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XX, strong association; X, reported association SIADH, syndrome of inappropriate antidiuretic hormone
Cancer
local effects of tumor growth, either in the primary site or at a distant site The term paraneoplasia has been coined to denote the remote effects of malignancy that cannot be attributed either to direct invasion or metastatic lesions These syndromes may be the first sign of a malignancy and may affect up to 15% of patients with cancer The paraneoplastic syndromes are of considerable clinical importance for the following reasons: 1 They may accompany relatively limited neoplastic growth and provide an early clue to the presence of certain types of cancer 2 The course of the paraneoplastic syndrome usually parallels the course of the tumor Therefore, effective treatment should be accompanied by resolution of the syndrome, and, conversely, recurrence of the cancer may be heralded by the return of systemic symptoms 3 The metabolic or toxic effects of the syndrome may constitute a more urgent hazard to life than the underlying cancer (eg, hypercalcemia, hyponatremia) The paraneoplastic syndromes are usually caused by the secretion of proteins not normally associated with a cancer s normal tissue equivalent Clinical findings may resemble those of primary endocrine, metabolic, hematologic, or neuromuscular disorders The mechanisms for such remote effects can be classified into three groups: (1) effects initiated by a tumor product (eg, carcinoid syndrome), (2) effects due to the destruction of normal tissues by tumor products (eg, hypercalcemia due to local secretion of cytokines), and (3) effects due to unknown mechanisms such as unidentified tumor products or circulating immune complexes stimulated by the tumor (eg, osteoarthropathy due to bronchogenic carcinoma and some neurologic syndromes) Even such nonspecific symptoms as fever and weight loss are truly paraneoplastic and are due to the production of specific factors (eg, tumor necrosis factor) by tumor cells or by normal cells in response to the tumor Paraneoplastic syndromes associated with ectopic hormone production are the best-characterized entities Tumor cells secrete a hormone or prohormone that may be of a higher or lower molecular weight than hormones secreted by the more differentiated normal endocrine cell (eg, parathyroid hormone-related peptide in hypercalcemia, ACTH in Cushing s syndrome, antidiuretic hormone in the syndrome of inappropriate antidiuretic hormone [SIADH] secretion) This ectopic hormone production by cancer cells is believed to result from activation of genes in malignant cells that are normally suppressed in most somatic cells A single syndrome such as hypercalcemia may be due to more than one of a variety of causes Effective antitumor treatment usually results in return of the serum calcium to normal, though additional therapy may be required (see Hypercalcemia, above) In some cases, a rapid response to cytotoxic chemotherapy may briefly increase the severity of the paraneoplastic syndrome in association with tumor lysis (eg, hyponatremia with SIADH) Several neurologic paraneoplastic syndromes have been found to be caused by the production of antineuronal antibodies that circulate in the serum and spinal fluid It is thought that the underlying tumor expresses a similar antigen, resulting in
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production of a cross-reactive antibody Treatment of the underlying tumor usually results in only modest improvement of the neurologic deficit Examples of antineuronal antibodies include the anti-Hu antibody causing sensory neuropathy or encephalitis, associated with small cell cancer of the lung; the anti-Yo antibody causing cerebellar degeneration, associated most often with breast or gynecologic malignancies; the stiff man syndrome, associated with breast cancer; and anti-Purkinje cell antibodies causing cerebellar ataxia, associated with Hodgkin s disease as well as gynecologic, breast, and lung cancers Other well-described paraneoplastic syndromes include those involving the skin with or without other organ involvement (eg, dermatomyositis, Sweet s syndrome), hematologic syndromes (eg, polycythemia, thrombocytosis), and those involving the kidneys, the gastrointestinal tract, and the joints The most common cancer associated with paraneoplastic syndromes is small cell cancer of the lung This is thought to be due to its neuroectodermal origin
Bataller L et al Paraneoplastic neurologic syndromes Neurol Clin 2003 Feb;21(1):221 47 [PMID: 12690651] Briemberg HR et al Neuromuscular complications of cancer Neurol Clin 2003 Feb;21(1):141 65 [PMID: 12690648] Dropcho EJ Update on paraneoplastic syndromes Curr Opin Neurol 2005 Jun;18(3):331 6 [PMID: 15891421] Falah M et al Neuromuscular complications of cancer diagnosis and treatment J Support Oncol 2005 Jul Aug;3(4):271 82 [PMID: 16092597] Mareska M et al Lambert-Eaton myasthenic syndrome Semin Neurol 2004 Jun;24(2):149 53 [PMID: 15257511] Mazzone PJ et al Endocrine paraneoplastic syndromes in lung cancer Curr Opin Pulmon Med 2003 Jul;9(4):313 20 [PMID: 12806246] Posner JB Immunology of paraneoplastic syndromes: overview Ann N Y Acad Sci 2003 Sep;998:178 86 [PMID: 14592873] Stone SP et al Life-threatening paraneoplastic cutaneous syndromes Clin Dermatol 2005 May Jun;23(3):301 6 [PMID: 15896545] Sutton I et al The immunopathogenesis of paraneoplastic neurological syndromes Clin Sci (Lond) 2002 May;102(5):475 86 [PMID: 11980564]
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