Thyroid cytopathology: how far can we go?

In our journal, Cytopathology, it is rather unusual to publish almost an entire issue devoted to a specific topic. Nevertheless, in this June issue, with its six articles on thyroid fine needle aspiration (FNA), it is very much the case. Thyroid FNAs are widely recommended by the national health ministries in most European and non-European developed countries, as well as in the USA, because of the high estimated prevalence of thyroid nodules worldwide, ranging from 20% to 76%, correlated with the high diagnostic accuracy of thyroid cytology: sensitivity ranging from 65% to 98%, usually more than 90%; specificity ranging from 58% to 100%. Therefore, many teams of endocrinologists, radiologists, internists and cytopathologists have developed this test and wish to publish their results, which explains the large number of articles on thyroid cytology. Thyroid FNA cannot be considered as a recent technique, as it was first implemented in the 1950s. Although numbers of thyroid FNAs remained low for many years, during the last two decades the numbers have increased strongly in parallel with the development of preventative medicine and events such as Chernobyl. The diagnosis has historically been exclusively based on morphology, which remains pivotal to this technique, offering, as mentioned above, a quite satisfactory diagnostic global accuracy. As thyroid cancers, mostly papillary carcinoma, represent 5–12% of thyroid nodules, which are, in the great majority, benign, thyroid FNA may, to some extent, be considered as a screening test aiming to detect malignant cases and to avoid surgery for most of the benign nodules. Regardless of the skill of those who perform FNA in providing representative samples, and the expertise of the cytopathologists, 20–25% of nodules remain ‘unclassified’, neither benign nor malignant, and represent a group of so-called ‘indeterminate’ nodules for which partial or total thyroidectomies, or repeat FNAs, are required so that malignant cases do not go undetected. This unsatisfactory situation has not been solved and, although poor samples are responsible for many cases with indeterminate or suspicious diagnoses, three recent major changes have taken place. The first is represented by a standardized terminology; the other two by immunocytochemistry (ICC) and molecular testing, both often linked to liquid-based cytology (LBC) or cell block techniques. The six articles published in this issue illustrate these new techniques. Considering that standardized cytology terminology could lead the way to better diagnosis, this long remained as something unusual and thus rather ignored in practice; perhaps the Papanicolaou classification for cervical smears, followed by the Bethesda terminology in 1991, were the first examples. The Bethesda system for reporting thyroid cytopathology (TBSRTC) was published in 2009–2010. There are some others: the Societ a Italiana di Anatomia Patologica e Citologia Diagnostica (SIAPEC) classification, here represented by the study of Pagni et al., and the UK terminology used by Poller and Glaysher and Johnson et al. TBSRTC was debated and then recommended during the European Congress of Cytology in Lisbon in 2009, and has been adopted by many European countries, including Croatia, Finland, France, Greece, Portugal and Turkey. These three terminologies are widely applied in the world and are all applicable: the Italian and UK classifications are five tiered, with subdivisions of their respective indeterminate categories, and TBSRTC is six tiered; all recognize benign, malignant, non-diagnostic categories, and some other categories named differently, representing the ‘indeterminate’ cases, and are more or less transposable. TBSRTC is the only classification with a published atlas, which includes explanations for the choice of a six-tier terminology, definitions for each category, many cytological images and an estimated percentage and risk of malignancy for each category. TBSRTC does not resolve the ‘borderline diagnoses’, but offers tools to help gain an acceptable interobserver reproducibility and therefore a more homogeneous management for patients. As TBSRTC is, for the first time, suitable for the comparison of observations obtained by different teams in the world, two major results have arisen: (1) in the most recent studies, the percentage and risk of malignancy for each category confirm those proposed by the TBSRTC, as well as its reproducibility; (2) in cases of discrepancy, a cause may be determined. For example, discrepancies may be caused by an epidemiological context, as reported DOI:10.1111/cyt.12160