Small cell carcinoma of the lung: cellular origin and relationship to other neoplasms

Many small cell carcinomas share morphological and physiological characteristics with normal and neoplastic cells of Pearse's APUD series, including pulmonary APUD cells and pulmonary carcinoid tumors. There is very likely more than one type of APUD cell in the lung, and conclusions that small cell carcinomas and carcinoids reflect neoplastic transformation of the same cell type are probably premature. The embryoogic lineage of pulmonary APUD cells is at present uncertain. The hypothesis that all APUD cells are derived from the neural crest is no longer tenable, and although some evidence does suggest a neural contribution to the pulmonary epithelium, additional embryologic studies are required. Some tumors that currently are classified as small cell carcinomas probably do not have APUD cell characteristics, and still others appear to have both APUD and non-APUD features. A subclassification of small cell carcinomas based on a combination of physiological and morphological features might prove to be of prognostic and therapeutic value, but current knowledge probably would not provide a sufficient foundation for a reliable or practical subclassification. Multidisciplinary studies of the differentiation and function of normal and neoplastic APUD cells in the lungs and elsewhere are needed.