The Bethesda system for reporting thyroid cytopathology: into the clinic

Abstract

Fine-needle aspiration (FNA) remains the most effective and safe method of evaluating thyroid nodules for potential surgical management. Since 2007, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized nomenclature for thyroid FNA and provided an evidence-based malignancy risk for each of its diagnostic categories. Using TBSRTC criteria, most thyroid nodules can effectively be categorized as either "benign" or "malignant" and referred for definitive management without further testing. However, many thyroid nodules fall into an indeterminate TBSRTC category, most notably atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). Efforts have been made to elucidate further clinical utility from indeterminate cases, including nomenclature modifications and molecular-based testing modalities. The use of "atypia qualifiers" in AUS/ FLUS cases appears to refine the diagnosis to provide a more specific risk of malignancy. Notably, AUS qualifiers of "cannot exclude papillary thyroid carcinoma" and "cannot exclude follicular neoplasm" appear to carry a higher risk of malignancy than other AUS qualifications in multiple studies. Molecular panels appear to hold particular promise as adjuncts in helping to delineate worrisome from non-worrisome thyroid nodules with indeterminate cytology. In particular, the miRInform test (Asuragen), an oncogene mutation panel, appears to show utility in its ability to "rule in" a malignant or neoplastic process, although it is limited by a relatively high false-negative rate. Conversely, the Afirma test (Veracyte), a gene expression classifier (GEC), appears to show clinical promise due to its high negative predictive value; albeit with a significant false-positive rate. Herein, we provide an overview of TBSRTC diagnostic categories and a literature review of new attempts to further refine indeterminate categories; as well as a review of the most commonly used commercial molecular panels used in thyroid cytopathology.

Comparison of Fine Needle Aspiration Cytology in Thyroid Lesions using The Bethesda System for Reporting Thyroid Cytopathology with Ultrasonography using Thyroid Imaging Reporting and Data System

“…ATA suggests that partially cystic nodules yielding ND aspirate need close observation or surgical excision, whereas surgery should be the considered if lesions are solid. [3,14] In our study, 7.4% of the cases were malignant on FNA. If we include the cases in TIRADS-V and TBSRTC-V, the prevalence rate of malignant lesions on thyroid is 9.25%, including the highly suspicious lesions for malignancy.…”

“…ND/USF cases range from 1.8% to 23.6% of all thyroid FNAs. [3] Thyroid FNAs are ND/USF mostly due to cystic nature, sampling error or poor preparation techniques. Around 7% of thyroid lesions will be ND/USF even on repeat FNAs.…”

“…[1] Out of these thyroid nodules, only around 5% are found to be malignant. [3] Therefore, the major concern about thyroid nodule is to rule out or confirm malignancy by USG and Fine Needle Aspiration (FNA). Surgical removal of all thyroid nodules is unnecessary and should be stratified by the use of USG and FNA.…”

“…[4] The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a standardized, category based evaluation of thyroid FNAs to provide a uniform diagnostic terminology for pathologists. [3,5,6] TBSRTC also provides an implied risk of malignancy and recommends clinical management of the thyroid lesions according to the category. [3,4,5] The six diagnostic categories suggested by TBSRTC are: I) Non-diagnostic or unsatisfactory; II) Benign; III) Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS); IV) Follicular Neoplasm (FN) or Suspicious for Follicular Neoplasm; V) Suspicious for Malignancy; VI) Malignant.…”

“…[3,5,6] TBSRTC also provides an implied risk of malignancy and recommends clinical management of the thyroid lesions according to the category. [3,4,5] The six diagnostic categories suggested by TBSRTC are: I) Non-diagnostic or unsatisfactory; II) Benign; III) Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS); IV) Follicular Neoplasm (FN) or Suspicious for Follicular Neoplasm; V) Suspicious for Malignancy; VI) Malignant. [5] The Thyroid Imaging Reporting and Data System (TIRADS), first proposed by Horvath et al [7] was established to standardize the scoring system of thyroid USG and provide recommendations for using FNA and to improve appropriate patient management.…”