Can Elastography Stretch Our Understanding of Thyroid Histomorphology?

Understanding the etiology of nodular thyroid disease is a fundamental prerequisite for its subsequent eradication (1–3). For this complex disorder, where the phenotypic presentation is based on an ill-defined interplay between genetic and environmental factors (3, 4), overwhelming evidence points at the amount of tobacco smoking (positively correlated) and decreasing iodine intake (negatively correlated) being the most important modifiable environmental triggers (3, 5, 6). Based on this, it is no surprise that the epidemiology and the phenotypic presentation vary with the population in focus. In a very simplified manner, at least at the level of the individual seeking medical care, the relative risk of harboring thyroid malignancy in a thyroid nodule, although still much lower than the likelihood of a benign disorder, is highest in an iodine-replete, nonsmoking individual. This is so because such individuals have a lower risk of having colloid goiter. It follows that the physician’s individualized risk assessment is probably a major determinant for the huge variation in the expert opinion regarding the diagnostic and therapeutic management of nodular thyroid disease, whether unior multinodular (1, 3). For diagnostic purposes, guidelines generally recommend the use of functional and morphological characterization using serum TSH for the former and a combination of clinical examination, diagnostic imaging, and fine-needle aspiration cytology (FNAC) for the latter (7). Using such a strategy combined with serum calcitonin to rule out the approximately 1% risk of medullary thyroid cancer, it is generally believed that the chance of overlooking thyroid malignancy can be reduced to less than 1% in the 60–70% of individuals who have a benign FNAC (7). The remaining 30–40% have thyroid malignancy or insufficient or indeterminate FNAC. These figures are based on a number of criteria for obtaining and analyzing the cytology material, as well as on the obvious disregard of a benign FNAC in the face of certain clinical (e.g. family history of thyroid malignancy, hard and/or rapidly growing nodule, signs of invasivegrowth,andregional lymphadenopathy, tomention but a few) or serological (elevated calcitonin) markers (7, 8). It is generally believed that ultrasound (US) criteria such as hypoechogenicity, the lack of a complete halo surrounding the nodule, microcalcifications, and marked intranodular and absent or slight perinodular vascularization using Doppler-flow (type III flow) are helpful in targeting nodules at the highest risk of harboring thyroid malignancy (7, 8). Used in a number of combinations, each characteristic increases the sensitivity but lacks adequate specificity for reliably diagnosing thyroid malignancy. During the last few years, a novel technology based on the elastic property of the tissue, US elastography (USE), has been added to the diagnostic armamentarium. The technology involves placing the probe and applying a uniform and slight pressure on the neck. A box, covering the target nodule and the immediate surrounding normal tissue, is highlighted on the scan image. Two US images, before and after tissue compression, are obtained. A dedicated software tracks the tissue displacement and displays this using a color scale ranging from red (highest elasticity corresponding to lowest risk of malignancy) over green (intermediate elasticity) to blue (lowest elasticity and correspondingly highest risk of malignancy). Although available for about two decades, USE was first evaluated in the context of the thyroid by Lyshchik et al. (9) in 2005. Since then, a number of studies have evaluated this technique (10–16). They uniformly suggest that USE increases the ability to discriminate between benign and malignant nodules. Based on these eight studies (9–