Neoplasia II: Paraneoplastic Syndrome

Paraneoplastic Syndrome Overview

• Defined as diseases or symptoms resulting from cancer, not due to the direct presence of tumor cells.
• Mediated by humoral factors like hormones or cytokines secreted by tumors or an immune response targeting tumors.

Significance of Paraneoplastic Syndrome

• May present as the earliest sign of neoplasm prior to tumor diagnosis.
• Can lead to serious clinical complications and may be life-threatening.
• Might mimic metastatic disease, complicating treatment decisions.

Pathogenesis

• Involves immune system response resulting in cross-reacting antibodies targeting both tumor and normal tissues.
• Tumors can produce active substances (hormones, enzymes, etc.) disrupting normal metabolic pathways, serving as tumor markers.
• Some mechanisms remain idiopathic (unknown cause).

Classification

• Categorized into multiple groups:
  • Endocrine
  • Hematological
  • Neurological
  • Mucocutaneous
  • Others (not specified)

Endocrinopathies

• Most frequent form of paraneoplastic syndromes, arising from tumors not of endocrine origin.
• Characterized by ectopic hormone production; tumors synthesize hormones typically produced in other tissues.

Common Endocrinopathies

• Cushing syndrome: Most prevalent; linked to small cell lung carcinoma, pancreatic carcinoma, neural tumors. Caused by excessive production of corticotrophin.
• SIADH (Syndrome of inappropriate antidiuretic hormone secretion).
• Hypercalcemia: Excess calcium in blood often due to cancer.
• Hypoglycemia, Polycythemia, Hyperaldosteronism, and Carcinoid syndrome also noted.

Neurological Effects

• Includes peripheral neuropathies, subacute cerebellar degeneration, and polymyopathy.
• Mechanisms poorly understood; antibodies against cancer cell antigens may react with nervous system antigens.

Specific Neurological Conditions

• Subacute cerebellar degeneration: Associated with small cell lung cancer, breast cancer, ovarian/uterine cancer, Hodgkin’s lymphoma. Mechanism is immunological.

Mucocutaneous Effects

• Acanthosis Nigricans: Characterized by thickened, darker skin in neck and armpits; linked to gastrointestinal tumors, prostate, breast, or ovarian cancer. Mechanisms involve immunological responses and secretion of epidermal growth factor.

Hematological Manifestations

• Conditions include venous thrombosis, disseminated intravascular coagulation (DIC), polycythemia, anemia, granulocytosis, thrombocytosis, and autoimmune thrombocytopenia.

Venous Thrombosis and DIC

• Mechanisms involve hypercoagulability via abnormal blood composition or increased clotting factors.
• Risk factors include chemotherapy leading to endothelial damage and prolonged immobilization.
• Commonly associated with pancreatic carcinoma and bronchogenic carcinoma for venous thrombosis, while DIC is linked to acute promyelocytic leukemia and prostatic carcinoma.

Polycythemia Vera

• Associated cancers include renal carcinoma, cerebellar carcinoma, and hepatocellular carcinoma.
• Mechanism may involve hypoxia or ectopic production of erythropoietin or similar substances.

Conclusion

• Paraneoplastic syndromes represent a diverse and critical aspect of cancer-related pathophysiology with significant clinical implications. Understanding their mechanisms, classifications, and manifestations is essential for effective diagnosis and treatment.