Head and Neck Pathol (2009) 3:82–85 Discussion FNA as a Screening Test for Follicular Carcinoma The application of FNA to distinguish benign follicular nodules from follicular carcinomas is problematic because the criteria for distinguishing between them are based upon histologic evidence of transcapsular or vascular invasion. Since invasion cannot be assessed by FNA, the question becomes ‘‘how can FNA be used to evaluate follicular neoplasia.’’ The answer is that FNA is used as a screening test for follicular carcinoma. The cytologic criteria used to distinguish benign from suspicious thyroid lesions includes the follicular group architecture, smear cellularity, amount of colloid, and cytologic atypia [8]. By far, the most important of these criteria is cytoarchitecture [9, 10]. Thus, while a speciﬁc diagnosis may not be given, it is possible to subcategorize these lesions into two groups: those which are almost certainly benign, and those which are suspicious for a follicular neoplasm and possibly malignant. This subcategorization identiﬁes a majority of patients with benign lesions for whom surgical intervention can usually be avoided. Benign thyroid nodules are characterized microscopi- cally by a macrofollicular pattern which features large ﬂat sheets of follicular cells with small dark round nuclei in a honeycomb arrangement, usually in a background of moderate to abundant colloid (Fig. 1). The ﬂat sheets of cells result from fragmentation of macrofollicles with extrusion of colloid during the smear preparation. In con- trast, thyroid aspirates composed of microfollicles (small follicular groups of 6–12 follicular cells in a ring with or without a small amount of central colloid), crowded tra- beculae, or 3-D groups of overlapping follicular cells are a 83 feature of follicular carcinomas as well as some adenomas (Fig. 2). These aspirates are diagnosed as ‘‘suspicious for a follicular neoplasm,’’ and it is this group of patients for whom thyroid lobectomy is generally considered warranted. By sorting follicular lesions into two groups based pri- marily upon cytoarchitecture, FNA can identify a large subset of nodules that are benign, and that do not require surgery. This approach works because follicular carcino- mas are rarely composed of predominantly normal-sized or macrofollicles [8, 10]. The key to using this approach is to focus upon the predominant cytoarchitectural pattern. A common pitfall is to identify a minor population of mi- crofollicles and ignore the overall pattern. In addition, it is important to also evaluate the nuclear features of the cells to avoid the pitfall of the follicular variant of papillary thyroid carcinoma. Unfortunately, while FNA as a screening test is highly sensitive, it lacks speciﬁcity. Approximately 15–30% of aspirates diagnosed as ‘‘suspicious for a follicular neo- plasm’’ are actually carcinomas while the remaining 70– 85% of nodules are benign. [11–13] A wide variety of immunohistochemical and molecular markers have been studied in an attempt to distinguish between benign thyroid nodules and follicular carcinomas in FNA samples; how- ever, to date, none has been identiﬁed with both high sensitivity and speciﬁcity. Until such marker is available, FNA will remain a screening test rather than a diagnostic test for follicular carcinomas. The Follicular Variant of Papillary Thyroid Carcinoma The follicular variant of papillary thyroid carcinoma is the most common subtype of papillary thyroid carcinomas [5]. Fig. 1 Thyroid FNA demonstrating a macrofollicular group of cells in a background of abundant watery colloid. These features are typical of a benign thyroid nodule. (Papanicolaou stain) Fig. 2 Thyroid FNA showing follicular cells in a predominantly microfollicular arrangement. This cytoarchitectural pattern is charac- teristic of a follicular neoplasm. (Papanicolaou stain)