When our bodies are exposed to carcinogens, free radicals are formed that try to steal electrons from other molecules in the body. These free radicals damage cells, affecting their ability to function normally, and the result can be cancerous growths.

Other medical factors

As we age, there is an increase in the number of possible cancer-causing mutations in our DNA. The risk of NHL increases as we age, and HL is most common between ages 16-34 and 55 years and older. Additional medical conditions that have been associated with higher lymphoma rates include infection with HIV, human T-lymphocytic virus type 1 (HTLV-1), Epstein-Barr virus, Helicobacter pylori, or hepatitis B or C; autoimmune disease (such as lupus); diseases that require therapies that suppress the immune system; and any other immunodeficiency diseases.

What are the symptoms of lymphoma?

Cancer symptoms are quite varied and depend on where the cancer is located, where it has spread, and how big the tumor is. Lymphoma usually first presents with swelling in the neck, underarm, or groin. Additional swelling may occur where other lymph nodes are located such as in the spleen. In general, enlarged lymph nodes can encroach on the space of blood vessels, nerves, or the stomach, leading to swollen arms and legs, to tingling and numbness, or to feelings of being full, respectively.

Lymphoma symptoms also include nonspecific symptoms such as fever, chills, unexplained weight loss, night sweats, lethargy, and itching.

How is lymphoma diagnosed and staged?

In order to diagnose lymphoma, physicians will request a complete physical exam as well as personal and family medical histories. An oncologist (cancer specialist) will usually be consulted to review the results of several tests.

Blood tests will be used to test blood cell, kidney, and liver performance. They can also detect a chemical called lactase hydrogenase (LDH), of which high levels have been associated with an aggressive form of NHL.

Several imaging techniques are employed in order to see if cancer exists and to find out how far they have spread. Common imaging tests include:

• X-rays
• Computerized tomography (CT) scans
• Magnetic resonance imaging (MRI)
• Lymphangiogram
• Gallium scan
• Positron emission tomography (PET) scans

Physicians may also perform bone marrow examinations to see if the lymphoma has infected the bone marrow. Bone marrow samples are often taken from the hip and examined for the presence of abnormal B or T cells.

The only absolute way to make a cancer diagnosis is to remove a small sample of the tumor and look at it under the microscope in a procedure called a biopsy. Doctors may gather the sample by inserting a needle through the skin, surgical methods, or laparoscopic methods. A pathologist examines the sample under a microscope to determine if cancer exists.

After a diagnosis is made, doctors analyze the tissue samples and test results to find out how far the cancer has spread and to determine the stage of the cancer. The stage lets oncologists know which choices will be available for treatment and it informs prognoses.

A common and simple classification scheme for Hodgkin's lymphoma considers it to be bulky (large tumor, worse prognosis) or nonbulky (small tumor, better prognosis). Non-Hodgkin's lymphoma is classified according to its microscopic appearance, location in the body, and genetic and molecular features. It is frequently divided into three grades. Low grade, or indolent, lymphomas grow slowly and often do not require immediate treatment. Intermediate grade lymphomas are rapidly growing and require immediate treatment. They are often curable. High grade lymphomas are aggressive and rapidly growing, require intesive and immediate treatment, and are often uncurable.

HL and NHL use a similar staging system to describe the extent of the disease.

• Stage I or early disease is when lymphoma is found in a single lymph node region or in a single organ outside the lymph node.


• Stage II or locally advanced disease is when two or more lymph node regions on the same side of the diaphragm or one lymph node region and a nearby tissue or organ carries lymphoma.


• Stage III or advanced disease is when two or more lymph nodes or a lymph node and an organ on the opposite side of the body are affected by lymphoma.


• Stage IV or widespread, disseminated disease is when the lymphoma has spread to the spleen, bone marrow, bone, or central nervous system.

Both types of lymphoma may also receive an A classification to indicate no symptoms like fever and weight loss, a B classification to indiciate such symptoms, or an E classification to indicate that the tumor has spread directly from a lymph node to an organ.

How is lymphoma treated?

Cancer treatment depends on the type of cancer, the stage of the cancer (how much it has spread), age, health status, whether or not one has received previous cancer treatment, and additional personal characteristics. Lymphoma treatment is usually designed to result in complete remission of the disease - a state where there may be lymphoma cells in the body, but they are undetectable and cause no symptoms. Common lymphoma treatments include chemotherapy, radiation therapy, and biological therapy.

The ultimate goal of lymphoma treatment is durable remission, or remission that lasts a long time. If the cancer comes back, this is called recurrence. After therapy the patient may see improvement (lymphoma shrinks), a stable disease (lymphoma is the same size), progression (lymphoma worsens), or a refractory disease (the lymphoma resists treatment). Patients may also undergo induction therapy that is designed to induce remission, salvage therapy that is designed to take over for a failing treatment, or maintenance therapy that is treatment meant to prevent recurrence.

Chemotherapy

Chemotherapy utilizes chemicals that interfere with the cell division process - damaging proteins or DNA - so that cancer cells will commit suicide. These treatments target any rapidly dividing cells (not necessarily just cancer cells), but normal cells usually can recover from any chemical-induced damage while cancer cells cannot. Chemotherapy is generally used to treat cancer that has spread or metastasized because the medicines travel throughout the entire body. Treatment occurs in cycles so the body has time to heal between doses. However, there are still common side effects such as hair loss, nausea, fatigue, and vomiting. Combination therapies often include multiple types of chemotherapy or chemotherapy combined with other treatment options.

Radiation

Radiation treatment, also known as radiotherapy, destroys cancer by focusing high-energy rays on the cancer cells. This causes damage to the molecules that make up the cancer cells and leads them to commit suicide. Radiotherapy utilizes high-energy gamma-rays that are emitted from metals such as radium or high-energy x-rays that are created in a special machine. Radiotherapy can be used as a standalone treatment to shrink a tumor or destroy cancer cells, and it is also used in combination with other cancer treatments.

Side effects of radiation therapy may include mild skin changes resembling sunburn or suntan, nausea, vomiting, diarrhea, and fatigue. Patients also tend to lose their appetites and have trouble maintaining weight, but most side effects subside a few weeks after completing treatment.

How can lymphoma be prevented?

There are no known ways to prevent lymphoma. However, physicians recommend avoiding known risk factors and avoiding viral infections or conditions that suppress the immune system.