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Paraneoplastic Syndrome

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Paraneoplastic Syndrome PARANEOPLASTIC SYNDROME Ingrid Dravecká I.Department of Internal medicine University Hospital, Košice Paraneoplastic syndrome Neoplastic cells can produce a variety of products that can stimulate o Hormonal o Hematologic o Dermatologic o Neurologic responses Paraneoplastic syndrome Disorders that acompany benign or malignant tumors Not directly related to mass effects or invasion Every type of tumor has potential to produce hormones, induce cytokines and immunological responses Paraneoplastic syndrome More common than generally appreciated Occurs in 7-15% of patients with cancer Atypical „clinical manifestation“ of cancer Presenting sign of an unknown neoplasma Precedes the diagnosis of malignancy The first sign of recurence Paraneoplastic syndrome dysfunction is not caused by invasion of neoplasm (i.e. not neoplastic) → paraneoplastic systemic or organic-specific effects cancers such as small cell carcinoma of the lung are more likely to cause paraneoplastic syndromes than others symptoms develop rapidly over days, weeks or months Autoimune hypothesis most paraneoplastic disorders are autoimmunity diseases certain protein antigens are sometime expressed in a cancer generate an immune response tumor cells express „onconeural“ antigens that are identical to molecules normally expressed by neurons antibodies that react with both the tumor and other tissue Hormonal hypothesis synthesis and secretion of peptide proteins (hormons) Treatment to identify the tumor and to treat it effectively stop progressing of symptoms immune supression (plasma exchange, i.v. immunoglobulin) Distribution Endocrine system Cutaneous system Neurological system Haematological system Gastrointestinal system Common and metabolic ENDOCRINE SYSTEM Ectopic production (by neoplastic cells) and expression of hormones Aberrant hormone expression Clinical or biochemical evidence of abnormal endocrine function in the absence of metastatic tumor spread to the respective endocrine gland Defective feedback control Hypercalcemia caused by ectopic production of PTHrP - etiology Common finding in patients with cancer of the lung, head, neck, skin, breast, lymphomas ... Ectopic secretion of parathormon related peptide (PTHrP) Elevated PTH-like activity (functionally similar but immunologically different) Bone metastasis can produce PTHrP o Cellular proliferation and differentiation in other tissues o Local osteolysis Syndrome of a inappropriate antidiuretic hormone secretion (SIADH) hyponatremia with plasma hypoosmolality and innapropriate concentrate urine absent cardial, renal, adrenal and thyroid disorders small cell carcinoma of the lung elevated level of ADH as possible marker of response to therapy Syndrome of a inappropriate antidiuretic hormone secretion (SIADH) Laboratory: hyponatremia (< 120 mmol/l) elevated levels of ADH Clinical manifestation mental status changes, confusion, lethargy, seizures Humoral hypercalcemia of malignancy Clinical manifestation fatigue, mental status change, weakness abdominal pain, constipation nausea, vomiting, anorexia, polyuria ecg: prolongation of PR and QRS intervals, shortening of QT interval, bradycardia Ectopic Cushing´s syndrome (ECS) uncontrolled secretion of ACTH from non-pituitary tissue manifestation of hypercorticolism 12% !!! of all cases of Cushing´s syndrome (50% - lungs tumors) aberrant processing of POMC Ectopic Cushing´s syndrome (ECS) Clinical manifestation ECS secondary to small cell carcinoma rarely shows all the clasic signs of Cushing syndrome proximal myopathy, moon faciei, hypokalemia, hyperglycemia ECS secondary to bronchial carcinoma is presented as hypertension and hypokalemia Ectopic secretion of gonadotropin leydig cell hyperplasia low to normal testosteron excessive estrogen production supression of FSH testicular atrophy gynecomastia Glucagonoma syndrome skin rash impaired glucose tolerance weight loss, anemia GhRH syndrome acromegaly Pseudofeochromocytoma Hypertension, hyperglycemia Hypoglycemia ectopic production of IGF-II Inhib. of glycogenolysis, gluconeogenesis CUTANEOUS PARANEOPLASTIC SYNDROMES Clubbing and hypertrophic osteoarthropathy digital clubbing – broadening and thickening of the distal phalanges of the fingers or toes, convexity of the nails symetrical painfull arthropathy squamous cell and adenocarcinoma of lung Pruritus associated with Hodgkin lymphoma, other lymphomas adenocarcinomas of various organs dissappears with eradication of the tumor and reappears with reccurence of the disease Erythromelalgia recurrent burning pain, redness and warmth of the extremities concomitant Raynaud´s phenomenon myeloproliferative disorders Palmar erythema commonly associated with hyperestrogenic states, liver disease, hyperthyroidism, rheumatoid arthritis 18.5% patients with malignant brain tumors correlation between intensity of the erythema and vascularity of the brain tumor other tumors: lung cancers, Hodgkin´s disease, gastric adenocarcinoma Erythroderma or exfoliative dermatitis diffuse erythema involving at least 90% of the body lymphoproliferative disorders, cancer of cervix, lungs.. skin changes precede the diagnosis of malignancy by several years Necrolytic migratory erythema or glucagonoma syndrome pruritic and painful mucocutaneous eruption presenting with the weight loss, anemia, diabetes lesions fluctuate and migrate on the body surface it is characteristic of glucagon secreting alpha cell pancreatic carcinoma high glucagon levels Raynaud´s syndrome acral ulcerations or digital ischemia, manifesting as blanching and or cyanosis of distal fingers after exposure to cold cancers of all types Dermatomyositis with or without polymyositis 15-30% of malignancies scaly of erythematous eruption affecting photoexposed areas of the face, neck Paraneoplastic pemphigus B-cell lymphoproliferative disorders mucosal erosions and eruptions Acquired ichthyosis lymphoproliferative disorders, solid tumors lower portion of the legs as large, adherent, scaly lesions with pretibial accentuation Acanthosis nigricans common marker for hyperinsulinism and insulin resistance asymptomatic hyperpigmented patches on the neck, axxile, antecubital and popliteal fossae paraneoplastic form: sudden onset, rapid and extensive spread develops concomitantly with malignancy Hypertrichosis lanuginosa acquista sudden appearance of lanugo hair diffusely on the face, trunk and extremities women between 40-70 years NERVOUS SYSTEM variety of central and peripheral nervous system syndromes any cancer has the potential to cause a paraneoplastic syndrome that will affect the nervous system severe nervous system disability spinal fluid often contains an excess of white cells and immunoglobulines NERVOUS SYSTEM Dementia Limbic encephalopathy the progressive change of personality to dementia Cellebelar degeneration NERVOUS SYSTEM Carcinoma associated retinopathy Amyotrophic lateral sclerosis Sensory neuropathy Sensorimotor polyneuropathy Myasthenia gravis autoimmunity disease – antibodies against ACCH receptors muscle weakness, fatigue, double vision, drop of eyelashes, malfunction of eye muscles Dermatomyositis muscle weakness, fatigue, pain – pelvic and arm muscles, joint disability, dysphagi Encephalomyelitis HAEMATOLOGICAL SYSTEM Erythrocytosis increased production of erythropoetine kidney, liver cancer Thrombocytosis IL-6 produced by tumor HAEMATOLOGICAL SYSTEM Phlebothrombosis Trousseau´s syndrome (adenocarcinoma of pancreas + thrombosis) pulmonary embolism Intravascular coagulation release and consuption of procoagulation factors GASTROINTESTINAL SYSTEM Enteropathies Hepatopathies Anorexia, cachexy Thanks for your attention .
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