Paraneoplastic syndrome
A paraneoplastic syndrome is a syndrome that is the consequence of cancer in the body, specifically due to the production of chemical signalling molecules by tumor cells or by an immune response against the tumor. Unlike a mass effect, it is not due to the local presence of cancer cells.
Paraneoplastic syndromes are typical among middle-aged to older patients, and they most commonly present with cancers of the lung, breast, ovaries or lymphatic system. Sometimes, the symptoms of paraneoplastic syndromes show before the diagnosis of a malignancy, which has been hypothesized to relate to the disease pathogenesis. In this paradigm, tumor cells express tissue-restricted antigens, triggering an anti-tumor immune response which may be partially or, rarely, completely effective in suppressing tumor growth and symptoms. Patients then come to clinical attention when this tumor immune response breaks immune tolerance and begins to attack the normal tissue expressing that protein.
The abbreviation PNS is sometimes used for paraneoplastic syndrome, although it is used more often to refer to the peripheral nervous system.
Signs and symptoms
Symptomatic features of paraneoplastic syndrome cultivate in four different ways: endocrine, neurological, mucocutaneous, and hematological. The most common presentation is a fever, but the overall picture will often include several clinical cases observed which may specifically simulate more common benign conditions.Endocrine
The following diseases manifest by means of endocrine dysfunction: Cushing syndrome, syndrome of inappropriate antidiuretic hormone, hypercalcemia, hypoglycemia, carcinoid syndrome, and hyperaldosteronism.Neurological
The following diseases manifest by means of neurological dysfunction: Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration, encephalomyelitis, limbic encephalitis, brainstem encephalitis, opsoclonus myoclonus ataxia syndrome, anti-NMDA receptor encephalitis, and polymyositis.Mucocutaneous
The following diseases manifest by means of mucocutaneous dysfunction: acanthosis nigricans, dermatomyositis, Leser-Trélat sign, necrolytic migratory erythema, Sweet's syndrome, Florid cutaneous papillomatosis, pyoderma gangrenosum, and acquired generalized hypertrichosis. Mucocutaneous dysfunctions of paraneoplastic syndromes can be seen in cases of itching, immune system depression, pancreatic tumors, and even dermic melanosis.Hematological
The following diseases manifest by means of hematological dysfunction: granulocytosis, polycythemia, Trousseau sign, nonbacterial thrombotic endocarditis, and anemia. Hematological dysfunction of paraneoplastic syndromes can be seen from an increase of erythropoietin, which may occur in response to hypoxia or ectopic EPO production/altered catabolism. Erythrocytosis is common in regions of the liver, kidney, adrenal glands, lung, thymus, and central nervous system.Other
The following diseases manifest by means of physiological dysfunction besides the categories above: membranous glomerulonephritis, tumor-induced osteomalacia, Stauffer syndrome, Neoplastic fever, and thymoma-associated multiorgan autoimmunity. Rheumatologic, renal, and gastrointestinal dysfunctions, for example, may relate to paraneoplastic syndromes.Mechanism
The mechanism for a paraneoplastic syndrome varies from case to case. However, pathophysiological outcomes usually arise when a tumor does. Paraneoplastic syndrome often occurs alongside associated cancers as a result of an activated immune system. In this scenario, the body may produce antibodies to fight off the tumor by directly binding and destroying the tumor cell. Paraneoplastic disorders may arise in that antibodies would cross-react with normal tissues and destroy them.Diagnosis
Diagnostic testing in a possible paraneoplastic syndrome depends on the symptoms and the suspected underlying cancer.Diagnosis may be difficult in patients in whom paraneoplastic antibodies cannot be detected. In the absence of these antibodies, other tests that may be helpful include MRI, PET, lumbar puncture and electrophysiology.
Types
A specifically devastating form of paraneoplastic syndromes is a group of disorders classified as paraneoplastic neurological disorders. These PNDs affect the central or peripheral nervous system; some are degenerative, though others may improve with treatment of the condition or the tumor. Symptoms of PNDs may include difficulty with walking and balance, dizziness, rapid uncontrolled eye movements, difficulty swallowing, loss of muscle tone, loss of fine motor coordination, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, and sensory loss in the limbs.The most common cancers associated with PNDs are breast, ovarian, and lung cancers, but many other cancers can produce paraneoplastic symptoms, as well.
The root cause is extremely difficult to identify for paraneoplastic syndrome, as there are so many ways the disease can manifest. Ideas may relate to age-related diseases, accumulation of damaged biomolecules, increased oxygen free radicals in the body, etc.
However, prophylactic efforts include routine checks with physicians especially when a patient notices subtle changes in his or her own body.
Treatment
Treatment options include:- Therapies to eliminate the underlying cancer, such as chemotherapy, radiation and surgery.
- Therapies to reduce or slow neurological degeneration. In this scenario, rapid diagnosis and treatment are critical for the patient to have the best chance of recovery. Since these disorders are relatively rare, few doctors have seen or treated paraneoplastic neurological disorders. Therefore, PND patients should consult with a specialist with experience in diagnosing and treating paraneoplastic neurological disorders.
Research directions
is the second most common urological malignancy to be associated with paraneoplastic syndromes after renal cell carcinoma. Paraneoplastic syndromes of this nature tend to occur in the setting of late stage and aggressive tumors with poor overall outcomes. A vast majority of prostate cancer cases document paraneoplastic syndrome as a major clinical manifestation of prostate cancer; and, the syndrome as an initial sign of disease progression to the castrate-resistant state. Urologist researchers identify serum markers that are associated with the syndrome in order to specific what type of therapies may work most effectively.Paraneoplastic neurological syndromes may be related immune checkpoint inhibitors, one of the underlying causes in inflammatory central nervous system diseases. The central idea around such research pinpoints treatment strategies to combat cancer related outcomes in the clinical arena, specifically ICIs. Research suggests that patients who are treated with ICIs are more susceptible to CNS disease. The purpose of this exploration was to shed light on immunotherapies and distinguishing between neurotoxicity and brain metastasis in the early stages of treatment. In other research, scientists have found that paraneoplastic peripheral nerve disorders may provide important clinical manifestations. This is especially important for patients who experience inflammatory neuropathies since solid tumors are often associated with peripheral nerve disorders. CV2 autoantibodies, which target dihydropyriminase-related protein 5 are also associated with a variety of paraneoplastic neurological syndromes, including sensorimotor polyneuropathies. Patients undergoing immune therapies or tumor removal respond very well to antibodies that target CASPR2.