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Paraneoplastic Syndrome

Paraneoplastic Syndromes

Paraneoplastic syndrome is a symptom complex resulting from a malignant neoplasm, but not resulting from the local presence of tumor cells.


Presentation

Paraneoplastic syndrome is usually associated with neurological dysfunctioning, endocrine and cutaneous disorders.

The following are the signs and symptoms of the syndrome:

Anemia
  • Three types of paraneoplastic anemias may be described, as follows: Chronic anemia resulting from an anti-erythropoietin factor, reduction in mean red blood cell (RBC) life, and poor iron availability Microangiopathic hemolytic anemia resulting from diffuse[emedicine.medscape.com]
  • The PNS included elevated erythrocyte sedimentation rate (ESR), hypertension, cachexia, anemia, pyrexia, abnormal liver function, hypercalcemia, polycythemia, varicocele and neuromyopathy.[ncbi.nlm.nih.gov]
Dyspnea
  • Review of systems was significant for hemoptysis, dyspnea on exertion and dull achy left anterior chest and shoulder pain. He denied any headaches, double vision or blurred vision.[healio.com]
Diarrhea
  • Refractory diarrhea is a paraneoplastic syndrome of NB and is rare. Patients aged 1-3 years who present with chronic intractable diarrhea should be followed closely.[ncbi.nlm.nih.gov]
  • We report a case of a 9-year-old child with UESL believed to be unresectable at presentation, who experienced life-threatening, refractory long QTc syndrome, Torsades de pointes, fevers of unknown origin, and secretory diarrhea necessitating emergency[ncbi.nlm.nih.gov]
  • Carcinoid tumors produce serotonin degradation products that lead to flushing, diarrhea, and breathing difficulty. Protein-losing enteropathies may result from tumor mass inflammation, particularly with lymphomas.[merckmanuals.com]
  • Carcinoid syndrome: Some lung cancers, as well as some carcinoid tumors of the lung ( neuroendocrine tumors ) secrete peptides such as serotonin that can cause facial flushing and diarrhea.[verywell.com]
  • Patients with NMDA-receptor antibody often present with headache, fever, nausea, vomiting, diarrhea, or upper respiratory tract symptoms.[clinlabnavigator.com]
Dysphagia
  • PATIENT: This 59-year-old man developed ophthalmoplegia, dysarthria, dysphagia, pruritus, ataxia, corticobulbar and corticospinal signs in association with prostate cancer.[ncbi.nlm.nih.gov]
  • In addition, there was a progression to a severe reduction in proximal muscle strength with severe dysphagia. The initial treatment was conducted, and the patient recovered from all symptoms and followed adjuvant cancer management.[ncbi.nlm.nih.gov]
  • About six months, later the patient started having dysphagia, regurgitation and weight loss, and was evaluated by gastroenterology. Barium swallow showed poor motility, poor emptying and distal esophageal narrowing.[healio.com]
  • Pleocytosis (42%) CNS imaging: Normal in 66%; Occasional changes in cortex, brainstem or cauda equina Ma syndromes: Brainstem & Cerebellar disorders Age: 58 to 63 years Clinical: Not uniform Cerebellar: trunk & extremities Brainstem: EOM limitation; Dysphagia[neuromuscular.wustl.edu]
Hypertension
  • Hypertension and hypercalcemia occurring as single PNS, although also correlated with advanced stage, require further investigation. Copyright 2012 S. Karger AG, Basel.[ncbi.nlm.nih.gov]
  • To the Editor: Hyperaldosteronism is the cause of about 0.5 to 2 percent of all cases of hypertension.[nejm.org]
  • Hypertension may result from abnormal epinephrine and norepinephrine secretion (pheochromocytomas) or from cortisol excess (ACTH-secreting tumors).[merckmanuals.com]
  • A 75-year-old man with hypertension, hyperglycemia, and edema. N. Engl. J. Med. 362, 156–166 (2010). 31. Agarwal, N., Hutson, T. E., Vogelzang, N. J. & Sonpavde, G.[doi.org]
Muscle Twitch
  • Myelitis is a term used to describe inflammation of the spinal cord and is characterized by weakness, muscle wasting, and involuntary muscle twitches.[brighamandwomens.org]
  • PTHRP causes hypercalcemia and its associated symptoms (polyuria, dehydration, constipation, muscle weakness); calcitonin causes a fall in the serum calcium level, leading to muscle twitching and cardiac arrhythmias.[merckmanuals.com]
  • Over the course of time, fine muscle twitching can progress to more pronounced abnormal movements and postures of the arms and legs (choreoathetosis). Many patients develop abnormal movements with the face, mouth or tongue (orofacial dyskinesias).[rarediseases.org]
Flexion Contracture
  • Abstract Palmar fasciitis and polyarthritis syndrome (PFPAS) is an uncommon disorder characterized by diffuse inflammation of the palmar fascia, tendon sheaths, and joints of the fingers and wrists, which rapidly progresses to flexion contracture of the[ncbi.nlm.nih.gov]
Flushing
  • Flushing may also occur and is likely related to tumor-generated circulating vasoactive substances (eg, prostaglandins).[merckmanuals.com]
  • .  Symptoms:  Episodes of flushing: hypotension and tachycardia (histamine and bradykinin)  Cutaneous venous teleangiectasia  Secretory diarrhoea (serotonin)  Cardiac valvular lesions (serotonin)  bronchospams 16.[slideshare.net]
  • […] lithic enzymes into the bloodstream, leading to adipose nodular necrosis of subcutaneous tissues; this condition is characterized by painful pink to dark-reddish nodules under the skin; these nodules often ulcerate, causing leakage of an oily material Flushes[emedicine.medscape.com]
Pruritus
  • PATIENT: This 59-year-old man developed ophthalmoplegia, dysarthria, dysphagia, pruritus, ataxia, corticobulbar and corticospinal signs in association with prostate cancer.[ncbi.nlm.nih.gov]
Keratosis
  • Dermatology: Leser Trelat sign  Explosive onset of multiple sebarrhoic keratosis on erythematous skin  Gastro-intestinal adenocarcinoma  breast/ lung/urinary tract cancer  Often associated with acanthosis nigricans 25.[slideshare.net]
Peripheral Neuropathy
  • Abstract POEMS (peripheral neuropathy, organomegaly, endocrinopathy, M protein, skin changes) syndrome is a rare multisystem paraneoplastic disorder.[ncbi.nlm.nih.gov]
  • Guillain-Barré syndrome, another ascending peripheral neuropathy, is a rare finding in the general population and probably more common in patients with Hodgkin lymphoma.[merckmanuals.com]
  • neuropathy Definition / general: Most common paraneoplastic syndrome May be associated with anti-Hu antibody in lung cancer patients Primary lateral sclerosis Definition / general: Rarely caused by breast cancer 50% develop lower motor neuron signs eventually[pathologyoutlines.com]
  • The peripheral neuropathy associated with osteosclerotic myeloma generally resolves when the tumor is treated with radiotherapy.[encyclopedia.com]
  • Polyneuropathy of Paraproteinaemia : Lymphplasmacytic lymphoma is associated with a peripheral neuropathy (sensory, motor or both) in 5-10% of the patients.[allaboutblood.com]
Guillain-Barré Syndrome
  • Guillain-Barré syndrome, another ascending peripheral neuropathy, is a rare finding in the general population and probably more common in patients with Hodgkin lymphoma.[merckmanuals.com]
  • Although the frequency of cancer in patients with Guillain-Barré syndrome is not increased, the association between this neuropathy and HL is well established. 92 Patients with NHL and monoclonal gammopathy can develop typical CIDP or predominantly sensory[bloodjournal.org]
  • Antibodies to LM1 and LM1-containing ganglioside complexes in GuillainBarré syndrome and chronic inflammatory demyelinating polyneuropathy. J. Neuroimmunol. 239, 87–90 (2011). 84. Kuwahara, M. et al.[doi.org]
  • Anti-CTLA-4 antibody-induced GuillainBarré syndrome in a melanoma patient. Ann. Oncol. 22, 991–993 (2011). 33. Liao, B., Shroff, S., Kamiya-Matsuoka, C. & Tummala, S.[doi.org]
Altered Mental Status
  • In contrast, severe, rapidly progressive hypercalcemia can be associated with significant volume depletion and acute renal insufficiency, as well as dramatic neurocognitive symptoms ranging from altered mental status to coma.[doi.org]

Workup

Diagnosis of paraneoplastic syndrome is a difficult affair and is often misdiagnosed. The diagnosis begins with preliminary clinical examination to study the reflexes, mental functioning, muscle tone and its strength, balance, coordination and sensory functioning.

Blood work would be done to analyze the antibodies associated with paraneoplastic syndrome [8]. A lumbar puncture examination to test the cerebrospinal fluid (CSF) for antibodies is carried out.

Several imaging tests such as CT scan, MRI, PET and PET-CT are employed for further diagnosis of the syndrome. Positron emission tomography (PET) scan is a method wherein radioactive elements are injected into the body to generate 3D images. This helps in studying the degree of metabolism of tumor cells and also provides information related to brain abnormalities.

Thrombocytosis
  • Lymphoma may be a cause of secondary thrombocytosis. Renal Paraneoplastic Syndrome About 10% patinets with idiopathic nephrotic syndrome have an underlying maligancy. Most of these patinets have membranoproliferative glomerulonephritis.[allaboutblood.com]
  • […] onset, but in some cases, DIC appears in an acute and severe form, characterized by typical thrombotic and/or hemorrhagic manifestations, and sometimes leading to thrombocytopenia Thrombocytopenia may also be caused by autoantibodies; the causes of thrombocytosis[emedicine.medscape.com]
Erythrocytosis
  • Erythrocytosis is common in cancers of the liver, kidney, adrenal glands, lung, thymus, and CNS as well as in gynecologic tumors and myosarcomas. It always disappears after removal of the primary tumor.[emedicine.medscape.com]
Fasting Hypoglycemia
  • hypoglycemia is one of its possible clinical manifestations.[mattioli1885journals.com]
  • Seen in febrosarcoma, haemangiofibropericytoma, hepatoma)  Diagnosis: fasting hypoglycemia  Plasma insulin/pro-insulin/peptide C during hypoglycemia  Treatment:  Anticancer treatment  Glucose/glucagon  Nocturnal meals 12.[slideshare.net]
Torsades De Pointes
  • We report a case of a 9-year-old child with UESL believed to be unresectable at presentation, who experienced life-threatening, refractory long QTc syndrome, Torsades de pointes, fevers of unknown origin, and secretory diarrhea necessitating emergency[ncbi.nlm.nih.gov]
Hepatocellular Carcinoma
  • Author information 1 Department of General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. dhirajk-ishore@gmail.com Abstract Polymyositis as a paraneoplastic syndrome associated with hepatocellular carcinoma is quite[ncbi.nlm.nih.gov]
  • Pigmented skin lesions, or keratoses, may appear, including acanthosis nigricans (GI cancer), generalized dermic melanosis (lymphoma, melanoma, hepatocellular carcinoma), Bowen disease (lung, GI, GU cancer), and large multiple seborrheic keratoses, ie[merckmanuals.com]

Treatment

The primary goal of treatment consists of managing the tumor cells and suppressing the immune system to stop the abnormal behavior. These objectives are carried out through various methods such as:

  • Surgical procedures along with chemotherapy and radiation therapy to remove the tumor cells and suppress its growth. Surgery is largely dependent on the nature and the location of the malignant cells.
  • Medications like corticosteroids and immunosupressants are employed for treating the condition. Corticosteroids work by reducing the inflammation and immunosupressants suppress the action of the immune system. Based on the type of paraneoplastic syndrome present, other medications are also given to decrease the seizures and enhance the nerve to muscle transmission.
  • Plasmaphersis is conducted to rid the body of the antibodies by replacing the blood plasma.
  • Individuals are also given intravenous immunoglobulin in which healthy antibodies from donors are transferred to the body [9].

In addition to the above mentioned treatment methods, individuals are also subjected to physical and speech therapies to improvise the walking ability and restore muscle control.

Prognosis

Prognosis of paraneoplastic syndrome is usually poor. There are no available treatments and this syndrome has no known cure. The stage at which the condition is diagnosed generally decides the outcome of the disease. Treatment methods employed to treat the cancer can have some positive effect on the condition. The majority of patients suffering from paraneoplastic syndrome succumbs to secondary infections which is the common cause of mortality [5].

Complications

Complications of paraneoplastic syndrome include the following:

Etiology

Paraneoplastic syndrome does not occur as a direct effect of the cancer cells [3]. It occurs due to activation of the immune system that behaves in an abnormal fashion in response to cancer cells and in turn attacks the body’s healthy cells giving rise to associated disease conditions.

A secondary phenomenon that explains the development of paraneoplastic syndrome is that the cancer cells releases cellular components which are physiologically active in nature. These components serve as tumor markers paving way for development of paraneoplastic syndrome.

Epidemiology

Paraneoplastic syndrome is a rare occurrence that commonly affects the adult and the elderly population. Children seldom fall prey to such syndromes. It has been estimated that about 20% of the population with cancer develop paraneoplastic syndrome. However, the exact incidence of this syndrome is not known.

Sex distribution
Age distribution

Pathophysiology

The pathophysiology of paraneoplastic syndrome is a complex one. There are basically two theories defining the onset of such a kind of syndrome. The preliminary one states that the immune system of individuals with cancer behaves in an abnormal fashion and begins attacking the normal cells along with the tumor cells [4]. Such an activity deteriorates the neurological functioning of the brain giving rise to paraneoplastic syndrome.

In yet another theory, researchers explain that the physiologically active components released by the tumor cells can attack the other body organs giving rise to several associated secondary conditions such as sensory neuropathy, neuromyotonia, myasthenia gravis, cerebellar degeneration, stiff–person syndrome and encephalomyelitis to name a few. These syndromes are collectively referred to as paraneoplastic syndrome.

Prevention

So far there are no approaches designed to prevent the development of paraneoplastic syndrome. However, if the condition is diagnosed on time then the onset of complications can be prevented to certain extent. Primary screening tests may be used among patients with strong familial history of breast and colon cancer [10].

Summary

Paraneoplastic syndrome is characterized by abnormal response of the immune system to the presence of malignant tumors. Patients suffering from cancer of the lungs, breast, lymphatic system or the ovaries are known to contract paraneoplastic syndrome.

Such a kind of a syndrome is also termed as paraneoplastic syndrome of the central nervous system because many affected individuals suffer from neurologic disorders [1]. In some instances, paraneoplastic symdrome involves the peripheral nervous system [2].

The signs and symptoms of the syndrome begin to show effect within days or weeks much before the tumor is diagnosed. Middle aged and the geriatric population fall easy prey to paraneoplastic syndrome.

Patient Information

Definition

Paraneoplastic syndrome is a rare group of disorders that develop in patients suffering from cancer. It however does not occur due to the direct effect of cancer but occurs as a result of abnormal behavior of immune system that attacks the body’s healthy cells. It can also occur due to the release of cellular components of the tumor cells that have an adverse effect on other organs of the body.

Cause

Paraneoplastic syndrome occurs in patients suffering from lung, stomach or breast cancer. The exact cause that triggers the development of such a syndrome is not known. However, researchers believe that the faulty behavior of the immune system can cause paraneoplastic syndrome.

Symptoms

Common symptoms of paraneoplastic syndrome include loss of muscle tone, difficulty in walking, speaking and swallowing, loss of fine motor skills, dementia, seizures, sleep problems, vertigo and dizziness. Individuals also suffer from memory loss, vision problems and loss of sensation in the limbs.

Diagnosis

Diagnosis of the syndrome is done by analyzing the clinical signs and symptoms. In addition, blood test and lumbar puncture test is done for detecting the presence of antibodies. Various imaging tests are carried out for detecting the tumor locations and determining the extent of spread of cancer.

Treatment

Primary mode of treatment consists of removal of the tumors from the body. This is followed by medications to suppress the immune response and also to improve the symptoms. Plasma transfer may also be required in some patients. 

References

Article

  1. Bataller L, Dalmau JO. Paraneoplastic disorders of the central nervous system: update on diagnostic criteria and treatment. Semin Neurol. Dec 2004; 24(4):461-71.
  2. Auche M. Des nevrites peripheriques chez les cancereux. Rev Med. 1890; 10:785-807.
  3. Hobbs CB, Miller AL. Review of endocrine syndromes associated with tumours of non-endocrine origin. J Clin Pathol. Mar 1966; 19(2):119-27. 
  4. Pittock SJ, Kryzer TJ, Lennon VA. Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. Nov 2004; 56(5):715-9.
  5. Leger S, Picard D, Ingen-Housz-Oro S, Arnault JP, Aubin F, et al. Prognostic factors of paraneoplastic pemphigus. Arch Dermatol. Oct 2012; 148(10):1165-72.
  6. Hagler KT, Lynch JW Jr. Paraneoplastic manifestations of lymphoma. Clin Lymphoma. Jun 2004; 5(1):29-36.
  7. Rubenstein M, Duvic M. Cutaneous manifestations of Hodgkin's disease. Int J Dermatol. Mar 2006; 45(3):251-6.
  8. Brain R, Norris FH Ed. The remote effects of cancer on the nervous system. New York: Grune & Stratton; 1965.
  9. Buchwald B, Ahangari R, Weishaupt A, et al. Presynaptic effects of immunoglobulin G from patients with Lambert-Eaton myasthenic syndrome: their neutralization by intravenous immunoglobulins. Muscle Nerve. Apr 2005; 31(4):487-94. 
  10. Kawasoe T, Yamamoto Y, Okumura Y, et al. A case report of paraneoplastic neurological syndrome associated with occult breast cancer. Breast Cancer.

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Last updated: 2018-06-21 23:34