|Year : 2016 | Volume
| Issue : 1 | Page : 9-14
Impact of the Bethesda System in Reporting Thyroid Cytopathology
S Prathima1, TN Suresh2, ML Harendra Kumar2, A Bhaskaran2
1 Department of Pathology, Vydehi Institute of Medical Sciences and Research Centre, Whitefield, Bengaluru, India
2 Department of Pathology and Surgery, Sri Devaraj Urs Medical College, Tamaka, Kolar, Karnataka, India
|Date of Web Publication||5-Jan-2016|
Vydehi Institute of Medical Sciences and Research Centre, Whitefield, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Context: Fine needle aspiration cytology (FNAC) has emerged as one of the well-established first-line diagnostic techniques in the evaluation of thyroid lesions as well as solitary thyroid nodule. But in the cytological diagnosis of borderline lesions, various diagnostic criteria have led to confusion and differences in reporting between cytopathologists and clinicians. To overcome this situation, the Bethescda System of Reporting Thyroid Cytopathology (TBSRTC) 2007 recommended by the National Cancer Institute put down six general diagnostic categories. Aims: The current study evaluates diagnostic utility, reproducibility, and prognostic significance of TBSRTC and report the malignancy risk for FNA of thyroid lesions. Settings and Design: Retrospective study. Materials and Methods: It is a retrospective study of FNAC in 178 patients presenting with thyroid swelling from January 2013 to December 2013 to cytopathology section at our rural based tertiary care center. Distribution of cases in different age groups, sex, size, and type was analyzed. FNAC slides were reviewed and reported by both conventional and TBSRTC method. Diagnostic efficacy was assessed by comparing subsequent histopathological examination wherever possible. Statistical Analysis Used: SPSS version 14. Results: Among the 178 thyroid FNA's, 60 were followed by surgical resection. The overall surgical yield of malignancy was 23.3%. The malignancy rate for the six diagnostic categories was as follows: Nondiagnostic: 33.3%, benign: 2.1%, atypia of undetermined significance: 50%, suspicious for follicular neoplasm: 1%, suspicious for malignancy: 67% and malignant: 100%. Conclusion: TBSTRC has been proven to be an efficient and robust thyroid classification scheme to guide the clinical treatment of patients with thyroid nodules.
Keywords: Fine needle aspiration cytology, The Bethesda System of Reporting Thyroid Cytopathology, thyroid
|How to cite this article:|
Prathima S, Suresh T N, Harendra Kumar M L, Bhaskaran A. Impact of the Bethesda System in Reporting Thyroid Cytopathology. Thyroid Res Pract 2016;13:9-14
|How to cite this URL:|
Prathima S, Suresh T N, Harendra Kumar M L, Bhaskaran A. Impact of the Bethesda System in Reporting Thyroid Cytopathology. Thyroid Res Pract [serial online] 2016 [cited 2017 Jun 22];13:9-14. Available from: http://www.thetrp.net/text.asp?2016/13/1/9/168900
| Introduction|| |
Fine needle aspiration cytology (FNAC) has emerged as one of the first-line diagnostic technique as it is safe, cost-effective, minimally invasive, and accurate method for triaging patients with thyroid nodules. FNAC was first described in the 1930's by Martin and Ellis. It plays an important role in evaluation of patients who present with thyroid nodule in euthyroid state as it reduces the rate of unnecessary thyroid surgery for patients with benign (BN) nodule and approximately triages patients with thyroid cancer to appropriate surgery.
With current thyroid FNA practice, the percentage of resected nodules that are malignant (MGT) surpasses 50%. Despite being a very effective method of evaluation of thyroid nodule, thyroid FNA suffers from confusion of reporting in especially borderline lesions, multiplicity of category names and variation in surgical pathology terminologies, creating confusion in some cases and hindering the sharing of clinical implications of thyroid FNA results both to clinicians and pathologists.
In an attempt to establish a standardized diagnostic criterion for reporting thyroid FNA and classification system, the National Cancer Institute (NCI) hosted the “NCI thyroid FNA state of the Science Conference” in 2007 and proposed the Bethesda System of Reporting Thyroid Cytopathology (TBSRTC) which represents a major step toward standardization, reproducibility and ultimately improved clinical significance, usefulness, and predictive value of thyroid FNAC.
A uniform reporting system for thyroid FNA will facilitate effective communication among cytopathologists, endocrinologists, surgeons, radiologists and other health care providers and facilitate research in epidemiology, and molecular pathology. There have been few studies validating utility, standardization, and reproducibility of the TBSRTC in identifying neoplasms and malignancies.
Aims and objectives
To study the diagnostic utility, reproducibility, and prognostic significance of TBSRTC and report the malignancy risk for FNA of thyroid lesions.
| Materials and Methods|| |
A total of 178 patients with thyroid swelling were included in the study period extending from January 2013 to December 2013. The cases included patients with diffuse thyroid swelling and solitary nodule.
Recurrent MGT thyroid lesions were excluded from the study. Few of the FNAs were performed under ultrasound guidance. Smears made were both fixed in alcohol and stained by Papanicolaou stain and hematoxylin and eosin stain or air dried and stained with Giemsa stain. Rapid assessment of adequacy was done by methylene blue staining. Slides were reviewed and reported TBSTRC method.
According to the recommendations of the Bethesda System of Reporting Thyroid Cytology 2007 NCI FNA State of the Science Conference, thyroid lesions were classified into six diagnostic categories as shown in [Table 1].
|Table 1: Diagnostic categories of TBSRTC with implied risk of malignancy and recommended clinical management|
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Nondiagnostic or unsatisfactory (ND/UNS)
A thyroid FNA sample is considered inadequate if fewer than six groups of well-preserved, well-stained follicular cell groups with 10 cells each, if the slide is poorly preserved, poorly stained or obscured follicular cells or if the thyroid FNA sample contains cyst fluid, with or without histiocytes and fewer than six groups of 10 BN follicular cells.
Benign/negative for malignancy/nonneoplastic (benign follicular neoplasm)
Benign follicular neoplasm applies to a cytological sample that is adequate for evaluation and consists predominantly of colloid and BN appearing follicular cells in varying proportions.
Atypia of undetermined significance/follicular lesion of undetermined significance
This diagnostic category “atypia of undetermined significance (AUS)” is reserved for specimens that contain cells with architectural and/or nuclear atypia that is not sufficient to be classified as suspicious for a follicular neoplasm (SFN), suspicious for a malignancy or MGT. This category was subdivided into two microscopic descriptive subcategories. One subcategory was for cases wherein predominance of microfollicles seen in a sparsely cellular aspirate with scanty colloid. The other subcategory was for cases showing features suggestive of papillary carcinoma, including nuclear grooves, enlarged nuclei with pale chromatin, and alterations in nuclear contour and shape in an otherwise predominantly BN appearing sample.
Follicular neoplasm/suspicious for a follicular neoplasm
Refers to a cellular aspirate comprised of follicular cells, most of which are arranged in an altered architectural pattern characterized by significant cell crowding and/or microfollicle formation with scanty or no colloid. The differential diagnosis included hyperplastic adenomatoid nodules, follicular adenoma, follicular carcinoma. This category also included cases that demonstrated a predominant population of hurthle cells which can be designated as hurthle cell neoplasm, which included hyperplastic adenomatoid nodule with hurthle cell change, hurthle cell adenoma, and hurthle cell carcinoma.
Suspicious for malignancy (SFM)
A specimen is suspicious for malignancy (SFM) when some features of malignancy raise a strong suspicion of malignancy, but the findings are not sufficient for a conclusive diagnosis which includes BN follicular cells are admixed with cells that have nuclear enlargement, pallor, grooving, nuclear molding/irregularity in a sparsely cellular smear, any evidence of cystic degeneration based on the presence of hemosiderin laden macrophages.
Positive for malignancy
This category applied to thyroid FNA smears that showed unequivocal evidence of MGT neoplasm that included papillary carcinoma of thyroid and its variants, medullary carcinoma, anaplastic carcinoma, lymphoma, and metastatic tumors.
Data were entered into a spreadsheet and analysed using IBM SPSS version 22.
| Results|| |
Of 515 FNA procedures performed at rural based tertiary center between January 2013 and December 2013, there were 178 thyroid FNAC's. The overall distribution of diagnosis of thyroid FNAs using TBSRTC is shown in [Table 2].
|Table 2: Frequency of cytological diagnosis on FNA thyroid using TBSRTC method|
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Among the 178 thyroid FNAs, 60 were followed by surgical resection (partial or total thyroidectomy). There were 14 cases of malignancy, 45 BN, and 1 remained as AUS on resection giving an overall surgical yield of malignancy of 23.3%. [Table 3] represents the total number and overall distribution of BN and MGT cases on surgical resection. The rate of malignancy on surgical resection for thyroid FNA's is depicted in [Table 4].
|Table 4: Rate of malignancy on surgical resection for FNA thyroid diagnostic categories using TBSRTC|
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Among the 178 thyroid FNAs, 21 were ND/UNS. Of these, there were four repeat FNAs for cases which persisted to be clinically suspicious yielding results as follows: 1 remained ND/UNS (25%; with no further clinical suspicion), 2 BN (50%), and 1 MGT (25%). Subsequent histological correlations among those with single and repeat FNAs together were available for 3 cases and were as follows: 1 lymphocytic thyroiditis, 1 nodular goiter, and 1 Papillary carcinoma thyroid. Overall 1 MGT diagnosis was made on resection yielding a malignancy risk of 33.3% on follow-up histology.
ND/UNS = No of MGT cases on surgical resection/no of cytohistological correlations × 100
=1/3 × 100
Of the 178 thyroid FNAs, 138 were categorized as BN, 94 cases of which were diagnosed as BN follicular cells failing to fulfill criteria for any special category, 44 cases were diagnosed as BN follicular lesions (10 colloid nodules, 7 nodular hyperplasia, 12 multinodular goiter, 15 lymphocytic thyroiditis). Follow-up histology was available for 42 of the BN cases, yielding the following diagnosis: 29 BN follicular nodules, 10 cases of lymphocytic thyroiditis, 1 case of follicular carcinoma and 2 cases of papillary carcinoma of thyroid. Overall, there were 3 cases of malignancy on resection of 138 BN FNAs leading to a malignancy risk of 2.1% on follow-up histology.
BN = No of MGT cases on surgical resection/total BN FNA × 100
=3/138 × 100
Among 178 thyroid FNAs, 1 case was diagnosed as AUS on FNA and subsequent histology it turned out to be medullary carcinoma. Other case on follow-up histology showed groups of atypical follicular cells with considerable degree of nuclear atypia but failing other morphological criteria for malignancy leading to an overall malignancy risk of 50%.
AUS = No of MGT cases on surgical resection/no of cytohistological correlation in this category × 100
=1/2 × 100
Four cases of 178 thyroid FNAs were classified as SFN. All the four cases had follow-up histology. The following diagnosis was made: One case each of Multinodular goiter, Lymphocytic thyroiditis, Follicular adenoma, and Follicular carcinoma. There was one MGT case leading to an overall malignancy risk of 25% on follow-up histology.
SFN = No of MGT cases on surgical resection/no of cytohistological correlation in this category × 100
=1/4 × 100
Among the 178 thyroid FNAs, 3 were SFM, of which all the 3 cases had follow-up histology. Two cases showed features of papillary carcinoma of thyroid and 1 case was BN with diagnosis of multinodular goiter. There were 2 malignancies leading to an overall malignancy risk of 67% on follow-up histology.
SFM = No of MGT cases on surgical resection/no of cytohistological correlation in this category × 100
=2/3 × 100
Five thyroid FNA samples were classified as MGT. Cytological categories for these were as follows: 3 papillary carcinoma thyroid, 1 follicular neoplasm (FN) and 1 Medullary carcinoma. Follow-up histology was available for all the 5 cases, which proven to be MGT. The diagnosis of malignancy on resection was as follows: 3 papillary carcinoma thyroid, 1 follicular carcinoma, and 1 Medullary carcinoma. There were 5 malignancies leading to an overall malignancy risk of 100% on follow-up histology.
MGT = No of MGT cases on surgical resection/no of cytohistological correlation in this category × 100
=5/5 × 100
[Table 5] and [Table 6] represent the analytical comparison of the percentage distribution of FNA thyroid diagnostic categories and follow-up malignancy rate of our study using TBSRTC with two other published studies.
|Table 5: Comparison of percentages of distribution of FNA diagnosis using TBSRTC among published studies|
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|Table 6: Comparison of percentages of follow-up malignancy rates among published studies|
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| Discussion|| |
The present study attempted to evaluate the efficacy of the new proposed six tier diagnostic classification system in reporting thyroid FNA results. Based on a cohort of 178 thyroid FNAs, 11.7% of the thyroid nodules were classified as unsatisfactory, 77.5% BN, 1.1% AUS, 3.9% SFN, 2.2% SFM, and 3.3% positive for malignancy.
Lee et al. performed a similar retrospective study using TBSRTC on 4966 thyroid aspirates and reported ND, 10%; BN, 67.7; AUS, 3.1%; SFN, 1.1%; SFM, 5.1%; and MGT, 13%.
A similar observation as reported by other studies using TBSRTC standardized nomenclature of thyroid lesions was observed for the risk of malignancy.
Jo et al. reported the following malignancy rates using TBSRTC on 3080 thyroid aspirates: ND, 8.9%; BN, 1.1%; AUS, 17%; SFN, 25.4%; SFM, 70%; and MGT, 98.1%.
The rate of malignancy in the present study was comparable in most of the categories to that mentioned in TBSRTC and other published studies except the ND/UNS and SFM. The ND/UNS category in our study yielded a malignancy rate of 33.3%. With one case turning out to be MGT among three follow-up resections. According to TBSRTC, a thyroid FNA sample is considered adequate for evaluation if it contains a minimum of six groups of well-visualized, well-stained and undistorted follicular cells with at least 10 cells/group preferably on a single slide. The diagnostic efficacy of thyroid FNAC can be enhanced by adopting the criteria and thereby improving the management for BN non neoplastic lesions.
Layfield et al. emphasized that nodules with an initial ND/UNS result should be reaspirated after a recommended three months interval to prevent false positive interpretations due to reactive and reparative changes and also mentioned ultrasound guidance with immediate on-site adequacy evaluation is preferred for repeat aspiration after an initial ND/UN specimen especially for solid nodules reduces the false negative diagnosis.
According to Raab et al., cystic lesions with a nondiagnostic aspirate should undergo repeat FNAC. In our study, the case that turned out to be MGT in ND/UNS category was cystic variant of papillary carcinoma. Cystic papillary carcinoma of thyroid has being recognized as a possible cause for false negative thyroid FNAs. However Barbara et al. emphasized that cellularity and adequacy are dependent not only on the technique of the aspirator but also on the inherent nature of the lesion.
According to TBSRTC, the following scenarios describe cases considered as nondiagnostic, if fewer than six well-preserved, well-stained follicular cell groups with 10 cells each, poorly prepared, poorly stained or obscured follicular cells and cyst fluid with or without histiocytes and fewer than 6 groups of 10 BN follicular cells.
In the AUS category, the malignancy rate in the present study is 50% as opposed to 5–15% as mentioned in TBSRTC and up to 41.2% in a study by Lee et al., The number of cases diagnosed as AUS in our study was less as the diagnostic criteria were strictly adhered. According to TBSRTC, AUS is a category of last resort and should not be used in discriminately and the frequency of AUS interpretation. The case diagnosed as AUS on FNAC was sparsely cellular consisting of monomorphic population of poorly cohesive small to medium sized cells with nuclear pleomorphism and high nuclear cytoplasmic ratio, which turned out to be medullary carcinoma of thyroid.
Layfield et al. reported that AUS is a heterogeneous category, which reflects the difficulty in the cytological diagnosis of the follicular lesions of thyroid. Definition of AUS according to TBSRTC is reserved for specimens that contain cells with architectural and/or nuclear atypia that is not sufficient to be classified as suspicious for FN, suspicious for malignancy or MGT. This recommended management for an initial AUS interpretation is the clinical and radiological correlation and for most cases, a repeat FNA at an appropriate interval.
At our institute, retrospective classification of FNAs of thyroid lesions among the rural population was done. The percentage of follow-up malignancy rate in our study showed BN: 2.1%, SFN: 25%, SFM: 67%, and MGT: 100%. Similar results were reported in a study by Jo et al.
The risk of malignancy for a diagnosis of suspicious for malignancy and positive for malignancy was 67% and 100%, respectively, consistent with the data 60–75% and 100%, respectively according to [Table 1] NCI guidelines. It is important to mention our MGT rate for AUS (50%), underscores the importance of using this terminology carefully and, therefore, prospective studies using the TBSRTC will lend further insight to our results and utility of TBSRTC.
In summary, our study shows that the six tier diagnostic approach of reporting thyroid FNA proposed by the NCI thyroid FNA Scientific conference is an excellent screening test in identifying patients who may harbor a follicular or hurthle cell neoplasm with an acceptable specificity of 67%. Using the same diagnostic approach, we have shown that FNA of thyroid is an excellent diagnostic test indentifying malignancies with a specificity of 100%. Although each category proposed by TBSRTC implies different risk of malignancy and clinical management to the practicing clinicians, TBSRTC helps in triaging the patients with thyroid nodules in euthyroid state to appropriate surgery. Our study proves that by the implementation of TBSRTC not only improves the quality of reporting by lowering the diagnostic inconsistencies but also decreases the overall surgery rates for thyroid nodules.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]