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Gupta, Bhardwaj, and Sharma: The interobserver variability of thyroid fine needle aspirates using The Bethesda System for Reporting Thyroid Cytopathology


Introduction

Thyroid diseases are among the commonest endocrine disorders worldwide. About 42 million people in India suffer from thyroid diseases.1 Fine needle aspiration cytology (FNAC) is the first‑line diagnostic procedure for evaluating thyroid lesions. It is a simple, rapid, cost-effective test that provides valuable information about the nature of a thyroid nodule and can effectively distinguish between neoplastic and non‑neoplastic lesions of the thyroid therefore guiding appropriate management i.e. follow-up or surgery thus reducing unnecessary surgery for patients with benign disease.4, 3, 2

Reporting of thyroid FNA specimens should follow a standard format that is clinically relevant in order to direct appropriate management.5 The terminology for reporting thyroid FNACs has varied markedly worldwide with use of many reporting formats varying from two category schemes to six or more category schemes with some relying on descriptive phrases instead of categories.4, 3 This lack of uniformity creates confusion amongst referring clinicians in the interpretation of thyroid cytopathology report, thereby affecting definitive clinical management.2

To address terminology and other issues related to thyroid FNA, the National Cancer Institute (NCI) hosted the "NCI Thyroid Fine Needle Aspiration State of the Science Conference", a multidisciplinary conference that took place in Bethesda, Maryland, United States in October 2007,that led to the formation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), a six-category scheme for reporting thyroid cytopathology that recommends each report should begin with a general diagnostic category. Each of the categories has an implied risk of malignancy that links it to a rational clinical management guideline.6

Recently published data support the clinical utility and wide acceptance of TBSRTC by both practicing pathologists and clinicians. In Indian perspective too, many studies have been carried out that have concluded TBSRTC to be an effective reporting system for thyroid FNA. It improves perceptions of diagnostic terminology between cytopathologists and clinicians and also provides clear management guidelines to the clinicians.4, 2 In our institution, reporting of thyroid lesions on FNA is variable and no standardized system of reporting is being followed. The present study was thus carried out to analyse the cytological features of thyroid fine needle aspiration smears and categorise them by The Bethesda System for Reporting Thyroid Cytopathology; and to assess interobserver variability between two independent reporting pathologists using The Bethesda System for Reporting Thyroid Cytopathology.

Materials and Methods

The present study was conducted in the Department of Pathology, Government Medical College, Jammu over a period of three years from Nov.2015 to Oct.2018. It included all patients presenting with thyroid swelling referred to this department from various clinical departments of this hospital and from other health care centers. Non-cooperative and morbid patients were excluded from the study.

Smears were prepared from the sample obtained by aspiration or non-aspiration method and were stained with May-Grunwald-Giemsa (MGG) and Papanicolau (PAP) stains. Stained smears were examined under light microscopy by two independent pathologists in a double blinded fashion. The cytological features were evaluated and reporting was done according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).

The definitions and cytomorphological criteria as described in the, The Bethesda System for Reporting Thyroid Cytopathology atlas were followed by the two reporting pathologists (Pathologist I and Pathologist II). After assessing the adequacy as per TBSRTC adequacy criteria, the thyroid fine needle aspirates were categorized into the six categories of The Bethesda System for Reporting Thyroid Cytopathology.7

Nondiagnostic/Unsatisfactory (ND/UNS)

Nondiagnostic is used to convey a sample that does not meet the adequacy criteria as given in the TBSRTC monograph. A thyroid FNA sample is considered adequate for evaluation if it contains a minimum of six groups of well-visualised follicular cells, with atleast ten cells per group, preferably on a single slide. Exceptions to this requirement apply to solid nodules with cytologic atypia, solid nodules with inflammation and colloid nodules where minimum number of follicular cells is not required for adequacy.

Nondiagnostic category included aspirates with fewer than six groups of well-preserved, well-stained follicular cell groups with ten cells each (excluding the exceptional circumstances); aspirates with poorly prepared, poorly stained, or significantly obscured follicular cells; cyst fluid, with or without histiocytes, and fewer than six groups of ten benign follicular cells.

Benign   

The aspiration smears were categorized as benign if they showed cytomorphological features of a benign follicular nodule, lymphocytic thyroiditis, granulomatous thyroiditis or other entities like acute thyroiditis as per TBSRTC.

Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS)

This diagnostic category was reserved for aspirates that contained cells with architectural and/or nuclear atypia that was not sufficient to be classified as suspicious for a follicular neoplasm, suspicious for malignancy, or malignant. On the other hand, the atypia was more marked than could be ascribed confidently to benign changes.

Follicular Neoplasm/ Suspicious for Follicular Neoplasm (FN/SFN)

This category included smears that were moderately or markedly cellular with significant alteration in follicular cell architecture, characterized by cell crowding, microfollicles, and dispersed isolated cells. Colloid was scant to absent.

Aspirates in this category were included as Follicular Neoplasm, Hurthle cell (Oncocytic) type if the aspirate consisted exclusively (or almost exclusively) of Hurthle cells having abundant finely granular cytoplasm, enlarged central or eccentrically located round nucleus, prominent nucleolus. Specimens were moderately to markedly cellular with usually little or no colloid and virtually no lymphocytes (excluding blood elements) or plasma cells.

Suspicious for Malignancy (SFM)

Cases showing cytomorphological features that raised a strong suspicion of malignancy (papillary thyroid carcinoma, medullary thyroid carcinoma, lymphoma or metastatic carcinoma) but the findings were not sufficient for a conclusive diagnosis were included in this category.

Malignant

This Bethesda category was applied whenever the cytomorphologic features were conclusive for malignancy. The malignancies included in this category were Papillary thyroid carcinoma, Medullary thyroid carcinoma, Anaplastic carcinoma, Poorly differentiated carcinoma, and lymphoma.

The results of both the pathologists were evaluated for interobserver variability by calculating the percentage of agreement, disagreement; and interobserver variability was statistically assessed using Cohen's kappa as a measure of concordance between the two observers beyond chance.

Results

A total of 610 patients were included in the study. The thyroid fine needle aspirates were categorized into the six categories of The Bethesda System for Reporting Thyroid Cytopathology by two independent pathologists.

Pathologist I reported 51 cases (8.36%) as Nondiagnostic, 524 cases (85.90%) as Benign, 2 cases (0.33%) as Atypia of Undetermined Significance, 15 cases (2.46%) as Follicular Neoplasm, 1 case (0.16%) as Suspicious for Malignancy, and 17 cases (2.79%) as Malignant while Pathologist II reported 50 cases (8.20%) as Nondiagnostic, 510 cases (83.61%) as Benign, 12 cases (1.97%) as Atypia of Undetermined Significance, 16 cases (2.62%) as Follicular Neoplasm, 6 cases (0.98%) as Suspicious for Malignancy, and 16 cases (2.62%) as Malignant (Table 1) (Figure 6, Figure 5, Figure 4, Figure 3, Figure 2, Figure 1).

Benign category was the largest category followed by Nondiagnostic category. Benign follicular nodule was the predominant subcategory followed by chronic lymphocytic thyroiditis as reported by both pathologists. Papillary Thyroid Carcinoma was the most common malignancy reported by both the pathologists in our study (Table 1).

The two pathologists were in agreement in 548 cases (89.84%) and disagreed in 62 cases (10.16%). Diagnostic agreement was highest in the Benign category (95.68%), followed by Malignant category (87.5%), Follicular Neoplasm (75%), Nondiagnostic (68%). No agreement was seen in AUS category and Suspicious for Malignancy category (0%, 0% respectively) between the two reporting pathologists (Table 2).

Discordant cases of Nondiagnostic category by one pathologist were categorized in Benign category by other pathologist. Discordant cases in Benign category were put into Non diagnostic, AUS, Follicular neoplasm and Suspicious for Malignancy categories by other pathologist. Of the two cases in AUS category by one pathologist, there was disagreement in both the cases with one case reported in Benign category and other case in Suspicious for Malignancy category by other pathologist. Of the 15 cases in Follicular neoplasm category by one pathologist, there was disagreement in 3 cases with 2 cases reported in Benign category and 1 case in Malignant category by other pathologist. Of one case in Suspicious for Malignancy category by one pathologist, there was complete disagreement with the case being reported in Malignant category by other pathologist. Of the 17 cases in Malignant category by one pathologist, there were 3 discordant cases, 2 cases in Benign category and 1 case in Suspicious for Malignancy category by other pathologist (Table 2).

The interobserver variability was statistically assessed using Cohen's kappa coefficient with observed value of 0.628; 62.8% (95% Confidence Interval 54.0-71.6) i.e. actual agreement between the two pathologists beyond chance was 62.8% (moderate) in our study.

Table 1
Bethesda Category Sub-categories Pathologist I Pathologist II
Number of cases Percentage (%) Number of cases Percentage (%)
I. Non diagnostic 51 8.36 50 8.20
Cyst fluid only 0 0.00 2 0.33
Virtually acellular specimen 42 6.89 42 6.89
Others (obscuring blood, clotting artifact, etc.) 9 1.47 6 0.98
II. Benign 524 85.90 510 83.61
Consistent with a benign follicular nodule (colloid nodule, adenomatoid nodule) 351 57.54 377 61.80
Consistent with chronic lymphocytic (Hashimoto) thyroiditis 162 26.56 118 19.34
Consistent with granulomatous (subacute) thyroiditis 3 0.49 6 0.98
Other 8 1.31 9 1.48
III. Atypia of Undetermined Significance 2 0.33 12 1.97
IV. Follicular Neoplasm 15 2.46 16 2.62
Follicular Neoplasm 12 1.97 11 1.80
Follicular Neoplasm, Hurthle Cell (Oncocytic) type 3 0.49 5 0.82
V. Suspicious for Malignancy 1 0.16 6 0.98
Suspicious for Papillary Thyroid Carcinoma 1 0.16 6 0.98
VI. Malignant 17 2.79 16 2.62
Papillary Thyroid Carcinoma 8 1.31 8 1.31
Poorly differentiated carcinoma 1 0.16 2 0.33
Medullary thyroid carcinoma 3 0.49 3 0.49
Undifferentiated(Anaplastic) carcinoma 4 0.66 3 0.49
Non-Hodgkin Lymphoma 1 0.16 0 0.00
Total 610 100.00 610 100.00

Distribution of cases into various categories and subcategories as per TBSRTC by Pathologists I and II

Table 2
Bethesda Category Pathologist I
Non Diagnostic Benign Atypia of Undetermined Significance Follicular Neoplasm Suspicious for Malignancy Malignant Total
Pathologist II I. Non diagnostic 34 16 0 0 0 0 50
II. Benign 17 488 1 2 0 2 510
III. Atypia Of Undetermined Significance 0 12 0 0 0 0 12
IV.Follicular Neoplasm 0 4 0 12 0 0 16
V. Suspicious for Malignancy 0 4 1 0 0 1 6
VI. Malignant 0 0 0 1 1 14 16
Total 51 524 2 15 1 17 610

Comparison of cases reported according to TBSRTC by two pathologists as agreement versus disagreement

Figure 1

Photomicrograph from a case of Colloid Nodule showing abundant colloid with few follicular cells (MGG 40 X).

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Figure 2

Photomicrograph from a case of Lymphocytic Thyroiditisshowing sheet of follicular cells infiltrated by mature lymphocytes along with numerous lymphoid cells in the background (MGG 400 X)

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Figure 3

Photomicrograph from a case of AUS showing few clusters as well as singly scattered follicular cells with mild anisonucleosis and focal microfollicle formation (PAP 400 X).

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Figure 4

Photomicrograph from a case of Follicular Neoplasm showing follicular cells arranged in crowded clusters and microfollicles (PAP 400 X).

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Figure 5

Photomicrograph from a case of Papillary Thyroid Carcinoma (Bethesda Malignant category) showing multiple complex papillae with peripheral palisading of the tumor cells (PAP 100 X).

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Figure 6

Photomicrograph from a case of Papillary Thyroid Carcinoma showing optically clear nuclei with intranuclear grooves (PAP 400 X).

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Discussion

TBSRTC has been widely adopted in the United States and in many places worldwide and has been endorsed by the American Thyroid Association.8, 7 The distribution of cases into various TBSRTC categories by the two pathologists in our study were compared with other studies as shown in Table 3.

The frequency of Nondiagnostic interpretations varies notably from laboratory to laboratory (range, 3-34%).7 The findings of our study (8.36%, 8.20%) are consistent with this range and are comparable with other studies.9, 4 As most thyroid nodules are benign, a benign result is the most common FNA interpretation (approximately 60-70% of all cases).7 The cases in benign category in our study are higher than this range (85.90%, 83.61%) and also from study by Jo et al.10 but are comparable with other studies.11, 9, 4, 2 Being the only tertiary care center of our province, it caters to a large number of patients on both direct and referral basis, so a large population representative of general population is encountered that could be a reason for higher number of cases in benign category.

Table 3
Bethesda category Mondal et al.2 Mehra et al.4 Bhat et al.9 Jo et al.10 Laishram et al.11 Present Study
Pathologist I Pathologist II
I Non diagnostic 1.2 7.2 6.6 18.6 5.2 8.36 8.20
II Benign 87.5 80 82 59 89.9 85.90 83.61
III AUS 1 4.9 2 3.4 0 0.33 1.97
IV Follicular Neoplasm 4.2 2.2 2.5 9.7 2.2 2.46 2.62
V Suspicious for malignancy 1.4 3.6 1.6 2.3 0.3 0.16 0.98
VI Malignant 4.7 2.2 5.1 7.0 2.2 2.79 2.62

Comparison of percentages of distribution of cases of present study with other studies

AUS/FLUS usage varies from 1% to 22% of thyroid FNAs with practical upper limit of 10%.7 AUS cases and Follicular Neoplasm cases reported in our study are comparable with studies in Table 3. Suspicious for Malignancy (SFM) diagnoses account for approximately 3% (range 1.0-6.3%) of all thyroid FNAs. As with any indeterminate diagnosis, this category should be used judiciously so that patients are managed as appropriately as possible.7 The SFM cases in our study as reported by Pathologist I are lesser than the lower limit of the given range (0.16%) but are comparable with study by Laishram et al.,11 while are 0.98% i.e. ~1% as reported by Pathologist II which are comparable with other studies.4, 2 A malignant thyroid FNA diagnosis accounts for approximately 5% (range, 2-16%) of all thyroid FNAs.7 Malignant cases (Category VI) in our study are within this range (2.79%, 2.62%) and comparable with studies in Table 3.

The two pathologists were in agreement in 548 cases (89.84%) and disagreed in 62 cases (10.16%) which is consistent with other studies.15, 14, 13, 12 Cohen's kappa score of 0.628 is comparable to kappa score in a study by Awasthi et al.12 In a study by Salillas et al.,14 the strength of agreement was very good with a kappa statistic of 0.90. In a study by Pathak et al.,15 unweighted Cohen's kappa score for consultant and SR was 0.7517 (strong), between consultant and JR was 0.5907 (moderate).

Diagnostic agreement was highest in the Benign category (95.68%), followed by Malignant category (87.5%) in our study. In a study by Bhasin et al.,13 maximum degree of agreements were noted in nondiagnostic (100%), malignant (100%) and benign (93.87%) categories. In a study by Awasthi et al.,12 there was absolute agreement on the cases in ND/US and AUS/FLUS categories followed by 94.8% concordance in benign category. Lesser number of cases reported under ND/US category in above two studies could be reason for absolute agreement in ND category in their studies. In a study by Salillas et al.,14 the category under which maximum degree of agreement was noted was malignant (100%, k=0.61) followed by benign (k=0.60).

In our study, no agreement was seen in AUS (0%) category and SFM (0%) category between the two reporting pathologists. In a study by Bhasin et al.,13 maximum disagreement was noted in AUS/FLUS category that is consistent with our study. Of 7 discordant cases in study by Salillas et al.,14 3 were SFM and 2 AUS which is consistent with our study. In a study by Pathak et al.,15 poor interobserver agreement level (K=0.1301) was observed in the AUS/FLUS category which is consistent with our study. In a study by Kocjan et al.,16 there was poor agreement for Thy3a (κ = 0.11) and Thy4 (κ = 0.17) categories which are similar to AUS and SFM categories respectively of Bethesda system and comparable to our study.

Low reproducibility for AUS/FLUS has been reported, variability in criteria used for AUS/FLUS is responsible for significant interobserver and inter-institutional variation in making diagnoses.15 The reproducibility of AUS/FLUS category is at best only fair.7 Significant interobserver variability of thyroid FNA though well established has been reported to be smaller (although still significant) for "benign" and "malignant" categories. AUS/FLUS category is one with the most interobserver variability among the cytopathologists. Differing threshold levels in applying the diagnostic criteria as noted in one of the studies could be a reason for this variability in our study too.17

Conclusion

The findings of our study are consistent with other published studies in literature. The systematic reporting according to TBSRTC has led to clear interpretation of the thyroid FNAC report. The use of this uniform terminology by two reporting pathologists revealed a moderate interobserver agreement that favours its use because of its relative ease of reproducibility. It also provides malignancy risk and management guideline for each category. Thus, the present study encourages the use of TBSRTC as a standardized reporting system in our institution and elsewhere for effective communication among pathologists and clinicians with regard to thyroid FNAC reporting and management.

Conflict of interest

The authors have no conflicts of interest to declare.

Source of funding

The study was not funded by any source.

References

1 

A G Unnikrishnan U V Menon Thyroid disorders in India: An epidemiological perspectiveIndian J Endocr Metab2011157881

2 

S K Mondal S Sinha B Basak D N Roy S K Sinha The Bethesda system for reporting thyroid fine needle aspirates: A cytologic study with histologic follow-upJ Cytol2013309499

3 

E S Cibas M A Sanchez The National Cancer Institute thyroid fine-needle aspiration state-of-the-science conference: Inspiration for a uniform terminology linked to management guidelinesCancer Cytopathol20081147173

4 

P Mehra A K Verma Thyroid cytopathology reporting by the Bethesda system: A two-year prospective study in an academic institutionPatholog Res Int201511

5 

S R Orell G F Sterrett Orell & Sterrett's Fine Needle Aspiration Cytology. 5th edRELX India Private Limited2012118155

6 

E S Cibas S Z Ali The Bethesda System for Reporting Thyroid CytopathologyAm J Clin Pathol2009132658665

7 

S Z Ali E S Cibas The Bethesda System for Reporting Thyroid Cytopathology. Definitions, Criteria and Explanatory Notes.2nd ed2018SpringerSwitzerland

8 

B R Haugen E K Alexander K C Bible American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid CancerThyroid20152611133

9 

S Bhat N Bhat H Bashir The Bethesda System for Reporting Thyroid Cytopathology: a two year institutional auditInt J Cur Res Rev201686511

10 

V Y Jo E B Stelow S M Dustin K Z Hanley Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda System for Reporting Thyroid CytopathologyAm J Clin Pathol2010134450456

11 

R S Laishram T Zothanmawii Z Joute P Yasung K Debnath The Bethesda system of reporting thyroid fine needle aspirates: A 2-year cytologic study in a tertiary care instituteJ Med Soc201731137

12 

P Awasthi G Goel U Khurana D Joshi K Majumdar N Kapoor Reproducibility of “The bethesda system for reporting thyroid cytopathology:” A retrospective analysis of 107 patientsJ Cytol20183513336

13 

T S Bhasin R Mannan M Manjari Reproducibility of “The Bethesda System for reporting Thyroid Cytopathology”: A Multicenter study with review of the literatureJ Clin Diagn Res20137610511054

14 

A L Salillas Fcs Sun E G Almocera Review of the Bethesda System for Reporting Thyroid Cytopathology: A Local Study in Bohol IslandActa Cytologica2015597782

15 

P Pathak R Srivastava N Singh V K Arora A Bhatia Implementation of the Bethesda system for reporting thyroid cytopathology: Interobserver concordance and reclassification of previously inconclusive aspiratesDiagn Cytopathol20144211944949

16 

G Kocjan A Chandra P A Cross The interobserver reproducibility of thyroid fine needle aspiration using the UK Royal College of Pathologists' Classification SystemAm J Clin Pathol2011135852859

17 

V Padmanabhan C B Marshall G A Barkan Reproducibility of atypia of undetermined significance/follicular lesion of undetermined significance category using the Bethesda system for reporting thyroid cytology when reviewing slides from different institutions: A study of interobserver variability among cytopathologistsDiagn Cytopathol20170017



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