Paraneoplastic Syndromes

What is a paraneoplastic syndrome?

A paraneoplastic syndrome is a set of signs and symptoms that can occur when you have cancer. The symptoms develop when a malignant tumor causes changes in your body that aren’t directly caused by the cancer itself. The tumor may secrete a hormone or protein that affects a particular body system. Often with paraneoplastic syndromes, your immune system releases antibodies to destroy the tumor. During this process, the antibodies also damage healthy cells (autoimmune response).

Paraneoplastic syndromes can affect multiple body systems and organs, including your nervous system, endocrine system (hormones), kidneys, bones, joints, skin and blood, etc.

Often, the symptoms of a paraneoplastic syndrome are the first signs of cancer.

Who is affected by paraneoplastic syndromes?

You’re more likely to have a paraneoplastic syndrome if you’re middle-aged or older and you have lung, lymphatic, ovarian or breast cancer. The same factors that increase your cancer risk can increase your chances of developing a paraneoplastic syndrome.

How common are paraneoplastic syndromes?

About 8% to 20% of people with cancer develop paraneoplastic syndromes.

What cancers are associated with paraneoplastic syndromes?

Anyone with a cancerous tumor can develop a paraneoplastic syndrome. The types of cancer most commonly associated with paraneoplastic syndromes are:

• Breast cancer.
• Stomach cancer.
• Leukemia.
• Lymphoma.
• Lung cancer (especially small-cell lung cancer).
• Ovarian cancer.
• Pancreatic cancer.
• Prostate cancer.
• Kidney cancer.
• Testicular cancer.

What causes paraneoplastic syndromes?

Some cancerous tumors secrete substances, like hormones or proteins, that cause certain organs in your body to work atypically. As a result, you may experience symptoms that wouldn’t occur without the tumor. These substances can permanently damage an organ or system without treatment.

Often, paraneoplastic syndromes occur because your body’s immune system mistakenly harms healthy tissue. Your immune system makes a substance called antibodies. Antibodies protect you from disease by identifying and destroying abnormal cells, like cancer cells. Sometimes, the signals get crossed, and antibodies attack healthy cells and tissue instead, causing symptoms associated with a paraneoplastic syndrome.

What are the symptoms of paraneoplastic syndromes?

Symptoms of paraneoplastic syndromes vary depending on the organ systems affected. In more than half of cases (60%), people experience symptoms before receiving a cancer diagnosis. Identifying a paraneoplastic syndrome early can help your healthcare provider diagnose cancer in its early stages when it’s easiest to treat.

Common symptoms of a paraneoplastic syndrome include:

• Fever.
• Loss of appetite and weight.
• Night sweats.

Paraneoplastic syndromes that affect particular organs or body systems may cause system-specific symptoms.

Nervous system

Paraneoplastic syndromes affecting your central nervous system (brain, spinal cord) and your peripheral nervous system (nerves outside of your brain and spinal cord) may cause:

• Dizziness.
• Double vision.
• Speech difficulty.
• Memory loss.
• Seizures.
• Muscle weakness.
• Reduced reflexes, sensation or coordination.
• Loss of feeling in your arms and legs.

Endocrine system

Paraneoplastic syndromes affecting your endocrine system may cause:

• Fatigue.
• High blood pressure.
• Muscle weakness.
• Nausea and vomiting.
• Unexplained weight gain.

Joints, bones and muscles (rheumatologic)

Paraneoplastic syndromes affecting your joints, bones, muscles and connective tissue may cause:

• Arthritis.
• Joint pain, swelling or stiffness.

Skin

Paraneoplastic syndromes affecting your skin may cause:

• Itching.
• Flushing (redness).
• Thickened skin.
• Benign (noncancerous) skin growths.

What are the types of paraneoplastic syndromes?

There are several paraneoplastic syndromes, including those that affect your nervous system, endocrine system, joints, blood, skin, kidneys, etc.

Nervous system paraneoplastic syndromes

Examples include:

• Cerebellar degeneration.
• Dysautonomia.
• Encephalitis.
• Encephalomyelitis.
• Lambert-Eaton myasthenic syndrome (LEMS).
• Myasthenia gravis (MG).
• Myelopathy.
• Neuromyotonia.
• Opsoclonus-myoclonus syndrome.
• Neuropathy (peripheral neuropathy).
• Stiff-person syndrome.

Endocrine system paraneoplastic syndromes

Examples include:

• Cushing’s syndrome.
• Hypercalcemia.
• Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).

Rheumatic paraneoplastic syndromes

Examples include:

• Eosinophilic fasciitis.
• Erythromelalgia.
• Hypertrophic osteoarthropathy.
• Palmar fasciitis.
• Paraneoplastic polyarthritis.

Blood paraneoplastic syndromes

Examples include:

• Paraneoplastic erythrocytosis.
• Paraneoplastic thrombocytosis.

Skin paraneoplastic syndromes

Examples include:

• Acanthosis nigricans.
• Dermatomyositis.
• Leukocytoclastic vasculitis.
• Paraneoplastic pemphigus.
• Sweet syndrome.

Paraneoplastic glomerulonephritis is a paraneoplastic syndrome that affects your kidneys.

How are paraneoplastic syndromes diagnosed?

Your healthcare provider will diagnose paraneoplastic syndromes with a medical history, physical exam and several tests.

• Neurological exam: Paraneoplastic syndromes often affect your nervous system, impacting your brain and muscle function. Your provider may ask you to perform specific tasks to check how your nervous system functions. They’ll want to judge any change in your abilities related to strength, memory and coordination.
• Imaging: Your provider may use imaging tests such as CT scans, MRIs and ultrasounds to look for a tumor that may be causing symptoms.
• Blood tests: Blood tests can reveal suspicious findings that suggest a tumor or that confirm you have antibodies linked to paraneoplastic syndromes. Blood tests can also help your provider rule out other conditions that may be causing your symptoms, like an infection, a hormone disorder or a metabolic disorder.
• Spinal tap: In some instances, your provider may perform a spinal tap (lumbar puncture) to test your cerebrospinal fluid for signs of antibodies attacking healthy cells. During a spinal tap, your provider inserts a needle into your lower back to withdraw a fluid sample. Later, your healthcare provider will test the liquid for antibodies.

How are paraneoplastic syndromes managed or treated?

Your healthcare provider will treat the underlying cancer that’s causing your symptoms. They’ll also work to manage your symptoms to decrease any damage to your body’s organs or systems.

Therapies used to manage paraneoplastic syndromes include:

• Corticosteroids: Medications, such as cortisone or prednisone, that reduce inflammation (swelling).
• Immunosuppression: Drugs that decrease your body’s immune response. The drug therapies your provider prescribes will be tailored to your paraneoplastic syndrome.
• Intravenous immunoglobulin: Treatment that destroys the harmful antibodies causing the syndrome. During the procedure, your provider gives you a shot of healthy antibodies that destroy the harmful ones.
• Plasmapheresis: A procedure that decreases the number of antibodies by removing plasma (liquid) from your blood. The plasma contains the antibodies that damage healthy tissue.
• Physical and speech therapy: Muscle exercises that can help improve functions like speech and movement. You may need this therapy if you have a neurological paraneoplastic syndrome.

What can I expect if I have a paraneoplastic syndrome?

Your prognosis mostly depends on your cancer. In some instances, paraneoplastic syndromes cause mild, temporary symptoms. In others, paraneoplastic syndromes cause severe symptoms that must be managed long-term.

Talk to your healthcare provider about how your stage of cancer and response to treatment will affect your prognosis.

What complications are associated with paraneoplastic syndromes?

You may experience a broad range of complications, some of which are minor and some that may be more serious or even life-threatening without treatment. Your healthcare provider will discuss potential complications and treatment options with you.

When should I call the doctor concerning paraneoplastic syndromes?

Contact your healthcare provider if you notice symptoms of a paraneoplastic syndrome that don’t have a clear cause. If you’re experiencing symptoms and you’ve been treated for cancer within the last five years, it’s a good idea to get re-screened. Re-screening can alert your provider that the cancer has returned.

What questions should I ask my doctor?

Questions to ask your healthcare provider include:

• What’s causing my symptoms?
• How will my paraneoplastic syndrome affect my cancer treatment plan?
• What are my treatment options?
• How will my paraneoplastic syndrome affect my prognosis?
• Will my symptoms improve once I receive cancer treatments?
• How can I manage symptoms in the short-term? In the long-term?

A note from Cleveland Clinic

Cancerous tumors cause unexpected changes in your body, including (sometimes) the symptoms of a paraneoplastic syndrome. There are multiple syndromes, and the symptoms are varied. As a result, it may take time for your healthcare provider to recognize your symptoms as cancer-related. Once they confirm your diagnosis, they can recommend treatments to address your symptoms and, most importantly, treat the underlying tumor causing the problem. Receiving the most effective cancer treatments provides the best outlook for managing a paraneoplastic syndrome.