POLYCLONAL AND MONOCLONAL THYROID-NODULES COEXIST WITHIN HUMAN MULTINODULAR GOITERS

Although somatic mutations have been identified in a subset of thyroid nodules, the pathogenesis of nodules in multinodular goiters remains unclear, Clonal analysis indicates whether a nodule arises from the po lyclonal proliferation of a group of cells or forms a clone from a gen etically altered cell. Individual thyroid nodules have been shown to b e of polyclonal or monoclonal origin. In this study we examined the cl onality of several different nodules in patients with multinodular goi ters. Clonality was established using the X-chromosomal probe M27 beta , which detects a multiallelic polymorphism at the locus DXS255 in 90% of females. Twenty-five nodules from 9 multinodular goiters were anal yzed; 9 nodules were polyclonal, and 16 were monoclonal. Three goiters contained only polyclonal nodules, whereas 3 contained only monoclona l nodules. Polyclonal and monoclonal nodules coexisted in 3 goiters. I n 2 goiters, the monoclonal nodules were shown to derive from differen t progenitor cells. We conclude that polyclonal and monoclonal nodules may coexist in multinodular goiters and that monoclonal nodules can o riginate from different cells. The coexistence of polyclonal and monoc lonal nodules suggests that different pathogenic mechanisms occur simu ltaneously or that monoclonal nodules emerge secondarily from a polycl onal population due to a growth advantage from a genetically altered c ell.