Thyroid Fine-Needle Aspiration Cytology Molecular Testing in the USA

Abstract

Each year in the USA, approximately 57,000 thyroid cancer cases are diagnosed, and 2000 patients die from this disease [1]. Compared to other common cancers (e.g., lung, pancreas, colorectal), the ratio of mortality to incidence is very low. The main reasons for this observation are threefold—(1) most primary thyroid cancers are differentiated carcinomas with low mortality rates, (2) the presentation of differentiated carcinomas at the higher stages (e.g., stage III or IV) is uncommon, and (3) the incidence of inherently aggressive dedifferentiated carcinomas (e.g., poorly differentiated carcinoma, anaplastic carcinoma) is also very low. In general, differentiated carcinomas come in two varieties—those that are solid, hypoechoic, round, and well circumscribed or encapsulated and those that show invasion into the capsule and/or infiltration into adjacent tissues. Since the radiologic, cytologic, and histologic features of the former type overlap with those of benign hyperplastic and low-grade neoplastic nodules, preoperative distinction between some benign lesions and low-grade carcinomas is challenging (Fig. 60.1). Accordingly, approximately 30% of thyroid fine-needle aspiration (FNA) specimens are placed in one of the indeterminate Bethesda System for Reporting Thyroid Cytopathology (BSRTC) categories [2, 3]. Furthermore, heterogeneity of the nodule and variability in sampling yields from the fine-needle aspiration (FNA) procedures may preclude a definitive diagnosis. For example, some follicular variant papillary thyroid carcinoma (FVPTC) may demonstrate diagnostic cytologic features only focally. In another example, a 0.5 cm anaplastic carcinoma (AC) may be present in a 3 cm classic papillary thyroid carcinoma (PTC). Due to the focality of the lesions, these areas may or may not be sampled by FNA. Furthermore, depending on the skill of the FNA operator, slide preparation technique, and nature of the thyroid nodule, the quality and quantity of lesional cells on the cytologic preparations may vary. In the USA, thyroid FNAs are performed by endocrinologists, surgeons, radiologists, otolaryngologists, and cytopathologists, and, therefore, not all cytology specimens are generated in the same manner. Processing of the aspirated specimens also varies—direct smears (e.g., Papanicolaou stain, Diff-Quik, or other Romanowsky-type stains), liquid-based cytology, and cell-block preparation. A cytopathology laboratory may use one or a combination of these methods. While patients with benign FNA diagnoses are observed, those with a malignant diagnosis often undergo surgery and/or other oncologic treatments. For the remaining indeterminate BSRTC diagnoses, the estimated risks of malignancy are too high for observation, and many are subjected to a diagnostic lobectomy or thyroidectomy. In this regard, the application of new technologies to elucidate the biologic nature of these nodules to minimize the number of diagnostic surgeries and maintain robust quality assurance has become an area of intense interest among clinicians, cytopathologists, and molecular pathologists.