Paraneoplastic Syndromes — The Dana Guide


by Jerome B. Posner

March, 2007

sections include: the underlying causetreatment 

Paraneoplastic syndromes are disorders of an organ or tissue caused by a cancer but not due to spread of the cancer to that organ or tissue. The term paraneoplastic comes from the Greek roots para (alongside or near), neo (new), and plastic (being formed or shaped), and thus means “beside a new formation, or cancer.” These syndromes can affect any organ or tissue, including the liver, skin, and muscles, but the nervous system itself is a common site. A paraneoplastic disorder may affect only one part of the nervous system, such as the cerebellum, or multiple areas at once. When more than one part of the nervous system is affected, the disorder is often called encephalomyelitis associated with cancer.

Paraneoplastic syndromes are rare, affecting fewer than 1 percent of patients with cancer. Nevertheless, they are important for several reasons. They usually precede identification of the cancer, so recognizing them may lead to early diagnosis and treatment of that cancer. The presence of a paraneoplastic syndrome may also predict slower growth of the cancer. Sadly, a paraneoplastic syndrome can cause severe neurological disability, incapacitating a person whose cancer is small and curable.

The Underlying Cause

Current evidence suggests that most paraneoplastic syndromes are the result of the way in which our immune systems respond to cancer. According to this hypothesis, the process starts with proteins normally present only in nerve cells. These proteins are also found, for unknown reasons, in some cancers. In nerve cells the proteins are probably essential for growth and maintenance, so they may also be essential for those cancers’ growth. When a person’s immune system senses a tumor growing in the body, it can respond by identifying those cancerous cells and the crucial protein or proteins within them as foreign, or “nonself.” The immune system thus responds with an attack on each protein and all the cells that contain it. The immune attack, if it is vigorous enough, can slow the growth of the tumor, but it also attacks the nerve cells that normally contain the protein(s). As a result, a person can develop severe nervous system problems, such as memory loss, lack of coordination, and weakness. Meanwhile, the growth of the cancer may be slowed so successfully that it becomes small and difficult to detect by conventional means.

The blood of many, but not all, people suffering from paraneoplastic syndromes contains antibodies that the immune system has produced in response to specific proteins. The presence of such antibodies can tell physicians that a person’s neurological disorder is paraneoplastic; it can also indicate the probable site of the cancer that is at the root of the trouble. For example, an antibody called anti-Yo causes paraneoplastic cerebellar degeneration (PCD), which results in severe loss of coordination while walking and moving one’s extremities. Most people with the anti-Yo antibody are also suffering from either breast or ovarian cancer. Another example is the anti-Hu antibody, associated with both encephalomyelitis and small cell cancer of the lung.

As you can see, nervous system problems can arise from a tumor in a seemingly unrelated part of the body, as when testicular cancer causes lapses in memory. Although paraneoplastic syndromes affecting the nervous system can cause a bewildering variety of symptoms, they tend to share certain characteristics that help doctors identify them:

  1. The neurological signs and symptoms usually appear rapidly—within a matter of days, weeks, or a few months. In contrast, degenerative diseases like Parkinson’s and Alzheimer’s develop gradually, over years.
  2. The neurological signs usually precede those of the cancer, which is often extremely small and difficult to detect.
  3. The neurological disorder usually causes severe disability. Many people with cerebellar degeneration become unable to walk. Many people with limbic encephalitis cannot function because they cannot remember ongoing events. While the cancer may still be restricted to one corner of the body, the immune response to that cancer is thorough and systematic.

Certain disorders have a high probability of being caused by a paraneoplastic syndrome. One example is Lambert-Eaton myasthenic syndrome (LEMS), characterized by muscles that are weak and easily fatigued. LEMS is caused by antibodies aimed at the voltage-gated calcium channel (VGCC) antigen, which binds to the junctions between nerves and muscles and prevents the release of acetylcholine, the chemical that causes muscles to contract. In about two thirds of patients who have this problem, the disorder is paraneoplastic, usually caused by small-cell lung cancer. Another example is PCD, a disorder of coordination. People with PCD cannot control fine movements of their extremities or even their tongues, and thus develop slurred speech, inability to walk, and often inability to feed themselves. This disorder can occur in adult life as a degenerative disease unrelated to cancer, but when it develops rapidly, about half of the sufferers will be found to have cancer.

Treatment

The treatment of paraneoplastic syndromes has two components. First, doctors try to remove the source of the antigens—in other words, they treat the cancer. Because the protein causing the immune reaction is in the tumor, treating the tumor sometimes reverses the neurological disease. The second measure doctors can take is to suppress the immune reaction. Various agents and techniques suppress immunity, including administering adrenocorticosteroids (such as cortisone), providing immunoglobulin through an IV, and even taking some of a person’s blood plasma, physically removing the troublesome antibody from it, and putting the plasma back in. These techniques help some people and do not seem to have the unwanted effect of promoting growth of the tumor.

 Unfortunately, most paraneoplastic syndromes do not respond to treatment of either the tumor or the immune system. A person with such a condition may remain substantially disabled even when the tumor that created the problem has been treated effectively. The paraneoplastic syndrome may have brought that cancer to light and allowed early treatment of it, but the neurological problem itself remains, and the person must usually learn to deal with it as a chronic condition.  

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