23 Diagnostic utility of molecular and imaging biomarkers 2 Introduction Indeterminate thyroid cytology is an eyesore to physicians. It largely corresponds to histopathologically follicular-patterned lesions, both benign and malignant, including follicular adenoma, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), (encapsulated) follicular variant of papillary thyroid carcinoma (FVPTC or EFVPTC) and follicular thyroid carcinoma (FTC). These neoplasms are particularly difficult to differentiate on fine needle aspiration cytology (FNAC). In the case of FTC, cytology lacks the insight into the tissue structure like histology does: it does not show the capsular and/or vascular invasion that distinguishes an FTC from a benign FA. In FVPTC, the growth pattern is follicular and clearly identifying nuclear features of PTC can usually not be identified cytologically [41-43]. Nevertheless, FNAC currently has a most prominent place in the diagnostic work-up of thyroid nodules. The Bethesda System for the Reporting of Thyroid Cytology was adopted in its current form in 2009, recognizing six diagnostic categories with an incremental risk of malignancy and clinical management guidelines. Although the Bethesda system created a much-used handhold by standardizing the cytological diagnosis and consecutive management of thyroid nodules worldwide, the system does not provide a clear answer for the heterogeneous group of nodules with indeterminate cytology [26, 44]. This includes cytology with atypia of undetermined significance or follicular lesion of undetermined significance (AUS/ FLUS, Bethesda III), and cytology (suspicious for a) follicular neoplasm (SFN/FN) or (suspicious for a) Hürthle cell neoplasm (SHCN/HCN, Bethesda IV). Similar indeterminate cytological categories are found in the British Thyroid Association Thy system and Italian SIAPEC-IAP classification: Thy3a and Thy3f, and TIR3A and TIR3B, respectively (Table 1) [45, 46]. Alongside a doubled incidence of thyroid carcinoma over the past two decades and a prevalence of thyroid nodules stretching far beyond the 5% for palpable nodules – explained by the incidental detection of nonpalpable nodules and clinically occult thyroid cancers on imaging studies – the need for a more accurate diagnostic procedure has grown [47]. This urge was further emphasized when other research groups were unable to reproduce the prevalence of the cytological categories and corresponding malignancy risks proposed by Cibas et al., especially those of the AUS category [44, 48, 49]. Insuperable variations in the worldwide patient populations, and intra- and interobserver variation in the assessment of thyroid cytology were named as likely underlying causes [26, 44, 49, 50]. Yet, it raised questions concerning the overall approach of thyroid nodule diagnosis and whether cytology is the best starting ground. Cost-effectiveness is a major benefit of cytological examination, yet a more accurate test may eventually replace cytological examination completely [51, 52]. At present, however, a supplemental diagnostic procedure is specifically warranted for cytologically indeterminate thyroid nodules. Diagnostic hemithyroidectomies are still customarily performed to obtain a definite histological diagnosis. With a benign histopathological result in approximately three in four cases, surgery was not only unbeneficial but also exposed the patient to unnecessary
RkJQdWJsaXNoZXIy MTk4NDMw