Paraneoplastic syndrome (also known as paraneoplastic syndrome) is the occurrence of symptoms that indicate the presence of a cancer in the body. Contrary to the typical symptoms of cancer, paraneoplastic syndromes are not related to the location in which the primary cancer develops. For example, the first symptom of lung cancer may be brain problems, and some types of skin lesions may be caused by gastrointestinal cancer. For this reason, associating symptoms with suspected cancer can be a difficult task. The alertness of doctors to the possibility that the experienced symptoms may be the first harbinger of neoplastic disease is very important for the early diagnosis and initiation of treatment. Find out how paraneoplastic syndromes develop, how they manifest themselves and which cancers are most common.
Paraneoplastic syndrome( paraneoplastic syndrome ) is the appearance of symptoms resulting from the development of a neoplastic disease in the body. However, this definition does not apply to those symptoms that are caused by local tumor growth or metastasis. Hence, the paraneoplastic syndrome is not haemoptysis in lung cancer or jaundice accompanying liver tumors, because these symptoms come directly from the organs affected by the neoplastic disease.
Paraneoplastic syndromes seemingly have nothing to do with cancer. However, it is estimated that they occur in about 8-10% of cancer patients. Their correct diagnosis may be the first sign of cancer suspicion and prompting additional tests. On the other hand, quick diagnosis and implementation of therapy are key to increasing the chances of success in oncological treatment.
How does a paraneoplastic syndrome develop?
Since it is already known that the symptoms of paraneoplastic syndrome arise beyond the location of the primary tumor, the question arises: what is the effect of a tumor in a given organ on other tissues?
At the beginning, it is worth noting that the exact basis of the development of many paraneoplastic syndromes is still unknown. However, two basic mechanisms of these phenomena are suspected.
The first is autoimmune reactions.The body's immune system recognizes a developing cancer and tries to fight it, among other things by producing the appropriate antibodies. Sometimes, however, these antibodies do not attack the cancer cells by mistake, but are directed against the he althy cells of the body. This process is called autoimmunity. When antibodies destroy he althy cells, it can cause a variety of symptoms. Autoantibodies are, among others, the cause of most neurological paraneoplastic syndromes, such as paraneoplastic degeneration of the cerebellum.
The second mechanism of the formation of paraneoplastic syndromes is the direct production of various molecules by the tumor. Cancer cells can produce hormones, proteins, enzymes, and many messenger substances. These molecules, along with the bloodstream, are distributed throughout the body and affect other tissues. For this reason, the effects of their production may be visible even in organs distant from the tumor. This mechanism underlies, for example, hormonal and metabolic paraneoplastic syndromes.
What cancers can be accompanied by paraneoplastic syndromes?
Paraneoplastic syndromes usually accompany specific types of cancer. The neoplasms that may coexist with the paraneoplastic syndrome include:
- lung cancer (especially small cell lung cancer)
- pancreatic cancer
- lymphiaki
- breast cancer
- ovarian cancer
- thyroid cancer
- melanoma
- grasiczak
At this point it is worth mentioning that some sources include general symptoms that can accompany virtually all types of malignant neoplasms. These include:
- weight loss
- chronic fever
- general weakness
- lack of appetite
- prolonged anemia
These symptoms should always be an alarm signal, prompting to undertake additional diagnostic tests.
Diagnostics of paraneoplastic syndromes
Suspicion of a relationship between the patient's symptoms and neoplastic disease requires multidirectional diagnostics. There is no one-size-fits-all scheme for recommended tests, diagnosis always depends on the type of paraneoplastic syndrome and the type of cancer suspected.
In the case of autoimmune paraneoplastic syndromes, specific antibodies that attack he althy cells of the body are searched for. Their concentrations can be determined both in the blood and, for example, in the cerebrospinal fluid (in the case of autoantibodiesdirected against cells of the nervous system)
If there is a specific suspicion of a neoplasm underlying the paraneoplastic syndrome, tests are performed to detect it. These include, for example, chest, abdominal or pelvic tomography, endoscopy of the gastrointestinal tract, and mammography if breast cancer is suspected.
In a situation where we have no suspicions as to the primary tumor, a PET examination is performed, which may reveal its location. Assessment of paraneoplastic skin syndromes may require biopsy and histopathological examination to differentiate them from other dermatological conditions.
The most common forms of paraneoplastic syndromes
Paraneoplastic syndromes cover a large group of diseases - it would be impossible to present each of them in this article. It is worth emphasizing, however, that these syndromes usually appear as disorders belonging to the following groups:
- hormonal and metabolic
- rheumatologic
- skin
- neurological
- hematological
The most common examples of paraneoplastic syndromes are as follows:
- cutaneous paraneoplastic syndromes
actinic keratosis
One example of cutaneous paraneoplastic syndromes is actinic keratosis (from Latinacanthosis nigricans ). In this condition, the skin becomes dark brown or black in color. The lesions most often appear on the face and neck, in skin folds (e.g. groin) and on the skin of the hands. Actinic keratosis may be the first sign of gastrointestinal malignancy or, more rarely, lung cancer. In many cases, this syndrome coexists with non-cancerous diseases, especially in obese patients and patients suffering from hormonal disorders.
dermatomyositis
Dermatomyositis (LatinDematomyositis ) is an inflammatory disease on the border of dermatology and rheumatology, mainly affecting the skin and skeletal muscles. The disease arises from autoimmune reactions. The most important symptoms include weakening of the muscles of the shoulder girdle and hips, as well as erythema on the face and hands. It is estimated that about 15-20% of dermatomyositis cases are associated with cancers of the internal organs.Dermatomyositiscan accompany cancers of the breast, prostate, gastrointestinal tract and lungs.
Leser-Trélat syndrome
We call the Lesler-Trélat syndrome suddenthe appearance of numerous seborrheic warts on the skin. The seborrheic warts themselves are benign lesions and are quite common in humans in singular form. However, their sudden spread, usually on the skin of the trunk, may be the first harbinger of gastrointestinal cancer.
paraneoplastic pemphigus
Pemphigus is another autoimmune skin disease associated with the presence of antibodies against cells in the skin. Painful blisters, erythematous changes and erosions may appear on the entire surface of the skin, as well as on mucous membranes. Paraneoplastic pemphigus is most often associated with neoplasms of the lymphatic system (lymphomas).
- paraneoplastic hormonal syndromes
syndrome of inappropriate vasopressin secretion (SIADH)
The syndrome of inadequate secretion of vasopressin, also known as the SIADH syndrome, is the result of the production of vasopressin by tumor cells. Vasopressin is a hormone that causes the body to retain water and regulates its electrolyte balance. The effect of the overproduction of vasopressin by the tumor is the excessive dilution of body fluids and the reduction of sodium concentration in the blood. Symptoms of SIADH include headache, memory loss, and general weakness. In serious cases, the syndrome can cause coma, swelling of the brain and even lead to death. Vasopressin is often produced by small cell lung cancer cells, although SIADH can also be associated with other cancers.
Cushing's syndrome
Paraneoplastic Cushing's syndrome is associated with elevated levels of one of the adrenal cortical hormones, cortisol. Cancer cells don't usually produce cortisol directly. However, they may be able to stimulate its production by secreting another hormone that stimulates the adrenal glands - ACTH (the so-called adrenocorticotropic hormone). Symptoms of Cushing's syndrome include abdominal obesity, high blood pressure, muscle wasting, diabetes and osteoporosis. Of course, paraneoplasticity is not the only mechanism of Cushing's syndrome - it can also be the result of long-term steroid therapy, adrenal hyperplasia or ACTH-producing pituitary adenoma.
- metabolic paraneoplastic syndromes
hypoglycemia
Hypoglycaemia, i.e. lowering blood glucose, is one of the more serious symptoms of some types of cancer. Severe hypoglycaemia can lead to coma and, in extreme cases, may be life-threatening. Lowering blood glucose levels bycancer usually occurs through a hormonal mechanism, through the production of insulin and similar factors that affect carbohydrate metabolism. Some pancreatic tumors are a common example of insulin-secreting cancers.
hypercalcemia
Paraneoplastic hypercalcemia is too much calcium in the blood. It is one of the most common paraneoplastic syndromes, accompanying e.g. breast cancer, myeloma and lymphomas. It is estimated that hypercalcemia occurs in about 10-15% of cancer patients. This symptom is associated with the secretion by the tumor of hormones modifying the body's calcium balance. The effect of their action is calcium retention in the kidneys and its release from bone tissue, which in turn contributes to an increase in the concentration of this element in the blood. Hypercalcemia has a negative effect on the work of, among others nervous system, muscle cells, digestive system and kidneys.
- rheumatological paraneoplastic syndromes
hypertrophic osteoarthritis
Symptoms of hypertrophic osteoarthritis are joint swelling and pain, periostitis, and thickening of long bones near their ends (most often in the phalanges). This paraneoplastic syndrome is typically associated with lung cancer. However, hypertrophic osteoarthritis can also accompany non-neoplastic diseases (e.g. heart defects) and be a primary genetic disease.
systemic lupus erythematosus
Systemic lupus erythematosus is an autoimmune disease, caused by the production of antibodies against the body's own tissues (the so-called antinuclear antibodies). Lupus is a multi-organ disease that affects, inter alia, joints, muscles, skin, kidneys and blood vessels. In paraneoplastic lupus, the production of antinuclear antibodies is caused by an abnormal reaction of the immune system to the developing cancer. Paraneoplastic lupus may coexist, inter alia, in with neoplasms of the lymphatic system.
- neurological paraneoplastic syndromes
Neurological paraneoplastic syndromes are disorders of the nervous system, most often resulting from the developing neoplastic disease.
Lambert-Eaton myasthenic syndrome
Lambert-Eaton's myasthenic syndrome is the most common paraneoplastic syndrome in the nervous system. This disease is similar to another muscle disease - myasthenia gravis, the main symptom of which is significant muscle weakness. Both disease entities have an immune background, although they are caused by other typesantibodies. Muscle weakness in Lambert-Eaton syndrome mainly affects the lower limbs. It is estimated that the disease coexists with malignant neoplasm (most often lung cancer) in 50% of cases.
paraneoplastic degeneration of the cerebellum
Paraneoplastic degeneration of the cerebellum is an example of a disease in which an inappropriate response of the immune system causes the destruction of normal nerve cells. The resulting damage to the cerebellum may be manifested by loss of motor coordination, difficulty with maintaining balance and speech disorders. The most common cancer that causes paraneoplastic degeneration of the cerebellum is small cell lung cancer.
- haematological paraneoplastic syndromes
Trousseau team
Many malignant tumors can cause changes in the blood clotting system. Most often they lead to hypercoagulability, which can cause serious complications (for example pulmonary embolism). One example of paraneoplastic syndromes associated with excessive blood clotting is Trousseau's syndrome. The disease consists in the formation of clots in superficial veins, on the basis of which the so-called wandering phlebitis. Trousseau's syndrome most often accompanies malignant neoplasms of the gastrointestinal tract (pancreas, stomach) and lungs.
eosinophilia
Eosinophilia, or increased concentration of eosinophils (one type of white blood cell), is in most cases caused by an allergy or parasitic infection. However, an unexplained excess of eosinophils can also be a paraneoplastic syndrome. One of the symptoms of eosinophilia is persistent itching of the skin.
Paraneoplastic syndromes - treatment
Treatment of paraneoplastic syndromes is always combined with treatment of the underlying neoplasm. Once the primary cancer is under control, most paraneoplastic syndromes disappear. The exception is damage to the nervous system, which in many cases is irreversible.
Additionally, autoimmune paraneoplastic syndromes are sometimes treated with agents that suppress the abnormal response of the immune system (the so-called immunosuppressive therapy).
If possible, symptomatic treatment is also used, depending on the type of paraneoplastic syndrome (for example, correcting electrolyte disturbances or various types of ointments for skin lesions).
About the author
Krzysztof BialaziteMedical student at Collegium Medicum in Krakow, slowly entering the world of continuousthe challenges of a doctor's job. She is particularly interested in gynecology and obstetrics, paediatrics and lifestyle medicine. A lover of foreign languages, travel and mountain hiking.
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