Paraneoplastic syndrome

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

A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of cancer in the body but that, unlike mass effect, is not due to the local presence of cancer cells.[1] In contrast, these phenomena are mediated by humoral factors (such as 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 (e.g., 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.

The abbreviation PNS is sometimes used for paraneoplastic syndrome, although it is used more often to refer to the peripheral nervous system.

Classification

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
Endocrine[6]
Cushing syndrome Ectopic ACTH and ACTH-like substance
SIADH antidiuretic hormone[7]
Hypercalcemia PTHrP (Parathyroid hormone-related protein), TGF-α, TNF, IL-1[7]
Hypoglycemia Insulin or insulin-like substance[7] or "big" IGF-II
Carcinoid syndrome Serotonin, bradykinin[7]
Hyperaldosteronism Aldosterone[8]
Neurological[9] Lambert-Eaton myasthenic syndrome (LEMS) Immunologic
Paraneoplastic cerebellar degeneration
Encephalomyelitis inflammation of the brain and spinal cord
Limbic encephalitis
Brainstem encephalitis
Opsoclonus myoclonus ataxia syndrome Autoimmune reaction against the RNA-binding protein Nova-1[10]
Anti-NMDA receptor encephalitis Autoimmune reaction against NMDA-receptor subunits
Polymyositis
Mucocutaneous[12] Acanthosis nigricans
  • Immunologic[7]
  • Secretion of EGF
Dermatomyositis Immunologic[7]
Leser-Trélat sign
Necrolytic migratory erythema Glucagonoma
Sweet's syndrome
Florid cutaneous papillomatosis
Pyoderma gangrenosum
Acquired generalized hypertrichosis
Hematological[14] Granulocytosis G-CSF
Polycythemia Erythropoietin[7]
Trousseau sign Mucins that activate clotting,[7] others
Nonbacterial thrombotic endocarditis
  • Advanced cancers[7]
 Hypercoagulability[7]
Anemia Unknown[7]
Others Membranous glomerulonephritis
Tumor-induced osteomalacia
Stauffer syndrome
Neoplastic fever [16]

Neurological

A particularly devastating form of paraneoplastic syndromes is a group of disorders classified as paraneoplastic neurological disorders (PNDs).[17] These paraneoplastic disorders affect the central or peripheral nervous system; some are degenerative,[18] though others (such as LEMS) may improve with treatment of the condition or the tumor. 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.

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.

References

  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. (1993), "Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies", Lancet, 341 (8836): 21–22, doi:10.1016/0140-6736(93)92485-c, PMID 8093269
  4. ↑ Roberts,W.K.; Darnell,R.B. (2004), "Neuroimmunology of the paraneoplastic neurological degenerations", Current Opinion in Immunology, 16 (5): 616–622, doi:10.1016/j.coi.2004.07.009, PMID 15342008
  5. ↑ Albert,M.A.; Darnell,R.B. (2004), "Paraneoplastic neurological degenerations: keys to tumour immunity", Nature Reviews Cancer, 4 (1): 36–44, doi:10.1038/nrc1255, PMID 14708025
  6. ↑ Paraneoplastic endocrine syndromes at the US National Library of Medicine Medical Subject Headings (MeSH)
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 Table 6-5 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
  8. ↑ 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.
  9. ↑ Nervous system paraneoplastic syndromes at the US National Library of Medicine Medical Subject Headings (MeSH)
  10. ↑ 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. doi:10.1016/0896-6273(93)90077-5. PMID 8398153.
  11. ↑ Dalmau J, Tüzün E, Wu HY, et al. (January 2007). "Paraneoplastic Anti–N-methyl-D-aspartate Receptor Encephalitis Associated with Ovarian Teratoma". Ann. Neurol. 61 (1): 25–36. doi:10.1002/ana.21050. PMC 2430743Freely accessible. PMID 17262855.
  12. ↑ Cohen PR, Kurzrock R (1997). "Mucocutaneous paraneoplastic syndromes". Semin. Oncol. 24 (3): 334–59. PMID 9208889.
  13. ↑ Hill, Catherine L; Zhang, Yuqing; Sigurgeirsson, Bardur; Pukkala, Eero; Mellemkjaer, Lene; Airio, Antti; Evans, Stephen R; Felson, David T (2001). "Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study". The Lancet. 357 (9250): 96–100. doi:10.1016/S0140-6736(00)03540-6. PMID 11197446.
  14. ↑ Staszewski H (1997). "Hematological paraneoplastic syndromes". Semin. Oncol. 24 (3): 329–33. PMID 9208888.
  15. ↑ Zadik Y, Nitzan DW (October 2011). "Tumor induced osteomalacia: A forgotten paraneoplastic syndrome?". Oral Oncol. 48 (2): e9–10. doi:10.1016/j.oraloncology.2011.09.011. PMID 21985764.
  16. ↑ Zell JA, Chang JC (November 2005). "Neoplastic fever: a neglected paraneoplastic syndrome". 13 (11): 870–7. doi:10.1007/s00520-005-0825-4. PMID 15864658.
  17. ↑ 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. doi:10.1136/jnnp.2004.040378. PMC 1765657Freely accessible. PMID 15146039.
  18. ↑ Darnell RB, Posner JB (2006). "Paraneoplastic syndromes affecting the nervous system". Semin Oncol. 33 (3): 270–98. doi:10.1053/j.seminoncol.2006.03.008. PMID 16769417.
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