Pathogenesis of thyroid nodules in multinodular goiter

Area of Science:

• Endocrinology
• Pathology
• Surgical Pathology

Background:

• Nodular goiters are common, but their pathogenesis, particularly the formation of individual nodules, remains incompletely understood.
• Previous studies often focused on distinct adenomas, potentially overlooking the contribution of polyclonal follicular hyperplasia within a constrained environment.

Purpose of the Study:

• To investigate the pathogenetic mechanisms underlying nodule formation in nodular goiters.
• To differentiate between true adenomas and hyperplastic nodules in the context of long-standing goiter.

Main Methods:

• Histopathological examination of over 100 nodular goiters from a subendemic region.
• Autoradiography of 60 surgical specimens to assess follicular function and heterogeneity.
• Analysis of the connective tissue network and its role in follicular growth.

Main Results:

• Only one classical, well-encapsulated adenoma was identified among the specimens.
• Most nodules were incompletely encapsulated and comprised morphologically and functionally similar follicles to non-nodular parenchyma.
• Autoradiography revealed significant interfollicular heterogeneity, indicating varied follicular activity.
• Nodular growth is attributed to follicles expanding within an inelastic, fibrous connective tissue network resulting from scarring and hemorrhage.

Conclusions:

• The majority of thyroid nodules in long-standing goiters are not distinct adenomas but rather polyclonal goiter follicles.
• These follicles expand and form nodules due to replication within a restrictive, poorly extensible connective tissue matrix.
• The nodular growth pattern is an inevitable consequence of follicular expansion constrained by the developing fibrous network.