| Paraneoplastic syndrome | |
|---|---|
| Specialty | Oncology |
| Frequency | Rare[1] |
Aparaneoplastic syndrome is asyndrome (a set ofsigns andsymptoms) that is the consequence of atumor in the body (usually acancerous one).[1] It is specifically due to the production of chemical signaling molecules (such ashormones orcytokines) bytumor cells or by animmune response against the tumor.[2] Unlike amass effect, it is not due to the local presence of cancer cells.[3]
Paraneoplastic syndromes are typical among middle-aged to older people, and they most commonly occur with cancers of thelung,breast,ovaries or lymphatic system (alymphoma).[4] Sometimes, the symptoms of paraneoplastic syndromes show before the diagnosis of amalignancy, which has been hypothesized to relate to the disease pathogenesis. In this paradigm, tumor cells express tissue-restricted antigens (e.g., neuronal proteins), triggering an anti-tumor immune response which may be partially or, rarely, completely effective[5] in suppressing tumor growth and symptoms.[6][7] Patients then come to clinical attention when this tumor immune response breaksimmune tolerance and begins to attack the normal tissue expressing that (e.g., neuronal) protein.
The abbreviation PNS is sometimes used for paraneoplastic syndrome, although it is used more often to refer to theperipheral nervous system.
Symptomatic features of paraneoplastic syndrome cultivate in four ways:endocrine,neurological,mucocutaneous, andhematological. The most common presentation is afever (release of endogenouspyrogens often related tolymphokines or tissue pyrogens), but the overall picture will often include several clinical cases observed which may specifically simulate more common benign conditions.[8]
The following diseases manifest by means ofendocrine dysfunction:Cushing syndrome,syndrome of inappropriate antidiuretic hormone,hypercalcemia,hypoglycemia,carcinoid syndrome, andhyperaldosteronism.[8]
The following diseases manifest by means ofneurological dysfunction:Lambert–Eaton myasthenic syndrome,paraneoplastic cerebellar degeneration,encephalomyelitis,limbic encephalitis,brainstemencephalitis,opsoclonus myoclonus ataxia syndrome,anti-NMDA receptor encephalitis, andpolymyositis.[8]
The following diseases manifest by means ofmucocutaneous dysfunction:acanthosis nigricans,dermatomyositis,Leser-Trélat sign,necrolytic migratory erythema,Sweet's syndrome,Florid cutaneous papillomatosis,pyoderma gangrenosum, andacquired generalized hypertrichosis. Mucocutaneous dysfunctions of paraneoplastic syndromes can be seen in cases ofitching (hypereosinophilia), immune system depression (latentvaricella-zoster virus insensory ganglia), pancreatic tumors (leading to adipose nodularnecrosis ofsubcutaneous tissues),flushes (prostaglandin secretions), and even dermicmelanosis (cannot be eliminated via urine and results in grey to black-blueish skin tones).[8]
The following diseases manifest by means ofhematological dysfunction:granulocytosis,polycythemia,Trousseau sign,nonbacterial thrombotic endocarditis, andanemia. Hematological dysfunction of paraneoplastic syndromes can be seen from an increase oferythropoietin (EPO), which may occur in response tohypoxia or ectopic EPO production/alteredcatabolism.Erythrocytosis is common in regions of the liver, kidney, adrenal glands, lung, thymus, and central nervous system (as well asgynecological tumors andmyosarcomas).[8]
The following diseases manifest by means of physiological dysfunction besides the categories above:membranous glomerulonephritis,tumor-induced osteomalacia,Stauffer syndrome,Neoplastic fever, andthymoma-associated multiorgan autoimmunity.Rheumatologic (hypertrophic osteoarthropathy),renal (secondary kidneyamyloidosis and sedimentation of the immunocomplexes innephrons), andgastrointestinal (production of molecules that affect the motility and secretory activity of the digestive tract) dysfunctions, for example, may relate to paraneoplastic syndromes.[8]
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 produceantibodies 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.[9]
Diagnostic testing in a possible paraneoplastic syndrome depends on the symptoms and the suspected underlying cancer.[citation needed]
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.[10]
A specifically devastating form of (neurological) paraneoplastic syndromes is a group of disorders classified asparaneoplastic neurological disorders (PNDs).[24] These PNDs affect the central or peripheral nervous system; some are degenerative,[25] though others (such asLEMS) may improve with treatment of the condition or the tumor. Symptoms of PNDs may includedifficulty with walking and balance,dizziness,rapid uncontrolled eye movements, difficulty swallowing, loss ofmuscle tone, loss of finemotor coordination, slurred speech, memory loss, vision problems, sleep disturbances,dementia,seizures, and sensory loss in the limbs.[citation needed]
The most common cancers associated with PNDs are breast, ovarian, and lung cancers, but many other cancers can produce paraneoplastic symptoms, as well.[citation needed]
The root cause is extremely difficult to identify for paraneoplastic syndrome, as there are so many ways the disease can manifest (which may eventually lead to cancer)[citation needed]. Ideas may relate to age-related diseases (unable to handle environmental or physical stress in combination withgenetic pre-dispositions), accumulation of damaged biomolecules (damages signaling pathways in various regions of the body), increased oxygenfree radicals in the body (alters metabolic processes in various regions of the body), etc.[citation needed].
However,prophylactic efforts include routine checks with physicians (particularly those that specialize in neurology and oncology) especially when a patient notices subtle changes in his or her own body.[citation needed]
Treatment options include:[citation needed]
A specificprognosis for those with paraneoplastic syndromes links to each unique case presented. Thus, prognosis for paraneoplastic syndromes may vary greatly. For example, paraneoplasticpemphigus often included infection as a major cause of death.[26] Paraneoplastic pemphigus is one of the three major subtypes that affectsIgGautoantibodies that are characteristically raised againstdesmoglein 1 anddesmoglein 3 (which are cell-cell adhesion molecules found indesmosomes).[27] Underlying cancer or irreversible system impairment, seen inacute heart failure orkidney failure, may result in death as well.[citation needed]
Prostate cancer is the second most common urological malignancy to be associated with paraneoplastic syndromes afterrenal cell carcinoma. Paraneoplastic syndromes of this nature tend to occur in the setting of late stage and aggressive tumors with poor overall outcomes (endocrine manifestations, neurological entities, dermatological conditions, and other syndromes). A vast majority of prostate cancer cases (over 70%) document paraneoplastic syndrome as a major clinical manifestation of prostate cancer; and (under 20%), the syndrome as an initial sign of disease progression to the castrate-resistant state.[28] Urologist researchers identifyserum markers that are associated with the syndrome in order to specific what type of therapies may work most effectively.[citation needed]
Paraneoplastic neurological syndromes may be relatedimmune checkpoint inhibitors (ICIs), one of the underlying causes in inflammatory central nervous system diseases (CNS). 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 (since the mechanism of ICIs induces adverse effects on the CNS due to augmented immune responses andneurotoxicity).[29] The purpose of this exploration was to shed light on immunotherapies and distinguishing between neurotoxicity andbrain metastasis in the early stages of treatment. In other research, scientists have found that paraneoplastic peripheral nerve disorders (autoantibodies linked tomultifocal motor neuropathy) may provide important clinical manifestations.[30] 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 (DRP5, or CRMP5) are also associated with a variety of paraneoplastic neurological syndromes, including sensorimotor polyneuropathies.[31][32] Patients undergoing immune therapies or tumor removal respond very well to antibodies that targetCASPR2 (to treat nerve hyperexcitability andneuromyotonia).[33][34]
