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EPIDEMIOLOGY

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Lung cancer is the leading cause of cancer-related mortality in the United States with over 172,000 new cases and over 163,000 deaths in 2005 with over 225,000 new cases and 160,000 deaths in 2013. Approximately 14% of lung cancers diagnosed between 2005 and 2009 were small cell lung cancer (SCLC), with the remainder being various subtypes of non-small cell lung cancer (NSCLC) such as adenocarcinoma, squamous cell, and large cell, among others. The proportion of new lung cancers diagnosed that are SCLC has been declining over the past few decades. The reasons for this are unclear but may relate at least in part to the changing composition of cigarettes and inhalation patterns.

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SCLC is associated with cigarette smoking in the vast majority of cases. Both duration of smoking and number of cigarettes per day are directly correlated with lung cancer risk. Patients who quit smoking decrease their lung cancer risk, although not to never-smoking levels (1).

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PATHOLOGY

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SCLC is a type of high-grade neuroendocrine lung cancer. The neuroendocrine lung tumors encompass a diverse spectrum that ranges widely in prognosis, from low-grade typical carcinoids and intermediate-grade atypical carcinoids to the higher-grade cancers including large cell neuroendocrine cancer and SCLC. SCLC and large cell neuroendocrine cancer behave similarly and have similar prognoses.

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Pathologically, SCLC is defined as "a proliferation of small cells (<4 lymphocytes in diameter) with unique and strict morphologic features, scant cytoplasm, ill-defined borders, finely granular salt and pepper chromatin, absent or inconspicuous nucleoli, frequent nuclear molding, and a high mitotic count" (2). Immunohistochemical staining is generally positive for epithelial cell markers such as keratin and epithelial membrane antigen. In addition, neuroendocrine markers such as chromogranin A and synaptophysin are positive in the majority of SCLCs.

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CLINICAL PRESENTATION

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Most patients present with symptoms that are related to the intrathoracic bulk of disease or widespread dissemination. Cough, dyspnea, weight loss, and weakness are the most common presenting symptoms (3).

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In addition, a variety of paraneoplastic syndromes are observed with SCLC. The ectopic production of hormones is a common culprit for the endocrine paraneoplastic disorders, which include hyponatremia (due to ectopic production of antidiuretic hormone), Cushing's syndrome (ectopic corticotropin production), and acromegaly (ectopic growth hormone releasing hormone). Neurologic paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome are caused by autoantibody-mediated damage to the nervous system. Treatment of the underlying tumor can help control these paraneoplastic syndromes; in addition, medical management of symptoms may be indicated (see Table 53-1).

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Table Graphic Jump Location
TABLE 53-1CLINICAL PRESENTATION
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DIAGNOSIS AND STAGING

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Radiographically, SCLCs tend to present as central ...

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