it is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm. Caution is required when diagnosing SCLC because small cell mesothelioma – an extremely rare subtype of lung cancer – can be mistaken for small cell lung cancer. It is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called Feyrter cells (named for Friedrich Feyrter). Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones like ADH and ACTH that may result in paraneoplastic syndromes and Cushing's syndrome. Approximately half of all individuals diagnosed with Lambert–Eaton myasthenic syndrome (LEMS) will eventually be found to have a small-cell carcinoma of the lung. Small-cell carcinoma is most often more rapidly and widely metastatic than non-small-cell lung carcinoma (and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes. The mechanisms of its metastatic progression are not well-understood. Combined small-cell lung carcinoma (c-SCLC) Small-cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer, including extremely complex malignant tissue admixtures. When it is found with one or more differentiated forms of lung cancer, such as squamous cell carcinoma or adenocarcinoma, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma (c-SCLC). C-SCLC is the only currently recognized subtype of SCLC. Although combined small-cell lung carcinoma is currently staged and treated similarly to "pure" small-cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type. Smoking is a significant risk factor. Symptoms and signs are as for other lung cancers. In addition, because of their neuroendocrine cell origin, small-cell carcinomas will often secrete substances that result in paraneoplastic syndromes such as Lambert–Eaton myasthenic syndrome. Extrapulmonary small-cell carcinoma Very rarely, the primary site for small-cell carcinoma is outside of the lungs and pleural space; in these cases, it is referred to as extrapulmonary small-cell carcinoma (EPSCC). Outside of the respiratory tract, small-cell carcinoma can appear in the cervix, prostate, liver, pancreas, gastrointestinal tract, or bladder. It is estimated to account for 1,000 new cases a year in the U.S. Histologically similar to small-cell lung cancer, therapies for small-cell lung cancer are usually used to treat EPSCC. First-line treatment is usually with cisplatin and etoposide. In Japan, first-line treatment is shifting to irinotecan and cisplatin. When