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Paraneoplastic Syndromes and Small Cell Lung Cancer

Medically reviewed by Adithya Cattamanchi, M.D., Pulmonology — By Daniel Yetman on October 11, 2022Paraneoplastic syndromes are groups of certain signs and symptoms that develop in some people with cancer. The name comes from the word “para” which means “alongside of,” and “neoplasm,” which means tumor. Some paraneoplastic syndromes develop when your immune system overreacts to a tumor and mounts a strong attack against it. This attack can lead to severe autoimmune damage to healthy cells that often exceeds the damage caused by the tumor. Other paraneoplastic syndromes are caused by cancer cells releasing hormones or other substances. Small cell lung cancer (SCLC) makes up about 15% of lung cancers in the United States. It is also one of the two main divisions of lung cancer along with non-small cell lung cancer. SCLC is the type of cancer most associated with the development of paraneoplastic syndromes. Researchers estimate that about 10% of people with SCLC develop a paraneoplastic syndrome. In this article, we take a deeper look at paraneoplastic syndromes and how they relate to SCLC.

What are paraneoplastic syndromes

The term paraneoplastic syndrome has been used since the 1940s to describe groups of signs and symptoms that develop in some people with cancer. These syndromes are estimated to develop in 1-7.4% of people with cancer. They can affect various body systems including your:endocrine systemnervous systemmusculoskeletal systemskin and connective tissueblood and blood cells Many paraneoplastic syndromes are triggered by an abnormal immune response where antibodies or a type of white blood cell called T cells attack and damage healthy cells. Others are caused by the production of hormones and other biologically active substances by cancer cells. Many different types of paraneoplastic syndromes have been identified. Some of the types linked to SCLC include:Syndrome of inappropriate antidiuretic hormone secretion (SIADH): SIADH is characterized by the overproduction of antidiuretic hormone, which causes your body to retain water. Ectopic Cushing syndrome: This occurs when tumor cells cause an overproduction of the hormone cortisol.Humoral hypercalcemia: Humoral hypercalcemia happens when cancer cells cause parathyroid hormone-related molecules to overproduce. This leads to elevated calcium levels in your blood.Acromegaly: Acromegaly is characterized by the abnormal secretion of growth hormone and insulin-like growth factor 1 by cancer cells.Lambert-Eaton myasthenic syndrome: Lambert-Eaton myasthenic syndrome is a rare autoimmune condition that causes miscommunication between your nerves and muscles.Myasthenia gravis: Myasthenia gravis is a condition that causes muscle weakness that worsens after activity and improves with rest.Limbic encephalitis: Limbic encephalitis is when inflammation occurs in the limbic system (a part of your brain) due to an inappropriate immune response.Subacute sensory neuropathy: Subacute sensory neuropathy causes damage to sensory nerves that can lead to symptoms such as burning, tingling, and numbness in your limbs.Paraneoplastic cerebellar degeneration: The syndrome is characterized by the degeneration of a part of your brain called the cerebellum. The cerebellum helps maintain balance and posture.Opsoclonus-myoclonus ataxia: This condition is characterized by abnormal movements of the limbs and eyes, sleep patterns, and language.

What s the connection between paraneoplastic syndromes and small cell lung cancer

SCLC is the type of cancer most often associated with paraneoplastic syndromes. About 10% of people with SCLC develop these syndromes. SCLC develops in neuroendocrine cells. These are cells that release hormones in response to neurological signals. When these cells become cancerous, they can overproduce hormones or other biologically active substances that lead to the development of endocrine paraneoplastic syndromes. The most common endocrine paraneoplastic syndromes in people with SCLC are SIADH and Ectopic Cushing syndrome. SIADH occurs in 7–16% of SCLC cases. Ectopic Cushing syndrome occurs in 1–5% of cases. An estimated 3–5% of people with SCLC also have neurologic syndromes. These syndromes can form when your immune system attacks healthy neurological cells. The most diagnosed type in people with SCLC is Lambert-Eaton myasthenic syndrome. Paraneoplastic syndromes tend to develop in middle-aged or older adults.

What are the symptoms of paraneoplastic syndromes with SCLC

Symptoms vary depending on which syndrome you have. Symptoms of paraneoplastic syndromes can precede (come before) symptoms of cancer. Below we list the potential signs and symptoms of three of the most common paraneoplastic syndromes associated with small cell lung cancer:

SIADH

fallingheadachesnauseafatiguemuscle crampsseizurestremorsdepressionhyponatremia (low blood sodium)

Ectopic Cushing syndrome

muscle weaknessperipheral edemahigh blood pressureweight gainhypokalemia (low blood potassium)elevated adrenocorticotrophic hormone (ACTH) not suppressed with dexamethasone

Lambert-Eaton myasthenic syndrome

progressively worsening leg weaknessdiminished or absent deep tendon reflexesfatiguedry mouthconstipationrespiratory weaknessblurred vision (rarely)double visiondroopy eyelids

How are paraneoplastic syndromes diagnosed

Doctors start the diagnostic process by performing a physical exam and considering your medical history. If they suspect a paraneoplastic syndrome, they may order one or more of the following tests:blood tests, including:complete blood countcomprehensive metabolic paneltests for hormone levelsserum protein electrophoresisother blood or urine tests to look for substances made by the cancer cellsimaging such as CT scans or ultrasounda biopsy

How are paraneoplastic syndromes treated

The first step in treating paraneoplastic syndromes is to treat the underlying cancer. Standard treatment options for SCLC include:chemotherapyradiation therapysurgeryimmunotherapylaser therapyan endoscopic stent placement to reopen airways Treatments to reduce autoimmune damage include:steroids such as cortisone or prednisonehigh dose intravenous immunoglobulinradiation therapy Plasmapheresis may ease symptoms of paraneoplastic syndromes that affect your peripheral nervous system. Other treatments may be used to target specific symptoms. For instance, physical or speech therapy.

Is there any way to prevent paraneoplastic syndromes from developing if you have SCLC

The best way to prevent paraneoplastic syndromes is to take steps to prevent SCLC. The top risk factor for developing SCLC is smoking tobacco. If you currently smoke and are finding it challenging to stop, you can reach out to a doctor for an approach that works best for you. Other ways you may be able to lower your chances of developing SCLC include:avoiding radonlimiting your exposure to other cancer-causing chemicalseating an overall healthy diet

What s the outlook for people with paraneoplastic syndromes

The outlook for someone with paraneoplastic syndromes and SCLC varies based on many factors, like the cancer stage and which syndrome you develop. Many people with SCLC have advanced cancer by the time they receive a diagnosis. According to the American Cancer Society, the 5-year relative survival rate for small cell lung cancer is 7%. If the cancer has spread to distant organs at the time of diagnosis, it drops to 3%. SIADH has been linked to poorer outcomes in people with SCLC. In a 2019 study, researchers found evidence that SCLC with Lambert-Eaton myasthenic syndrome was associated with better outcomes than SCLC alone. The overall 5-year survival rate in the study was 4.4% for people with SCLC and 21% for people with SCLC and Lambert-Eaton myasthenic syndrome. However, the study had a fairly small sample size, so more research is needed.

What is a relative survival rate

A relative survival rate gives you an idea of how long someone with a specific condition may live after their diagnosis compared with someone without the condition. For example, a 5-year relative survival rate of 70% means that someone with that condition is 70% as likely to live for 5 years as someone without the condition. It is important to remember that these figures are estimates. Remember to talk with your doctor about your specific condition.

Takeaway

Paraneoplastic syndromes are a group of syndromes that develop in some people with cancer. Small cell lung cancer is the most common cancer to cause paraneoplastic syndromes. Treating paraneoplastic syndromes starts by treating the underlying cancer which is causing the syndrome. Your doctor or treatment team may also recommend medications to limit autoimmune damage, as well as supportive treatments like physical therapy. The overall outlook for paraneoplastic syndromes varies widely. Last medically reviewed on October 11, 2022

How we vetted this article

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ncbi.nlm.nih.gov/pmc/articles/PMC7656388/Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Current Version Oct 11, 2022 By Daniel Yetman Edited By Willow Banks Medically Reviewed By Adithya Cattamanchi, MD Copy Edited By Jamie Elmer Share this articleMedically reviewed by Adithya Cattamanchi, M.D., Pulmonology — By Daniel Yetman on October 11, 2022

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