[Pathology and biology of small cell lung cancer]

Small cell lung carcinoma (SCLC) is histologically simple, and shows a characteristic ultrastructure and very complex functions. Recently, a large amount of information has been accumulated by fundamental research, largely involving studies on many cultured cell lines. Now their potential application to the therapy of SCLC is being sought. A characteristic ultrastructural feature is the presence of dense-cored neurosecretory-type granules 100-200 nm in diameter. In addition, epithelial cell characteristics are noted. Predominance of either a neurosecretory or epithelial nature may affect the responsiveness of tumors to therapy. Many kinds of brain-gut hormones are produced by SCLC. Gastrin-releasing peptide (GRP) has attracted much attention as an autocrine growth factor for SCLC. Aromatic L-amino acid decarboxylase (AADC), neuron-specific enolase (NSE) and creatine kinase BB (CK-BB) are rather specific to SCLC. NSE and CK-BB together with GRP are good monitoring markers during treatment. Amplification of c-myc, N-myc and L-myc is seen in SCLCs. Areas both with and without N-myc amplification are found in both the primary site and metastatic sites in a single case. Del 3p(14-23) is characteristic for SCLC but SCLCs without such deletion are also present. A cytologically "variant" type is composed of cells simulating "large cells", in which the doubling time is short, AADC and GRP are undetectable, granules are rare, and the cells are resistant to radiation. However, one cell line of the classic type has revealed reversible squamous cell change in the absence of retinoic acid, becoming radioresistant without showing any remarkable changes in AADC, NSE or CK-BB. Since SCLC mixed with "large cells" or "small cell carcinoma of undifferentiated type" is resistant to therapy and possesses a more epithelial nature, small cell carcinoma with a large cell component has been proposed as a subtype. The question of whether this subclassification is practical should be confirmed by prospective study.