Paraneoplastic syndromes

Background

• Syndrome associated with cancer, but not due to direct, local effects of neoplasm
• Result of hormones/substances secreted by malignant cells or immune response to cancer cells/products

Examples

Syndrome	Main causal cancers	Mechanism
Cushing syndrome	Small cell lung cancer, pancreatic carcinoma, neural tumors, thymoma	Ectopic ACTH/ACTH-like substance production
SIADH	Small cell lung cancer, CNS malignancies	Ectopic ADH production
Hypercalcemia	Lung (esp. SCC), breast, renal/bladder, ovarian, multiple myeloma, adult T cell leukemia/lymphoma, squamous cell carcinoma
Hypoglycemia	Sarcomas, insulinoma, hepatocellular carcinoma	Insulin/IGF production
Carcinoid syndrome	Bronchial adenoma, pancreatic and gastric carcinoma	Serotonin or bradykinin production
Hyperaldosteronism	Adrenal adenoma, non-Hodgkin's lymphoma, ovarian carcinoma, lung cancer	increased/ectopic aldosterone production
Lambert-Eaton myasthenic syndrome	Small cell lung cancer	Immune-mediated
Paraneoplastic cerebellar degeneration	Lung, ovarian, breast cancers, Hodgkin's lymphoma
Opsoclonus myoclonus syndrome	Neuroblastoma (occurs in 2-3% of peds cases), breast, ovarian, small-cell carcinoma	Autoimmune; s/sx include opsoclonus/myoclonus and other cerebellar dysfunction, aphasia, lethargy/irritability
Brain-stem or limbic encephalitis	Small cell lung cancer, germ-cell testicular tumors	Autoantibodies against intracellular neuronal proteins
Anti-NMDA receptor encephalitis	Gyn tumors (esp. teratomas)	Anti-NMDA receptor auto-antibodies
Polymyositis/Dermatomyositis	Lymphoma, lung, pancreatic, stomach, bladder, ovarian	autoimmune
Acanthosis nigricans	Gastric, lung, uterine	Epidermal growth factor secretion
Misc. derm conditions (Sweet's syndrome, Leser-Trelat sign, pyoderma gangrenosum, florid cutaneous papillomatosis, necrolytic migratory erythema, hypertrichosis)	lung, GI adenocarcinomas, breast and GU cancers, lymphoma
VTE, thrombophlebitis	any advanced cancer. Pancreatic and bronchogenic carcinomas associated w/trousseau's sign	Hypercoagulability
Polycythemia	Renal cell carcinoma, cerebellar hemangioma, hepatocellular carcinoma	Increased erythropoietin production
Granulocytosis	various	C-GSF
Membranous glomerulonephritis		tumor antigens/immune complexes
Thymoma-associated multiorgan autoimmunity	Thymoma	similar to GVHD