What is Paraneoplastic Syndromes?
Paraneoplastic syndromes are rare disorders that are triggered by a hidden cancer that changes the immune system. Simply put, cancerous cells don’t directly produce symptoms indicating cancer has spread. Instead, these cells produce substances like autoantibodies (proteins that our bodies incorrectly view as harmful), cytokines (small proteins important for cell signaling), hormones, or peptides (small proteins) that affect various parts of the body including the nervous system, skin, gut, glands, blood, and heart.
These symptoms might show up before or after the diagnosis of the cancer itself. As a result, it’s vital that doctors recognize these syndromes quickly to find and diagnose the hidden cancer and enhance the patient’s health outcomes.
What Causes Paraneoplastic Syndromes?
Paraneoplastic syndromes are medical conditions that occur as a result of a hidden or unidentified cancer, but the exact process of how this happens is still not fully understood. These syndromes commonly show up in patients who have lung cancer, breast cancer, blood cancers, a type of thyroid cancer called medullary thyroid cancer, cancers of the female reproductive system, and prostate cancer.
Risk Factors and Frequency for Paraneoplastic Syndromes
Paraneoplastic syndrome is a rare condition and we don’t know exactly how often it occurs. It can happen in people with any type of cancer, and research indicates it might affect up to 8% of cancer patients. The most common signs of this syndrome are neurological symptoms, such as nerve disorders. Both men and women are equally likely to be affected by this condition.
Signs and Symptoms of Paraneoplastic Syndromes
Paraneoplastic syndromes are conditions caused by a hidden cancer that affect various organs and functions in the body. They come with a complex mix of symptoms. These symptoms are classified based on the system of the body they affect.
Neurological Paraneoplastic syndromes:
- When the central nervous system is involved, patients may have cognitive dysfunction, depression, personality changes, seizures, sleepiness, and sometimes hormonal dysfunction, among other symptoms.
- If the neuromuscular junction is affected, a patient might experience muscle weakness and breathing difficulties.
- When the peripheral nervous system is involved, symptoms can include dry mouth and eyes, bladder or bowel dysfunction, orthostatic hypotension, paresthesias, neuropathic pain, and decreased sensation.
Endocrine Paraneoplastic syndromes:
- Patients can develop a spectrum of conditions from mild symptoms to severe ones due to secretions from cancer cells.
Rheumatological Paraneoplastic syndromes:
- Among symptoms are migratory non-erosive, asymmetric polyarthritis, pain and stiffness in the shoulder girdle, neck, and hip girdle, papules, nodules, and destructive polyarthritis.
Hematological Paraneoplastic syndromes:
- Patients may be fatigued or have difficulty breathing, and blood tests may show different abnormal conditions related to the blood cells.
Dermatological Paraneoplastic syndromes:
- Patients may develop a range of skin symptoms such as thickened hyperpigmented skin, blistering and erosion of the trunk, palms, and soles, painful, erythematous plaques, and other conditions.
Renal Paraneoplastic syndromes:
- Patients may experience electrolyte imbalances or kidney diseases due to hormones produced by cancer cells
There are also widespread symptoms that may occur, such as fever, extreme weight loss and muscle weakness, loss of appetite, and an unpleasant taste sensation.
Testing for Paraneoplastic Syndromes
Paraneoplastic syndrome is a condition that is linked to cancer, although it is not caused by the cancer itself. Instead, it’s a reaction your body has to the presence of cancer. This syndrome often involves complications that affect the nervous system. When this condition is suspected, doctors often need to rule out other possible causes first, given its typically vague symptoms.
If your doctor suspects paraneoplastic syndrome, they may use a mix of laboratory tests, imaging scans, studies of nerve function (electrodiagnostic studies), and possibly a tissue sample (biopsy) to confirm the diagnosis. These might include:
- A complete blood count: This is a type of blood test that measures the numbers of different cells in your blood.
- A comprehensive metabolic panel: This blood test provides information about your body’s chemical balance and metabolism.
- A urinalysis: This urine test can detect a variety of disorders, such as diabetes or kidney disease.
- Tumor markers: These are substances found at higher than normal levels in the blood, urine, or body tissues of some people with certain types of cancer.
- Hormone tests: These measure levels of certain hormones that could be produced by a tumor.
- Cerebrospinal fluid analysis: This test looks at the fluid that surrounds your brain and spinal cord to check for signs of disease.
- A protein electrophoresis: This is a test of the blood and cerebrospinal fluid that can help detect certain diseases.
- Assay of paraneoplastic antibodies: These are special proteins in the blood and cerebrospinal fluid that are associated with certain cancers.
- Skin biopsy: A procedure in which a small sample of skin is removed for testing.
- Muscle biopsy: This test looks for abnormalities in muscle tissue. It can be useful when a type of skin inflammation related to cancer, called dermatomyositis, is suspected.
Experts in neurology have come up with criteria to categorize paraneoplastic syndromes based on symptoms suggesting disease of the nervous system, the presence of antibodies linked to these syndromes, and the timing of cancer diagnosis. They’ve defined several classical syndromes, including, among others, encephalomyelitis, limbic encephalitis, subacute cerebellar degeneration, and dermatomyositis.
Based on these criteria, cases are split into:
- Definite Paraneoplastic Syndrome: Where a classical neurological condition is present along with confirmed paraneoplastic antibodies. In such cases, an undiagnosed cancer is likely to be detected within five years.
- Possible Paraneoplastic Syndrome: Cases where a classical neurological condition is present but there are no paraneoplastic antibodies or cancer, where an antibody not fully understood is present without a confirmed cancer, or where a non-traditional syndrome is present but cancer is diagnosed within two years.
Remember, paraneoplastic syndrome can be a complex disease, but it is manageable when detected and treated correctly. This is why the information provided by these tests is so important.
Treatment Options for Paraneoplastic Syndromes
Paraneoplastic syndrome management depends on the type, severity, and location of the syndrome. If we find a hidden cancer causing the syndrome, we treat this first with chemotherapy, radiation, or surgery when possible. The syndrome is an autoimmune process; in other words, it’s an incorrect response from the body’s immunity system, normally designed to protect against diseases, but it attacks its own cells in this case. Hence, treatments that suppress the immune system might help. These include high-dose corticosteroids (a type of anti-inflammatory medication), intravenous (directly into the vein) immunoglobulins (proteins used by your immune system to fight infections), plasma exchange, or plasmapheresis (a process that filters the blood to remove harmful antibodies).
If a patient with a paraneoplastic syndrome also has tumor-related high calcium levels (above 14mg/dl or 3.5mmol/L), we need to treat this aggressively with intravenous fluids. But if they are taking in too much fluid (a condition we call fluid overload), a medication called Lasix might be considered. If the calcium levels don’t decrease, we might use intravenous calcitonin (a hormone that regulates calcium levels) alongside Bisphosphonates (a group of drugs that prevent loss of bone mass). Although calcitonin can lower the calcium levels quickly, there’s a risk of developing quick resistance to the drug, a condition known as tachyphylaxis. Bisphosphonates will help but might take 1 to 2 days to lower the calcium levels.
What else can Paraneoplastic Syndromes be?
In managing different medical conditions, healthcare professionals often need to consider and rule out various possibilities. Let’s take a look at examples of what a doctor might need to consider when dealing with various conditions:
- For toxic-metabolic encephalopathy, the doctor must rule out underlying infections and any abnormalities in electrolytes (substances in our blood that could affect our body functions).
- In cases of infectious encephalitis, they need to rule out any bacterial, viral, or fungal causes.
- Personality disorders may be associated with underlying depression.
- Myelitis necessitates ruling out infectious or inflammatory causes to determine the real problem.
- In bone marrow failure, ruling out other causes may require performing a bone marrow biopsy, a procedure that involves extracting a small amount of bone marrow tissue for studying.
- Patients suffering from chronic fatigue syndrome may present with non-specific symptoms, necessitating careful monitoring and regular check-ups.
- Mixed connective tissue disorder may include checks for specific antibodies (anti-ribonucleic acid Ab or anti-RNP), considering that these patients may also have co-existing rheumatological disorders like systemic lupus erythematosus, scleroderma, and polymyositis.
- In non-tumor-related dermatomyositis, doctors should look for specific antibodies. These patients may have anti-Jo-1 and anti-Mi-2 antibodies. These doctors must also check for ovarian, breast, and gastrointestinal cancers.
- Polymyalgia rheumatica is commonly seen in elderly patients and involves the shoulder area. These patients have elevated ESR (a blood test that can indicate inflammation in the body) and could respond well to low-dose steroids.
- For patients with nephrotic syndrome, healthcare professionals must rule out all other potential causes.
What to expect with Paraneoplastic Syndromes
Paraneoplastic syndromes, a group of conditions that occur as a reaction to cancer in the body, can show a wide range of symptoms, which means that their effects and outcome can differ greatly from person to person. In some cases, these conditions may go away on their own or with the primary treatment of cancer, as it happens with paraneoplastic hypertrophic osteoarthropathy, which is a rare condition causing bone and joint changes.
In a particular study, the mortality rate for inpatients within 30 days of those who had paraneoplastic hypercalcemia, a condition where there is too much calcium in the blood, was found to be around 50%. People with paraneoplastic thrombocytosis, a condition that leads to a high platelet count and is often a sign of cancer, are typically diagnosed at a severe stage of cancer and have the most serious outcome.
Death in these cases can occur due to the advancement of the underlying cancer, complications arising from the treatments of cancer, or a severe impairment of the body systems that can’t be reversed. This irreversible impairment often involves acute respiratory failure (a condition where there is not enough oxygen in your blood), heart failure, or kidney failure.
Possible Complications When Diagnosed with Paraneoplastic Syndromes
Paraneoplastic disorders can affect various parts of your body and can lead to complications in the endocrine, neurologic, skin, rheumatic, and blood systems. If a patient’s symptoms are severe and they do not respond well to traditional treatments, it’s likely they’re experiencing complications from this disorder.
At the onset of this condition, you might see these complications show up in lab tests:
- Endocrine:
- Severe low salt levels in the blood (less than 125 meq/l)
- High levels of calcium in the blood; between 12 and 14 mg/dl
- Severe low blood sugar which may be as low as 20mg/dl
- Hematologic (related to blood):
- An increase in platelets (numbers more than 400 X 10/L)
- A decrease in the number of red blood cells (hematocrit less than 20)
- An increase in granulocytes (neutrophil count greater than 8 X 10/L)
- Elevated eosinophils (more than 0.5 X 10/L)
It’s also important to be aware of complications from treatment. Paraneoplastic syndromes are mostly treated with medications that help modulate the immune system. Despite that, the primary treatment is to tackle the root cause – the cancer – through chemotherapy and radiation. Therefore, patients may experience high rates of complications relating to treatment, putting them at greater risk for toxicity in the liver, kidneys, heart, and lungs.
Preventing Paraneoplastic Syndromes
For patients experiencing paraneoplastic syndromes, where your body’s immune response to a cancerous tumor affects other parts of your body, it’s crucial to understand the journey that this disease will take. The high risks of certain treatment-related issues, which may make your condition worse or may even become life-threatening, should be transparently discussed with you and your family members.
People with this condition often have advanced-stage cancer, meaning the cancer has spread significantly, and their life expectancy might be limited. Since the health status is severe, it’s important for you and your close members to have early conversations with your medical team about your treatment goals. By doing so, the care provided aligns better with your individual desires and expectations for your treatment journey.
