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Paraneoplastic syndrome
Classification and external resources
DiseasesDB 2064
eMedicine med/1747
MeSH D010257

A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells.[1] These phenomena are mediated by humoral factors (by hormones or cytokines) excreted by tumor cells or by an immune response against the tumor. Paraneoplastic syndromes are typical among middle aged to older patients, and they most commonly present with cancers of the lung, breast, ovaries or lymphatic system (a lymphoma).[2] Sometimes the symptoms of paraneoplastic syndromes show before the diagnosis of a malignancy, which has been hypothesized to relate to the disease pathogenesis. In this paradigm, tumor cells express tissue-restricted antigens (such as neuronal proteins), triggering an anti-tumor immune response which may be partially or, rarely, completely effective[3] in suppressing tumor growth and symptoms.[4][5] Patients then come to clinical attention when this tumor immune response breaks immune tolerance and begins to attack the normal tissue expressing that (e.g. neuronal) protein.

Many of these conditions are of interest to psychologists as they have neurological implications.


A particularly devastating form of paraneoplastic syndromes is a group of disorders classified as paraneoplastic neurological disorders (PNDs).[6] These paraneoplastic disorders affect the central or peripheral nervous system; some are degenerative,[7] though others (such as LEMS) may improve with treatment of the condition or the tumour. Symptoms of paraneoplastic neurological disorders may include ataxia (difficulty with walking and balance), dizziness, nystagmus (rapid uncontrolled eye movements), difficulty swallowing, loss of muscle tone, loss of fine motor coordination, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, sensory loss in the limbs.

examples include:

The most common cancers associated with paraneoplastic neurological disorders are breast, ovarian and lung cancer, but many other cancers can produce paraneoplastic symptoms as well.

Treatment options include:

  1. Therapies to eliminate the underlying cancer such as chemotherapy, radiation and surgery, and
  2. Therapies to reduce or slow neurological degeneration. Rapid diagnosis and treatment are critical for the patient to have the best chance of recovery. Since these disorders are relatively rare, few doctors have seen or treated PNDs. Therefore, it is important that PND patients consult with a specialist with experience in diagnosing and treating paraneoplastic neurological disorders.


Paraneoplastic syndromes can be divided into four main categories: Endocrine, neurological, mucocutaneous and hematological paraneoplastic syndromes, as well as others that may not fit into any of the above categories:

Syndrome class Syndrome Main causal cancers Causal mechanism
Cushing syndrome Ectopic ACTH and ACTH-like substance
SIADH antidiuretic hormone[9]
Hypercalcemia PTHrP (Parathyroid hormone-related protein), TGF-α, TNF, IL-1[9]
Hypoglycemia Insulin or insulin-like substance[9] or "big" IGF-II
Carcinoid syndrome Serotonin, bradykinin[9]
Polycythemia See hematological paraneoplastic syndromes
Hyperaldosteronism Aldosterone[10]
Neurological[11] Lambert-Eaton myasthenic syndrome (LEMS) Immunologic
Paraneoplastic cerebellar degeneration
Encephalomyelitis inflammation of the brain and spinal cord
Limbic encephalitis
Brainstem encephalitis
Paraneoplastic Opsoclonus (involving eye movement)-Myoclonus
  • breast carcinoma
  • ovarian carcinoma
  • small-cell lung carcinoma
  • neuroblastoma (in children)
Autoimmune reaction against the RNA-binding protein Nova-1[12]
Anti-NMDA receptor encephalitis Autoimmune reaction against NMDA-receptor subunits
Mucocutaneous[14] Acanthosis nigricans
  • Immunologic[9]
  • Secretion of EGF
Dermatomyositis Immunologic[9]
Leser-Trélat sign
Necrolytic migratory erythema Glucagonoma
Sweet's syndrome
Florid cutaneous papillomatosis
Pyoderma gangrenosum
Acquired generalized hypertrichosis
Hematological[16] Granulocytosis G-CSF
Polycythemia Erythropoietin[9]
Trousseau sign Mucins that activate clotting,[9] others
Nonbacterial thrombotic endocarditis
  • Advanced cancers[9]
Anemia Unknown[9]
Others Membranous glomerulonephritis
Tumor-induced osteomalacia
Stauffer syndrome
Neoplastic fever [18]


  1. Paraneoplastic Syndromes, 2011, Darnell & Posner
  2. NINDS Paraneoplastic Syndromes Information Page National Institute of Neurological Disorders and Stroke
  3. Darnell,R.B., DeAngelis,L.M., Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies, [[{{{publisher}}}|{{{publisher}}}]], [[{{{date}}}|{{{date}}}]].
  4. Roberts,W.K., Darnell,R.B., Neuroimmunology of the paraneoplastic neurological degenerations, [[{{{publisher}}}|{{{publisher}}}]], [[{{{date}}}|{{{date}}}]].
  5. Albert,M.A., Darnell,R.B., Paraneoplastic neurological degenerations: keys to tumour immunity, [[{{{publisher}}}|{{{publisher}}}]], [[{{{date}}}|{{{date}}}]].
  6. Rees JH (2004). PARANEOPLASTIC SYNDROMES: WHEN TO SUSPECT, HOW TO CONFIRM, AND HOW TO MANAGE. J. Neurol. Neurosurg. Psychiatr. 75 Suppl 2 (Suppl 2): ii43–50.
  7. Darnell RB, Posner JB (2006). Paraneoplastic syndromes affecting the nervous system. Semin Oncol 33 (3): 270–98.
  8. MeSH Paraneoplastic+endocrine+syndromes
  9. 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17 9.18 9.19 9.20 9.21 9.22 9.23 9.24 9.25 9.26 9.27 9.28 9.29 9.30 9.31 9.32 9.33 9.34 9.35 9.36 9.37 9.38 9.39 9.40 Table 6-5 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology, Philadelphia: Saunders. 8th edition.
  10. Mulatero P, Rabbia F, Veglio F. "Paraneoplastic hyperaldosteronism associated with non-Hodgkin's lymphoma.", New England Journal of Medicine. 2001 May 17;344(20):1558-9. Retrieved on 29 August 2012.
  11. MeSH Nervous+system+paraneoplastic+syndromes
  12. Buckanovich RJ, Posner JB, Darnell RB (1993). Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system. Neuron 11 (4): 657–72.
  13. Dalmau J (January 2007). Paraneoplastic Anti–N-methyl-D-aspartate Receptor Encephalitis Associated with Ovarian Teratoma. Ann. Neurol. 61 (1): 25–36.
  14. Cohen PR, Kurzrock R (1997). Mucocutaneous paraneoplastic syndromes. Semin. Oncol. 24 (3): 334–59.
  15. (2001). Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. The Lancet 357 (9250): 96.
  16. Staszewski H (1997). Hematological paraneoplastic syndromes. Semin. Oncol. 24 (3): 329–33.
  17. Zadik Y, Nitzan DW (October 2011). Tumor induced osteomalacia: A forgotten paraneoplastic syndrome?. Oral Oncol 48 (2): e9–10.
  18. Zell JA, Chang JC. Neoplastic fever: a neglected paraneoplastic syndrome. PMID 15864658

External linksEdit

Template:Paraneoplastic syndromes

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