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Paraneoplastic syndromes

Last updated: September 14, 2021

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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., malignant 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 articles of associated conditions.

Common paraneoplastic manifestations are cachexia, hyperthermia, increased risk of thrombosis. [1]

Overview of the most common paraneoplastic syndromes [1][2]
Type Syndrome Etiology Associated cancer(s) Characteristic features


  • Presynaptic voltage-gated calcium channels (VGCC) (P/Q-type) autoantibodies
  • Proximal muscle weakness affecting both sides (progresses within weeks to months)
  • Muscle tenderness
  • Paraneoplastic antibody-mediated vasculopathy
  • Paraneoplastic encephalomyelitis
  • Paraneoplastic cerebellar degeneration
  • Opsoclonus-myoclonus syndrome
  • Rapid, multidirectional, involuntary movements of the eyes (opsoclonus) and muscles (myoclonus)
  • Ataxia
  • Irritability, sleep disturbance
  • Hypercalcemia of malignancy
  • Malignant acanthosis nigricans
  • Brown to black, intertriginous and/or nuchal hyperpigmentation and dermal thickening
  • Can turn into itching, papillomatous, poorly-defined rash
  • Rapid growth and verrucous or papulous surface
  • Most commonly localized in the axilla, groin, neck, and genital/anal region
  • Leser-Trélat sign

  • Not fully understood
  • Multiple areas of centrifugally spreading erythema
  • Predominantly face, perineum, and lower extremities affected
  • Develop into painful and pruritic crusty patches with central areas of bronze-colored induration
  • Tend to resolve and reappear in a different location
  • Good syndrome
  • Most cancers

Rising or high hematocrit levels are paraneoplastic!” Renal cell carcinoma, Hepatocellular carcinoma, Hemangioblastoma, Leiomyoma, and Pheochromocytoma are associated with polycythemia.

Patients with OMS are described as having “dancing eyes” (opsoclonus) and “dancing feet” (myoclonus).

  1. Paraneoplastic Syndrome . Updated: December 31, 2016. Accessed: December 31, 2016.
  2. Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clinic Proceedings. 2010; 85 (9): p.838-54. doi: 10.4065/mcp.2010.0099 . | Open in Read by QxMD
  3. Matsumoto H, Ugawa Y. [Paraneoplastic opsoclonus-myoclonus syndrome--a review].. Brain and nerve = Shinkei kenkyu no shinpo. 2010; 62 (4): p.365-9.