Paraneoplastic syndrome refers to conditions caused by cancer that are not directly related to the tumor's local presence, affecting approximately 10-15% of cancer patients, predominantly in older individuals. These syndromes can manifest through systemic effects, including hormone production and immune response, potentially serving as early indicators of hidden malignancies. They are categorized into endocrine, neurological, mucocutaneous, and hematological syndromes, with specific mechanisms and underlying cancers associated with each type.

1. PARANEOPLASTIC
SYNDROME

2. What is
Paraneoplastic
Syndrome ?

4. 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

5. •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).

7. What is the Importance ?
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

9. 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

10. • 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

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

13. 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

14. Endocrinopathies
1. Cushing syndrome
2. SIADH
3. Hypercalcemia
4. Hypoglycemia
5. Polycythemia
6. Hyperaldosteronism
7. Carcinoid syndrome

15. CUSHING
SYNDROME

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

18. SIADH

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

22. HYPERCALCEMIA

25. 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

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

28. HYPOGLYCEMIA

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

31. POLYCYTHEMIA VERA

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

34. CARCINOID SYNDROME

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

37. CONN’S SYNDROME

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

40. 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

41. MYASTHENIA
SYNDROME

43. Myasthenia
•Bronchogenic carcinoma
•Thymic neoplasms
Mechanism:
•Immunological

44. Mucocutaneous
1. Acanthosis nigricans
2. Dermatomyositis

45. Acanthosis nigricans
• Gray black patches
• Thickened
• Hyperkeratotic skin
• Velvety appearance

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

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

49. Hematological
1. Venous thrombosis( trousseau phenomenon)
2. DIC
3. Non bacterial thrombotic endocarditis
4. Red cell aplasia

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

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

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

53. 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