Description

• Collection of disorders resulting from an abnormal immune response to cancer or the production of hormones and other soluble factors by the malignancies
• Originates far from the primary tumor or metastasis
• Found in as many as 8% of cancer patients
• Hypercalcemia of malignancy (HCM):
  • 20% of all cancer patients
  • Most common paraneoplastic syndrome
  • Osteoclast-mediated bone resorption is the most common factor mediating HCM
  • Risk factors include squamous cell cancers (lung, head, and neck), breast, kidney, bladder, and ovarian cancers, lymphoma
• Syndrome of inappropriate antidiuretic hormone (SIADH):
  • 2% of all cancer patients
  • Risk factors: SCLC
  • Impaired water excretion leading to hyponatremia with hypervolemia or euvolemia as a result of unsuppressed or increased levels of antidiuretic hormone (ADH) (vasopressin)
• Cushing syndrome:
  • 2% of all cancer patients, found in 10–45% of SCLC patients
  • Due to glucocorticoid excess as a result of exaggerated adrenal cortisol production or long-term glucocorticoid therapy
• Limbic encephalitis (LE):
  • Less than 1%
  • Associated with pituitary adenoma, adrenal and carcinoid tumors
  • Neurologic disorder affecting the limbic system that occurs in association with working memory deficits, seizures, and psychiatric symptoms
• Paraneoplastic cerebellar degeneration:
  • 3% of SCLC patients
  • Associated with Hodgkin lymphoma, breast cancer
  • Characterized by the rapid development of severe pan-cerebellar dysfunction, including truncal and appendicular ataxia, dysarthria, and downbeat nystagmus
• Lambert–Eaton myasthenic syndrome (LEMS):
  • 3% of SCLC patients
  • Associated with SCLC, prostate cancer, lymphoma
  • Autoimmune disorder of neuromuscular transmission due to antibodies directed against presynaptic voltage-gated P/Q calcium channels on motor and autonomic nerve terminals
• Paraneoplastic thrombocytosis:
  • 5–20% of patients with solid tumors
  • Associated with lung, colorectal, mesothelioma
• Paraneoplastic erythrocytosis:
  • 4% of patients
  • Associated with renal cell carcinoma, hepatocellular carcinoma
• Paraneoplastic glomerulonephritis:
  • 2–4% of patients
  • Risk factors: Hodgkin lymphoma, thymoma, prostate cancer
• Myasthenic gravis (MG):
  • 15% of thymoma patients
  • Autoimmune disorder caused by antibodies against elements in the postsynaptic membrane at the neuromuscular junction, which leads to muscle weakness
• Opsoclonus myoclonus syndrome (OMS):
  • Less than 1%
  • Associated with SCLC, breast cancer, ovarian teratoma in adults, neuroblastoma in children
  • Rare neurologic condition characterized by unintentional rapid eye movements in all directions (opsoclonus) and sudden involuntary jerking of the limbs and trunk (myoclonus)

Etiology

Mainly caused ectopic production of hormones and peptides leading to derangements:

• HCM:
  • Production of parathyroid hormone-related peptide (PTHrP)
• SIADH:
  • Ectopic production of ADH resulting in inappropriately concentrated urine and natriuresis
• Cushing syndrome:
  • Ectopic production of ACTH resulting in production of cortisol and other glucocorticosteroids from the adrenal glands refractory to normal HPA feedback
• Paraneoplastic erythrocytosis:
  • Inappropriate production of erythropoietin (EPO), associated with renal cell carcinoma
• Paraneoplastic thrombocytosis:
  • Overproduction of inflammatory cytokines, IL-6 resulting in thrombopoietin (TPO) mRNA expression and protein synthesis in the liver
• Paraneoplastic glomerulonephritis:
  • Acute renal failure in the setting of a malignancy not explained by direct tumor involvement of the kidneys or genitourinary system
• Paraneoplastic neurologic syndromes (MG, OMS):
  • Onconeural antibodies produced in response to developing cancer causing cross-reactivity between tumor cells and components of nervous system