• Clinical science

Paraneoplastic syndromes


Paraneoplastic syndromes are a set of clinical features that are caused by either an altered immune response to a systemic malignancy or because of substances (e.g., hormones, cellular proteins) produced by tumors. They are caused neither by the local mass effect nor by metastasis of the associated cancer. Paraneoplastic syndromes present with a wide range of findings and are most commonly associated with lung, ovarian, lymphatic, and breast cancers. Small cell lung cancer is especially notorious for its numerous and distinct paraneoplastic syndromes. Some paraneoplasias are associated with many different malignancies, such as tumor-induced hypercalcemia, which is caused by parathyroid hormone-related protein (PTHrP) produced from tumor cells. Other paraneoplasias (e.g., acanthosis nigricans) are almost pathognomonic for specific malignancies and their presence demands an immediate search for the underlying tumor. A general overview of the most common paraneoplastic syndromes and their associations is presented here. Further details for individual syndromes can be found in learning cards of associated conditions.


  • Common paraneoplastic manifestations: cachexia, hyperthermia, increased risk of thrombosis
  • Specific paraneoplasias
Type Syndrome Underlying cause Associated cancer(s)


  • Immune reaction against neural antigens in the cerebellum (e.g., Yo antigens of Purkinje cells, Tr antigens, Hu antigens)
  • Exogenous ADH
  • Exogenous transforming growth factor TGF-α and epidermal growth factor (GF)
  • Gastric and other gastrointestinal cancers
  • Lung
  • Uterine
  • Activation of epidermal growth factor receptors → manifests as multiple, sudden-onset seborrheic keratoses
  • Solid cancers (especially gastrointestinal cancers)
  • Granulocytosis
  • Possibly exogenous substances with granulocyte colony-stimulating factor
  • Most cancers
  • Polycythemia
  • Exogenous EPO
  • Renal
  • Hepatocellular
  • Cerebellar hemangioma
  • Malignancy-related hypercoagulability → recurring clots that resolve and appear again elsewhere in the body (migrans)
  • Neoplastic fever
  • Most cancers