Paraneoplastic syndrome

PARA NEOPLASTIC SYNDROMES

1. PARANEOPLASTIC SYNDROME Dr.T.Arivazhagan Post Graduate Dept Of Pathology

2. What is Paraneoplastic Syndrome ?

3. Definition A paraneoplastic syndrome is 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 in 10% 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 the Importance ? This may the earliest manifestation of an occult neoplasm They cause significant clinical problems & may even be lethal They may mimic metastatic disease & therefore confound treatment

6. Pathophysiology When tumor arises Body may 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 results from 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

8. Classification 1.Endocrine 2.Neurological 3.Mucocutaneous 4.Hematological

9. Endocrinopathies Most common paraneoplastic syndromes Responsible cancer are not of endocrine origin The secretory activity of such tumors is referred to as ectopic hormone production

10. Endocrinopathies Cushing syndrome SIADH Hypercalcemia Hypoglycemia Polycythemia Hyperaldosteronism Carcinoid syndrome

11. CUSHING SYNDROME

12. Cushing syndrome Most common Endocrinopathy Underlying cancers: Small cell carcinoma of lungs Pancreatic carcinoma Neural tumors Mechanism: excessive production of corticotrophin & corticotrophin like peptides

13. SIADH

14. SIADH Underlying cancers: Small cell carcinoma of lung Intracranial neoplasms Mechanism: Excessive production of antidiuretic hormone Atrial natriuretic hormones

15. HYPERCALCEMIA

16. 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

17. Mechanism: Excessive production of parathyroid hormone And its related proteins Production of TNF, IL-1

18. HYPOGLYCEMIA

19. Hypoglycemia Underlying cancer: Ovarian carcinoma Fibro sarcoma Other mesenchymal sarcomas Mechanism : Excessive production of insulin & insulin like substance

20. POLYCYTHEMIA VERA

21. Polycythemia Underlying carcinoma: Renal carcinoma Cerebellar carcinoma Hepatocellular carcinoma Mechanism: Excessive production of erythropoietin

22. CARCINOID SYNDROME

23. Carcinoid syndrome Bronchial adenoma ( carcinoid type) Pancreatic carcinoma Gastric carcinoma Mechanism: Serotonin Bradykinin

24. CONN’S SYNDROME

25. Hyperaldosteronism Adrenal adenoma Non-Hodgkin's lymphoma Ovarian carcinoma Mechanism: Aldosterone

26. NEUROLOGICAL Peripheral neuropathies Cortical cerebellar degeneration Polymyopathy Myasthenia syndromes Pathogenesis: Poorly understood Some cases antibodies produced by tumor cell cross react with neuronal cell antigens

27. MYASTHENIA SYNDROME

28. Myasthenia Bronchogenic carcinoma Thymic neoplasms Mechanism: Immunological

29. Mucocutaneous Acanthosis nigricans Dermatomyositis

30. Acanthosis nigricans Gray black patches Thickened Hyperkeratotic skin Velvety appearance

31. Underlying cancer: Gastric carcinoma Lung carcinoma Uterine carcinoma Mechanism: Immunological – secretion of epidermal growth factor

32. Dermatomyositis Bronchogenic carcinoma Breast carcinoma • Ovarian cancer Pancreatic cancer Stomach cancer Mechanism: immunological

33. Hematological Venous thrombosis( trousseau phenomenon) DIC Non bacterial thrombotic endocarditis Red cell aplasia

34. Venous Thrombosis Pancreatic carcinoma Bronchogenic carcinoma Mechanism: Tumor products – mucin that activate clotting system

35. DIC Acute promyelocytic leukemia Prostatic carcinoma Mechanism: Tumor products – activate clotting

36. Non bacterial thrombotic endocarditis Advanced mucin secreting adenocarcinoma Fibrinous vegetation's Mechanism: Hypercoagulability

37. Osseous & soft tissue changes Hypertrophic osteoarthropathy Periosteal new bone formation Arthritis of near by joints Clubbing of the fingers Underlying carcinomas: Bronchogenic carcinoma Thymic neoplasms Unknown mechanisms