Abstract
Aim
Bethesda System for reporting thyroid cytopathology established in 2009 was updated for the first time in 2017. Since its introduction very few studies have been done on the utility of recently introduced “The 2017 Bethesda System for Reporting Thyroid Cytopathology” (TBSRTC II) and estimation of risk of malignancy in various categories.
Material and methods
This was a prospective study done on thyroid lesions in which lesions were evaluated cytologically and classified according to TBSRTC II. Histopathological correlation was done, wherever possible. ROM was calculated for each Bethesda category in both ways as per TBSRTC II i.e. with NIFTP and excluding NIFTP from the malignant category.
Results
Using 2017 TBSRTC, 190 cases of thyroid FNACs were classified into 6 diagnostic categories. Cytohistological correlation was available in 60 cases. ROM was calculated which changed only in category III and V as only these two categories showed one case each of NIFTP. However there was an overestimation of ROM in category II and III as there are selection biases and not all thyroid nodules underwent surgical resections.
Conclusion
To conclude, the risk of malignancy calculated in two ways in the recent 2017 Bethesda system may have higher clinical relevance as those lesions with high ROM are defined for surgical excision. Thus we recommend that “The 2017 Bethesda system for Reporting Thyroid Cytopathology” should be implemented uniformly in our country as it provides a homogenous and standardised terminology resulting in better management of patients with thyroid nodular disease.
Keywords: The 2017 Bethesda system, Thyroid cytopathology, Cytohistological correlation, Risk of malignancy
Introduction
FNAC is a simple, cost effective, easy and quick OPD procedure for diagnosis of thyroid lesions [1]. However, despite widespread use of thyroid FNACs, there was a terminology flaw in the reporting of the thyroid aspirates which varied markedly, thus making it difficult for the clinicians to interpret the reports and decide the management protocol [2]. The need for simplicity of communication and standardization of terminology for thyroid FNACs led to the introduction of Bethesda System for Reporting Thyroid Cytopathology in 2009 [3]. By 2016, certain revisions were planned for the better use of these diagnostic categories, the associated risks of malignancy and appropriate management. The 2017 revision of the Bethesda System recalculated risk of malignancy, gave revised guidelines for the management of patients with thyroid nodules along with the introduction of molecular testing [4]. Global studies of the incorporation of TBSRTC I in diagnostic algorithms for patients with thyroid nodules had concluded that TBSRTC reduces unnecessary thyroidectomies while also ensuring the quality of thyroid malignancy detection [5]. However there is paucity of literature on the utility of recently introduced TBSRTC II. Therefore with this background, we planned our study aiming to classify thyroid FNACs using recent TBSRTC nomenclature along with its histopathological correlation and estimation of risk of malignancy in our institution.
Materials and methods
The present study was conducted prospectively over a period of one and half year from November 2018 to May 2020 in the Department of Pathology, of a tertiary care hospital. Ethical clearance was taken from Institutional ethical committee.
The study participants were selected using convenience sampling technique. All patients referred for FNAC of thyroid lesions (with or without USG guidance) were included in the study and written informed consent was taken from them. FNAC procedure was done and cytological material was obtained either by one or both of the following techniques: Fine needle aspiration (FNA) technique or Fine needle capillary (FNC) / Non-aspiration technique.
The cytological features of thyroid lesions were evaluated and classified into six diagnostic categories according to “The 2017 Bethesda System for Reporting Thyroid Cytopathology.” Histopathological correlation with cytological diagnosis was done, wherever possible and the risk of malignancy for each Bethesda category was calculated with and without including NIFTP (Non Invasive Follicular Thyroid Neoplasm with Papillary- like Nuclear features) in the malignant category.
Results
A total of 190 cases of thyroid fine needle aspirates were included in the study. Cytological diagnosis was done according to “The 2017 Bethesda system for Reporting Thyroid Cytopathology” (TBSRTC II).
Figure 1 shows the age distribution of our study population. Mean age of the patients was 37.7 ± 13.5 years. Majority of the patients belonged to the age group 31–40 years followed by 21–30 years age group. In our study, female preponderance was seen with male to female ratio of 1:5.8 (28/162 cases). Out of 190 cases, 62.1% (118/190) cases presented with nodular thyroid swelling followed by 28.4% (54/190) cases with diffuse enlargement of thyroid and 9.5% (18/190) cases with solitary thyroid nodule. FNAC without ultrasound guidance was done in 158 cases (83.1%), while USG guided FNAC was performed in 32 cases (16.8%).
Fig. 1.
Age distribution of study population
The thyroid aspirates were categorised into 6 diagnostic categories as per “The 2017 Bethesda System for Reporting Thyroid Cytopathology.” Table 1 shows distribution of 190 cases of thyroid aspirates into various Bethesda categories which is as follows: 1.1% Non -diagnostic / Unsatisfactory (category I), 81% Benign (category II), 5.8% FLUS (category III), 4.2% Suspicious for Follicular Neoplasm (Category IV), 3.2% Suspicious for Malignancy (Category V) and 4.7% Malignant (Category VI).
Table 1.
Distribution of study cases according to “The 2017 Bethesda System for Reporting Thyroid Cytopathology”
| Bethesda diagnostic category | Number of cases in each category (n = 190) |
Percentage (%) |
|---|---|---|
| Nondiagnostic/ Unsatisfactory (Category I) | 2 | 1.1 |
| Benign (Category II) | 154 | 81 |
|
Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance (Category III) |
11 | 5.8 |
| Follicular Neoplasm or Suspicious for Follicular a Neoplasm Category (IV) | 8 | 4.2 |
| Suspicious for Malignancy (Category (V) | 6 | 3.2 |
| Malignant (Category VI) | 9 | 4.7 |
Category I (Non-diagnostic/Unsatisfactory) had least number of cases (2 cases, 1.1%) and both the cases were reported as cyst fluid only. None of these two cases underwent surgical excision. Majority of the cytology cases (154 cases, 81%) were categorised into Bethesda Category II. Out of these 154 cases, 108 cases (70%) were consistent with benign follicular nodule, 26 cases (16.7%) with lymphocytic/Hashimoto thyroiditis, 13 cases (8.4%) with Granulomatous thyroiditis and 7 cases (4.5%) were categorised as “Others” which included hyperplastic goitre as well as thyroglossal cyst. Amongst the 154 cases in Category II (Benign), 31 cases (20%) were operated in our hospital, either due to cosmetic reasons or pressure symptoms. Of these, 22 cases were reported as colloid goitre, 3 cases as thyroglossal cyst, 2 cases each as Hashimoto’s thyroiditis and follicular adenoma. Two cases from category II turned out to be malignant on histopathological examination. Both were reported as papillary thyroid carcinoma thus giving a false negative rate of 6.5%.
Category III (Follicular lesion of undetermined significance) had total of 11 cases (5.8%), out of which 9 cases were subjected to histopathological examination based on clinical/radiological findings. Histology showed varied results, 2 cases were reported as colloid goitre, one case as adenomatoid goitre, 3 cases as follicular adenoma and 2 cases as malignancy. Out of 2 malignant cases, one case was reported as papillary thyroid carcinoma and another as follicular thyroid carcinoma. One borderline case of Non-invasive follicular neoplasm thyroid with papillary-like nuclear features (NIFTP) was also seen.
Category IV (Follicular neoplasm/Suspicious for follicular neoplasm) had a total of 8 cases (4.2%). There were 3 cases of Hurthle cell neoplasm and 5 cases suspicious for follicular neoplasm were reported on cytologic evaluation. Out of these 8 cases, histopathology was done in 7 cases. 5 cases were reported as benign on histopathology with 3 cases reported as Hurthle cell adenoma and 2 cases as Follicular adenoma. There were 2 cases of malignancy in this category too, both reported as follicular thyroid carcinoma on histopathological examination.
Of 6 cases in Category V (Suspicious for malignancy), histopathology was available in 5 cases. 3 cases were reported as papillary thyroid carcinoma, 01 case as anaplastic carcinoma and one case as indolent borderline neoplasm i.e. NIFTP.
Out of the nine cases placed in malignant category (Bethesda category VI), eight cases were operated in our hospital and all of these cases proved to be malignant on histopathological examination, thus achieving 100% cytohistological correlation (Table 2). They comprised of 5 cases of papillary thyroid carcinoma, one case each of medullary thyroid carcinoma, poorly differentiated carcinoma and malignant spindle cell neoplasm of thyroid.
Table 2.
Cytohistological correlation with assessment of risk of malignancy
| Bethesda category | No. of cases (n = 190) |
Cases that underwent surgery | Histopathological diagnosis | Risk of malignancy if NIFTP ≠ CA (%) |
Risk of malignancy if NIFTP = CA (%) |
||
|---|---|---|---|---|---|---|---|
| Benign | Borderline (NIFTP) |
Malignant | |||||
| Category I | 2 (1.1%) | 0 | - | - | - | - | - |
| Category II | 154 (81%) | 31 | 29 | 0 | 2 | 6.5 | 6.5 |
| Category III | 11 (5.7%) | 9 | 6 | 1 | 2 | 22.2 | 33.3 |
| Category IV | 8 (4.2%) | 7 | 5 | 0 | 2 | 28.6 | 28.6 |
| Category V | 6 (3.2%) | 5 | 0 | 1 | 4 | 80 | 100 |
| Category VI | 9 (4.7%) | 8 | 0 | 0 | 8 | 100 | 100 |
Table 3 shows risk of malignancy (ROM) calculated for each Bethesda category with and without NIFTP as per recent 2017 TBSRTC. Since Category III and Category V showed one case each of NIFTP therefore risk of malignancy changed only in these two categories. In Bethesda category I, risk of malignancy was not calculated as none of the 2 cases were surgically resected. In the category II, risk of malignancy was 9.4%. Category III had a risk of malignancy of 33% with NIFTP and 22.2% without NIFTP.In Category IV, risk of malignancy was 28%. In category V, when NIFTP was included in the malignant category, ROM was 100% and on excluding NIFTP, the ROM was 80%. In Category VI risk of malignancy was 100%.
Table 3.
Comparison of risk of malignancy (ROM) in present study with “The 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC II)”
| Bethesda category | Risk of malignancy if NIFTP ≠ CA (%) – |
Risk of malignancy if NIFTP = CA (%) – |
Risk of malignancy if NIFTP ≠ CA (%)- |
Risk of malignancy if NIFTP = CA (%) – |
Usual management |
|---|---|---|---|---|---|
| PRESENT STUDY | PRESENT STUDY | TBSRTC II | TBSRTC II | ||
| Category I | - | - | 5–10 | 5–10 | Repeat FNA with ultrasound guidance |
| Category II | 6.5 | 6.5 | 0–3 | 0–3 | Clinical and sonographic follow up |
| Category III | 22.2 | 33.3 | 6–18 | 10–30 | Repeat FNA, molecular testing, or lobectomy |
| Category IV | 28.6 | 28.6 | 10–40 | 25–40 | Molecular testing, lobectomy |
| Category V | 80 | 100 | 45–60 | 50–75 | Near total thyroidectomy or lobectomy |
| Category VI | 100 | 100 | 94–96 | 97–99 | Near total thyroidectomy or lobectomy |
Discussion
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a standardized framework for the classification of thyroid FNA specimens based on cytomorphologic criteria, and has been endorsed by the latest ATA guidelines for the management of patients with thyroid nodules [6]. Each of the 6 interpretive categories of TBSRTC is associated with an approximate risk of malignancy (ROM), which clinicians use to guide management of patients with a thyroid nodule [7].
In the present study, the age of patients ranged from 8 to 75 years. Mean age was 37 years which was comparable to a study by Naz et al. [8] Out of 190 cases, 162 (86.3%) were females and 28 (14.7%) males. Thyroid lesions are more prevalent in females as affirmed by the present study which showed a male: female ratio of 1:5.8. This was similar to results noted by Yassa et al., Yang et al. and Sawarkar et al. which also showed female preponderance [9–11].
Our study results with regard to incidence of lesions in all Bethesda categories were comparable with the study of Mondal et al. [12] Only category III (FLUS) cases were slightly higher in our study (5.3%) as compared to category III (1%) in comparison to study by Mondal et al.
The present study had 2 (1.1%) cases in Category I in which only cyst fluid was aspirated which was much lower than study of Joe et al. which had 18.6% cases in category I [12]. Reason for lower percentage of cases in our study can be attributed to the fact that FNAC is being done from at least two sites at the same setting in our institute and is usually performed by experienced cytopathologists. Preferably USG guided FNAC is done from smaller nodules so that adequate aspirate can be procured from the exact pathological site. The recommended management for this category is repeat FNAC with ultrasound guidance.
In the present study Category II comprised of majority of cases (81.5%) followed by Category IV (4.2%) which correlates well with the other studies [6, 14, 15]. Although surgery is not recommended in Benign (Bethesda category II), the operative procedure was done in 31 patients primarily for cosmetic purposes or due to associated pressure symptoms.
It was seen that the distribution of cases as per the six tier Bethesda system in our study differed from that in other studies, with the percentage of cases in the Benign (Bethesda category II ) being higher and that in the Non- diagnostic/Unsatisfactory (Bethesda category I) being lower [13]. The reason for the number of cases in the Benign (Bethesda category II) being higher, can be attributed to the fact that our hospital and cytology facilities are easily accessible to the urban slum population located in close proximity to our hospital. So a large number of lesions, representative of the general population is encountered in our institute. Therefore, the proportion of benign cases which are higher in the general population is reflected proportionately in our study. According to Jo et al., most of the studies have been done in tertiary care centres, where patients come only on a referral basis and, hence, is not exactly representative of the general population [13].
Diagnostic category of Follicular lesion of undetermined significance (Category III) is heterogeneous suggesting high variability across institutions [16]. The risk of malignancy estimated in FLUS (Category III) was 33.3% with inclusion of NIFTP and 22.2% without NIFTP in comparison with TBSRTC II in which ROM was 10–40% with inclusion of NIFTP and 25–40% without NIFTP.
There were 8 cases (4.2%) in our study placed under Suspicious for a follicular neoplasm (Bethesda category IV). Incidence of cases in category IV in our study was similar to the study by Mondal et al. [12] However rates reported by Yassa et al. were much higher compared to our study [9].
Incidence of cases in Suspicious for a Follicular Neoplasm (Bethesda category V) in our study were concordant with most other studies [10, 17]. except Savarkar et al. [11] (0.5%) and Yassa et al. [9]
Incidence of cases in category VI of our study was similar to study by Mondal et al. [12] Yassa et al. [9] and Nayar et al. [17] One case of Malignant spindle cell neoplasm of thyroid and the patient was advised IHC for proper characterisation. However, the patient did not underwent IHC evaluation due to financial constraints and as such definitive diagnosis could not be rendered.
In our study a total of 2 cases turned out to be Non-invasive Follicular Thyroid neoplasm with Papillary-like nuclear features (NIFTP) on histopathological examination, one from Bethesda category III (Follicular lesion of undetermined significance) which was showing focal features of papillary carcinoma and one from Bethesda category V (Suspicious for Malignancy) in which few follicles showed intranuclear inclusions but no papillae or grooves or chewing gum colloid was seen.
NIFTP is a recently introduced entity which has significant implications not only in the practice of thyroid cytopathology but also for surgical pathology and for molecular testing creating significant challenges. The risk of malignancy in category V (Suspicious For Malignancy) with NIFTP is 80% and without NIFTP is 100%. The risk of malignancy in category VI (Malignant) was 100%. Our study was able to accurately predict the ROM in Bethesda category V (SFM) and Bethesda category VI (Malignant).
The Bethesda system of reporting thyroid cytopathology has an added advantage of predicting risk of malignancy which enables the clinicians to plan for follow-up or surgery and also the extent of surgery [18–20]. According to Mahajan et al. TBSRTC has helped in appropriate surgical planning in 96.4% of their patients [21].
In the first edition of TBSRTC, the implied risk of malignancy for each diagnostic category was calculated and provided a range based on review of the literature at that time. In the second edition these ranges have been revised, especially for the so –called indeterminate categories. In our study we also determined risk of malignancy for each Bethesda category in both ways as per TBSRTC II i.e. with NIFTP and excluding NIFTP [22].
In Bethesda category I (Nondiagnostic/Unsatisfactory) risk of malignancy could not be calculated as none of the cases were surgically resected. In Bethesda category II (Benign) risk of malignancy was 6.5% which was slightly higher than the range given in TBSRTC II. The actual risk of malignancy of Bethesda category III (FLUS) is difficult to determine, since confirmatory diagnosis is only available in a subset of patients selected for surgery [19]. The associated risk of malignancy in category III in our study was 33.3% with NIFTP and 22.2% without NIFTP which was similar to rates found by Yassa et al. (24%) and Yang et al. (19%) although this was as per TBSRTC I. In category IV (Follicular neoplasm/Suspicious for a Follicular Neoplasm) risk of malignancy was 28.6% which is almost similar to other studies [6, 8, 12]. The risk of malignancy in category VI (Malignant) was 100%. Our study was able to accurately predict the ROM in Bethesda category V (SFM) and Bethesda category VI (Malignant).
Even on extensive research we did not come across any study assessing the risk of malignancy as per the new 2017 Bethesda System (TBSRTC II) especially in India. It is also important to mention that the percentage of NIFTP diagnosis and ROM is different among western and Asian studies. This is due to several factors as there is a higher rate of FVPTC diagnosis in western countries, which might affect the rate of NIFTP, or the higher resection rate of the thyroid nodules in the western practice compared to the conservative strategy management of the Asian one [23].
Our study was limited in terms of small single -centre hospital based study with histological follow up available in only 31.5% of patients. Therefore, a multicentric study with larger sample size maybe undertaken to yield accurate risk of malignancy. Further risk of malignancy could not be calculated in ND/UNS Bethesda category I as no case was surgically resected. Moreover, estimation of risk of malignancy in indeterminate thyroid lesions category III, category IV is limited by the fact that not all nodules undergo surgery. In TBSRTC II 2017, molecular testing has also been recommended which aids in providing additional information regarding the malignant risk of indeterminate thyroid lesions, specifically Bethesda category III (AUS/FLUS) and category IV (FN/SFN) but because of the financial constraints molecular testing could not be done in our study.
Conclusion
The TBSRTC II has an advantage of predicting the risk of malignancy which will enable the clinicians to plan for follow up or surgery with every institution calculating their own ROM We also conclude that the recent 2017 Bethesda system enhances the diagnostic accuracy of FNAC thyroid and improves the quality of reporting by decreasing the diagnostic discrepancies, facilitate diagnostic correlation with histopathology and enables estimation of risk of malignancy, leading to more consistency in management plans.
Footnotes
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