Paraneoplastic syndromes

Last updated: July 28, 2023

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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.

Overviewtoggle arrow icon

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

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


Lambert-Eaton myasthenic syndrome
Myasthenia gravis
Stiff person syndrome
  • Generalized increase in skeletal muscle rigidity
  • Lumbar or cervical hyperlordosis
  • Gait abnormalities
  • Episodic painful muscle spasms
  • Proximal muscle weakness affecting both sides (progresses within weeks to months)
  • Muscle tenderness
  • Paraneoplastic antibody-mediated vasculopathy
Neurological Paraneoplastic encephalomyelitis
Paraneoplastic cerebellar degeneration
Opsoclonus-myoclonus syndrome
  • Rapid, multidirectional, involuntary movements of the eyes (opsoclonus ) and muscles (myoclonus)
  • Ataxia
  • Irritability, sleep disturbance
Limbic encephalitis [4]
Paraneoplastic pure sensory neuropathy
Endocrine Cushing syndrome
Syndrome of inappropriate ADH secretion
Hypercalcemia of malignancy
Mucocutaneous 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
Necrolytic migratory erythema
  • 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
Hypertrichosis lanuginosa acquisita
Skeletal Hypertrophic pulmonary osteoarthropathy (Bamberger-Marie syndrome)
Tumor-induced osteomalacia
Hematological Polycythemia
Pure red cell aplasia
Good syndrome
Trousseau syndrome (thrombophlebitis migrans)
Nonbacterial thrombotic endocarditis
Miscellaneous Neoplastic fever
  • Most cancers
Membranous glomerulonephritis

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).

Referencestoggle arrow icon

  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.
  4. Limbic encephalitis. . Accessed: September 14, 2021.
  5. Soomro Z, Youssef M, Yust-Katz S, Jalali A, Patel AJ, Mandel J. Paraneoplastic syndromes in small cell lung cancer. Journal of Thoracic Disease. 2020; 12 (10): p.6253-6263.doi: 10.21037/jtd.2020.03.88 . | Open in Read by QxMD

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