Paraneoplastic syndromes are rare diseases that people may develop as a side effect of neoplasms (cancerous tumors). Paraneoplastic syndromes can occur with many cancers, including lung cancer.

Understanding the connection between paraneoplastic syndromes and lung cancer is important because having a paraneoplastic syndrome can worsen the prognosis (outlook) of the underlying cancer, particularly if the paraneoplastic syndrome is ignored or untreated.

What Are Paraneoplastic Syndromes?

Generally, paraneoplastic syndromes are caused by abnormal immune system responses to neoplasms. These syndromes develop as a result of tumor-related antibodies that cause the immune system to “panic.” Essentially, because of the tumor, a person’s body begins attacking their own healthy cells.

Although the causes of paraneoplastic syndromes are similar, they can each cause many types of diseases depending on the parts of the body they affect. These parts of the body include:

• The nervous system (brain, spinal cord, and nerves)
• The endocrine (hormone) system
• Skin
• Blood
• Joints

People with cancer may experience sleep disturbances, weight loss, and other symptoms from paraneoplastic syndromes.

Symptoms of Paraneoplastic Syndromes

Many symptoms are associated with paraneoplastic syndromes, and they can range in severity:

• Fever
• Night sweats
• Weight loss
• Appetite loss
• High blood pressure
• Dizziness
• Difficulty with speech
• Weakness
• Weight gain
• Double vision
• Loss of coordination or sensation
• Slower reflexes
• Skin discoloration
• Benign (noncancerous) skin growths
• Itching
• Neuropathy (damage to nerves)

How Common Are Paraneoplastic Syndromes?

Paraneoplastic syndromes develop in 8 percent to 20 percent of people who have cancer. Being middle-aged and having lung, ovarian, breast, or lymphatic cancer raises your risk for paraneoplastic syndromes.

However, rates for specific types of paraneoplastic syndromes are much lower. The number of people with each paraneoplastic syndrome is very small. As a result, there is little scientific research available on prevalence rates for each syndrome. In fact, most of the available data come from small case reports of just one person with a paraneoplastic syndrome.

Paraneoplastic Syndromes and Small Cell Lung Cancer

Paraneoplastic syndromes are more common in lung cancer than in other types of cancer. In particular, small cell lung cancer (SCLC) has the highest rates.

Researchers have discovered a long list of paraneoplastic syndromes that have occurred in people with lung cancer. Some types include:

• Hormonal syndromes — Affecting the endocrine (or hormone) system
• Neurological syndromes — Affecting the brain, spinal cord, and nerves
• Dermatological syndromes — Affecting the skin
• Rheumatological syndromes — Affecting the connective tissues and joints
• Hematological syndromes — Affecting the blood
• Ophthalmological syndromes — Affecting the visual system

Paraneoplastic Hormonal Syndromes

The two most common paraneoplastic syndromes associated with lung cancer affect the endocrine system. They’re called humoral hypercalcemia of malignancy (HHM) and syndrome of inappropriate antidiuretic hormone secretion (SIADH).

HHM in squamous cell carcinoma is caused by too much of a hormone called parathyroid hormone-related peptide. Mild cases of HHM don’t always cause symptoms. People may experience bone pain, muscle weakness, and confusion in more severe cases.

A common complication of SCLC, SIADH causes the body to produce too much antidiuretic hormone, which causes the body to retain water. This can lead to symptoms like nausea, dizziness, fatigue, and problems with memory and cognition.

Other paraneoplastic syndromes of the endocrine system associated with lung cancer include:

• Ectopic Cushing’s syndrome — High levels of glucocorticoid hormones, leading to headache, weakness, and body changes such as a prominent stomach with thin arms and legs
• Hypoglycemia — Low blood glucose (sugar), causing a fast heartbeat, anxiety, sweating, and hunger
• Acromegaly — Too much growth hormone, causing enlarged hands and feet, joint and muscle weakness, and facial changes

Paraneoplastic Neurological Syndromes

Around 3 percent to 5 percent of people with small cell lung cancer develop at least one paraneoplastic neurological syndrome. Paraneoplastic neurological syndromes associated with lung cancer include:

• Encephalomyelitis — Inflammation of the brain and/or spinal cord, causing seizures, sensitivity to light and sound, fever, and neck stiffness
• Limbic encephalitis — Inflammation of the brain’s limbic system (amygdala and hippocampus), with symptoms such as personality changes, irritability, depression, seizures, memory loss, confusion, and dementia
• Cerebellar degeneration — Deterioration of the brain region known as the cerebellum, affecting muscle control, speech, and balance
• Lambert-Eaton myasthenic syndrome (LEMS) — Damage to nerve cells, leading to muscle weakness, depressed tendon reflexes, and autonomic changes
• Chronic gastrointestinal pseudo-obstruction — Nervous system problems that cause the gut to not propel food forward without any physical obstructions
• Polymyositis or dermatomyositis — Inflammation of the body’s connective tissues (tendons and ligaments), most commonly associated with SCLC and squamous cell carcinoma
• Opsoclonus-myoclonus — Dysfunction of the nervous system, affecting eye and muscle movements
• Sensory neuropathy — Damage to sensory nerves, causing numbness, a tingling or burning sensation, and a reduced ability to feel temperature or pain

Paraneoplastic Dermatological Syndromes

Dermatologic paraneoplastic syndromes affect the skin. They include:

• Acrokeratosis paraneoplastica (Bazex syndrome) — Marked by hyperpigmentation (darkened patches) of the skin, brittle nails, and skin lesions
• Acanthosis nigricans, tripe palms, and the sign of Leser-Trelat — Trio of symptoms including thickened, hyperpigmented skin; thickened, velvety skin on the palms with distinctive grooves; and the sudden appearance of many seborrhoeic keratoses (tan, brown, or black skin growths that are waxy or raised)
• Erythema gyratum repens — A rare skin condition that causes unusual, wave-like red marks to appear on your skin
• Cutaneous leukocytoclastic vasculitis — Inflammation of the small blood vessels that causes a rash, usually on the lower legs

Paraneoplastic Rheumatological Syndromes

Rheumatological diseases (those involving joints) can also be paraneoplastic syndromes associated with lung cancer. Hypertrophic pulmonary osteoarthropathy, for example, causes clubbing of the fingers and toes (also seen in lung cancer), inflammation of the tubular (long) bones, and arthritis.

Paraneoplastic Hematological Syndromes

Hematological syndromes (those involving blood) associated with lung cancer include:

• Granulocytosis (neutrophilia) — Too many neutrophils, causing dizziness, shortness of breath, and vision or hearing problems
• Hypereosinophilia — Too many white blood cells, specifically eosinophils, causing fatigue, muscle pain, fever, rash, and cough
• Thrombocytosis — Too many platelets in the blood, leading to headaches, weakness, dizziness, and numb hands and feet

Paraneoplastic Ophthalmological Disorders

Other rare paraneoplastic disorders can also affect the eyes or retinal systems.

Treatment of Paraneoplastic Syndromes

The prompt diagnosis of paraneoplastic syndromes is important because paraneoplastic syndromes can affect clinical outcomes related to lung cancer. In fact, people may notice the symptoms of a paraneoplastic syndrome before they notice any symptoms from the underlying cancer. Sometimes, the diagnosis of paraneoplastic syndromes comes after the cancer diagnosis.

There are lots of treatment options for paraneoplastic syndromes. First-line treatments for paraneoplastic syndromes focus on treating the underlying cancer. Paraneoplastic conditions vary depending on the body system affected, so their treatment will also vary.

Because these syndromes are related to inflammation and the autoimmune system, treatment options can include:

• Corticosteroids — Drugs used to reduce inflammation
• Intravenous immunoglobulins — Substances that can boost healthy antibodies
• Immunosuppressants — Drugs used to manage the immune system’s response
• Plasmapheresis — A technique that helps to reduce the amount of antibodies in the blood
• Speech and physical therapy — Therapies that help people speak and move better

Paraneoplastic Syndromes and Lung Cancer Life Expectancy

As paraneoplastic syndromes vary from one person to the next, the prognosis of these syndromes will also vary. In some cases, symptoms can be easily managed. In other cases, symptoms can be life-threatening. Since paraneoplastic syndromes are rare and each case is different, there is no established data on life expectancy for specific types.

The life expectancy for people with lung cancer is slowly but steadily improving. However, paraneoplastic syndromes can worsen the prognosis of the underlying cancer, so it’s important to recognize them when they occur.

If you are experiencing new or unusual symptoms, talk to your doctor immediately. Getting the right diagnosis for paraneoplastic syndromes can help your doctor manage your symptoms better and improve your quality of life.

Talk With Others Who Understand

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