CNS Lymphoma – Causes, Signs and symptoms

CNS

Also called: Secondary Central Nervous System Lymphoma, Diffuse Histiocytic Lymphoma, CNS Lymphoma, CNSL, Primary Central Nervous System Lymphoma, Reticulum Cell Sarcoma

Summary

Lymphoma is a cancer of the lymphoid tissue, which is part of the lymphatic system. As a major component of the immune system, the lymphatic system manufactures lymphocytes (a type of white blood cells). It also transports lymph (fluid composed of plasma and a small number of white blood cells) from tissues in the body to the bloodstream. The lymphatic system consists of organs, lymph nodes and lymphatic vessels. Lymphoma is the only form of cancer that originates in the lymphatic system, although other forms of cancer may spread into the system. 

The tissue found in the lymphatic system is formed by various types of immune cells that work together to fight off infection and other threats, such as cancer. In lymphoma, abnormal lymphocytes continue to grown in the lymphoid tissue. This results in an enlargement of the lymph nodes and other organs in the body containing lymphocytes, which in turn causes lumps to develop in the body,

Lymphoma is a cancer of the lymphatic system, which is found all over the body, and which includes circulating lymphocytes. For this reason, the disease easily spreads to tissues throughout the body. Primary central nervous system (CNS) lymphoma is a type of cancer that develops in the lymph tissue in the brain and/or spinal column. It should not be confused with cancers that originate elsewhere in the body and metastasize (spread) to the lymphatic system.

There are two types of lymphoma, each of which begins with distinctly different cells. Hodgkin’s lymphoma is a rare form of cancer that is characterized by the presence of specific cells called Reed-Sternberg cells.Non-Hodgkin’s lymphoma is far more common and includes all lymphomas not diagnosed as Hodgkin’s lymphoma. CNS lymphoma is a type of non-Hodgkin’s lymphoma.

Although the causes of CNS lymphoma are unknown, it is known that white blood cells, which are part of the immune system, become malignant.These cells are carried to the central nervous system through the lymph system and blood. When CNS lymphoma continues to grow, the cancer usually does not spread outside of the central nervous system or the eye. 

People with compromised immune systems are at the greatest risk, especially those with immune system diseases or those who have been infected with certain viruses, such as HIV.  Also, heart and other organ transplant patients are at risk because their immune systems are weakened by the anti-rejection medications they take.

Symptoms of CNS lymphoma are similar to those of any brain tumor and may include headaches, seizures, facial paralysis and confusion. The actual symptoms depend on the location of the cancer in the central nervous system. If an initial examination indicates the possibility of CNS lymphoma, a spinal tap, blood tests, imaging tests and bone marrow biopsies may be performed to determine the location and stage of the cancer.

Because CNS lymphoma can be widespread, surgery is not a form of effective treatment. Standard treatment for this type of cancer includes chemotherapy, radiation therapy and steroid therapy. Survival rate or prognosis is determined by the patient’s age, the location and type of tumor and spread of the cancer.

There is no known method of pre-screening for CNS lymphoma or preventing this type of cancer at this time. Although the prognosis is generally poor for patients with CNS lymphoma there have been recent advances in treatment. About 30 percent of people live at least five years with a diagnosis of CNS lymphoma, according to the American Cancer Society

About central nervous system lymphoma

Lymphoma is a cancer that forms in the lymphocytes of the lymph system. The lymph system includes the lymphocytes, lymph nodes, lymph vessels and other organs. The lymphocytes circulate through the bloodstream and lymph system to all the tissues in the body. The central nervous system, which is comprised of the brain and spinal cord, receives signals and controls responses for the body.

Central nervous system (CNS) lymphoma is a type of cancer that occurs in the lymphoid tissue in the brain, spinal cord or membranes around the brain and spinal cord (called the meninges). CNS lymphoma should not be confused with cancers that start elsewhere in the body, such as the breast, and metastasize (spread) to the lymphatic system.

When cancerous lymphocytes travel in and out of the central nervous system through the bloodstream and the lymph system, they may cause malignant nerve cells to grow. CNS lymphoma rarely spreads outside of the central nervous system, but the cancer can spread to the eyes, because of their close proximity to the brain. In this case, it is called ocular lymphoma.

CNS lymphoma is a type of non-Hodgkin’s lymphoma. Unlike Hodgkin’s lymphoma, which tends to spread from one area to a surrounding area, non-Hodgkin’s lymphoma does not spread in a consistent manner. Also, though it originates in lymphocytes, it may be considered to be a type of brain tumor.

CNSL (also known as primary brain lymphoma) is relatively rare, occurring in about 3.5 percent of primary brain tumors, but the number of cases is rising. CNS lymphoma can affect all age groups; however, it mostly occurs in adults.

The incidence of CNS lymphoma has increased in transplant patients and in non-immune-comprised populations for unknown reasons. In these patients, it is slightly more common in men than women. It has decreased among high-risk AIDS patients in the last decade, possibly because of more effective use of immune system medications. Among AIDS patients with CNS lymphoma, a large majority of the patients are male.

Although the prognosis is generally poor for all patients with CNSL, there have been recent advances in chemotherapy and radiation therapy treatments. About 30 percent of people diagnosed of CNS lymphoma can live at least 5 years, according to the American Cancer Society. Prognosis is slightly poorer for patients with AIDS because of additional complications.

Risks factors and causes of CNS lymphoma

The exact cause of central nervous system (CNS) lymphoma is unknown, but a compromised immune system appears to be the greatest risk factor. Immune system deficiencies may be:

  • Present at birth
  • A side effect of chemotherapy
  • Related to anti-rejection drugs for organ transplants
  • Caused by HIV infection or AIDS
  • Related to other conditions, such as Epstein-Barr virus (causes mononucleosis and is associated with Burkitt’s lymphoma)

Certain inherited diseases also increase the risk of CNS lymphoma, including:

  • Family history of lymphoma.

  • Neurofibromatosis type 2. Inherited genetic disorder that causes brain tumors.

  • Tuberous sclerosis. An inherited genetic disorder that causes benign tumors that affect the brain, eyes, skin and internal organs. It is also associated with mental retardation and seizures.

  • Von Hippel-Lindau disease. Inherited genetic disorder that causes tumors of blood vessel cells that form in the retina, brain, spinal cord, pancreas, kidneys, and other organs.

  • In addition, age (45 to 70), exposure to environmental toxins, obesity and radiation therapy may also be risk factors.

Signs and symptoms of CNS lymphoma

Symptoms of central nervous system (CNS) lymphoma usually begin gradually and worsen over time. However, they can also occur suddenly and dramatically, as occurs in a stroke. Symptoms that the patient develops depend on the location of the tumors in the central nervous system (CNS). Central nervous system lymphoma is primarily confined to the brain, spinal cord and eye.

General symptoms of physical pressure to the brain from a tumor include:

  • Headaches
  • Nausea
  • Blurred vision
  • Lethargy and sleepiness
  • Coma

Brain and spinal cord symptoms due to nerve damage include:

  • Loss of specific functions
  • Weakness or paralysis
  • Loss of hearing or vision
  • Coordination and task impairment
  • Difficulty walking or speaking
  • Swallowing problems (dysphagia)
  • Thought and personality changes
  • Seizures

Patients exhibiting these symptoms should consult their physician. The above symptoms may indicate any number of diseases, many less life-threatening than CNS lymphoma. Less than 1 percent of the above symptoms are caused by tumors in the central nervous system, according to the American Cancer Society (ACS). Ten percent of new onset seizures are caused by brain tumors.

A physician can prescribe diagnostic tests to determine the cause of the symptoms.

Diagnosis methods for CNS lymphoma

In most individuals, CNS lymphoma is not diagnosed until symptoms appear. A medical history and physical examination are usually the first steps toward diagnosis. This may include a neurological examination to evaluate brain and nerve function for muscle strength, coordination and mental status.

This initial exam may be performed by a general physician. If abnormalities are found, the patient probably will be referred to a neurologist or a neurosurgeon for more detailed testing.

Blood tests may be performed to determine the patient’s white blood cell count, as well as to identify cancer cells. These findings may indicate the need for more in-depth testing. Additional blood tests may be conducted to diagnose the following conditions due to their close association with CNS lymphoma:

  • HIV test. HIV antibodies (substance produced by the body as a defense to invaders) are measured in the blood.

  • Epstein-Barr virus (EBV) test. EBV antibodies are measured in the blood or cerebrospinal fluid (CSF).

Imaging tests to help diagnose CNSL may include:

  • CAT scan. Cross-sectional images are taken of the body from different angles using computer technology. CAT scans may be performed with contrast medium (a dye) to help locate cancer cells in the body. For primary CNS lymphoma, CAT scans focus on the brain, spinal cord, chest, abdomen and pelvis.

  •  Magnetic resonance imaging(MRI). Magnetic field and radio waves are used to create detailed images of internal organs to locate cancer in the CNS. A contrast material may also be used. This diagnostic test is very useful in locating cancer along spinal fluid pathways.
  • Positron emission tomography (PET) scan.  A radioactive sugar is injected into the bloodstream and is rapidly absorbed by the cancer cells, creating hot spots. These spots are detectable images and are strong indicators of cancer.
  • X-rays. The use of radiation to create images of organs in the body.

  • Magnetic resonance spectroscopic imaging (MRSI). Magnetic and radio waves are used to interact with atomic features of the cancer to create detailed images of the tumors that are not visible by MRI. This test is used experimentally at this time.

  •  Angiography. A dye is injected into the bloodstream to show the blood vessels in and around the cancer cells while images are taken of the brain and spinal cord. This test provides useful details prior to surgery to help the surgeon plan for surgical procedures.

  • Lumbar puncture (spinal tap). A sample of cerebrospinal fluid (CSF) is taken from the spinal canal and observed under a microscope to detect cancer cells and nervous system infections. Also, high levels of protein and other substances in the CSF may indicate the presence of cancer. This is typically performed after CT and MRI scans indicate cancer cells are present especially along the spinal fluid pathway.

If tumors in or near the nerves of the eyes are found, the following tests may be performed:

  • Slit lamp eye exam. Narrow bands of light are beamed into the eye to check for abnormalities.

  • Vitrectomy. Thin incisions are made in the eye to extract vitreous humor (gel-like fluid) from the eyeball to be examined under a microscope for cancer cells.

Diagnosis of CNS lymphoma is dependent on a biopsy which can be obtained by several methods, including:

  • Biopsy. Biopsies (samples of tissue taken by using an invasive method with anesthesia) of the brain, spinal cord, lymph node or bone marrow tissue can be taken. The sample is analyzed by a pathologist to determine the type and stage of the cancer.  
  • Stereotactic biopsy and surgery. In this procedure, a neurosurgeon with use of anesthesia drills a hole in the skull and removes a small piece of tumor tissue guided by CT and MRI scans. If the neurosurgeon determines it is partially treatable with surgery, as much as possible of the tumor is surgically removed (debulking).

Treatment and prevention of CNS lymphoma

Central nervous system lymphomas tend to spread widely through the brain and spinal cord making surgery difficult as a treatment option. Surgery is usually performed for biopsies to obtain a tumor sample and determine the cell type for diagnosis. Stereotactic biopsy with surgery is not commonly used with CNS lymphoma patients.

Treatment options are determined based on the patient’s age, cancer stage, its spread and whether it is recurring. Also, the patient’s general health, including whether or not the patient has AIDS or other autoimmune diseases will determine the course of treatment.

As a result of immune system weakness, the cancer cells grow more aggressively in AIDS patients. AIDS patients often develop more severe side effects from treatment than other patients. Organ and heart transplant patients also are at high risk because the anti-rejection medication they take weakens their immune system.

Most patients with CNS lymphoma are treated with a combination of therapies, including:

  • Chemotherapy. The use of powerful drugs given by injection or taken orally to control the growth of cancer cells by killing them or preventing cell division. Use of chemotherapy releases drugs into the bloodstream where they can reach cells throughout the body even to metastasized sites. When placed directly in locations such as the abdomen or spinal column, the drugs may mainly affect the cancer cells in those areas.

    Chemotherapy medications may also be placed in the central openings inside the brain (ventricles). The method of administration depends on where the cancer cells are located. Blood brain barrier disruption drugs may be used to make openings between cells to allow the chemotherapy drugs to penetrate the tumor.

  • Lumbar puncture. If lymphoma cells are present in the spinal fluid, chemotherapy medications can be injected into the spinal canal (intrathecal chemotherapy). An Ommaya reservoir (a device with a very thin tube) can be inserted into the scalp to feed the drugs into the ventricles in the brain. This treatment may be preferred because it is more comfortable than repeated lumbar punctures.
  • Radiation therapy. In external radiation, specialized x-ray beams are focused directly on targeted areas to kill or shrink cancer cells. Brachytherapy or internal radiation involves putting radioactive treatment materials, such as small “seeds,” directly into the site of the tumor.

    Because of potential damage to brain tissue with radiation therapy, clinical trials have tested chemotherapy alone or before radiation therapy to reduce damage to brain tissue. Radiation may be given if a considerable spread of the cancer is located along the cerebrospinal fluid pathway.

  • Stereotactic radiotherapy. High dosage of radiation is directed at the cancer to reduce damage to surrounding brain tissue. This is a useful procedure in areas where debulking (stereotactic surgery) is not possible.

  • Steroid therapy. Steroid hormones are made into drugs in the laboratory. Glucocorticoids (steroids with an anti-cancer effect), for example, are used to counteract the inflammation and growth of lymphomas.

  • Biological therapy. This treatment, also called immunotherapy, is used to stimulate the immune system to fight cancerous cells as invaders. In some cases, biological therapy attacks the cancer directly.  Monoclonal antibodies are one type of biological therapy.
  • Stem cell transplant. Stem cells (immature blood cells with the ability to form new replacement mature blood cells) are removed from the blood and bone marrow while high dose chemotherapy is administered. The stem cells are then infused into the blood and bone marrow to restore the patient’s blood supply. This treatment is being tested in clinical trials.

Treatment procedures for CNS lymphoma in patients with AIDS are different because side effects are more severe in these patients. Treatments often begin with steroid therapy and then may progress to include radiation and chemotherapy. A patient’s physicians will determine treatment of the disease based on a number of factors.

CNS lymphoma tends to produce distant disease as well as local recurrences. It recurs most often after it has been treated in the brain or the eye. Prognosis is based on the following factors:

  • Patient’s age (prognosis is better under 60 years)

  • Neurological damage and disability

  • Level of impairment to functioning

  • Whether the patient has AIDS (prognosis is better without AIDS)

  • Cell type (obtained through biopsy)

  • Cell grade (rate of aggressiveness of spread)

  • Location and size of the tumors (prognosis is better if cells are contained in cerebrum, the largest part of the brain)

  • Spread to cerebrospinal fluid and other parts of the brain and spinal cord

Prognosis without treatment after diagnosis is one to three months. Survival rate is three to four years or more with chemotherapy treatments. Younger patients have a better prognosis and chance of survival than older patients.

Ongoing research for CNS lymphoma

Research is being conducted in all areas of non-Hodgkin’s lymphoma, including CNS lymphoma. Some of the areas that scientists are investigating include:

  • The changes in DNA that may cause the development of lymphoma cells from normal lymphocytes.
  • Genetic mutations that can cause the cancer cells to grow rapidly and not develop into the normal cells of the immune system. Scientists are also studying gene therapy, including agents that prevent cells from becoming malignant and drugs that interfere with proteins that cause cancer.
  • Development of microarrays, which are tests that can detect abnormal genes in a tumor. These tests may also provide information as to how the cancer will respond to chemotherapy treatments.
  • New chemotherapy drugs and combinations of drugs for the most effective treatment. Clinical studies are also examining approaches to reduce resistance to chemotherapy drugs and improve the response rate to treatment.
  • Biological therapy that can help destroy lymphoma cells while minimizing the harm to normal tissues.
  • Immunotherapy that uses immune cells or antibodies to fight the cancer. Studies are examining monoclonal antibodies, which are laboratory-produced proteins that can destroy cancer cells. Some antibodies are being linked to radioactive material while others are added to chemotherapy treatments.
  • The use of vaccines that could inhibit the growth of cancer cells and prevent cancer from recurring. Some vaccines contain antigens from cancer cells and  others contain DNA that targets specific cells.
  • Advances in stem cell transplantation including more precise matching, the use of immunosuppressive drugs in patients and techniques to improve outcomes.

Many of these treatment strategies are available only through clinical trials. The physicians on a patient’s cancer care team can best determine if the individual is a candidate for a clinical trial.

Questions for your doctor about CNS lymphoma

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about CNS lymphoma:

  1. What tests will you use to diagnose CNS lymphoma?
  2. How and when will the tests be conducted?
  3. Will you conduct a biopsy?
  4. When and from whom will I receive the test results?
  5. Where is the lymphoma located in my body?
  6. What is the type and stage of my cancer?
  7. What is the prognosis for my cancer?
  8. What are my treatment options?
  9. What are the risks associated with these treatments?
  10. Am I a candidate for any clinical trials?
  11. How will my condition be monitored during treatment?
  12. What are the chances my cancer will return?
  13. Will my children have a greater risk of developing this cancer?
  14. Are there any genetic tests than can predict their risk of the disease?
  15. Can you refer me to a cancer support group?
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