Assessment of The Bethesda System for Reporting Thyroid Cytopathology

Abstract

Objectives

Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA).

Methods

Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated.

Results

Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM).

Conclusions

Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

There have been many recent advances in thyroid fine-needle aspiration (FNA). Utilization of ultrasound guidance has improved the ability to obtain diagnostic material. Improved imaging techniques and increased surveillance for nonthyroid malignancies have increased the detection of incidental nodules.^1-4 The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), introduced in 2009 and subsequently widely implemented, has standardized diagnostic terminology.⁵ Based on the evidence available at the time, TBSRTC provided an estimated risk of malignancy (ROM) for each cytology diagnostic category, and these were used to develop management guidelines for each category.⁵ In 2015, the American Thyroid Association provided updated recommendations for the management of thyroid nodules and endorsed TBSRTC for this purpose.⁶ Determining appropriate management for indeterminate nodules (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS] and suspicious for follicular neoplasm/follicular neoplasm [SFN/FN]) remains challenging. Molecular testing of aspirated material from thyroid nodules has emerged to assist in perioperative decision making.^7-9 However, molecular profiling has limitations, and unnecessary surgery and, consequently, morbidity remain important challenges in the treatment of thyroid nodules.

The most recent advance in thyroid pathology is the reclassification of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).¹⁰ This nomenclature was proposed in an effort to reduce overtreatment of indolent thyroid nodules.^10-12

Long-term clinical follow-up in addition to histology is important for minimizing surgical selection bias when determining performance characteristics of thyroid FNA, but most prior studies include only pathology (histology with or without cytology) follow-up.^4,13 To address this void in the literature, we evaluated the performance characteristics of thyroid FNA before and after implementation of TBSRTC terminology at our institution using histologic and long-term clinical follow-up, and we investigated the potential impact of NIFTP nomenclature.

Materials and Methods

Study Cohorts

Following institutional review board approval from Mayo Clinic, Rochester, MN, two cohorts were identified: all patients undergoing initial thyroid FNA by endocrinologists or interventional radiologists at Mayo Clinic (Rochester, Minnesota) during 3-year periods prior to (2001-2003) and following (2010-2013) implementation of TBSRTC. The cytology preparation used for diagnosis during this timeframe was alcohol-fixed Papanicolaou-stained direct aspirate smears. Aspirations from multiple nodules in the same patient were counted separately. All nodules were included, regardless of size. A sensitivity analysis excluding nodules 1 cm or less did not change the findings.

Data were collected using REDCap electronic data capture held at Mayo Clinic, Rochester, MN.¹⁴

Cytology Diagnoses

TBSRTC was used to classify all cytology diagnoses and includes the following diagnostic categories: nondiagnostic/unsatisfactory (ND/UNS), benign, AUS/FLUS, SFN/FN, suspicious for malignancy (SFM), and malignant.⁵ Prior to implementing TBSRTC, the diagnostic criteria and reporting at our institution were similar to those suggested by TBSRTC and included all of the major TBSRTC diagnostic categories other than AUS/FLUS. Instead of a using a distinct diagnostic category of “atypical,” descriptive interpretations were provided for atypical cases.

Follow-up

All available pathology follow-up was extracted from the laboratory information system. Only surgical pathology data for nodules previously aspirated were included. Whenever possible, the site of the surgical pathology findings was correlated with the site of the initial FNA. Incidental histologic findings not involving previously aspirated nodules were excluded. All available endocrinology clinical follow-up, including examination and ultrasound (for nodules without subsequent pathology), was obtained via the electronic medical record with detailed review of subsequent clinical examinations and imaging studies performed at least 3 months following initial aspiration. A minimum of 3 years of clinical follow-up was required for study inclusion. To evaluate thyroid cytology in a cohort of patients for whom longer clinical follow-up was available, performance characteristics were determined for patients with either histologic or a minimum of 10 years of clinical follow-up available. Patients from both pre- and post-TBSRTC with histologic follow-up and patients from the pre-TBSRTC cohort with a minimum of 10 years of clinical follow-up were included in this analysis.

NIFTP Review

All available surgical pathology slides for all EFVPTCs in both cohorts were retrospectively reviewed. Nodules meeting consensus criteria for NIFTP (ie, encapsulated nodules with follicular growth pattern and nuclear features of papillary thyroid carcinoma but no areas of papillary or solid growth or psammoma bodies) were reclassified as such.¹⁰ All nodules reclassified as NIFTP underwent microscopic examination of the entire capsule, another criterion for NIFTP classification.

Statistical Analysis

Follow-up data were used to determine the performance characteristics of thyroid FNA in both cohorts, including negative predictive value (NPV) and positive predictive value (PPV)/ROM for each cytology diagnostic category. For the purposes of this study, a “true result” (malignant vs benign) was determined for each nodule as follows: surgical pathology diagnosis for the nodule aspirated was used if surgery was performed following baseline cytology, repeat cytology diagnosis was used if there was a subsequent FNA but no surgery, and most recent clinical assessment including a clinical examination by an endocrinologist and ultrasound was used if no subsequent pathology was available. “Malignant” was defined as any malignant histology, including papillary microcarcinomas, lymphoma, and metastases, or a repeat cytology result of SFM or malignant (if no subsequent surgery) or clinically malignant (if no subsequent surgery or repeat cytology). Benign neoplasms on histology were considered “benign.” A total of six nodules (one in the pre-TBSRTC cohort that was a SFN on initial cytology and five in the post-TBSRTC cohort [one nondiagnostic, one atypical, and three SFNs on initial cytology]) without surgical follow-up but repeat cytology diagnoses of SFN were excluded from the analysis since these remain indeterminate. For nodules without subsequent pathology, clinical documentation of stability with respect to size and sonographic characteristics was used to establish whether an unresected nodule was benign.

NPV and PPV/ROM were calculated separately within each baseline cytology category, based on true benign and malignant percentages within each group, respectively. Prevalence of malignancy was determined by number of malignant nodules divided by all nodules. Performance characteristics of thyroid FNA were also calculated following NIFTP reclassification. Since NIFTP is associated with a very low risk of adverse outcome¹⁰ and since the second edition of the TBSRTC (TBSRTC II) provides reduced ROM for categories affected by NIFTP, nodules reclassified as NIFTP were considered “benign” for the purposes of calculating performance characteristics for this study. However, the authors do recognize that NIFTP is currently considered an indolent but not benign neoplasm in clinical practice. Ninety-five percent score confidence intervals (CIs) were reported.

Age at baseline FNA was compared between cohorts with a t test. Sex and selected performance measures, including NPV and PPV within selected cytology diagnoses, were compared between cohorts with χ² tests. All P values are two-sided, and P values less than .05 were considered statistically significant. Given the low number of statistical tests and the descriptive nature of this analysis, no P values have been adjusted for multiple testing. Analyses were performed using SAS version 9.4 (SAS Institute).

Results

Study Cohorts and Follow-up

In total, 5,175 total aspirates (1,949 and 3,226, pre- and post-TBSRTC, respectively) were performed in 4,502 patients. Follow-up was obtained for 2,893 aspirates: 1,277 (1,134 patients) and 1,616 (1,393 patients), pre- and post-TBSRTC, respectively. Median clinical follow-up among patients without subsequent pathology was 9.9 years (range, 3.0-15.2 years) in the pre-TBSRTC cohort and 4.4 years (range, 3.0-6.3 years) in the post-TBSRTC cohort. The percentages of nodules in the ND/UNS, SFN/FN, and SFM categories decreased, while the percentage of benign diagnoses increased post-TBSRTC. The atypical rate (ie, percentage of AUS/FLUS diagnoses) in both cohorts was less than 1% Table 1 and Image 1. Demographics of patients with follow-up are shown in Table 2.

Table 1.

Performance Characteristics of Thyroid Fine-Needle Aspiration

Cytology Category	Pre-TBSRTC				Post-TBSRTC
		Follow-up				Follow-up
	All Nodules, No. (%)	No. (%)	NPV, %	PPV, %a	All Nodules, No. (%)	No. (%)	NPV, %	PPV, %b
ND/UNS	335 (17.2)	217 (17.0)	94.0	6.0	338 (10.5)	202 (12.5)	96.5	3.5
Benign	1,102 (56.6)	607 (47.5)	97.0	3.0	2,350 (72.8)	945 (58.5)	98.5	1.5
AUS/FLUS	14 (0.7)	5 (0.4)	100	0	25 (0.8)	20 (1.2)	85.0	15.0
SFN/FN	237 (12.2)	208 (16.3)	91.8	8.2	177 (5.5)	147 (9.1)	88.4	11.6
SFM	87 (4.5)	78 (6.1)	26.9	73.1	77 (2.4)	70 (4.3)	12.9	87.1
Malignant	174 (8.9)	162 (12.7)	1.9	98.1	259 (8.0)	232 (14.3)	1.7	98.3
Total No.	1,949	1,277			3,226	1,616

AUS/FLUS, atypia of undetermined significance/follicular lesion of undetermined significance; ND/UNS, nondiagnostic/unsatisfactory; NPV, negative predictive value; PPV, positive predictive value; SFM, suspicious for malignancy; SFN/FN, suspicious for follicular neoplasm/follicular neoplasm; TBSRTC, The Bethesda System for Reporting Thyroid Cytopathology.

^aPrevalence = 20.7% (264/1,277).

^bPrevalence = 20.4% (330/1,616).

Image 1.

A, Aspirate of a thyroid nodule with rare follicular cells containing atypical features, including nuclear enlargement, micronucleoli, and rare nuclear grooves. Given the scant nature of this specimen, a diagnosis of atypia of undetermined significance (AUS) was rendered (Papanicolaou, ×400 and ×600 [inset]). Follow-up histology showed follicular variant of papillary thyroid carcinoma (not shown). B, Aspirate of a thyroid nodule with sheets of follicular cells with atypical features, including nuclear enlargement, open chromatin, and nuclear grooves (Papanicolaou, ×400 and ×600 [inset]). Follow-up histology showed a benign follicular adenoma in a background of thyroiditis (not shown). C, A hypocellular aspirate of a thyroid nodule with a rare area demonstrating a microfollicular pattern. Due to the scant nature of this aspirate, a diagnosis of AUS was most appropriate Papanicolaou, ×200). Follow-up histology showed a benign follicular adenoma (not shown).

Table 2.

Demographics of Patients With Follow-up

Characteristic	Pre-TBSRTC	Post-TBSRTC
Aspirates, No.	1,277	1,616
Patients, No.	1,134	1,393
Sex, % female	76.3	71.6a
Age, mean (SD), y	54.4 (15.1)	57.3 (14.2)b

SD, standard deviation; TBSRTC, The Bethesda System for Reporting Thyroid Cytopathology.

^a  P = .008.

^b  P < .001.

Performance Characteristics of Thyroid FNA Pre- and Post-TBSRTC

Prevalence of malignant thyroid diagnoses was 20.7% (95% CI, 18.5%-23.0%) and 20.4% (95% CI, 18.5%-22.5%) for pre- and post-TBSRTC cohorts, respectively. PPV for malignant diagnoses was over 98% in both cohorts (95% CI, 94.7%-99.4% and 95.7%-99.3% pre- and post-TBSRTC, respectively). While the percentage of SFN/FN nodules decreased, the PPV for SFM increased from 73.1% to 87.1% (P = .03), and NPV for benign cytology increased significantly from 97.0% pre-TBSRTC to 98.5% post-TBSRTC (P = .04; Table 1).

Overall Outcomes in Patients With Surgical or 10 or More Years of Clinical Follow-up

Surgical follow-up or a minimum of 10 years of clinical follow-up was obtained for 1,964 nodules. In this cohort, NPV of combined ND/UNS, benign, and AUS/FLUS cytology diagnoses was 94.9% (95% CI, 93.4%-96.1%) and combined benign and AUS/FLUS diagnoses only was 95.3% (95% CI, 93.6%-96.6%) Table 3. No deaths from thyroid cancer occurred in patients with a minimum of 10 years of clinical follow-up, but there were two deaths due to thyroid cancer (2.7 and 3.6 years following baseline cytology) in the post-TBSTRC cohort. In the cohort with a minimum of 10 years of clinical follow-up, 58 (85.3%) of 68 nodules (from 65 patients) initially classified as benign, AUS/FLUS, or SFN by baseline cytology, which were eventually diagnosed as malignant by surgical pathology, were diagnosed by histology within 3 years of initial FNA.

Table 3.

Performance Characteristics of Thyroid Fine-Needle Aspiration in Patients With Surgical Pathology or Minimum of 10 Years of Clinical Follow-up

Cytology Category	All Nodules, No. (%)	Follow-up Available
		No. (%)	NPV, %	PPV, %
ND/UNS	673 (13.0)	335 (17.1)	94.0	6.0
Benign	3,452 (66.7)	726 (37.0)	95.6	4.4
AUS/FLUS	39 (0.8)	22 (1.1)	86.4	13.6
SFN/FN	414 (8.0)	343 (17.5)	90.1	9.9
SFM	164 (3.2)	147 (7.5)	20.4	79.6
Malignant	433 (8.4)	391 (19.9)	1.5	98.5
Total No. of nodules	5,175	1,964	1,373	591

AUS/FLUS, atypia of undetermined significance/follicular lesion of undetermined significance; ND/UNS, nondiagnostic/unsatisfactory; NPV, negative predictive value; PPV, positive predictive value; SFM, suspicious for malignancy; SFN/FN, suspicious for follicular neoplasm/follicular neoplasm.

Impact of NIFTP Classification

After rereview of surgical pathology from all nodules in both cohorts originally diagnosed as EFVPTC, a total of 11 nodules were reclassified as NIFTP: seven pre-TBSRTC (one benign, two SFN/FN, and four SFM cases) and four post-TBSRTC (one SFN/FN, one SFM, and two malignant cases) Image 2 and Image 3. PPVs decreased while NPVs increased slightly in the cytology categories affected by NIFTP reclassification. SFM categories in both cohorts were affected the most Table 4.

Image 2.

Thyroid nodule with an initial cytology diagnosis of suspicious for papillary thyroid carcinoma (Papanicolaou, ×400 [A] and ×600 [B]). Original histology diagnosis was follicular variant of papillary thyroid carcinoma. This nodule would currently be classified histologically as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (H&E, ×100 [C] and ×400 [D]).

Image 3.

Thyroid nodule with initial cytology diagnosis of benign (Papanicolaou, ×200 [A] and ×600 [B]). Original histology diagnosis was follicular variant of papillary thyroid carcinoma. This nodule would currently be classified histologically as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (H&E, ×100 [C] and ×400 [D]).

Table 4.

Impact of NIFTP Reclassification on Performance Characteristics of Thyroid Fine-Needle Aspiration

Cytology Categorya	Pre-TBSRTC				Post-TBSRTC
	NPV, %		PPV, %		NPV, %		PPV, %
	Original	NIFTP	Original	NIFTP	Original	NIFTP	Original	NIFTP
Benign	97.0	97.2	3.0	2.8
SFN/FN	91.8	92.8	8.2	7.2	88.4	87.3	11.6	12.7
SFM	26.9	32.1	73.1	67.9	12.9	14.3	87.1	85.7
Malignant					1.7	2.6	98.3	97.4

NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NPV, negative predictive value; PPV, positive predictive value; SFN/FN, suspicious for follicular neoplasm/follicular neoplasm; SFM, suspicious for malignancy; TBSRTC, The Bethesda System for Reporting Thyroid Cytopathology.

^aOnly categories affected by reclassification included.

Discussion

We observed an increase in number of thyroid FNAs performed at our institution and an increase in benign nodules post-TBSRTC. The increase in benign diagnoses is likely multifactorial and possibly related to (1) increase in incidentally identified nodules from increased radiologic surveillance for nonthyroid tumors, (2) fewer ND/UNS aspirates with improved ultrasound technique, and (3) shift in diagnoses following TBSRTC. In particular, utilization of more strict criteria for SFN/FN may have shifted some diagnoses to the benign category.

An important strength of this study is the inclusion of long-term clinical follow-up. When only histology is used for follow-up of thyroid FNA, surgical selection bias may contribute to overestimation of ROM.^4,13 In the current study, some patients followed clinically were lost to follow-up. Therefore, there may be some overestimation of ROM in the current study due to less follow-up available for nodules without surgical management. Institutional referral bias and publication bias also contribute to overestimated ROMs.¹³ Although Mayo Clinic is a referral center, it also serves the local community; therefore, the risk of referral bias is somewhat restricted in this study. ROM is also overestimated in studies that include incidental microcarcinomas detected on surgical pathology that were not the nodule targeted for FNA.¹³ In the current study, the surgical reports were closely reviewed so that, to the best of our ability, the histology follow-up included only nodules that were previously aspirated, whereas incidental microcarcinomas detected histologically but not previously aspirated were excluded in follow-up data.

In the cohort of patients with 10 years of clinical follow-up, most malignancies were detected within 3 years of baseline cytology in patients whose nodules were initially diagnosed as benign or indeterminate by cytology but later diagnosed as malignant by histology. This finding suggests that 3 years of clinical follow-up may be sufficient for studying the performance of thyroid FNA as a screening test for clinically significant thyroid cancer resulting in mortality. Another study that investigated long (ie, >4 years) and short (ie, minimum of 6 months) interval follow-up of thyroid nodules with benign cytology diagnoses found that malignancy and mortality did not differ between the two follow-up intervals.¹⁵

The first edition of TBSRTC recommended limiting ND/UNS diagnoses to less than 10% of thyroid FNA diagnoses, but several reports indicate nondiagnostic rates of up to 34% at some institutions.^5,6,16-22 Although ultrasound guidance has been used at our institution as early as 2001, the improved nondiagnostic rate post-TBSTRC may partly be related to increased training and experience with ultrasound guidance over time. Like the first edition, TBSRTC II provides predicted ROMs for each cytology category but updated based on additional data published since 2009. The predicted ROM for ND/UNS in TBSRTC II increased to 5% to 10%.²³ However, recent studies report ROMs for ND/UNS of up to 9% to 32% in surgically resected nodules.^{5,18,20,21,24} In the current study, ROMs for ND/UNS categories were 6.0% and 3.5%, pre- and post-TBSRTC, respectively, and much lower than reported by studies without clinical follow-up.

The predicted ROM of 0% to 3% for the benign category did not change in TBSTRC II.²³ In the current study, ROMs for the benign category in both cohorts fell within this range. A meta-analysis of studies prior to 2010 from 21 institutions reported ROM of 1% to 10% for benign cytology.²⁵ However, these studies likely overestimate ROM since only histologic follow-up was used. Our study, which uses both clinical and histologic follow-up, shows lower ROMs in the benign categories.

Overutilization of the AUS/FLUS category reduces the power of thyroid FNA as a screening test and may result in unnecessary surgery.²⁶ Although repeat FNA is the recommended clinical management following an AUS/FLUS diagnosis, reported rates of surgery following AUS/FLUS diagnoses have ranged from 19% to 54%.^19,20,27-33 TBSRTC II recommends limiting AUS/FLUS to less than 10% of all thyroid FNA diagnoses and cautions that it is “an interpretation of last resort and should be used judiciously.”²³ In clinical practice, however, AUS/FLUS rates vary considerably among institutions, and many report rates of well over 10%. A meta-analysis of studies from 51 institutions (2009-2014) found AUS/FLUS rates of 12.5% to 50%.³⁴ One study that did include clinical follow-up (minimum of 6 months) in addition to pathology follow-up reports an AUS/FLUS rate of 6.4% with an overall malignancy rate of 28.5%.³⁵ However, these values are higher than the findings of the current study, which uses a longer clinical follow-up. The low rate of AUS/FLUS at the study institution was achieved by utilization of TBSTRC criteria to place nearly all cases into more definitive categories whenever possible and to avoid the use of AUS/FLUS except in rare cases that could not be placed in more definitive categories.

In addition, there is only moderate reproducibility of AUS/FLUS among pathologists.³⁶ Minimal use of AUS/FLUS did not increase the rate of other indeterminate diagnoses in this study. Rather, the rate of SF/SFN decreased and the rate of benign diagnoses increased post-TBSTRC. While this increase in benign nodules is likely partially related to increased detection of incidental thyroid nodules, it is also likely that many nodules that would be placed in the AUS/FLUS category at other institutions were placed in the benign category. Minimal use of AUS/FLUS with increased use of the benign category at our institution appears to be appropriate since we demonstrate high NPVs and low ROMs for benign diagnoses.

In general, the ROMs for the cytology diagnostic categories in both cohorts of this study fit within the ranges suggested in TBSRTC II. Determining an accurate ROM for the AUS/FLUS category is challenging since conservative management is recommended and surgical resection is rare.⁶ However, ROM for AUS/FLUS in our post-TBSRTC cohort was 15%, which falls within the range of 10% to 30% in TBSRTC II.²³ The ROMs for SFN/FN in both cohorts (8.2% and 11.6%, pre- and post-TBSRTC, respectively) were lower than the predicted ROM of 25% to 40%, while the ROM for the SFM category in our post-TBSRTC was higher (87.1%) than the 50% to 75% predicted. The ROMs in our malignant categories fit within the TBSRTC II predicted range.²³

TBSRTC II provides additional predicted ROMs for each category when NIFTP is considered an indolent neoplasm.²³ When adjusted for NIFTP, decreases in ROM generally occur in the indeterminate categories (AUS/FLUS, SFN/FN, and SFM).^37-42 Since AUS/FLUS is only rarely used at our institution, the SFN/FN and SFM categories were affected the most when nodules were reclassified using NIFTP criteria. However, given the low number of NIFTP diagnoses in this study, no statistically significant changes in the performance characteristics of thyroid FNA were observed. The implications of NIFTP on thyroid FNA diagnoses remain to be studied in large cohorts with long-term follow-up.

An important strength of this study is the use of a minimum of 3 years of clinical follow-up for patients without subsequent pathology for determining the performance characteristics of thyroid FNA. Another strength is the comparison to a subgroup of patients with a minimum of 10 years of clinical follow-up or surgical pathology follow-up. An important limitation is that it is impossible to adequately control for all variables that influence thyroid cytology diagnoses, including operator experience with thyroid FNA, shifting patient populations, and changes in personnel over the study time periods, including turnover in both the cytopathologists interpreting aspirates as well as endocrinologists and interventional radiologists performing ultrasound-guided thyroid FNAs. Another limitation of this study is that the data are from a single institution and the findings may not be applicable to other institutions with differing rates of the various TBSRTC diagnostic categories. However, it is also difficult for multi-institutional studies to control for diagnostic differences among pathologists, in both interpretation of thyroid FNAs as well as surgical pathology diagnoses for histology follow-up. Data from a single institution are more likely to have more diagnostic consistency among pathologists.

Like many prior studies investigating the effectiveness of TBSRTC, the overall findings of this study demonstrate that use of TBSRTC improves cytopathology diagnoses of thyroid FNA. This study is unique and adds to the large body of literature on TBSRTC in two ways. First, long-term clinical follow-up was used in addition to surgical follow-up to obtain more accurate positive and negative predictive values for cytopathology diagnostic categories. Second, unlike other prior studies with higher rates of AUS/FLUS diagnoses, the findings of the current study demonstrate that it is possible to achieve a very low rate of AUS/FLUS diagnoses using TBSRTC criteria while accurately identifying benign and malignant nodules, achieving appropriate ROMs in indeterminate categories (ie, AUS/FLUS and SFN/FN), and maintaining overall excellent performance characteristics of thyroid FNA. These findings are an important addition to the current literature on TBSRTC, as the field is moving toward efforts to prevent overtreatment of thyroid nodules, and pathologists can contribute to this effort by attempting to limit the use of the AUS/FLUS category whenever it is possible to use a more definitive TBSRTC category.

This work was supported by departmental funding from the Division of Anatomic Pathology, Mayo Clinic, Rochester, MN.