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Paraneoplastic Syndromes

by Bruce A. Chabner, MD, Elizabeth Chabner Thompson, MD, MPH

Paraneoplastic (associated with cancer) syndromes occur when a cancer causes unusual symptoms due to substances that circulate in the bloodstream. These substances may be hormones produced by the tumor or antibodies produced by the immune system. They can affect the function of various tissues and organs and cause symptoms at sites distant from the tumor. Paraneoplastic syndromes may affect many different organ systems, including the nervous system and the endocrine (hormone) system, causing such problems as nervous system changes, low blood sugar, diarrhea, or high blood pressure.

About 20% of people with cancer develop a paraneoplastic syndrome. The most common cancers associated with paraneoplastic syndromes include

  • Lung carcinoma (most common)

  • Renal carcinoma

  • Hepatocellular carcinoma

  • Leukemias

  • Lymphomas

  • Breast tumors

  • Ovarian tumors

  • Gastric cancers

  • Pancreatic cancers

General paraneoplastic syndromes

People with cancer often experience fever, night sweats, loss of appetite, and weight loss. The syndromes below are less common.

Skin syndromes

Itching is the most common skin symptom people with cancer have. Flushing is also common. People may develop noncancerous skin growths or shingles.

Neurologic syndromes

Polyneuropathy is a dysfunction of peripheral nerves (nerves outside the brain and spinal cord), resulting in weakness, loss of sensation, and reduced reflexes. Subacute sensory neuropathy is a rare form of polyneuropathy that sometimes develops before the cancer is diagnosed. It causes a disabling loss of sensation and incoordination but little weakness. Guillain-Barré syndrome is another type of nerve dysfunction that causes a general loss of muscle strength. It is more common in people with Hodgkin lymphoma.

Subacute cerebellar degeneration occurs rarely in patients with breast cancer, ovarian cancer, small cell carcinoma of the lung, or other solid tumors. This disorder may be caused by an autoantibody (an antibody that attacks the body's own tissues) that destroys the cerebellum. Symptoms can include unsteadiness in walking, incoordination of the arms and legs, difficulty speaking, dizziness, and double vision. Symptoms may appear before the cancer is detected.

Uncontrollable eye movements (opsoclonus) and quick contractions of the arms and legs (myoclonus) can occur in some children with neuroblastoma.

Subacute motor neuronopathy occurs in some people with Hodgkin and non-Hodgkin lymphoma. The nerve cells of the spinal cord are affected, weakening the arms and legs.

A variety of unusual symptoms may result from antibodies directed against the tumor that also interact with brain tissue to cause a change in mental function, disorientation, vision changes, and muscle weakness.

Eaton-Lambert syndrome occurs in some people with small cell carcinoma of the lung. This syndrome is characterized by extreme muscle weakness caused by lack of proper activation of the muscle by the nerve.

Subacute necrotizing myelopathy is a rare syndrome in which rapid loss of neurons in the spinal cord leads to paralysis.

Endocrine syndromes

Small cell carcinoma of the lung may secrete a substance that stimulates the adrenal gland to produce increased levels of the hormone cortisol , which can cause weakness, weight gain, and high blood pressure (Cushing syndrome). Small cell carcinoma of the lung may also produce antidiuretic hormone, causing water retention, decreased sodium levels, weakness, confusion, and seizures in some people.

Very high calcium levels in the blood (hypercalcemic syndrome) may occur in people with solid tumors or leukemias. Hypercalcemic syndrome can occur when the cancer secretes into the blood a hormone-like substance (similar to parathyroid hormone) that causes release of calcium from bone. High calcium levels may also result if the cancer directly invades bone, thereby releasing calcium into the bloodstream. As a result of the high calcium levels in the blood, the person develops kidney failure and confusion, which can progress to coma and even death if not recognized and treated promptly.

Excessive production of other hormones, usually by pancreatic carcinoid tumors, can cause carcinoid syndrome—flushing, wheezing, diarrhea, and heart valve problems.

Other syndromes

Polymyositis is muscle weakness and soreness resulting from muscle inflammation. When polymyositis is accompanied by skin inflammation, the condition is called dermatomyositis.

Hypertrophic osteoarthropathy can occur in people with lung cancer. This syndrome alters the shape of the fingers and toes and can cause painful swelling of some joints.

People with cancer may develop various abnormalities in blood cells. They may have too few red blood cells (anemia), too many platelets, or too many of some types of white blood cells. Cancers of the kidneys or liver may cause the body to produce too many red blood cells, while others may invade the bone marrow and interfere with the production of blood cells (including red blood cells, white blood cells, and platelets).