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The clinical manifestations of cancer are usually due to pressure effects of local tumor growth, infiltration or metastatic deposition of tumor cells in a variety of organs in the body, or certain systemic symptoms. General problems observed in many patients with advanced or widespread metastatic cancer include anorexia, malaise, weight loss, and sometimes fever. Except in the case of functioning tumors such as those of the endocrine glands, systemic symptoms of cancer usually are not specific. "Paraneoplastic" refers to features of a cancer considered to be due to its remote effects that cannot be attributed either to its direct invasive or its metastatic properties. Instead, symptoms are due to aberrant tumor production of hormones, peptides, or cytokines or to the body's immune attack on normal tissues due to shared antigens with tumor tissues. In paraneoplastic syndromes, clinical findings may resemble those of primary endocrine, dermatologic, rheumatologic, hematologic, or neuromuscular disorders. In endocrine paraneoplastic syndromes (associated with ectopic hormone production), tumor tissue itself secretes the hormone producing the syndrome. Ectopic hormones secreted by neoplasms are often pro-hormones of higher molecular weight than those secreted by the more differentiated normal endocrine cell. Many of the neuromuscular, dermatologic, and rheumatologic paraneoplastic syndromes are caused by antibodies directed against tumor antigens that share epitopes with normal tissue; testing for antibodies can often detect syndrome-specific antibodies. Small cell lung cancer (SCLC) is the one type of cancer most likely to be associated with paraneoplastic syndromes (eTable 39–1).

eTable 39–1.Paraneoplastic syndromes associated with cancer.

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