Morphological and functional polymorphism within clonal thyroid nodules.

Abstract

Thirty-nine thyroid nodules, removed because of recent growth, were analyzed morphologically by serial histological sections for the classical histomorphological hallmarks of follicular cell replication and for immunohistochemically demonstrable overexpression of the growth-associated ras-gene product p21ras. Clonal analysis was performed using the highly informative probe M27 beta that detects polymorphisms on the locus DXS255 of the X-chromosome. Twenty-four nodules were of clonal and 15 nodules were of poly-clonal origin. Only 3 out of the 24 clonal nodules were histomorphologically uniform. In all others, the structural hallmarks of active growth and the P21ras growth-marker expression were remarkably heterogeneous throughout the tumors. There were no histomorphological characteristics distinguishing these clonal tumors from polyclonal nodules. Even if a clonal thyroid tumor may be originally homogeneous in respect to the parameters studied here, mechanisms must exist that create wide heterogeneity of growth and of morphogenetic potential among the individual follicular cells during further expansion of the nodule. Thus, clonal nodules are much more common in nodular goiters than hitherto assumed on grounds of the classical morphological criteria. The diagnosis of a true monoclonal nodule can no longer rely on morphological and functional criteria alone but requires molecular or cytogenetic analysis of clonality.

Follicular thyroglobulin enhances gene expression necessary for thyroid hormone secretion

“…4, 'Merge'), indicating that the action of Tg is independent of the localization of the target protein, and that it suppresses or induces gene the thyroid follicle, or the 'follicular cycle model', well explains the nature of follicular heterogeneity [2,4,5,19,22,23]. Thus, the activities of the follicles, which are the minimum functional units of the gland, are not synchronized but heterogeneous despite having similar TSH supplies [24][25][26][27][28][29]. The model hypothesizes that each follicle repeats 'synthesis phase', 'storage phase' and 'secretion phase' without apparent synchronization, which primarily depends on the variable follicular Tg accumulation [19].…”

Clonality as Expression of Distinctive Cell Kinetics Patterns in Nodular Hyperplasias and Adenomas of the Adrenal Cortex

“…Endocrine hyperplasias have shown polyclonal patterns in hereditary and nonhereditary hyperparathyroidism 30,31 or multinodular goiters. 32,33 Most parathyroid or thyroid adenomas have been found to be monoclonal. [31][32][33] Those findings support the concept of multistep tumorigenesis and Knudson's hypothesis.…”

“…32,33 Most parathyroid or thyroid adenomas have been found to be monoclonal. [31][32][33] Those findings support the concept of multistep tumorigenesis and Knudson's hypothesis. 34 However, monoclonal hyperplasias (parathyroid, in multiple endocrine neoplasia type 1 (MEN-1) and uremic patients, and multinodular goiters) 33,35 and polyclonal adenomas (parathyroid and thyroid) 30 have also been reported.…”

The Association of Warthin Tumor with Salivary Ductal Inclusions in Intra and Periparotid Lymph Nodes

“…Under exogenous stimulations such as smoking, transition from hyperplasia and metaplasia to neoplasia may occur [14], as is thought in some other organs (for example in thyroid multinodular goiter) [15,16].…”