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 Table of Contents    
ORIGINAL ARTICLE  
Year : 2019  |  Volume : 36  |  Issue : 1  |  Page : 48-52
Histopathological review of diagnostic categories of the Bethesda system for reporting thyroid cytopathology – An institutional experience of 5 years


1 Department of Pathology, BP Koirala Institute of Health Sciences, Karnali Province, Nepal
2 Department of Pathology, Province Hospital, Karnali Province, Nepal
3 Department of Community Medicine, BP Koirala Institute of Health Sciences, Karnali Province, Nepal

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Date of Web Publication17-Jan-2019
 

   Abstract 


Context: Fine needle aspiration (FNA) plays a crucial role in the evaluation of patients with thyroid lesions. The Bethesda system for reporting thyroid cytopathology (TBSRTC) was designed with a mission to standardize the process of diagnosis and management of thyroid lesions by FNA cytology (FNAC). Aim: We aim to see the benefits of adopting TBSRTC, seek the cytological pitfalls in the diagnosis of thyroid FNAC, and identify the spectrum of thyroid lesions in our setup. Settings and Design: This is a hospital-based cross-sectional study conducted from June 2009 to June 2014 of all thyroid FNACs with available histopathology reports. Cases were designated a specific diagnostic category according to TBSRTC. Materials and Methods: A total of 109 cases were included in the study. Sixty-eight cases had been reported without using TBSRTC and were reviewed and reclassified according to TBSRTC seeking the common reasons for interpretative errors. Statistical Analysis Used: Data were analyzed using SPSS ver. 11.5. Results: In both pre- and post-TBSRTC era, benign neoplasms constituted the major bulk. After the use of TBSRTC, there was increased ability to look for follicular neoplasms, improvement in making definitive diagnosis of the cases, decline in the suspicious category, and an improvement in diagnostic accuracy, and we were in line with the implied risk outlined by TBSRTC in most of the cases except the nondiagnostic or unsatisfactory category. Conclusion: Application of TBSRTC results in uniformity in reporting among pathologists and better interdisciplinary communication and patient management.

Keywords: Bethesda, diagnostic categories, thyroid

How to cite this article:
Upadhyaya P, Dhakal S, Adhikari P, Adhikari B, Khadka D, Niraula SR. Histopathological review of diagnostic categories of the Bethesda system for reporting thyroid cytopathology – An institutional experience of 5 years. J Cytol 2019;36:48-52

How to cite this URL:
Upadhyaya P, Dhakal S, Adhikari P, Adhikari B, Khadka D, Niraula SR. Histopathological review of diagnostic categories of the Bethesda system for reporting thyroid cytopathology – An institutional experience of 5 years. J Cytol [serial online] 2019 [cited 2019 Apr 25];36:48-52. Available from: http://www.jcytol.org/text.asp?2019/36/1/48/250132





   Introduction Top


Fine needle aspiration (FNA) plays a crucial role in the evaluation of thyroid nodules.[1] However, studies have shown that up to 30% of thyroid FNA were diagnosed previously as “atypical,” “indeterminate,” and “suspicious for malignancy.”[1] Thus in October 2007, the Bethesda system for reporting thyroid cytopathology (TBSRTC) was designed to establish uniformity in diagnosing thyroid FNA cases and guiding the clinical management. In this study, a comparison was attempted between reports given 2.5 years before and after implementation of TBSRC in our institution. This study aims to identify pitfalls in the diagnosis of thyroid FNA cytology (FNAC) and identify the spectrum of thyroid lesions.


   Materials and Methods Top


This is a hospital-based cross-sectional study of 109 cases conducted in a tertiary care center from June 2009 to June 2014. Ethical clearance was obtained from Institutional Review Committee. (Code No. IRC/477/015). All thyroid FNACs performed during the study period were included in the study. Cases in which histopathology report was not available were excluded from the study.

All these cases were designated a specific diagnostic category according to TBSRTC as follows:[2]

  1. Nondiagnostic or unsatisfactory (ND/UNS)
  2. Benign
  3. Atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)
  4. Follicular neoplasm/”suspicious” for follicular neoplasm
  5. Suspicious for malignancy
  6. Malignant.


Of the total 109 cases studied, in 68 cases, FNAC reports had not been provided according to TBSRTC. The remaining of 41 cases had been reported using TBSRTC. All cases (68) were reviewed independently (by PU and SD) and reclassified according to TBSRTC. Cases with mismatch between histopathological and cytological correlation were also reviewed by two investigators (PU and SD) independently and were recategorized into TBSRTC. The common reasons for morphologic interpretative errors in cytology were sought and are presented in subsequent tables. Data were entered into Microsoft Excel 2007 and converted into SPSS ver. 11.5 for statistical analysis.


   Results and Discussion Top


The category names used in this study to categorize reports before TBSRTC were as follows: inadequate, descriptive reports, benign, suspicious for malignancy, and malignancy. The spectrums of thyroid lesions categorized with and without using TBSRC are shown in [Figure 1] and [Figure 2], respectively.
Figure 1: Diagrammatic representation of cytological and histopathological correlation of pre-TBS

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Figure 2: Diagrammatic representation of cytological and histopathological correlation of post-TBS

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Comparison between the two eras revealed that there was a total absence of vague descriptive reports from 7.3% to 0% in the post-Bethesda era [Table 1]. We also observed that there was an ability to look out for follicular neoplasm from 0% to 11.9% once we confined ourselves to the diagnostic tier of TBSRTC. There was an improvement in making a definite diagnosis of malignancy from 14% to 19% and therefore a corresponding decrease on suspicious diagnoses from 13% to 4%.
Table 1: Frequency distribution of diagnostic categories of FNAC reports before and after implementation of TBSRTC

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After having categorized the FNAC reports into two types, the next step was to compare these diagnostic categories with biopsy reports. In the pre-Bethesda era, 60% of the indeterminate cases turned out to be follicular neoplasm on histopathology. However, after the implementation of TBSRTC, 83.3% of these cases were suspected as follicular neoplasm on FNAC. The fraction of cases that actually turned out to be malignant out of the category labeled as “suspicious” increased in the post-Bethesda era to 80% from that of 33% of the pre-Bethesda era. Therefore, the category “suspicious for follicular neoplasm” acted as a safety zone or as an emergency collection basket which could save from misdiagnosis of thyroid neoplasm into other benign categories. And the exact diagnosis could be sorted out later during histopathology.

The next step was to calculate the strength of the 68 FNAC reports given without using TBSRTC in predicting malignancy on histopathology. Sensitivity was 62.5%, specificity was 100%, positive predictive value (PPV) was 100%, negative predictive value (NPV) was 89.7%, and accuracy was 91.7%.

Similarly, the strength of the FNAC reports given using TBSRTC category in predicting malignancy was also calculated. Sensitivity was 75%, specificity was 100%, PPV was 100%, NPV was 92%, and accuracy was 93.57%. There were a total of 109 FNAC reports which were reported implementing TBSRTC. This includes all the previous 68 cases reported in the pre-TBSRTC method, because all cases were screened and appropriately fitted into the TBSRTC. There was an improvement in the diagnostic accuracy and sensitivity where sensitivity increased from 62.5% to 75% and the diagnostic accuracy increased from 91.17% to 93.57%.

We in our study have also tried to analyze the common cytologic features that hamper accurate diagnosis. Histopathology was considered as the gold standard for final diagnosis in all cases.

Two common scenarios were identified: overdiagnosis of malignancy and underdiagnosis of follicular neoplasm or malignancy. In the first scenario, hyperplastic changes in nodular goiter and Hashimoto's thyroiditis were misdiagnosed as papillary thyroid carcinoma (PTC). In nodular goiter, increased cellularity, large sheets of follicular cells with round nucleus, pale chromatin, and occasional nuclear grooving were the cytological features misleading to diagnosis of PTC. The sheets of follicular cells entangled within the blood clots also gave impression of pale clear chromatin. The cases of Hashimoto's thyroiditis with focal pale powdery chromatin, occasional nuclear inclusion, and intranuclear grooving were the culprit for the diagnosis of PTC.

Overdiagnosing PTC on the basis of few cytological features in the focal areas should be interpreted with caution. The following nuclear features should be carefully looked for: enlarged oval or irregularly shaped nuclei with longitudinal nuclear grooves and intranuclear cytoplasmic pseudo-inclusions, pale powdery chromatin, and solitary or multiple marginally placed nuclei.

In the other scenario, cases with limited cellularity, presence of more number of large follicles over microfollicles, and failure to pick up these microfollicles lead to underdiagnosis of follicular neoplasm as benign nodules. Awareness about microfollicles thus becomes important. There was failure to pick up atypical histiocytoid cells on cytological slides. Scattered groups and sheets of follicular cells with pale nuclei with occasional nuclear grooving and absence of intranuclear inclusion were considered as a part of cystic degeneration in colloid goiter and not as PTC, thereby leading to an underdiagnosis.

The beauty of TBSRTC is that the diagnosis is accompanied by an implied cancer risk for that particular category and it comes with recommendation [Table 2].[2] In most of the categories, we were in line with the implied risk outlined by TBSRTC except the nondiagnostic category where we exceeded the cut-off value outlined by TBSRTC [Table 3]. Classification of thyroid lesions according to TBSRTC standardized nomenclature yielded almost similar overall distribution between categories in different studies [Table 4].[3],[4]
Table 2: The Bethesda system for reporting thyroid cytopathology: Implied risk of malignancy and recommended clinical management

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Table 3: Implied cancer risk in each category after TBS implementation

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Table 4: Comparison of overall distribution of TBSRTC categories in this study to other studies

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Comparison between the two eras revealed that there was a total absence of indeterminate cases (7.3% to 0%), an increase in ability to look out for follicular neoplasm (0% to 11.9%), improvement in making a definite diagnosis of malignancy (14% to 19%), and minimizing suspicious cases (13% to 4%).

Our study has shown a total absence of indeterminate cases after implementation of TBSRTC similar to that of Theoharis et al. which showed a dramatic reduction in percentage of thyroid FNA with indeterminate diagnosis after the use of TBSRTC.[1] Although the cytologic features of follicular neoplasm have been well-described in text books, these were mostly categorized as indeterminate in the pre-Bethesda era, hence were missed/miscommunicated. With the implementation of TBSRTC, most of the follicular neoplasms were picked up on FNA itself (0% to 11%). We would like to stress that a reporting cytopathologist should pay attention to the amount of colloid and architectural arrangement of follicular cells for the diagnosis of follicular neoplasm on FNAC. It is also said that when attention to the above scenarios/pitfalls are paid, it would definitely be easier to classify the indeterminate cases. Some studies (Gerhard et al. and Guo et al.) have also highlighted an important role of second opinion in categorizing thyroid FNA under a specific category.[5],[6]

In our study, there was an increase in the fraction of cases diagnosed as suspicious for PTC that were ultimately malignant after resection (60% to 80%) and this finding is similar to that of Olson et al. Similarly, there was a decrease in the suspicious category from 13.23% to 4.6% and 4.5% to 2.4%, respectively, in ours and theirs.[7] Therefore, it was noticed that the decrease in suspicious category complemented the increase in definite malignant category. However, along with the increase in the diagnosis of malignancy on FNA, the authors also noticed an increase in the rate of AUS.[7] TBSRTC recommends judicious use of AUS category stating that it preferably be limited to 7%.[1] The increase in the rate of AUS category over this limit was also observed by Wu et al. and Sullivan et al. from 3% to 7%.[8],[9] This finding is contrary to our study where the indeterminate cases dropped from 7.3% to 0%, and Crowe et al. have also experienced a similar drop in the rate of indeterminate reports from 3.7% to 0.5% after the implementation of TBSRTC similar to our study.[10] Mondal et al., Mahajan et al., and Dawish et al. have also derived the conclusion from their study that application of TBSRTC has aided in minimizing indeterminate reports and thus helped in providing specific diagnosis, thereby helping in proper management of each cases.[4],[11],[12]

A thyroid FNA sample is considered adequate for evaluation if it contains a minimum of six groups of well-visualized follicular cells with at least 10 cells per group, preferably on the same slide. The use of these well-defined criteria for adequacy is helpful as they improve diagnostic efficiency of thyroid FNA. The most common pitfalls for false-negative diagnoses in thyroid FNA consisted of suboptimal materials and underdiagnoses of PTC due to cystic degeneration.[1],[10] Theoharis et al. found a significant decrease in the rate of nondiagnostic category after implementation from 10% to 30%.[1] Brister et al. found that there was a significant decrease in usage of suboptimal benign including cyst category (21%–3.2%) in the second era, however, at the cost of significant increase in the rate of AUS (3.7%–12%).[13]

TBSRTC holds the advantage of having a standardized reporting format and uniformity of reports thereby being more informative to clinicians. The predictive value of thyroid fine needle aspirates has increased significantly with the use of thyroid FNA. The rate of malignancy in this study was comparable in most of the categories to that mentioned in TBSRTC, except the ND/UNS and AUS category [Table 3].[1],[3],[4],[14] The ND/UNS category in our study yielded a malignancy rate of 33.3%, when compared with 1%–4% in TBSRTC. Of the three cases in the ND/UNS category, one turned out to be malignant.

The common pitfalls for false-negative diagnosis in ND/UNS category are suboptimal material and underdiagnosis of PTC due to cystic changes – “geographical miss.” Fibrosis and calcification are also other causes of sampling error along with excessive blood in the sample. However, it is important to stress that a “ND/UNS specimen does not mean a negative specimen.”

The high rate of false-negative diagnoses in ND/UNS category in our study probably could be due to less sample size. Srbova et al. also found a similar result. They state that it could be due to selection bias as patients with suspicious clinical and sonographic findings were selected for surgery. When patients with clinical follow-up were included, malignancy rate reduced from 5% to 2.5% in their study.[14]

Wong and Balochin their review have also analyzed that the implied cancer risk of the ND/UNS category has shown marked variability in literature, most of them moving beyond the 1%–4% as outlined by TBSRTC.[15] Similarly, Jo et al. have also reported the implied cancer risk of ND/UNS category as 8.9% which definitely exceeds the upper limit of 4% of TBSRTC.[16]

Similarly, category III (AUS/FLUS) lesions were also seen to have a much higher risk of malignancy (26.6%–37.8%) than that outlined by TBSRTC (5%–15%) in a study by Ho et al. and the authors concluded that TBSRTC may warrant reconsideration of current recommendation for AFLUS category.[17] Tepeoğlu et al. also concluded that the classification and management recommendations of TBSRTC are applicable to practical setting, except the AFLUS category.[18]

In our study, after the application of TBSRTC, sensitivity increased from 62.5% to 75% and diagnostic accuracy from 91.17% to 93.57%. This finding is similar to that of other studies except for Srbova et al. who did not notice any improvement in the diagnostic category between the two eras.[14] They recommend that when in uncertainty, both cytopathologist's recommendation and clinical decision including ultrasonograpy evaluation should be taken into consideration. Nevertheless, the authors accept that TBSRTC is useful for communication between centers. Bongiovanni et al. in their meta-analysis of TBSRTC also conclude that TBSRTC has proven to be an effective scheme to guide the clinical management of patients with thyroid nodules as evidenced by its high sensitivity and high NPV. They also stated that there was a growing trend across institutions to adopt TBSRTC because of its clear and comprehensible reports.[19]

We conclude that application of TBSRTC results in reduction in percentage of indeterminate (noncommittal descriptive reports) cases, uniformity in reporting among pathologists in categorization of thyroid lesion, improvement in our capability to diagnose follicular neoplasm, improvement in our capacity to diagnose thyroid carcinoma, end of descriptive reports, and an adoption of more consistent and uniform reporting with better interdisciplinary communication and patient management.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Theoharis C, Adeniran AJ, Roman S, Ann Sosa J, Chhieng D. The impact of implementing the Bethesda system for reporting of thyroid FNA at an academic center. Diagn Cytopathol 2013;41:858-63.  Back to cited text no. 1
    
2.
Cibas E, Ali S. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 2009;132:658-65.  Back to cited text no. 2
    
3.
Mufti ST, Molah R. The Bethesda system for reporting thyroid cytopathology: A five-year retrospective review of one center experience. Int J Health Sci (Qassim) 2012;6:159-73.  Back to cited text no. 3
    
4.
Mondal SK, Sinha S, Basak B, Roy DN, Sinha SK. The Bethesda system for reporting thyroid fine needle aspirates: A cytologic study with histologic follow-up. J Cytol 2013;30:94-9.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Gerhard R, Boerner S. Evaluation of indeterminate thyroid cytology by second-opinion diagnosis or repeat fine needle aspiration: Which is the best approach? Acta Cytol 2015;1-8.  Back to cited text no. 5
    
6.
Guo A, Kaminoh Y, Forward T, Schwartz FL, Jenkinson S. Fine needle aspiration of thyroid nodules using the Bethesda system for reporting thyroid cytopathology: An institutional experience in a rural setting. Int J Endocrinol 2017;2017:9601735.  Back to cited text no. 6
    
7.
Olson M, Boonyaarunnate T, Atlinboga A, Ali S. “Suspicious for papillary thyroid carcinoma” before and after the Bethesda system for reporting thyroid cytopathology: Impact of standardized terminology. Acta Cytol 2013;58:15-22.  Back to cited text no. 7
    
8.
Wu H, Rose C, Elsheikh T. The Bethesda system for reporting thyroid cytopathology: An experience of 1382 cases in a community practice setting with the implication of risk of neoplasm and risk of malignancy. Diagn Cytopathol 2012;40:399-403.  Back to cited text no. 8
    
9.
Sullivan P, Hirschowitz S, Fung P, Apple S. The impact of atypia/follicular lesion of undetermined significance and repeat fine-needle aspiration: 5 years before and after implementation of the Bethesda system. Cancer Cytopathol 2014;24:832-9.  Back to cited text no. 9
    
10.
Crowe A, Linder A, Hameed O, Salih C, Roberstson J, Gidley J, et al. The impact of implementation of the Bethesda system for reporting thyroid cytopathology on the quality of reporting, “risk” of malignancy, surgical rate, and rate of frozen sections requested for thyroid lesions. Cancer Cytopathol 2011;119:315-21.  Back to cited text no. 10
    
11.
Mahajan A, Lin X, Nayar R. Thyroid Bethesda reporting category, “suspicious for papillary thyroid carcinoma,” pitfalls and clues to optimize the use of this category. Cytopathology 2013;24:85-91.  Back to cited text no. 11
    
12.
Dawish MA, Robert AA, Muna A, Eyad A, Ghamdi AA, Hajeri KA, et al. Bethesda system for reporting thyroid cytopathology: A three-year study at a tertiary care referral center in Saudi Arabia. World J Clin Oncol 2017;8:151-7.  Back to cited text no. 12
    
13.
Brister KJ, Singh RS, Wang HH. Reporting thyroid FNA before and after implementation of the Bethesda system – One institution's experience. Diagn Cytopathol 2015;43:28-31.  Back to cited text no. 13
    
14.
Srbova L, Gabalec F, Ryska A, Cap J. Results of retrospective classification of thyroid FNAs according to the Bethesda system: Would this have improved accuracy? Cytopathology 2014;1-7.  Back to cited text no. 14
    
15.
Wong LQ, Baloch ZW. Analysis of the Bethesda system for reporting thyroid cytopathology and similar precursor thyroid cytopathology reporting schemes. Adv Anat Pathol 2012;19:313-9.  Back to cited text no. 15
    
16.
Jo V, Stelow E, Dustin S, Hanley K. Malignancy risk for fine needle aspiration of thyroid lesions according to the Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 2010;134:450-6.  Back to cited text no. 16
    
17.
Ho A, Sarti E, Jain K, Wang H, Nixon I, Shaha A, et al. Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid 2014;24:832-39.  Back to cited text no. 17
    
18.
Tepeoğlu M, Bilezikçi B, Bayraktar SG. A histological assessment of the Bethesda system for reporting thyroid cytopathology (2010) abnormal categories: A series of 219 consecutive cases. Cytopathology 2014;25:39-44.  Back to cited text no. 18
    
19.
Bongiovanni M, Spitale A, Faquin W, Mazzucchelli L, Baloch Z. The Bethesda system for reporting thyroid cytopathology: A meta analysis. Acta Cytol 2012;56:333-9.  Back to cited text no. 19
    

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Correspondence Address:
Dr. Bindu Adhikari
Department of Pathology, BP Koirala Institute of Health Sciences, Dharan
Nepal
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JOC.JOC_64_18

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