Paraneoplastic Syndrome

What is Paraneoplastic Syndrome?

Paraneoplastic syndromes are a bunch of symptoms or disorders that occur in response to the various substances released by the tumor (benign or malignant) developed in a patient’s body, often known as neoplasms.

Different cancers found to be associated with paraneoplastic syndrome include leukemia, lymphomas, cancer of breast, liver, lungs, and ovaries as well as various neural, renal and gastric cancers. Often at least, 20% of patients experience Paraneoplastic syndrome like fever, vertigo, dizziness, difficulty in swallowing or body movements, loss of memory or muscle tone etc. However, mostly these symptoms go unnoticed.

Paraneoplastic syndrome represents very complex pathophysiology. When a tumor occurs in the body, the immune cells or the fighter cells of the body produce antibodies against the tumor cells to destroy them. However, sometimes there is miscommunication between these biomolecules because of which antibodies may start killing normal cells of bodies. Apart from this tumor may also produce various hormones, enzymes, proteins, cytokines etc. which may affect the normal metabolic pathways of the body and thus may cause immune suppression or other related disorders. Thus, rare disorders of these kinds caused due to the effect of various biomolecules released from a tumor at a distant location away from the tumor itself may be referred to as a paraneoplastic syndrome.

General Symptoms of Paraneoplastic syndrome

These disorders are generally found in middle-aged or old peoples and the most common symptoms seen are dizziness, vertigo, difficulty in swallowing, difficulty in walking, loss of movements, insomnia, dementia, difficulty in speaking, blurred vision etc. The paraneoplastic syndrome affects multiple organ systems and hence the symptoms may be neurological, endocrine, cardiovascular, cutaneous, hematological or miscellaneous type. Thus, broadly paraneoplastic syndrome symptoms may be described as below:

Skin/Cutaneous syndromes

• Itching is the most common symptom and associated with Hodgkin’s Lymphoma and is caused due to increase in eosinophil.
• Necrosis in the subcutaneous layer is often associated with patients suffering from pancreatic tumor because of the release of various lipases in the bloodstream.

Endocrine syndromes

• Here the normal release of hormones is affected like in case of Cushing’s syndrome where the normal functioning of the pituitary gland is affected. Levels of antidiuretic hormones are increased in patients with small cell lung carcinoma causing altered sodium levels, water retention, and confusion.

Neurologic Syndromes

• Reduced reflexes, loss of sensory nerves and weakness may be caused due to non-functioning of the peripheral nervous system also known as polyneuropathy.
• The loss of muscle strength due to nerve impairment is often seen in patients with Hodgkin’s lymphoma, known as Guillain-Barre syndrome.
• Children suffering from neuroblastoma often complaints with uncontrolled eye-movement and sudden contractions in the arms and legs.
• Extreme weakness in the muscles due to impairment in nerve cells of muscles is known as the Eaton-Lambert syndrome and is accompanied by small cell lung carcinoma patients.

Hematologic syndromes

• Tumors associated with liver, lungs, thymus, and kidney are associated with erythrocytosis syndrome, which often disappears after the removal of the tumor. Erythrocytosis is caused due to increased levels of erythropoietin hormone because of altered metabolism of the hormone.
• A very common paraneoplastic syndrome associated with most of the neoplasms is anemia. Thrombocytopenias, Leukopenia, autoimmune hemolytic anemia, microangiopathic hemolytic anemia are the different types of paraneoplastic syndromes associated with various tumors.

Other Syndromes

• A condition where Inflammation of muscle cells causes soreness and weakness of the muscles is called as Polymyositis. Swelling of the joints and altered shape of fingers and toes is known as hypertrophic osteoarthropathy. These symptoms are often found associated with patients suffering from lung cancer.
• Cancer of the kidneys and liver may cause severe abnormalities in blood cells. They may cause a decrease in the production of red blood cells and on the other hand alter the production of various platelets and white blood cells.

General causes of the Paraneoplastic syndrome

Paraneoplastic syndromes are caused due to secretions of various biological molecules like hormones, antibodies, immune complexes, protein or growth factor etc. which cross-reacts with the normal immune function of the body.  As the symptoms are caused due to the interference of various biomolecules streaming in the blood system, the effects are produced in the remote area (target organ) and not in the vicinity of the tumor.

Many different organ systems are affected by the paraneoplastic syndrome like the nervous and endocrine system, causing a rise in blood pressure, low sugar levels, changes in the nervous system or hormonal changes.

The paraneoplastic syndrome occurs due to the miscommunication in the biomolecules released by the tumor, which causes blocking of the normal functions of hormones, immune cells, enzymes etc. causing immune suppression or miscommunication causing altered function.

For example, Ectopic Cushing’s syndrome is one of the well-known paraneoplastic syndrome associated with patients suffering from Lung Tumors. Abnormal functioning of pituitary glands due to overproduction of adrenocorticotrophic hormone causes Cushing’s syndrome. Thus, in this case, secondary effects are produced in the pituitary gland, whereas the primary organ affected is the lung.

Treatment methods for Paraneoplastic syndrome

As discussed above, the Paraneoplastic syndrome is caused due to autoimmune suppression caused due to the presence of tumor in the body, hence the first efforts are to treat the tumor followed by treatments for autoimmune suppression. Paraneoplastic syndrome symptoms may be the first sign of the presence of tumor in the body and hence shall not be neglected.

Treatment options for paraneoplastic syndrome in general include

1. Treating the underlying cause of syndrome that is the tumor or cancer. Various therapies used are radiation therapy, chemotherapy, surgery or a combination of these therapies.
2. Next is to find out the biomolecule or mediators causing the paraneoplastic syndrome and suppressing their effect. Various therapies may be used to reduce the autoimmune response which includes the use of steroids like cortisone, prednisone etc. Use of irradiation techniques and intravenous immunoglobulin are also very often used techniques to reduce the neurological degeneration.
3. In patients suffering from paraneoplastic syndromes related to the peripheral nervous system often a technique used to cleanse the blood from antibodies is used which is often termed as Plasmapheresis.
4. Very often secondary therapies like speech and physical therapies may be used to regain normal motor functions of the body.

Paraneoplastic syndromes are very often ignored as early symptoms of the tumor, hence rapid diagnosis and effective treatment regime are very important for speedy recovery. When a patient comes with typical paraneoplastic symptoms, with no history of the presence of a tumor, investigation of the possibilities of cancer shall not be neglected.

Medical management for a person with paraneoplastic symptoms should be well managed by a team of Oncologist, Radiologist, Endocrinologist, Neurologist and a surgeon together. It is recommended to consult a specialist who has good experience in treating paraneoplastic syndrome as often the symptoms are misdiagnosed and untreated.

Medical References:

emedicine.medscape.com/article/280744-overview

ninds.nih.gov/Disorders/All-Disorders/Paraneoplastic-Syndromes-Information-Page

msdmanuals.com/professional/hematology-and-oncology/overview-of-cancer/paraneoplastic-syndromes

medicinenet.com/paraneoplastic_syndrome_symptoms_and_signs/symptoms.htm

ninds.nih.gov/Disorders/All-Disorders/Paraneoplastic-Syndromes-Information-Page

en.wikipedia.org/wiki/Paraneoplastic_syndrome

merckmanuals.com/home/cancer/overview-of-cancer/paraneoplastic-syndromes

encyclopedia.com/medicine/diseases-and conditions/pathology/paraneoplastic-syndromes

theoncologist.alphamedpress.org/content/11/3/292.full

rareconnect.org/uploads/documents/treatment-options-for-paraneoplastic-neurological-disorders.pdf

cancernetwork.com/articles/paraneoplastic-syndromes-earliest-sign-some-cancers

ncbi.nlm.nih.gov/pmc/articles/PMC2931619/

library.med.utah.edu/WebPath/NEOHTML/NEOPL068.html