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Heterogeneity of multinodular goitre |
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Heterogeneity is a main feature of multinodular goitre. The clinical presentation and the progression of the disease, as well as the appearence of thyroid scintigrams may be most varied between patients. Furthermore, histological and autoradiographical studies have demonstrated excessive heterogeneity of goitre tissue removed by surgery. The majority of nodules and internodular tissues are heterogeneous with widely varying appearance of the follicles and with follicles and clusters of cells within follicles having highly diverse functional activity. Scattered necrotic areas, connective tissue strands, cysts and even calcifications may be found in longstanding multinodular goitre. Ascintigram of a universially affected thyroid in a hyperthyroid patient is shown in fig 4.
Figure 4:
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Pertechnetate scintigram of a multinodular goitre in a hyperthyroid patient. Note the universal but heterogeneous affection of the gland. |
The pathogenesis of this heterogeneity has been studied extensively by Studer and collaborators2. One mechanism may be amplification of natural heterogeneity of thyroid cells during generation of new follicles. However, this cannot explain more recent findings on the relation between clonal origin and heterogeneity of multinodular goitre. Heterogeneous nodules in a multinodular goitre may be of either mono- or polyclonal origin without significant difference in histological structure. Only few (monoclonal) nodules have the relative uniform histological structure of a "true" adenoma. Thus, even parts of the thyroid developing from a single cell (monoclonal origin), may become heterogenous during goitrogenesis.
Multinodular goitre is basically a polyfocal and polyclonal abnormality. On top of this, more distinct nodules have developed, some of which are of monoclonal origin. Some of the more distinct hot and monoclonal nodules of a multinodular goitre harbour the same somatic point mutations activating the TSH receptor as found in solitary hot nodules of otherwise normal thyroid glands
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