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Paraneoplastic syndrome
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- 3. Definition •A paraneoplastic syndromeis a disease or symptom that is the consequence of cancer in the body but, not due to the local presence of cancer cells. •These phenomena are mediated by humoral factors (by hormones or cytokines) excreted by tumor cells or by an immune response against the tumor
- 4. •They appear in10% to 15% of patients with cancer. •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 (a lymphoma).
- 5. What is theImportance ? 1. This may the earliest manifestation of an occult neoplasm 2. They cause significant clinical problems & may even be lethal 3. They may mimic metastatic disease & therefore confound treatment
- 6. Pathophysiology When tumor arises Bodymay produce antibodies to fight and destroy the tumor cells Unfortunately the antibodies cross react with the normal tissues Destroy them To produce paraneoplastic syndromes
- 7. • PNS resultsfrom production & release of physiologically active substance from the tumor cells • It may produce hormones , hormones precursors, enzymes, cytokines • Some cancer cells produce proteins that are physiologically expressed in utero in embryonic & fetal cells but not in adult cells • These serves as tumor markers • Ex : CEA, alpha feto protein
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- 10. Endocrinopathies •Most common paraneoplasticsyndromes •Responsible cancer are not of endocrine origin •The secretory activity of such tumors is referred to as ectopic hormone production
- 11. Endocrinopathies 1. Cushing syndrome 2.SIADH 3. Hypercalcemia 4. Hypoglycemia 5. Polycythemia 6. Hyperaldosteronism 7. Carcinoid syndrome
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- 14. Cushing syndrome • Mostcommon Endocrinopathy • Underlying cancers: • Small cell carcinoma of lungs • Pancreatic carcinoma • Neural tumors Mechanism: excessive production of corticotrophin & corticotrophin like peptides
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- 17. SIADH • Underlying cancers: •Small cell carcinoma of lung • Intracranial neoplasms • Mechanism: • Excessive production of antidiuretic hormone • Atrial natriuretic hormones
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- 20. Hypercalcemia • Most common •Symptomatic hypercalcemia more often associated • Osteolysis induced by cancer • Production of calcemic humoral substances • This consider to be paraneoplastic syndrome • Underlying cancer: • Squamous cell carcinoma of lung • Breast carcinoma • Renal carcinoma • Adult T cell leukemia/lymphoma
- 21. •Mechanism: •Excessive production ofparathyroid hormone •And its related proteins •Production of TNF, IL-1
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- 24. Hypoglycemia •Underlying cancer: • Ovariancarcinoma • Fibro sarcoma • Other mesenchymal sarcomas •Mechanism : • Excessive production of insulin & insulin like substance
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- 27. Polycythemia • Underlying carcinoma: •Renal carcinoma • Cerebellar carcinoma • Hepatocellular carcinoma • Mechanism: • Excessive production of erythropoietin
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- 30. Carcinoid syndrome • Bronchialadenoma (carcinoid type) • Pancreatic carcinoma • Gastric carcinoma • Mechanism: • Serotonin • Bradykinin
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- 33. Hyperaldosteronism •Adrenal adenoma •Non-Hodgkin's lymphoma •Ovariancarcinoma •Mechanism: • Aldosterone
- 34. NEUROLOGICAL 1. Peripheral neuropathies 2.Cortical cerebellar degeneration 3. Polymyopathy 4. Myasthenia syndromes Pathogenesis: • Poorly understood • Some cases antibodies produced by tumor cell cross react with neuronal cell antigens
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- 38. Mucocutaneous 1. Acanthosis nigricans 2.Dermatomyositis
- 39. Acanthosis nigricans • Grayblack patches • Thickened • Hyperkeratotic skin • Velvety appearance
- 40. • Underlying cancer: •Gastric carcinoma • Lung carcinoma • Uterine carcinoma • Mechanism: • Immunological – secretion of epidermal growth factor
- 42. Dermatomyositis • Bronchogenic carcinoma •Breast carcinoma • Ovarian cancer • Pancreatic cancer • Stomach cancer • Mechanism: • immunological
- 43. Hematological 1. Venous thrombosis(trousseau phenomenon) 2. DIC 3. Non bacterial thrombotic endocarditis 4. Red cell aplasia
- 44. Venous Thrombosis •Pancreatic carcinoma •Bronchogeniccarcinoma •Mechanism: • Tumor products – mucin that activate clotting system
- 45. DIC •Acute promyelocytic leukemia •Prostaticcarcinoma •Mechanism: •Tumor products – activate clotting
- 46. Non bacterial thromboticendocarditis •Advanced mucin secreting adenocarcinoma •Fibrinous vegetation's •Mechanism: •Hypercoagulability
- 47. Osseous & softtissue changes • Hypertrophic osteoarthropathy • Periosteal new bone formation • Arthritis of near by joints • Clubbing of the fingers • Underlying carcinomas: • Bronchogenic carcinoma • Thymic neoplasms • Unknown mechanisms