paraneoplastic syndrome
Summary
Paraneoplastic syndromes are clinical manifestations caused indirectly by a tumor, mediated by ectopic hormone production, autoimmune cross-reactivity, or cytokine release, rather than by direct tumor invasion or metastasis. They often precede diagnosis of the underlying malignancy and can involve endocrine, neurologic, dermatologic, or hematologic systems.
Detail
Paraneoplastic syndromes arise from substances secreted by tumor cells (hormones, hormone-like peptides, cytokines) or from an immune response against tumor antigens that cross-reacts with normal tissue. Recognizing these syndromes is important because they may be the presenting sign of an occult malignancy, can be used to monitor tumor recurrence, and sometimes cause more morbidity than the tumor itself. Key examples for boards: SIADH (ectopic ADH) and Lambert-Eaton myasthenic syndrome (antibodies against presynaptic voltage-gated calcium channels) - both classically associated with small cell lung cancer. Cushing syndrome from ectopic ACTH (small cell lung cancer, bronchial carcinoids). Hypercalcemia of malignancy from PTHrP (squamous cell lung cancer, renal cell carcinoma, breast cancer) - distinguish from bone metastases causing hypercalcemia via osteolysis. Polycythemia from ectopic erythropoietin (renal cell carcinoma, hepatocellular carcinoma, hemangioblastoma). Dermatomyositis and acanthosis nigricans (gastric adenocarcinoma). Trousseau syndrome (migratory superficial thrombophlebitis) associated with pancreatic adenocarcinoma. Anti-Hu (ANNA-1) antibodies causing subacute sensory neuropathy and encephalomyelitis, associated with small cell lung cancer. Anti-Yo antibodies causing cerebellar degeneration, associated with ovarian and breast cancer. Opsoclonus-myoclonus associated with neuroblastoma in children and small cell lung cancer in adults. Membranous nephropathy associated with solid tumors. Understanding the mechanism (hormone secretion vs autoantibody-mediated) helps predict whether symptoms improve with tumor resection (hormone-mediated typically does, immune-mediated may persist due to autoantibodies).
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- UpToDate: Overview of paraneoplastic syndromes
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.