Pulmonary carcinoid tumors: Enzymic discriminants, growth rate, and early age of inception

Abstract

Analyses of enzymes from various metabolic pathways in pulmonary carcinoid tumors and radiological measurements of their volume increase were compared with those for lung carcinomas of various cell types. The results describe new biochemical features in carcinoid tumors, present the first quantitative evidence for their slow growth rate (i.e., long doubling time) in vivo, and show that measurement of 2 or 3 appropriate enzymes in biopsy samples can guard against instances in which carcinoids and adeno- or oat cell carcinomas are mistaken for one another on histological examination. The uridine kinase to thymidine kinase ratio as well as the beta-galactosidase concentration of carcinoid tumors were 5 times higher than of carcinomas, and their gamma-glutamyl transpeptidase was below that of all 35 adeno- and the 11 squamous cell carcinomas. Thymidine kinase, which bears a quantitative inverse correlation to volume doubling time (irrespective of cell type), had much lower titers in the 9 carcinoids than in the 6 oat cell carcinomas and reflects most clearly their very different (despite common histogenesis) clinical malignancy. Owing to their long doubling time, carcinoid tumors on the average required a much longer period (40.5 years) to attain final volume than did carcinomas (17.8 years). The calculated mean age of the subjects when growth began, -0.5 years (as opposed to 51 years for carcinomas), suggests a prenatal or early childhood inception for pulmonary carcinoid tumors.