Paraneoplastic syndrome

What is meant by the term "paraneoplastic syndrome"? Usually, this is the name given to a combination of symptoms and laboratory indicators of oncopathology that are not associated with the development of the original tumor and metastasis.

The syndrome is a non-specific response of the body to the growth of a neoplasm, as well as to the production of bioactive compounds by cancer cells. Paraneoplastic syndrome is characterized by damage to the endocrine system, skin, heart and blood vessels, nerves, muscles, kidneys, digestive system, and hematopoietic organs - separately or in combination with each other.

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Epidemiology

Paraneoplastic syndrome does not occur in all patients with cancer: according to statistics, only about 15% of patients are affected.

In approximately one patient in three, the development of paraneoplastic syndrome is explained by a hormonal imbalance. In other cases, neurological, hematological, or rheumatic disorders have been found.

It is believed that signs of paraneoplastic syndrome in patients with cancer tumors can develop during the course of the disease in approximately 60-65% of cases.

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Causes paraneoplastic syndrome

The main reason for the appearance of paraneoplastic syndrome is considered to be the active state of a cancerous tumor, as well as the formation of the body's response to this active state.

Cancer cells produce bioactive proteins, enzymes, IG, PG, cytokines, hormonal substances, growth factors that affect the functioning of a particular organ or system. The interaction of healthy tissue and tumor tissue leads to the emergence of immune reactions, which, in turn, stimulates the emergence of autoimmune disorders.

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Risk factors

It is generally accepted that any type of cancer can trigger the development of paraneoplastic syndrome. But most often the syndrome appears in the following pathologies:

• in lung cancer;
• in ovarian cancer;
• in breast cancer;
• in testicular cancer;
• in case of malignant lesions of the lymphatic system.

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Pathogenesis

Paraneoplastic syndrome can develop in different ways. A malignant neoplasm can lead to disruption of tissue processes as a result of ectopic release of hormonal factors. For example, a decrease in the calcium level in the blood in oncology occurs due to ectopic release of PTH-related proteins, which differ from PTH, but exhibit the same physiological activity. This can explain increased bone resorption. At the same time, parathyroid proteins contribute to increased growth of the neoplasm and the initiation of the metastasis process. Such a reaction is most characteristic of lung and kidney cancer.

Another variant of paraneoplastic syndrome development may be caused by oncoantigens, which cause the body to respond by producing autoantibodies. Modern medicine has data on more than 400 types of such antigens. The clinical role of most antigens, unfortunately, is unknown.

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Symptoms paraneoplastic syndrome

The first signs of paraneoplastic syndrome in most cases appear within a short time, sometimes over several weeks or months. Symptoms may vary depending on the type of paraneoplastic syndrome and which organ is affected.

The syndrome is characterized primarily by myopathy and arthropathy, together with non-specific signs of the disease.

Types of syndrome	Symptoms
Syndrome with dermatomyositis and polymyositis	Progressive myasthenia, skin rashes.
Myasthenic syndrome	Myasthenia gravis, drooping eyelid, diplopia.
Hypertrophic arthropathy	Painful enlargement of fingers and toes, periostitis, joint pain.
Paracancerous polyarthritis	Asymmetrical arthritis of the joints of the legs.
Amyloidosis syndrome	Weakness in the joints, dermatological purpura, the appearance of subcutaneous nodules, weakness of the heart muscle.
Lupus syndrome	Inflammation of the lungs, pericardium, joints, Raynaud's syndrome.
Sympathetic-dystrophic syndrome	Pain in the arms, trophic disorders, fasciitis, aggressive form of polyarthritis.

• Neurological paraneoplastic syndrome

Neurological (neuromuscular) paraneoplastic syndrome is characterized by damage to the peripheral and central nervous system.

The syndrome may manifest itself by the development of encephalitis, neuroses, dementia. Often the disease occurs against the background of Guillain-Barré syndrome, which is a type of peripheral neuropathy that occurs in patients suffering from Hodgkin's lymphoma. The development of other types of peripheral neuropathies is also possible.

• Paraneoplastic syndrome in lung cancer

In patients with small cell lung cancer, paraneoplastic syndrome is usually accompanied by the development of Cushing's syndrome and water-electrolyte imbalance.

Cushing's syndrome is hypercorticism caused by elevated levels of endogenous or exogenous GC in the blood. The pathology manifests itself in disorders of fat, carbohydrate and protein metabolism, development of immunodeficiency, ecchymosis, myasthenia, disorders of hormonal regulation in the sexual sphere, etc.

• Endocrine paraneoplastic syndromes

Endocrine and metabolic paraneoplastic syndromes are manifested by all sorts of disturbances in hormonal balance and metabolic processes.

In case of thyroid cancer, hypocalcemia may develop, which is characterized by a latent course and excessive neuromuscular excitability.

• Hematological paraneoplastic syndromes

Hematological paraneoplastic syndromes are most frequently detected in patients with malignant tumors. In most cases, we are talking about moderate or mild normochromic anemia. A general blood test can often reveal an elevated ESR, an elevated leukocyte level with a left shift in the leukocyte formula.

In b-cell tumors of lymphoid tissues, paraneoplastic syndrome may occur against the background of hemolytic anemia of autoimmune genesis, and in patients with Hodgkin's lymphoma or melanoma - against the background of agranulocytosis. In blood cancer, thrombocytopenia is observed, and in cancerous lesions of the liver or kidney - erythrocytosis.

Stages

Stages of the malignant process

1. Transformative stage (inductive) – transformation of a healthy cell into a cancerous one.
2. Active stage (promotion stage) – proliferation of degenerated cells.
3. The progressive stage is the period of growth of a malignant neoplasm.
4. The final stage is the outcome of the malignant process.

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Complications and consequences

Neoplastic syndrome itself is a complication of the cancer process, so its only consequence can be an unfavorable outcome - the death of the patient due to impaired function of organs and systems. Most often, death occurs from cardiac or renal failure.

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Diagnostics paraneoplastic syndrome

Patients with suspected paraneoplastic syndrome are first assigned laboratory tests:

• general blood test (anemia, accelerated ESR, leukocytosis, etc.);
• general urine analysis;
• cerebrospinal fluid analysis;

A blood test for tumor markers allows one to determine the presence of a tumor in cases where there are no clinical symptoms of a malignant lesion.

Instrumental diagnostics are performed to determine the location of the original cancerous tumor. As a rule, the results of computer and magnetic resonance imaging are used. In the presence of endocrine pathology caused by hormone-dependent tumors, scintigraphy may be prescribed.

In the presence of cancerous neoplasms of the respiratory or digestive system, biopsy and endoscopy are informative.

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Differential diagnosis

Differential diagnosis is performed with non-paraneoplastic lesions. Sometimes positron emission tomography is used for differentiation.

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Treatment paraneoplastic syndrome

Treatment of paraneoplastic syndrome is, first of all, treatment of the original cancerous tumor. In some cases, additional medications are prescribed that suppress immune processes that serve as an impetus for the development of paraneoplastic syndrome.

Medicines are used as an additional treatment in combination with chemotherapy. Depending on the type of paraneoplastic syndrome, the following groups of drugs may be relevant:

• corticosteroids (prednisolone series);
• immunosuppressant drugs (cyclophosphamide, azathioprine);
• drugs for stimulation of neuromuscular conduction (pyridostigmine, diaminopyridine);
• anticonvulsant drugs (carbamazepine).

	Method of administration and dosage	Side effects	Special instructions
Methylprednisolone	Treatment begins with fundamentally small doses of the drug. Presumably, the dosage may be about 200 mg of the drug per day.	Dryness, atrophy of the skin, osteoporosis, pain in muscles and joints, dyspepsia, suppression of the production of own hormones, irritability, vertigo.	Long-term treatment with the drug is not recommended.

	Method of administration and dosage	Side effects	Special instructions
Cyclophosphamide	The drug can be taken orally, as well as by injection (the route of administration is determined by the doctor). The amount of the drug per course should be from 8 to 14 g.	Anorexia, toxic hepatitis, impaired consciousness, myelosuppression, hemorrhagic cystourethritis, hair loss.	Blood transfusions are required throughout the course of treatment.

	Method of administration and dosage	Side effects	Special instructions
Azathioprine	The standard dose is 1.5-2 mg per kilogram of weight per day, in three doses. The duration of therapy is determined individually.	Myelodepression, pancreatitis, hemolytic anemia.	During treatment, it is necessary to regularly monitor the blood picture.

	Method of administration and dosage	Side effects	Special instructions
Pyridostigmine	The drug is prescribed individually. The average daily dose is 30-60 mg, in three or four doses.	Increased sweating, salivation, lacrimation, frequent urination, bradycardia, decreased blood pressure.	The drug is not prescribed for problems with the respiratory system.

	Method of administration and dosage	Side effects	Special instructions
Carbamazepine	Taken orally, 100 to 400 mg 1-2 times a day.	Drowsiness, fatigue, depressive states, dermatitis, dyspepsia, allergies.	The drug is clinically incompatible with alcohol.

Along with drug treatment and chemotherapy, it is recommended to take vitamins, which also have an anti-cancer effect to varying degrees:

• Vitamin A is considered an antioxidant and has a reparative effect on cancer cells;
• B vitamins are responsible for metabolic processes in the body and also normalize the function of the central and peripheral nervous system;
• Vitamin C reduces the severity of side effects from chemotherapy and also protects cells and tissues from the negative effects of free radicals;
• Vitamin D restores calcium metabolism and stimulates cellular differentiation processes;
• Vitamin E has high antioxidant activity, which allows it to be taken to prevent the recurrence of tumors.

Physiotherapy treatment

After consultation with an oncologist, the following physiotherapy procedures are allowed for paraneoplastic syndrome:

• dosed UV radiation;
• DDT;
• SMT;
• electrosleep;
• muscle electrical stimulation;
• ultrasound;
• electrophoresis;
• hydrotherapy;
• magnetic therapy;
• mineral waters.

It is contraindicated to use thermal effects, high-frequency procedures and massage directly on the area where the neoplasm is located.

Folk remedies

• For paraneoplastic syndrome, it is recommended to take propolis orally, 2 g daily, with food (for breakfast, lunch and dinner). The course of treatment is 45 days.
• A good effect is expected from taking propolis in combination with honey. Thus, it is recommended to take 15 drops of propolis tincture and 1 teaspoon of honey before meals twice a day. The course of therapy is three months. After a month's break, the course can be repeated. The proposed treatment can be long-term, up to 3 years.
• It is useful to use a mixture based on badger fat: to prepare the medicine, take 500 ml of aloe juice, cognac, liquid honey and badger fat. Take 1 tbsp. in the morning, half an hour before lunch and before dinner.
• You can also use the following folk medicine recipe: chop freshly picked cherry leaves, place 4 tbsp. of such leaves in 0.5 l of boiling milk, boil for 5 minutes, cover with a lid. After 1 hour, filter the infusion and take ½ cup three times a day for a month. If necessary, the course can be repeated.

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Herbal treatment

• Prepare a mixture of 100 g sage, 70 g yarrow, 70 g anise seeds, 100 g betony. Place three tablespoons of the mixture in a thermos and pour 750 ml boiling water (overnight). In the morning, filter the infusion and drink 150 ml 4 times a day 20-30 minutes before meals.
• Prepare a mixture based on equal parts of plantain leaves, sage, calamus, elecampane and licorice. At night, steam 2 tbsp of the mixture in a thermos per 0.5 l of boiling water. In the morning, filter the infusion and take 100-150 ml 4 times a day, half an hour before meals.
• Pour 4 tbsp. of chamomile flowers into 250 ml of boiling water, leave for 20 minutes. Drink 150 ml daily at least 4-5 times a day.
• Take hemlock tincture three times a day, 2 drops per 1 tablespoon of water.

Homeopathy

Homeopathic treatment for paraneoplastic syndrome is prescribed in combination with the main treatment and has a number of advantages:

• helps reduce the severity of side effects from chemotherapy and radiation;
• slows down the growth of neoplasms;
• improves the quality of life and prolongs it;
• prevents metastasis and tumor recurrence;
• does not have its own side effects.

Homeopathic medicines are prescribed strictly individually, since their dosage directly depends on the stage and severity of the cancer process, on the localization and duration of the paraneoplastic syndrome.

• Aloe - used for cancer in the intestines and rectum.
• Aurum muriaticum is used for cancer of the mucous membranes.
• Barita carbonica is prescribed for cancerous brain tumors.
• Hekla lava is used to alleviate the condition of patients with cancerous lesions of the skeletal system.
• Hydrastis is prescribed for malignant processes in the digestive system.
• Lachesis is recommended for use in malignant processes in the reproductive system (ovarian and uterine cancer).
• Lilium tigrinum is used for oncopathology of the genital area.

Prevention

The only possible prevention of paraneoplastic syndrome is timely and high-quality treatment of the initial cancer process. The earlier the treatment is prescribed, the more favorable the prognosis of the disease will be.

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Forecast

Paraneoplastic syndrome can manifest itself in different ways and affect fundamentally different organs and organ systems. Therefore, the prognosis can be different and depend on both the degree of neglect of the cancerous tumor (its stage) and the type of paraneoplastic syndrome. For example, the development of DIC syndrome (disseminated intravascular coagulation syndrome) indicates the onset of irreversible processes in the body, and the development of hypertrophic arthropathy deserves a relatively favorable prognosis.

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