MORPHOLOGICAL AND FUNCTIONAL POLYMORPHISM WITHIN CLONAL THYROID-NODULES

Thirty-nine thyroid nodules, removed because of recent growth, were an alyzed morphologically by serial histological sections for the classic al histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-assoc iated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27beta that detects polymorphisms on the lo cus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of polyclonal origin. Only 3 out of the 24 clonal nod ules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression wer e remarkably heterogeneous throughout the tumors. There were no histom orphological characteristics distinguishing these clonal tumors from p olyclonal nodules. Even if a clonal thyroid tumor may be originally ho mogeneous in respect to the parameters studied here, mechanisms must e xist that create wide heterogeneity of growth and of morphogenetic pot ential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular go iters than hither-to assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rel y on morphological and functional criteria alone but requires molecula r or cytogenetic analysis of clonality.