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SMALL CELL CARCINOMAS OF THE LUNG


SMALL CELL CARCINOMAS OF THE LUNG
Small cell carcinoma is defined as a malignant epithelial tumor consisting of small cells with scant cytoplasm. If other histologic types of non–small cell carcinoma are also present, then it is classified as combined small cell carcinoma. The cells contain neuroendocrine granules, and it is usually considered as a neuroendocrine tumor at the most malignant end of the neuroendocrine spectrum. It usually stains positive for the neuroendocrine markers CD56, chromogranin, and synaptophysin. This cell type has the strongest association with cigarette smoking and rarely occurs in people who have never smoked. Small cell histology accounts for 14% of all lung cancers (13% in men; 15% in women) in the Surveillance, Epidemiology and End Results database (http://seer.cancer.gov). This cell type generally has the fastest growth rate and a tendency to early spread.

SMALL CELL CARCINOMAS OF THE LUNG

Small cell carcinoma is centrally located in the large majority of cases and therefore present with symptoms of cough, hemoptysis, chest pain, or obstructive pneumonia. Because of the tendency for early spread, many individuals present with signs and symptoms of regional or distant metastasis. Mediastinal lymph node spread may result in hoarseness or a change in voice caused by vocal cord paralysis, dysphagia caused by esophageal compression, or superior vena cava syndrome (dis- cussed later). Symptoms caused by brain, bone, or liver metastases may be the first signs of the disease. Small cell carcinoma is the most common cell type associated with paraneoplastic syndromes (discussed later).
Ten percent or fewer of small cell carcinomas present as a peripheral mass or solitary pulmonary nodule. Supraclavicular lymph node metastases may be present and are an easy source for tissue diagnosis. Sputum cytology is rarely positive. Bronchoscopy is the most common method of diagnosis. The tumor is frequently located submucosally, and bronchoscopic biopsies may not yield a diagnosis if deep submucosal samples are not obtained. Pleural fluid cytology may be diagnostic; however, in many cases, the pleural fluid is due to a parapneumonic effusion and not caused by malignant seeding of the pleural space.
Small cell carcinoma is usually staged as limited or extensive stage disease. Limited disease is defined as disease confined to one hemithorax and mediastinal lymph nodes with or without ipsilateral supraclavicular nodes. It is generally disease that can be safely confined within a thoracic radiotherapy field of treatment. Extensive stage is defined as spread of disease beyond the hemithorax with distant metastases. Malignant pleural effusion, cytologically documented, is considered to be extensive stage.
The treatment of limited stage disease is combined concurrent chemotherapy and thoracic radiotherapy in patients with a good performance score and minimal weight loss. Recent cooperative group trials of concurrent treatment have resulted in median survival times of 18 to 20 months and 5-year survival rates of 20% to 25%. For patients with extensive stage disease, the usual treatment is chemotherapy for four to six cycles with a platinum based doublet. The median survival time is 8 to 10 months with 10% or less 2-year survival and virtually no 5-year survivors. Chemotherapy treatment for small cell carcinoma has plateaued with no major advances for the past 2 decades.