What is bethesda category 1?

Epidemiological studies show that thyroid nodules are palpable in approximately 5% of women and 1% of men living in iodine-sufficient areas [1-3]. Using thyroid ultrasonography (US), this prevalence increases to 19–67%, with a predominance in females, the elderly, and populations living in areas with insufficient iodine consumption [1-4]. When a nodule is diagnosed, thyroid function is then assessed; in the presence of a normal level of thyroid stimulating hormone, it is important to exclude thyroid carcinoma, which occurs in approximately 5–15% of nodules, 95% of which are well-differentiated thyroid carcinoma [1-6].

In Brazil, the current estimated incidence of thyroid cancer is 24 cases per 100,000 inhabitants, and it is the fourth-most common neoplasm found in women [1, 2, 7]. As thyroid US has become widely used, a higher number of thyroid nodules have been detected, resulting in an increased diagnosis of thyroid cancer, particularly microcarcinomas (< 10 mm in diameter) [8-10].

Some sonographic features, such as hypoechogenicity, the presence of microcalcifications, irregular margins, and a taller than wide shape, are used to evaluate the risk of malignancy, but these findings alone cannot be used to distinguish between benign and malignant lesions [3, 4]. In general, a cytological analysis with fine-needle aspiration (FNA) under US guidance is recommended for nodules with intermediate or highly suspicious sonographic patterns and with the greatest dimension being at least 1 cm [1, 3].

The Bethesda System for Reporting Thyroid Cytopathology [11], published in 2007, has been widely used. It classifies the cytological results into 6 categories and presents their respective malignancy rates and approaches to treatment. These 6 categories are: nondiagnostic or unsatisfactory (ND, Bethesda I), benign (Bethesda II), atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS, Bethesda III), follicular neoplasm or suspicious for follicular neoplasm (FN/SFN, Bethesda IV), suspicious for malignancy (SM, Bethesda V), and malignant (Bethesda VI) [11-13].

Since its publication, several centers in different countries have applied the Bethesda classification system to their population, reporting a correlation between their cytological findings and malignancy rates in each category [14-21]. The majority of these studies found similar incidence rates for each category but different malignancy rates, mainly in the ND and AUS/FLUS categories [14-19]. Some questions have arisen over the proper use of the Bethesda diagnostic categories, their associated risks of malignancy and appropriate management, leading to a recently published revision of the guidelines in 2017 [13].

Although the Bethesda classification is currently used in Brazil, there are no data related to the prevalence of each cytological category for the evaluation of thyroid nodules or the validation of whether the malignancy rates reported in the literature could be applied to the Brazilian population. The aim of this study was to evaluate the performance of the Bethesda classification in a Brazilian reference center and correlate cytological and histopathological results in patients undergoing surgery.

After approval from the Institutional Ethics Committee, we retrospectively collected data from FNA results obtained between January 2012 and December 2013 in the Thyroid Diseases Center at the Division of Endocrinology, Department of Medicine, Universidade Federal de São Paulo, SP, Brazil.

All patients were referred to the reference center when diagnosed with thyroid nodules, and they underwent thyroid palpation and a neck US. If a thyroid nodule with at least 1 cm in the greatest dimension and/or suspicious sonographic characteristics for malignancy was detected (hypoechogenicity, microcalcifications, irregular margins, and a tall shape), an FNA under US guidance was performed. The cytological results of each nodule were classified according to the Bethesda classification, and then compared with histopathological data obtained from the patients who underwent surgery.

A total of 585 patients were evaluated, including patients with > 1 nodule. A total of 980 FNAs were performed, and 50 nodules were submitted to a second FNA during follow-up. Ninety percent of the patients were women, and the mean age of the patients was 51 years (range 16–83 years). The surgery rate was 41.8% (245 patients).

Neck US examinations were performed with a linear, multifrequency transducer (7.5–10 MHz) integrated with color Doppler and all were performed by the same radiologist. The samples obtained by FNA were fixed and stained by panoptic techniques, and the analysis of all samples was performed by the same pathologist.

Patients with nodules classified as benign were referred to clinical follow-up. Patients with nodules classified as FN/SFN, SM, or malignant underwent surgery. Patients with nodules classified as ND or AUS/FLUS underwent another FNA, with an interval of approximately 3 months in between. After the second FNA, surgery was indicated if the cytological results were reclassified as FN/SFN, SM, or malignant, or if they were reclassified in the same category (ND or AUS/FLUS) but with significant nodule growth or suspicious sonographic patterns. Surgery was also indicated if the nodule, in any category, presented with a large size (> 3.0 cm), significant growth during follow-up, or SM characteristics on US, or if the patient had compressive symptoms.

The incidence of each cytological category was calculated by dividing the number of FNAs in each category by the total number of FNAs performed during the study. The malignancy rates for each category were calculated by dividing the total number of malignant histological results by the total number of cases submitted to surgery.

Indices relating to the FNA procedure, such as sensitivity, specificity, positive predictive value (VPP) and negative predictive value (VPN), were calculated using the formulae of Galen and Gambino [22]. True-negative samples were considered to be nodules with both a benign cytology and histology, and true-positive samples were considered to be nodules with undetermined (FN/SFN or SM) or malignant cytology, and malignant histological results. Samples classified as ND and AUS/FLUS were excluded from the analysis due to the indication for repeated FNA instead of surgical excision. For nodules submitted to multiple FNAs, the cytological sample that was the most suspicious was considered and correlated with the histological result.

According to the Bethesda classification, the cytological results in the 980 nodules were: 11% (n = 108) ND, 59.8% (n = 587) benign, 7.1% (n = 70) AUS/FLUS, 8.5% (n = 84) FN/SFN, 5.1% (n = 50) SM, and 8.2% (n = 81) malignant.

Regarding the 108 nodules classified as ND, 27 were submitted to a second FNA and 20 (74%) were reclassified as: benign (n = 14, 70%), AUS/FLUS (n = 4, 20%), FN/SFN (n = 1, 5%), and SM (n = 1, 5%) The other 7 (25.9%) remained classified as ND. Six of the 27 nodules were resected; 5 (1 ND, 3 benign, and 1 FN/SFN) had an histology report of benign, and 1 (also benign) presented with a follicular microcarcinoma.

A total of 47/108 nodules were followed up with periodic US with no changes in size or sonographic pattern. Thirty-five of 108 nodules were submitted to surgery in the presence of another nodule in the gland > 3 cm (28.5%) in size, in the presence of another nodule with a suspicious cytological result (57.2%), or both (14.3%). Surgical procedures for these patients were indicated due to the presence of another nodule in the gland (rather than the ND).

The malignancy rate in nodules classified as ND was 25.7% (9/35), with 66.6% (6/9) being papillary microcarcinomas. The remaining tumors were 2 papillary carcinomas (1.3 cm in size) and 1 follicular carcinoma (1.5 cm in size). Among the malignant lesions in the ND category, 6/9 were found as multifocal tumors and 4 of them were papillary microcarcinomas.

Regarding the 587 nodules classified as benign, 12 were submitted to a second FNA and were reclassified as follows: 10 (83.3%) remained benign and 2 (16.7%) were considered as FN/SFN. Six of the 12 nodules were resected; 3 presented histologically benign results (reclassified as benign), and 3 presented as papillary carcinoma (2 reclassified as FN/SFN and 1 as benign). The median tumor size in the reaspirated group was 2.1 cm.

After the first FNA, 166/587 nodules were resected due to the size of the nodule (> 3.5 cm) or the presence of another suspicious cytological nodule in the gland. The malignancy rate in this category was 6% (10/166), with a tumor size ranging from 0.4 to 6.4 cm. The remaining 409 nodules were followed up with periodic US.

An AUS/FLUS classification was assigned to 7.1% of the FNAs performed (70/980). Eleven of 70 nodules were reaspirated and reclassified (Fig. 1). After a second FNA, 7 nodules were resected; 4 presented histologically benign results (2 benign, 1 FN/SFN, and 1 SM), 2 presented as papillary carcinoma (1 SM and 1 malignant), and 1 presented a fibromyxoid sarcoma located near the thyroid gland (reclassified as SM).

A total of 25/70 nodules were submitted to surgery due to the size of the nodule or the presence of another suspicious cytological nodule in the gland. The malignancy rate in this category was 12% (3/25) and the average tumor size was 1.3 cm (range 0.8–2 cm). The other 34 nodules were followed up with periodic US.

A total of 215 nodules classified as FN/SFN (n = 84), SM (n = 50), and malignant (n = 81) were referred to surgery, and data from 192 of these were included in the analysis. At the end of this study, 23 patients had not yet undergone surgery due to unforeseen circumstances, such as patient dropout and surgery refusal.

Among the 84 nodules classified as FN/SFN, 77 were resected. The malignancy rate was 20.8% (16/77) and the tumor sizes ranged from 1.3 to 6.9 cm. Among the 50 nodules classified as SM, 40 were resected. The malignancy rate in this category was 72.5% (29/40), with a predominance of papillary carcinomas. The tumor sizes ranged from 0.5 to 8.5 cm. Among the 81 nodules classified as malignant, 75 were resected. The malignancy rate in this category was 97.3% (73/75), with a predominance of papillary carcinomas, and 2 medullary carcinomas, 1 follicular carcinoma, and 1 anaplastic carcinoma. The tumor sizes ranged from 0.4 to 6.9 cm.

The percentage of cases submitted to surgery and their respective cytohistological results are described in Table 1.

Considering the categories of FN/SFN, SM, and malignant with their respective histological results, the sensitivity, specificity, VNP and VPP were 92.1, 67.8, 93.9, and 61.4%, respectively.

Regarding the 140 (33.4%) malignant histological results, papillary carcinomas were diagnosed in 93.6% (131/140), medullary carcinoma in 2.9% (4/140), follicular carcinoma in 2.1% (3/140), anaplastic carcinoma in 0.7% (1/140), and fibromyxoid sarcoma located near the thyroid gland in 0.7% (1/140).

Prior to the Bethesda System for Reporting Thyroid Cytopathology, there was no standard classification and no application of reproducible cytological reporting of thyroid nodule FNA results. The Bethesda System proposed the classification of 6 categories of cytological results, with the aim of standardizing the findings described by different interobservers, reporting malignancy rates, and applying a different approach in each category [11-13].

In this study, the incidence of each cytological category was in accordance with that proposed by the Bethesda classification and literature [3, 12], i.e., 11% ND (2–20%), 59.8% benign (55–74%), and 7.1% AUS/FLUS (up to 7% according to The Bethesda System and 2–18% in the literature). The incidences of FN/SFN and SM, compared with the literature, were 8.5% (2–25%) and 5.1% (1–6%), respectively [3, 12], but these frequencies are not reported by The Bethesda System [11, 12]. The incidence of malignant FNA found in this study (8.2%) was higher than that observed in the literature (2–7%), but this was to be expected, as the study was carried out in a thyroid reference center.

The Bethesda System proposes that ND nodules should be submitted to a second FNA at an appropriate interval; in many cases (50–88%) [11, 12], this second FNA allows them to be reclassified into a distinct category. In this study, 27/108 (25%) of the ND nodules were submitted to a second FNA, and 20 of these 27 (74%) were reclassified into a different category: 70% (14/20) benign (41.7 to 87.5% in the literature), 20% (4/20) AUS/FLUS, 5% (1/20) FN/SFN, and 5% (1/20) SM. Seven of the 27 (25.9%) remained classified as ND after a second FNA, which is in accordance with the literature (1.2–47.9%) [16-19]; however, this finding is higher than that suggested by the Bethesda classification (7–10%) [11, 12]. In this study, the comparatively low percentage of ND nodules submitted to another FNA, i.e., 25% of the total, probably contributed to this result, which could turn out to be different if all of the ND nodules had been submitted to a second procedure.

Clinical follow-up is recommended for nodules classified as benign (Bethesda II). If significant growth or sonographic changes are observed, another FNA should be performed [11, 12]. In this study, 12/587 (2%) benign nodules were submitted to a second FNA; 10 (83.3%) remained benign and 2 (16.6%) were reclassified as FN/SFN (Bethesda IV). In the literature, Yang et al. [16] performed a second FNA in 11.7% benign nodules; 82.1% of these remained benign and 9.1% were reclassified.

According to The Bethesda System, AUS/FLUS nodules (Bethesda III) should be submitted to another FNA after an adequate interval, and the majority of them are reclassified into another category [11]. In this study, 50% of AUS/FLUS nodules were reclassified as benign after a second FNA, in agreement with the literature (42.7–73.1%), which allows a clinical follow-up approach instead of a surgical procedure [16, 23-25]. On the other hand, 9% of AUS/FLUS nodules submitted to a second FNA remained in the same category. This result was in agreement with what was proposed in the Bethesda classification (approx. 20%) [11, 12] and in the literature (3.8–38.5%) [16, 23-25].

In this study, the malignancy rates obtained in each cytological category were in agreement with those proposed by the original Bethesda classification, the revised Bethesda System [13], and the literature: 6% in benign nodules (0–3%, The Bethesda System; 1–10%, the literature), 12% in AUS/FLUS (5–15%, the original Bethesda classification; 10–30%, the revised Bethesda System and the literature), 20.8% in FN/SFN (15–30%, the original Bethesda classification and the literature; 25–40%, the revised Bethesda System), 72.5% in SM (60–75%, the original Bethesda classification and the literature; 50–75%, the revised Bethesda System), and 97.3% in the malignant category (97–99%, the original Bethesda classification, the revised Bethesda system, and the literature) [3, 11-19, 25].

The malignancy rate obtained in the ND category was 25.7%, with 67% of the cases being microcarcinomas. This result was in agreement with previous studies published in the literature (10–35%) [14-17], but higher than that proposed by the original and the revised Bethesda System (1–4% and 5–10%, respectively) [11-13]. One possible reason for this finding is that the majority of ND nodules were submitted to surgery before performing a second FNA, due to the presence of other suspicious nodules in the gland or a nodule size > 3 cm. If those nodules had been submitted to a second FNA, they probably would have been reclassified in the suspicious category.

In conclusion, this study found that The Bethesda System can be applied to the Brazilian population since the frequency of each category and malignancy rates were similar to those described by the system’s classification. However, a higher malignancy rate was observed in the ND category. In the presence of a multinodular goiter with an ND result and another nodule > 3.0 cm, or with another suspicious cytological nodule, the occurrence of multifocal tumors should be carefully evaluated.

These 6 categories are: nondiagnostic or unsatisfactory (ND, Bethesda I), benign (Bethesda II), atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS, Bethesda III), follicular neoplasm or suspicious for follicular neoplasm (FN/SFN, Bethesda IV), suspicious for malignancy (SM, ...

Introduction. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a significant step to standardize the reporting of thyroid fine needle aspiration (FNA). It has high predictive value, reproducibility, and improved clinical significance. Aim. The study was aimed to evaluate the diagnostic utility and reproducibility of “TBSRTC” at our institute. Methods and Material. The study included 646 thyroid FNAs which were reviewed by three pathologists and classified according to TBSRTC. Cytohistological correlation was done for 100 cases with surgical follow-up and the sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and risk of malignancy (ROM) were calculated. The interobserver variation among three pathologists was also assessed. Results. The distribution of cases in various TBSRTC categories is as follows: I—nondiagnostic 13.8%, II—benign 75.9%, III—atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) 1.2%, IV—follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN) 3.7%, V—suspicious for malignancy (SM) 2.6%, and VI—malignant 2.8%. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy are 72.4%, 94.3%, 84%, 89.2%, and 87.9%, respectively. The ROM of various TBSRTC categories were II—8.5%; III—66.7%; IV—63.6%; and V and VI—100%. Cohen’s Weighted Kappa score was 0.99 which indicates almost perfect agreement among the three pathologists. Conclusions. Our study substantiates greater reproducibility among pathologists using TBSRTC to arrive at a precise diagnosis with an added advantage of predicting the risk of malignancy which enables the clinician to plan for follow-up or surgery and also the extent of surgery.

Thyroid nodules are a common clinical problem. It is important to differentiate benign from malignant nodules. Fine needle aspiration (FNA) is utilized as a preoperative diagnostic technique which is safe, simple, and cost effective for triaging patients with thyroid nodules [1].

Proper communication among pathologists, clinicians, radiologists, and surgeons along with cytohistological correlation is essential for reporting of thyroid FNA. Hence, consistent diagnostic terminology is vital.

To achieve standardization of diagnostic terminology, morphologic criteria, and risk of malignancy for reporting of thyroid FNA, in 2007, the National Cancer Institute (NCI) organized the NCI Thyroid Fine Needle Aspiration State of the Science Conference which proposed a 6-tier system and named it The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The categories and their risk of malignancy for I—nondiagnostic, II—benign, III—atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), IV—follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN), V—suspicious for malignancy (SM), and VI—malignant were 1–4%, 0–3%, 5–15%, 15–30%, 60–75%, and 97–99%, respectively [2].

The study aimed to evaluate the diagnostic utility and reproducibility of “The Bethesda System for Reporting Thyroid Cytopathology” at our institute.

All thyroid FNA smears and thyroidectomy specimens received from January 2013 to June 2018 in the Department of Pathology, at our institute, were included in the study after obtaining approval from the Institute Ethics Committee. The FNA smears were reviewed and categorized according to the Bethesda system. Cytohistological correlation was done for cases with surgical follow-up.

Statistical analysis was performed using R software version 3.5.1 (R Core Team) and Microsoft Office Excel 2007. Mean, median, and Standard Deviation (SD) were calculated for continuous variables like age. Categorical variables were expressed as frequencies and percentages. ANOVA test was used to calculate the value. A value <0.05 was considered statistically significant.

The diagnostic values (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) and risk of malignancy for FNAs using the Bethesda system were calculated for cases with surgical follow-up. FNA smears interpreted as nondiagnostic were excluded. True negative cases were defined as nodules with benign FNA cytology and surgical pathology. Follicular neoplasm/suspicious for follicular neoplasm, suspicious for malignancy, and malignant cases confirmed to be malignant upon final histology were considered true positive. Nodules with cytological results of FN/SFN or suspicious for malignancy or malignant diagnosed as benign on surgical excision were interpreted as false positive. False negative samples included cases with benign cytology that were found to be malignant upon histopathology.

Cross tabulation and Cohen’s Weighted Kappa (κ) were applied to evaluate the concordance among the three observers. The Kappa coefficient was interpreted as follows: 0–0.2 indicates poor agreement, 0.3–0.4 indicates fair agreement, 0.5–0.6 indicates moderate agreement, 0.7–0.8 indicates strong agreement, and >0.8 indicates almost perfect agreement.

The study included 646 patients with complaints of thyroid swelling evaluated by FNA. The age group of the patients ranged from 7 to 85 years with a mean of 41.78 years. The male: female ratio was 1 : 6.3.

Out of 646 cases, 75.9% were benign of which 34.7% was nodular goitre. Scant cellularity contributed with 7.8% of the nondiagnostic category. The distributions of AUS/FLUS (III) and FN/SFN (IV) were 1.2% and 3.7%, respectively. Category-V constituted 2.4% cases suspicious for papillary carcinoma. Papillary carcinoma (2%) was the most common malignancy in category-VI (Table 1).

Cytohistological correlation was done for 100 patients with surgical follow-up. On histopathology, 71 cases were confirmed to be benign of which the most common was nodular goitre. Out of 100 cases, 29 were malignant. Papillary carcinoma (17%) was the most common malignancy followed by follicular carcinoma (6%) (Table 2).

Risk of malignancy was assessed for 100 cases with surgical follow-up. Out of 100 cases, one was excluded since it was reported as nondiagnostic on cytology. To calculate the risk of neoplasm the surgical resections were divided into three groups: benign nonneoplastic lesions, benign neoplasms, and malignant lesions (Table 2).

The total of 99 cases was divided into two groups. One group comprised of Bethesda categories II and III for which surgery is not recommended due to low malignancy risk and the other group consisted of Bethesda categories IV, V, and VI for which surgery is recommended due to high malignancy risk. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy hence obtained are 72.4%, 94.3%, 84%, 89.2%, and 87.9%, respectively (Table 3).

Cross tabulation and Cohen’s Weighted Kappa (κ) were applied to evaluate the concordance among the three observers. Cohen’s Weighted Kappa score was 0.99 which indicates almost perfect agreement among the three pathologists.

The goal of thyroid FNA is to successfully differentiate benign from malignant lesions and to triage patients requiring surgery. The six-tired Bethesda system provides standardized nomenclature for reporting thyroid FNA smears which enables better communication and understanding between clinicians and pathologists. The advantage of this systematic approach is that each of the six Bethesda categories has implied risk of malignancy which helps the clinicians to plan appropriate therapy necessary for the patient [3].

Nondiagnostic (ND) thyroid FNA result remains a major constraint in arriving at a definitive diagnosis and is the most common cause of false negative reports [4]. It is difficult to assess the risk of malignancy for the ND category because only a small subset of ND nodules undergoes resection. Hence there is disparity in the malignancy rate among various studies which ranges from 0% to 63.2% [5, 6].

Gunes et al. stated that the clinical expertise of the person performing the FNA, ultrasound guidance, and rapid on-site evaluation for specimen adequacy were not uniform between studies which contributes to the wide range of malignancy rate. All these determinants make the comparison between studies cumbersome and should be taken into consideration while labelling a specimen as nondiagnostic and assessing the risk of malignancy [4]. Some of the studies stated that the operator experience and the number of passes made during FNA correlate with the nondiagnostic result [7, 8].

In our study, the nondiagnostic yield was 13.8% which was high when compared to TBSRTC consensus. Sampling error and technical quality due to the above-mentioned reasons and strict adherence to the adequacy criteria explain the high rate of ND smears.

Mondal et al. and Nandedkar et al. found high incidence of category II lesions since the patients directly visit a tertiary care center for primary diagnosis without any referral which was also the case in our study [6, 9].

The incidence of benign lesions in our study was 75.9% when compared to studies done in USA ranging from 64% to 66% which can be attributed to the regional variation in the incidence of thyroid disorders and where majority of patients come only on a referral basis and hence are not exactly representative of the general population [10, 11].

The implied risk of malignancy for category II is 0% to 3% with the recommended management being clinical follow-up of patients [2]. Although surgery is not recommended for category II lesions, the patients in our study were operated mainly for cosmetic purpose and pressure symptoms.

The indeterminate category, AUS/FLUS, has led to confusion due to inconsistent usage amongst pathologists of various institutions. This category should be used as a last resort in reporting with the expectation of 7% or less cases to receive this diagnosis as proposed by TBSRTC. Layfield et al. reported a variation of 2.5–28.6% among individual pathologists and 3.3–14.9% among three academic institutions [12].

There were less number of cases (1.2%) diagnosed under the category AUS/FLUS in our study which was due to rigid adherence to the diagnostic criteria and the pathologists endeavor to avoid ambiguity and keep the use of AUS/FLUS to a minimum which was in similarity to a study by Nandedkar et al. which had 0.8% of cases in category III out of 606 FNA’s [9]. Jo et al. and Yassa et al. have reported 3.4% and 4% lesions as AUS/FLUS, respectively [13, 14].

Mondal et al. reported a lower percentage (1%) of AUS/FLUS cases which was a result of performing ultrasound guided FNA in small and heterogeneous nodules with suspicious features on palpation and radiological evaluation, so that the aspirate can be obtained from the exact site of lesion which is a routine practice even at our institute [6].

The actual risk of malignancy of category III is difficult to determine, since confirmatory diagnosis is only available in a subset of patients selected for surgery who have suspicious clinical or USG features. The patients are also subjected to selection bias which overestimates the prevalence of malignancy [15].

The risk of malignancy of AUS/FLUS cases was 69% in a study done by Park et al. which was higher when compared to our study and TBSRTC guidelines. This was because patients with high index of clinical suspicion for malignancy undergo surgery without a repeat FNA. Patients tend to be more concerned about false positive results than false negative results, which might have pressurized cytopathologists to underdiagnose cases to avoid making false positive diagnosis [16].

Our study was held in a teaching hospital, where FNAs were performed by different persons with varied level of experience during their training period. This factor could have resulted in hemodilution and artefactual changes during smear preparation which might have contributed to a higher ROM in category III (Figure 1). Repeat FNAs of such cases along with clinicoradiological correlation could have decreased the proportion of cases reported in this category as well as the ROM.

Based on cytology it is difficult to distinguish follicular carcinoma from follicular adenoma [2, 12] (Figure 2). Melo-Uribe et al. correlated the results of thyroid FNA reported using the TBSRTC with histopathology, from three different hospitals in Columbia. There was significant variation in the malignancy risk of category IV which measured 56.3% in oncology centers and 23.5% in nononcology centers which was attributed to the selection bias of the patients requiring surgery [17].

The high ROM in categories III and IV in our study when compared to other studies may be due to the following reasons. Firstly, it is due to the heterogeneity of the indeterminate categories III and IV which are subject to variation in interpretation across institutions [3]. Secondly, it is because of variations in number of patients with surgical follow-up and also the selection bias of patients requiring surgery.

Our study had 2.4% cases suspicious for papillary thyroid carcinoma (PTC) which was similar to the lower range of rate of suspicious for PTC in the following study [15]. The ROM of category V in a study by Williams et al. was less when compared to our study which may be due to variation in cohort characteristics and underdiagnoses of lesions leading to hemithyroidectomy rather than total thyroidectomy [18].

The ROM in a study by Partyka et al. was in good correlation with our study in categories V and VI which was 100% each after inclusion of papillary microcarcinoma [19] (Figure 3). Our study was able to accurately predict the ROM for suspicious for malignancy and malignant nodules due to the practice of correlating cytologic features with clinical, biochemical, and USG findings while reporting (Table 2).

The risk of neoplasm (RON) gives an overall estimate of predicting both benign and malignant lesions. Our study had nil risk of neoplasm in the nondiagnostic category (Table 2). This was due to repeat FNA of cases with high index of clinical and ultrasound features suspicious for malignancy.

The RON of category II was similar to the study done by Wu et al. (Table 4) [20]. This was due to false negative reporting of 2 papillary microcarcinoma, 1 Hurthle cell carcinoma, and 1 follicular carcinoma as benign. Two cases of conventional papillary carcinomas were misdiagnosed as benign due to sampling error (Table 2). Follicular carcinoma and Hurthle cell carcinoma are difficult to diagnose on FNA and need to be confirmed by histopathology. Papillary microcarcinoma is a lesion that measures 1 cm or less which can be easily missed on FNA unless the aspirator hits the target.

Our study was able to accurately predict the RON of categories III, V, and VI when compared to the study done by Wu et al. which could be attributed to the routine practice of correlating cytology with clinical, biochemical, and radiological features at our institute (Table 4) [20].

The FN/SFN category had RON of 81.8% which was high compared to the study by Wu et al. This was due to classification of two cases of nodular goitre as category IV lesion (Table 2). Another possible reason could be the variation in sample size and less number of cases with surgical follow-up in our study (Table 4) [20].

Mehra and Verma in their study found that the method of statistical analysis can alter the results of diagnostic values. If suspicious lesions are considered positive, the sensitivity increases while the specificity decreases. If suspicious lesions are excluded, then the sensitivity decreases and the false negative rates increase. In their study diagnostic values were calculated by either excluding FN/SFN or including it with either benign or malignant diagnosis to highlight the effect on diagnostic values [21].

Shi et al. suggested that eliminating the diagnosis of category III substantially decreases the sensitivity of thyroid FNAs (the sensitivity for detecting PTC dropped from 100% to 27%) and increases both false positive and false negative rates. The authors concluded that AUS/FLUS category should not be eliminated but recommended using it minimally [22].

The findings from our study indicate that the calculation of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of thyroid FNAs according to the Bethesda system are less reliable because of the arbitrary nature of cases classified under categories III (AUS/FLUS) and IV (FN/SFN) (Table 3).

The main purpose of TBSRTC was to eliminate the ambiguity and to follow uniformity in the reporting of thyroid FNAs thereby enabling ease of communication among pathologists and clinician and to plan appropriate treatment for the patients [2]. Table 5 shows comparison of interobserver reproducibility of our study with that of other studies [23–25].

Our study differed from a study done by Padmanabhan et al. which assessed the interobserver reproducibility in reporting AUS/FLUS category among seven cytopathologists which revealed fair agreement (Fleiss kappa score 0.23) and recommended review of AUS/FLUS cases for more definite categorization [25]. We observed a trend that the less the number of observers (2-3), the more the chance of interobserver agreement (Table 5).

Thyroid FNA smears reported using the Bethesda system helped in achieving more precise cytological diagnosis. Our study substantiates greater reproducibility among pathologists using TBSRTC for reporting thyroid FNA. The Bethesda system has an added advantage of predicting the risk of malignancy which enables the clinician to plan for follow-up or surgery and also the extent of surgery.

The raw data used to support the findings of this study have not been made available because of patient’s confidentiality and privacy rules.

The yield of nondiagnostic aspirate was high due to the varied experience level of the persons who performed the thyroid FNA. Repeat USG guided FNA would have reduced the number of nondiagnostic aspirates but it was feasible only for patients with high index of clinical and radiological features suspicious of malignancy.

The authors declare that they have no conflicts of interest.

With its inception, The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized reporting system with a limited number of diagnostic categories for thyroid fine-needle aspiration (FNA) specimens. Using TBSRTC, cytopathologists can communicate their interpretations to the referring physician in terms that are succinct, unambiguous, and clinically useful (1–3).

TBSRTC has been widely adopted in the United States and in many places worldwide and has been endorsed by the American Thyroid Association (4). It has improved communication and provided a uniform template for sharing data among investigators. Since its acceptance in clinical practice, however, questions have arisen over the proper use of the diagnostic categories, the associated risks of malignancy, and the appropriate management. By 2016, the time had come to consider revisions. The 2017 revision described herein was inspired by new data and new developments in the field of thyroid pathology: revised guidelines for the management of patients with thyroid nodules (4), the introduction of molecular testing as an adjunct to cytopathologic examination, and the reclassification of the noninvasive follicular variant of papillary thyroid carcinoma as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (5). Much of the groundwork for this revision was laid down by a symposium entitled “The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC): Past, Present, and Future” at the 2016 International Congress of Cytology in Yokohama, Japan. Preparations for the symposium began 12 months earlier with the designation of a steering group and the appointment of an international panel of 16 cytopathologists and an endocrinologist, whose task was to review and summarize the published literature in English since the introduction of TBSRTC.

The symposium, moderated by Drs. Syed Ali and Philippe Vielh, took place on May 30, 2016, and the discussions and recommendations from the symposium have been summarized in a publication by Pusztaszeri et al. (6). Based on the panel's recommendation, the six original general categories (“nondiagnostic/unsatisfactory” [ND/UNS], “benign,” “atypia of undetermined significance/follicular lesion of undetermined significance” [AUS/FLUS], “follicular neoplasm/suspicious for a follicular neoplasm” [FN/SFN], “suspicious for malignancy” [SUS], and “malignant”) have been retained in the 2017 revision, and a revised atlas is in press, with updated and expanded chapters devoted to these categories and refined definitions, morphologic criteria, and explanatory notes (7).

For clarity of communication, the 2017 BSRTC continues to recommend that each report begin with a general diagnostic category. Because they are more ambiguous and less clearly descriptive, numerical designations alone (e.g., “Bethesda III”) are discouraged for the purposes of cytologic reporting, although the numerical designations may be used in conjunction with the category name, for example “atypia of undetermined signficance (Bethesda III).”

The six general diagnostic categories are unchanged and are shown in upper case in Table 1. Some categories have two alternative names. A laboratory should choose the one it prefers and use it exclusively for that category. Synonymous terms (e.g., AUS and FLUS) should not be used to denote two distinct interpretations. Each of the categories has an implied cancer risk (ranging from 0% to 3% for the benign category to virtually 100% for the malignant category) that links it to an evidence-based clinical management guideline (Table 2).

For some of the general categories, some degree of subcategorization can be informative and is often appropriate (see Table 1). Additional descriptive comments (beyond such subcategorization) are optional and are left to the discretion of the cytopathologist.

Notes and recommendations are not required but can be useful in certain circumstances, particularly if the cytomorphologic features raise the possibility of NIFTP. Some laboratories, for example, may wish to state the risk of malignancy (ROM) associated with the general category, based on its own data or those found in the literature.

Table 2 shows revised risks of malignancy (ROM) based on data since 2010. NIFTP has added a wrinkle in this regard by excluding the noninvasive follicular variant of papillary thyroid carcinoma from the list of thyroid carcinomas. NIFTP is, nonetheless, a “surgical disease”—surgery is necessary for these nodules—and Table 2 shows “ROMs” calculated two ways: when NIFTP is not considered a malignancy, and when NIFTP is still included among the “carcinomas.” The higher risk estimates arguably have more clinical relevance because they are defined for surgical disease.

Every thyroid FNA should be evaluated for specimen adequacy. Inadequate samples are reported as “nondiagnostic” (ND) or “unsatisfactory” (UNS). Examples include specimens with obscuring blood, poor cell preservation, and an insufficient sample of follicular cells. For a thyroid FNA specimen to be satisfactory for evaluation (and benign), at least six groups of benign follicular cells are required, each group composed of at least 10 cells. The minimum requirement for group size allows one to determine (by the evenness of the nuclear spacing) whether it represents a fragment of a macrofollicle.

Given that the great majority of ND/UNS nodules prove to be benign, one may question whether the criteria for adequacy are too stringent. Lowering the required number of follicular cells would save many patients a repeat FNA. Preliminary data suggest that doing so would substantially reduce ND/UNS interpretations without significantly impacting the false-negative rate (8,9). There is no consensus on a lower number, however, and therefore the criteria have been retained, with the understanding that this is an evolving area that would benefit from more evidence.

The 2017 BSRTC reinforces several exceptions to the numerical requirement of benign follicular cells. Any specimen that contains abundant colloid is adequate (and benign), even if six groups of follicular cells are not identified: a sparsely cellular specimen with abundant colloid is, by implication, a predominantly macrofollicular nodule and therefore almost certainly benign. Whenever a specific diagnosis (e.g., lymphocytic thyroiditis) can be rendered, and whenever there is any significant atypia, the specimen is, by definition, adequate for evaluation.

Specimens that consist only of cyst contents (macrophages) are ND/UNS. The significance (and clinical value) of a ND/UNS, “cyst contents only” result depends in large part on sonographic correlation. If the nodule is entirely cystic, with no worrisome sonographic features, an endocrinologist might proceed as if it were a benign result. On the other hand, it might be clinically unsatisfactory if the sonographic features are worrisome and the endocrinologist is not convinced that the sample is representative.

The ROM for an ND/UNS interpretation is difficult to calculate because most ND/UNS nodules are not resected. Among surgically excised nodules initially reported as ND/UNS, the malignancy rate is 9–32%. Surgically resected nodules, however, are a selected subset that were either repeatedly ND/UNS or had worrisome clinical/sonographic features or both. Thus, surgically resected ND/UNS nodules overrepresent malignancies compared to the entire cohort of ND nodules. A reasonable extrapolation of the overall ROM is 5–10% (Table 2) (4).

A repeat aspiration with ultrasound guidance is recommended for cytologically ND/UNS nodules and is diagnostic in most cases, but some nodules remain persistently ND/UNS. Excision is considered for persistently ND/UNS nodules.

In the past, it was often recommended that the patient with an ND/UNS cytology wait three months before a repeat FNA, but this delay often causes patient anxiety. It was reasoned that a transient follicular cell atypia induced by the inflammation that results from a recent FNA might confound interpretation, but a pair of studies does not support this assumption (10,11). The ATA guidelines now state that there is no need to wait several months before repeating the FNA (4).

Unless specified as ND/UNS, the FNA is considered adequate for evaluation; an explicit statement of adequacy remains optional.

The 2017 BSRTC has essentially made no changes to the usage, definition, criteria, or usual management association for this category. Data continue to support a very low false-negative rate (<3%).

This category has two alternative names. A laboratory should choose the one it prefers and use it exclusively when criteria are fulfilled for this category. AUS and FLUS are therefore synonyms and should not be used to denote two distinct interpretations. It is worth pointing out that, of the two, AUS is more versatile; FLUS applies only to follicular lesions of undetermined significance and cannot be used if the cells are not clearly follicular in origin (e.g., lymphoid, parafollicular, parathyroid, etc.).

AUS/FLUS has been studied extensively since the advent of TBSRTC, but calculating the ROM associated with this interpretation has been challenging. Because only a minority of AUS/FLUS cases undergo excision, estimating the ROM based on histologic follow-up alone overestimates the ROM due to selection bias: AUS/FLUS nodules (much like Benign and ND/UNS nodules) are usually resected only if there are worrisome clinical or sonographic features, an abnormal repeat aspiration result, and/or an abnormal molecular testing result. AUS/FLUS nodules with a benign repeat aspiration and/or a benign molecular test result remain (appropriately) unresected. On the other hand, when calculated using the total number of AUS/FLUS specimens (regardless of surgical follow-up) as the denominator, assuming that unresected nodules are benign, the ROM is underestimated. The actual ROM is between the values obtained using these two different calculations and thus requires extrapolation. It is likely that the ROM of AUS/FLUS has been further overestimated due to publication bias (unexpected/discrepant results are more likely to be published than expected findings) (12).

Although the overall low-risk nature of AUS/FLUS aspirates has been borne out, new (pre-NIFTP) data suggest that the ROM is higher than originally estimated and closer to 10–30% (Table 2). On the other hand, if the risk is recalculated by removing NIFTPs from the tally of malignancies, the risk diminishes to 6–18% because early data suggest that NIFTP constitutes a substantial proportion of the “malignancies” hidden in this category (13,14).

The ROM differs according to the nature of the atypia. The 2017 BSRTC recommends subclassification of the atypia, even though this will not generally affect patient management. Descriptive language such as “cytologic atypia” and “architectural atypia” is preferred (rather than “rule out papillary carcinoma,” etc.) due to its less provoking nature, as follows:

It is good to think of AUS/FLUS as a category of last resort. The original TBSRTC recommended that an effort be made to limit its use to approximately ≤7% of all thyroid FNAs. This proved a difficult challenge for many laboratories, and a more realistic limit might be 10%.

The usual management now includes consideration of molecular testing.

This category likewise has two alternative names. A laboratory should choose the one it prefers and use it exclusively. FN and SFN are synonymous terms and should not be used to denote two distinct interpretations. SFN is preferred by some laboratories because a significant proportion of cases (up to 35%) prove not to be neoplasms but rather hyperplastic proliferations of follicular cells, most commonly those of multinodular goiter (18–22).

The 2017 BSRTC includes a modification to the definition and diagnostic criteria for this category in light of NIFTP. In the original BSRTC, cases that demonstrated the nuclear features of papillary thyroid carcinoma were excluded from this category. The new definition reads as follows: “Follicular-patterned cases with mild nuclear changes (increased nuclear size, nuclear contour irregularity, and/or chromatin clearing) can be classified as FN/SFN so long as true papillae and intranuclear pseudoinclusions are absent; a note that some nuclear features raise the possibility of a follicular variant of papillary thyroid carcinoma (FVPTC) or NIFTP can be included” (7).

If the cytologic features raise the possibility of FVPTC or NIFTP (a predominance of microfollicles and only mild or focal nuclear changes), the following optional note (or something similar) may be useful:

This note will apply only to a subset of FN/SFN cases: those with mild nuclear changes.

As with AUS/FLUS, if the ROM for FN/SFN is recalculated by removing NIFTPs from the tally of malignancies, the risk diminishes (see Table 2). Early data suggest that NIFTP constitutes a substantial proportion of the “malignancies” hidden in this category as well (13,14).

The recommended management of a patient with a diagnosis of FN/SFN is surgical excision of the lesion, most often a hemithyroidectomy or lobectomy, but molecular testing may be used to supplement risk assessment rather than proceeding directly to surgery.

As with AUS/FLUS and FN/SFN, if the ROM for this category (“SUS”) is recalculated by removing NIFTPs from the tally of malignancies, the risk diminishes (see Table 2). Early data suggest that NIFTP constitutes a substantial proportion of the “malignancies” hidden in this category as well (13,14).

Some but not all of the cases in this category raise the possibility of FVPTC or NIFTP. For this subset, the following optional note (or something similar) may be useful (23):

This can be useful in guiding the clinical team in the direction of lobectomy rather than thyroidectomy for this subset of SUS cases.

The general category “malignant” is used whenever the cytomorphologic features are conclusive for malignancy. Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any.

Based on early studies, NIFTP constitutes only a very small fraction of cases that are interpreted as “malignant.” Nevertheless, the 2017 BSRTC has modified the definition and criteria for cases of papillary thyroid carcinoma that belong in the malignant category. To avoid false-positives due to NIFTP, it suggests limiting use of the malignant category to cases with “classical” features of papillary thyroid carcinoma (true papillae, psammoma bodies, and nuclear pseudoinclusions) (6,23). Nevertheless, it is likely that a small number of malignant cytologic interpretations will be followed by a histologic NIFTP diagnosis, and thus the following optional note may be used when the diagnosis “malignant; papillary thyroid carcinoma” is made:

The original six categories remain unchanged, but a number of enhancements have been introduced with the 2017 BSRTC:

It is our hope that the 2017 BSRTC will continue to stimulate interest in the improvement of thyroid cytopathologic diagnosis and the betterment of patients with thyroid nodular disease. Subsequent experience, it is expected, will lead to further refinements to this terminology framework.

The authors thank Dr. Erik Alexander for his review of the manuscript and helpful comments.

The authors thank the many individuals who laid the foundation for the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in 2007 and contributed to the publication of the two monographs (TBSRTC 2010 and TBSRTC II 2018). This includes the organizers and participants of The National Cancer Institute (NCI) Thyroid Fine Needle Aspiration (FNA) State of the Science Conference in Bethesda, Maryland in 2007 and the International Academy of Cytology (IAC)-sponsored special symposium “TBSRTC-Past, Present and Future” at the ICC congress in Yokohama in 2016.

Participants of the NCI Conference (2007) and TBSRTC 2010 Atlas Contributors:

Andrea Abati, MD (Organizer, NCI Conference); Susan J. Mandel, MD, MPH (Co-moderator, NCI Conference); Zubair W. Baloch, MD, PhD (Committee Chair, Terminology and Morphologic Criteria, NCI Conference).

Pedro Patricio de Agustin, MD, PhD, Erik K. Alexander, MD, Sylvia L. Asa, MD, PhD, Kristen A. Atkins, MD, Manon Auger, MD, Zubair W. Baloch, MD, PhD, Katherine Berezowski, MD, Massimo Bongiovanni, MD, Douglas P. Clark, MD, Béatrix Cochand-Priollet, MD, PhD, Barbara A. Crothers, DO, Richard M. DeMay, MD, Tarik M. Elsheikh, MD, William C. Faquin, MD, PhD, Armando C. Filie, MD, Pinar Firat, MD, William J. Frable, MD, Kim R. Geisinger, MD, Hossein Gharib, MD, Ulrike M. Hamper, MD, Michael R. Henry, MD, Jeffrey F. Krane, MD, PhD, Lester J. Layfield, MD, Virginia A. LiVolsi, MD, Britt-Marie E. Ljung, MD, Claire W. Michael, MD, Ritu Nayar, MD, Yolanda C. Oertel, MD, Martha B. Pitman, MD, Celeste N. Powers, MD, PhD, Stephen S. Raab, MD, Andrew A. Renshaw, MD, Juan Rosai, MD, Miguel A. Sanchez, MD, Vinod Shidham, MD, Mary K. Sidawy, MD, Gregg A. Staerkel, MD, Edward B. Stelow, MD, Philippe Vielh, MD, PhD, Jerry Waisman, MD, Helen H. Wang, MD, Dr.PH, Grace C. H. Yang, MD, Matthew A. Zarka, MD.

Participants of the IAC-sponsored Thyroid Symposium, Yokohama (2016) and TBSRTC II 2018 Atlas Contributors:

William C. Faquin, MD, PhD (Group leader, ICC Symposium 2016); Marc Pusztaszeri, MD (Lead Panelist, ICC Symposium 2016); Diana Rossi, MD, PhD (Lead Panelist, ICC Symposium 2016); Philippe Vielh, MD, PhD (Co-moderator, ICC Symposium 2016).

Fine needle aspiration (FNA) biopsy of the thyroid nodule is an aspiration of thyroid cells by using a very thin needle right through the skin. It is an outpatient procedure and it is done in the office. The needle used is thinner than the one for drawing blood and is attached to a syringe to apply suction during the biopsy. It is a simple procedure, similar to drawing blood from your arm.

THYROID BIOPSY

Biopsy under ultrasound guidance

Ultrasound guidance

Slides preparation by cytologist

Follow up care for the patients AFTER THYROID BIOPSY

Ultrasound view of the Thyroid Nodule in the right thyroid lobe

Ultrasound guided fine needle aspiration (FNA) biopsy of the right thyroid nodule (needle bevel is indicated by arrow)

The Bethesda System for Reporting Thyroid Cytopathology with Risk of Malignancy.

Bethesda Category I. Nondiagnostic or Unsatisfactory (risk of malignancy 1-4%) - means that there are not enough or no cells precent at all to make a diagnosis. This result would require additional testing and repeting the biopsy. If biopsy of a solid nodule is non-diagnostic on three consequtive occasions, then surgery is indicated to rule-out cancer.

Bethesda Category II. Benign (risk of malignancy 0-3%) - means that the nodule or lump is not a malignant tumor. Even though that biopsy is benign, there is still small possibility of a cancer because no technique is 100% accurate. If This is the reason thta patient still has to follow with annual thyroid ultrasound to make sure threr are no changes in size or appearance of the nodule.

*Bethesda Category III. Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS) (risk of malignancy 5-15%) - means that the result is an inconclusive, althoght there are some abnormal changes that were found but not enough to make a diagnosis of a cancer. An additional testing or surgery are required.

*Bethesda Category IV. Follicular Neoplasm or Suspicious for a Follicular Neoplasm (risk of malignancy 15-30%) - means that the result is an inconclusive, althoght there are significant changes are presant even compare to a prior Category III, but still not enough to make a diagnosis of a cancer. An additional testing or surgery are required.

Bethesda Category V. Suspicious for Malignancy (risk of malignancy 60-75%) - there is a high liklihood of a cancer and surgery is indicated.

Bethesda Category VI. Malignant (risk of malignancy 97-99%) - means that the nodule is cancerous and surgery is indicated.

[*- so called indeterminate cytology]

(E.Cibas, AJCP, 2009)

Molecular Markers Assessment Genetic Analysis on THYROID FNA BIOPSY

Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer (RECOMMENDATION 8; THYROID, Volume 19, Number 11, 2009) considered use of molecular markers (e.g., BRAF, RAS,RET/PTC, Pax8/PPARg, or galectin-3) for patients with indeterminate cytology on FNA to help guide management (Recommendation rating: C). Guidelines stated that Indeterminate cytology, reported as ‘‘follicular neoplasm’’ or ‘‘Hurthle cell neoplasm’’ can be found in 15–30% of FNA specimens and carries a 20–30% risk of malignancy, while lesions reported as atypia or follicular lesion of undetermined significance are variably reported and have 5–10% risk of malignancy. While certain clinical features such as male sex and nodule size (>4 cm) (66), older patient age, or cytologic features such as presence of atypia can improve the diagnostic accuracy for malignancy in patients with indeterminate cytology, overall predictive values are still low. Many molecular markers have been evaluated to improve diagnostic accuracy for indeterminate nodules. Many of these markers are available for commercial use in reference laboratories.

I am able to perform two molecular assessments on routine FNA thyroid biopsy: for DNA-based markers (Asuragen) and RNA-based markers (Afirma-Veracyte):

1. Asuragen - Molecular Markers Assessment

Asuragen miRInform Thyroid is a Panel of molecular markers which improves preoperative diagnostic accuracy for patients with indeterminate thyroid nodules. In addition, the Panel can aid in the characterization of malignancy. The Panel consists of 7 analytically validated molecular markers and utilizes fine needle aspirate (FNA) specimens, collected in an easy-to-use nucleic acid preservation solution. miRInform Thyroid can aid physicians in diagnosis and patient management decisions.

Asuragen miRInform panel of molecular markers

Sample of Asuragen biopsy report

2. Afirma (Veracyte) - Gene Classifier

The Afirma Thyroid FNA Analysis combines specialized cytopathology and the novel Afirma Gene Expression Classifier (GEC). Physicians submit to Veracyte thyroid nodule FNA samples collected in a single patient visit. Then, a thyroid cytopathology specialist at Thyroid Cytopathology Partners (TCP), an independent partner of Veracyte, performs cytopathology assessment of a thyroid nodule FNA sample under the microscope. If the cytopathology diagnosis is benign or malignant, the analysis is complete. Only when TCP's cytopathology diagnosis is indeterminate (a recent study showed TCP’s indeterminate rate to be 16%) is the proprietary Gene Expression Classifier performed.

Afirma Test Kit

Afirma Chip for Gene Expression Classifier (GEC)

Sample of Afirma biopsy report

Thyroglobulin (TG) measurement on fine-needle washout fluids of LYMPH NODES BIOPSY

Thyroglobulin (Tg) measurement on fine-needle aspiration (FNA) specimens of neck lymph nodes is useful in the management of patients with papillary thyroid carcinoma when we suspect metastatic disease. The diagnosis of lymph node metastasis in patients with papillary thyroid cancer is an important factor when deciding to perform neck dissection at the initial surgery, as well as for evaluating the lymph node enlargement after the surgery.

FNA biopsy is performed with the single needle stick (25GA). The sample then will be placed into the vial and send out to the laboratory. It takes about 10 business days to get the result.

Presence of thyroglobulin (TG) within the lymph node indicates metastatic disease.

Ultrasound view of the Neck Lymph Node with metastatic disease in patient with Papillary Thyroid Carcinoma

Example of the Report from Neck Lymph Node FNA biopsy in patient with metastatic papillary thyroid carcinoma into the neck lymph nodes.

THYROID CYST ETHANOL ABLATION

If thyroid nodule is completely cystic, than there is an option of percutaneous aspiration and ethanol injection (ablation) into the cyst. It is effective in managing predominantly cystic nodules and sometimes requires repeated injections. Procedure is done under ultrasound guidance, it is outpatient and performed in the office. not every patient with cystic nodule would benefit. Only selected patients meet criteria for ethanol ablation.

Before ethanol ablation

One year after ethanol ablation