84 In FNA specimens, it can pose a diagnostic challenge due to the abundance of microfollicles or monolayer tissue fragments mimicking a follicular neoplasm. In fact, among those FNAs diagnosed as ‘‘suspicious for a follicular neo- plasm’’ that are malignant in histologic follow-up, over 30% are identiﬁed as the follicular variant of papillary thyroid carcinoma [13, 14]. In contrast to the hyperchro- matic chromatin seen in follicular neoplasms, the follicular variant of papillary thyroid carcinoma exhibits pale, pow- dery chromatin along with nuclear grooves and occasional intranuclear pseudoinclusions (Fig. 3). The cells tend to be round to oval and less pleomorphic than the conventional type of papillary carcinoma. Variable amounts of dense colloid are frequently seen in this variant, and multinu- cleated giant cells may also be identiﬁed. Usually the cytologic diagnosis of the follicular variant of papillary carcinoma is not difﬁcult, but in a subset of cases, the nuclear features can be quite subtle resulting in misclassi- ﬁcation of the lesion. Development of methods to detect RET/PTC rearrangements or point mutations of the BRAF gene in routine thyroid FNA samples may prove useful for solving this problem [15]. Reporting of Thyroid FNAs A major challenge in the application of FNA to the diagnosis of thyroid lesions has been the inconsistent use of termi- nology for reporting results of thyroid FNAs both within laboratories and between different institutions. Not only has this hindered the sharing of information between different institutions, but it has created difﬁculties for clinicians managing patients with thyroid disease. A major advance on this front was made by the NCI Thyroid FNA State of the Science Conference which convened on October 22–23, Fig. 3 The follicular variant of papillary thyroid carcinoma is characterized by cells with pale chromatin, somewhat enlarged oval nuclei, and occasional longitudinal nuclear grooves in a background of variable amounts of colloid. (Papanicoloau stain) Head and Neck Pathol (2009) 3:82–85 2007 in Bethesda, Maryland. It addressed issues including indications for thyroid FNA, training, techniques, reporting terminology, ancillary testing, and management guidelines [16, 17]. Based upon the ﬁndings, a Bethesda System-type diagnostic framework for reporting thyroid FNA results was proposed that consists of seven general diagnostic categories (Table 1). Importantly, the terms used for reporting results are associated with a risk of malignancy which will impact recommendations for patient management [16]. Atypical Cells of Undetermined Signiﬁcance (ACUS) While most follicular-patterned lesions can be accurately assessed using thyroid FNA, a small subset of lesions exhibit cytologic features that are intermediate between benign and neoplastic. This so-called ‘‘indeterminate’’ category has been used in various ways by different laboratories. Some have used this category for any aspirate with atypia, for others the category has been used to mean ‘‘indeterminate for malignancy’’ or ‘‘indeterminate for neoplasia.’’ In the pro- posed Bethesda System for thyroid cytology, the ACUS or indeterminate category is speciﬁcally designated for use when the ‘cytologic and/or architectural atypia encountered is of uncertain signiﬁcance: it is of an insufﬁcient degree to qualify for any of the suspicious or malignant categories’ [18]. At the same time, the cytologic or architectural atypia is more than would be acceptable within the ‘‘benign’’ cate- gory. There are many different situations in which an ACUS diagnosis would be used, but some of the most common include the following: (1) a sparsely cellular aspirate with a predominance of microfollicles, (2) cytologic atypia in the setting of preparation artifact, (3) a mixed cytoarchitectural pattern that includes nearly equal proportions of macrofol- licles and microfollicles (Fig. 4), (4) focal atypia suggestive of papillary carcinoma in an otherwise predominantly benign-appearing sample (Fig. 5). Because of the potential to overuse the ACUS category, it should be less than 7% of all thyroid FNA interpretations [18]. For thyroid aspirates diagnosed as ACUS, the recommended management is clinicoradiologic correlation and in most cases, a repeat Table 1 Proposed 7-tiered Bethesda system for reporting of thyroid cytologya Diagnostic category Risk of malignancy (%) Insufﬁcient for diagnosis 1–4 Benign \1 Atypical cells of undetermined signiﬁcance 5–10 Suspicious for a follicular neoplasm 15–30 Suspicious for a Hurthle cell neoplasm 15–45 Suspicious for malignancy 60–75 Malignant 97–99 a Modiﬁed from Cibas and Ali 2009