Thyroid nodules in recurrent multinodular goiters are predominantly polyclonal

Not only thyroid adenomas and carcinomas, but also the majority of single and well delimited goiter nodules, even if morphologically heterogeneous, are of clonal origin. However, it is still unknown whether the nodules of rapidly growing, recurrent goiters are clonal or polyclonal. We investigated by PCR-based analysis of exon 1 of the human androgen receptor gene clonality of nodules grown in recurrent multinodular goiters (MNG) of 14 female patients. The total goiter volume varied widely between 15 ml and 170 ml. The mean age of patients undergoing surgery for recurrent goiter at the time of their first operation was significantly lower with 34.6 +/- 10.9 yr in comparison to 50 consecutive patients who were operated for MNG for the first time (53.7 +/- 13.5 yr). The interval between first and recurrent operation was 18 +/- 8.5 yr. The mean volume of well circumscribed nodules selected for the present investigation was 3.8 +/- 1.4 ml. Assessment of clonality in at least 2 samples of each lesion revealed a polyclonal pattern in 10 out of 14 nodules, whereas only 3 nodules were clonal and in one case the result remained unclear. The unexpected finding that most nodules within MNG, that had re-grown after a first subtotal thyroidectomy, were of polyclonal rather than clonal composition, suggests that these lesions are generated by de novo-proliferation of cohorts of differing thyrocytes sharing the common trait of an exceedingly high intrinsic growth rate or alternatively, by unknown growth stimulating molecular events acting focally on clusters of cells derived from different ancestors. In addition, the relatively young age of patients with recurrent MNG at the time of their first surgery and the comparatively short interval between first and second operation point to a genetic element in the occurrence of growth-prone thyrocytes.