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Paraneoplastic Syndromes and Lung Cancer

Posted on December 23, 2021
Medically reviewed by
Todd Gersten, M.D.
Article written by
Brooke Dulka, Ph.D.

Paraneoplastic syndromes are rare diseases that people may develop as a side effect of cancerous tumors (neoplasms). 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 diseases that 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, the body begins to attack healthy cells.

Although the causes of paraneoplastic syndromes are similar, the syndromes can cause many types of diseases depending on the parts of the body that are affected. This can include the nervous system (brain, spinal cord, and nerves), endocrine system (hormone system), skin, blood, and joints. People with cancer often experience fever, night sweats, loss of appetite, and weight loss from paraneoplastic syndromes.

Symptoms of Paraneoplastic Syndromes

There are many symptoms of paraneoplastic syndromes. These symptoms can range in severity and can include:

  • Fever
  • Night sweats
  • Weight loss
  • Loss of appetite
  • High blood pressure
  • Dizziness
  • Difficulty with speech
  • Weakness
  • Weight gain
  • Double vision
  • Loss of coordination or sensation
  • Slower reflexes
  • Discoloration of the skin
  • Noncancerous (benign) skin growths
  • Itching
  • Neuropathy (damage to nerves)

How Prevalent Are Paraneoplastic Syndromes?

Paraneoplastic syndromes are thought to develop in about 20 percent of people who have cancer. Middle-aged people who have lung, ovarian, breast, or lymphatic cancer are considered to be most at risk for paraneoplastic syndromes.

However, prevalence rates for individual paraneoplastic syndrome types can be 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 data that is available typically comes from small studies of just one person with the disease.

Paraneoplastic Syndromes in Lung Cancer

Paraneoplastic syndromes may be most common in lung cancer compared to other types of cancer. Paraneoplastic syndromes have been estimated to affect 10 percent of people with lung cancer.

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

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

Paraneoplastic Hormonal Syndromes

The two most common paraneoplastic syndromes associated with lung cancer affect the endocrine (hormone) system.

Humoral hypercalcemia of malignancy (HHM) in squamous cell carcinoma is caused by too much of a hormone called parathyroid hormone-related peptide. Mild cases of HHM can cause no symptoms, but HHM can also cause symptoms across the body, including increased thirst and urination, nausea, muscle weakness, bone pain, and abnormal heart rhythms.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer is a disease in which the body makes too much antidiuretic hormone, which makes the body 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 sugar (or glucose), 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

Three 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 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 a 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 small cell lung cancer 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:

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, inflammation of the long (tubular) 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, 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 and Prognosis 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.

Paraneoplastic syndromes can be treated in many ways. 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

As paraneoplastic syndromes vary from one person to the next, the prognosis (outlook) of these syndromes will also vary. In some cases, symptoms can be easily managed. In other cases, symptoms can be life-threatening.

Paraneoplastic syndromes can make the prognosis of the underlying cancer worse, so it is important to recognize them when they occur. If you are experiencing new or unusual symptoms, talk to your doctor immediately.

Talk With Others Who Understand

MyLungCancerTeam is the social network for people with lung cancer and their loved ones. On MyLungCancerTeam, more than 4,700 members come together to ask questions, give advice, and share their stories with others who understand life with lung cancer.

Do you or a loved one have paraneoplastic syndromes and lung cancer? Share your experience in the comments below, or start a conversation by posting on MyLungCancerTeam.

References
  1. Paraneoplastic Syndromes Information Page — National Institute of Neurological Disorders and Stroke
  2. Prognostic Impact of Paraneoplastic Syndromes in Patients With Small Cell Lung Cancer, Real-World Data — Journal of Clinical Oncology
  3. Paraneoplastic Syndromes of the Nervous System: Symptoms and Causes — Mayo Clinic
  4. Paraneoplastic Syndromes — Merck Manual
  5. Paraneoplastic Syndromes — Cleveland Clinic
  6. Paraneoplastic Syndromes Associated With Lung Cancer — World Journal of Clinical Oncology
  7. Malignancy-Related Hypercalcemia — StatPearls
  8. Syndrome of Inappropriate Antidiuretic Hormone Secretion — StatPearls
  9. Ectopic Cushing’s Syndrome — UCLA Health
  10. Hypoglycemia: Symptoms and Causes — Mayo Clinic
  11. Acromegaly: Symptoms and Causes — Mayo Clinic
  12. Paraneoplastic Encephalomyelitis — StatPearls
  13. Limbic Encephalitis — Genetic and Rare Diseases Information Center
  14. Paraneoplastic Cerebellar Degeneration — StatPearls
  15. Lambert-Eaton Myasthenic Syndrome (LEMS) — Muscular Dystrophy Association
  16. Chronic Intestinal Pseudo-Obstruction — World Journal of Gastroenterology
  17. Polymyositis and Dermatomyositis — Cedars Sinai
  18. Opsoclonus-Myoclonus Syndrom — Genetic and Rare Diseases Information Center
  19. Sensory Neuropathy — Diabetes.co.uk
  20. Acrokeratosis Paraneoplastica (Bazex Syndrome): Report of a Case Associated With Small Cell Lung Carcinoma and Review of the Literature — Journal of Radiology Case Reports
  21. Acanthosis Nigricans, Tripe Palms, and Sign of Leser-Trélat in a Patient With Gastric Adenocarcinoma: Case Report and Literature Review in China — International Journal of Dermatology
  22. Erythema Gyratum Repens: A Rare Paraneoplastic Rash — Western Journal of Emergency Medicine
  23. Leukocytoclastic Vasculitis — StatPearls
  24. Hypertrophic Osteoarthropathy: Clinical and Imaging Features — RadioGraphics
  25. Neutrophilia as Prognostic Biomarker in Locally Advanced Stage III Lung Cancer — PLOS One
  26. Hypereosinophilic Syndrome: Symptoms and Causes — Mayo Clinic
  27. Case Series of Cancer-Associated Retinopathy (CAR) — Cureus
  28. Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment — Mayo Clinic Proceedings
All updates must be accompanied by text or a picture.
Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Brooke Dulka, Ph.D. is a freelance science writer and editor. She received her doctoral training in biological psychology at the University of Tennessee. Learn more about her here.

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