Clonality of Endocrine Proliferative Lesions: A Critical Reappraisal

The distinction between nodular hyperplasia and benign tumors of the endocrine system is problematical. Although numerous parameters including lesional size, multicentricity and histological features have been suggested as distinguishing criteria, none of these is absolute. Analyses based on X-chromosome inactivation have provided conflicting results with respect to the clonal origins of these lesions, and at least some lesions conventionally classified as hyperplastic nodules appear to be monoclonal, Although clonality has been generally equated with neoplasia, it is likely that clonal expansion of genetically normal cells can occur in the endocrine system as a result of a variety of growth of promoting stimuli. Multiparametric studies employing markers for X-chromosome inactivation together with methods for identification of unique non-X-linked genetic alterations will be required to resolve the many questions relating to the pathogenesis of endocrine proliferative lesions.