|Year : 2019 | Volume
| Issue : 2 | Page : 60-65
Fine-needle aspiration cytology of nodular thyroid lesions: A 1-year experience of the thyroid cytopathology in a large regional and a University Hospital, with histological correlation
Kaumudi Konkay1, Radhika Kottu2, Mutheeswaraiah Yootla3, Narendra Hulikal4
1 Department of Pathology, Sri Venketaswara Institute of Medical Sciences, Tirupati, Andhra Pradesh; Department of Pathology, Guntur Medical College, Guntur, Andhra Pradesh, India
2 Departments of Pathology, Sri Venketaswara Institute of Medical Sciences, Tirupati, Andhra Pradesh; Department of Pathology, M. N. R Medical College, Hyderabad, Telangana, India
3 Department of General Surgery, Sri Venketaswara Institute of Medical Sciences, Tirupati, India
4 Department of Surgical Oncology, Sri Venketaswara Institute of Medical Sciences, Tirupati, India
|Date of Web Publication||15-Jul-2019|
Dr. Radhika Kottu
Department of Pathology, Sri Venketaswara Institute of Medical Sciences, Tirupati, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: Fine-needle aspiration cytology (FNAC) plays an important role in evaluation of nodular thyroid lesions and in planning appropriate management.
Aim: the aim of the study is to reinterpret the FNAC diagnosis using the new 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and explore its utility and to review the accuracy by correlating with histopathology and analyze the distribution of thyroid lesions.
Settings and Design: A retrospective study for a period of 1 year will be undertaken, and all the cases of thyroid FNAC during the study period will be included in the study.
Materials and Methods: All FNACs of the thyroid, which were done during the year 2011, were retrieved. The results of adequate FNAC samples were correlated with the histological diagnoses in 50 cases.
Statistical Analysis: the statistical analysis was performed using MedCalc Statistical Software
Results: About 592 cases were included in the study, after recategorization according to the TBSRTC, Bethesda I – 2 cases (0.33%), Bethesda II – 473 cases (79.8%), Bethesda III – 54 cases (9.1%), Bethesda IV – 23 cases (3.8%), Bethesda V – 3 cases (0.5%), and Bethesda VI – 37 cases (6.25%). The false-negative rate is 9%, accuracy rate is 91%, and rate of malignancy in atypical lesions is 53.3%, with overall rate of accuracy of 61.5%. The incidence of microcarcinoma was 4/50 (8%).
Conclusions: The distribution of thyroid lesions in our institute is similar to that seen elsewhere. The rate of malignancy in indeterminate lesions was 33.33%. FNA has a low false-negative rate for diagnosis of thyroid malignancy; however, controversy exists regarding the accuracy of FNA for nodules smaller than 1 cm. The nomenclature change of follicular variant of papillary thyroid carcinoma to noninvasive follicular thyroid neoplasm with papillary-like nuclear features has led to necessary changes in definitions of various categories in 2017 TBSRTC as well and is discussed in this paper.
Keywords: Atypia of undetermined significance/follicular lesion of undetermined significance, Bethesda system, thyroid cytopathology
|How to cite this article:|
Konkay K, Kottu R, Yootla M, Hulikal N. Fine-needle aspiration cytology of nodular thyroid lesions: A 1-year experience of the thyroid cytopathology in a large regional and a University Hospital, with histological correlation. Thyroid Res Pract 2019;16:60-5
|How to cite this URL:|
Konkay K, Kottu R, Yootla M, Hulikal N. Fine-needle aspiration cytology of nodular thyroid lesions: A 1-year experience of the thyroid cytopathology in a large regional and a University Hospital, with histological correlation. Thyroid Res Pract [serial online] 2019 [cited 2020 Jan 24];16:60-5. Available from: http://www.thetrp.net/text.asp?2019/16/2/60/262730
| Introduction|| |
Fine-needle aspiration cytology (FNAC) plays an important role in evaluation of solitary thyroid nodule and in planning appropriate management. Although thyroid is one of the organs most commonly subjected for FNAC, its interpretation remains challenging. Lack of uniformity in reporting in thyroid cytopathology further complicates the scenario. These problems can be overcome to some extent by adopting the Bethesda System for Reporting Thyroid Cytopathology, (TBSRTC); however, the interobserver variability exists in this as well, especially in Category 3 atypical lesions. This paper discusses the various aspects of thyroid FNAC.
Aims and objectives
The study was undertaken with an aim to reclassify the thyroid FNAC cases according to the new 2017 TBSRTC and explore its utility and to correlate these results with the histopathology of the excised specimens and analyze the distribution of thyroid lesions that were seen in our institute.
| Materials and Methods|| |
All FNACs of the thyroid which were done during the year 2011were retrieved by retrospective search of hospital records. The patient data and other relevant information were retrieved from hospital information system.
A total of 600 cases were retrieved and there corresponding hematoxylin and eosin, Papanicolaou, and May–Grunwald–Giemsa slides were reviewed. The interpretations were recorded according to TBSRTC. The results of adequate FNAC samples were correlated with the histological diagnoses in 50 cases in which surgery was performed, and the malignancy rates, especially in indeterminate categories, were evaluated.
Statistical analysis was performed using MedCalc (MedCalc for Windows, version 15.0, MedCalc Software, Ostend, Belgium) Statistical Software.
| Results|| |
A total of 600 cases were retrieved, of which 592 cases were included in the study, after excluding cases with repeat FNACs. Of these, complete details were available for 579 cases.
The age range of these cases was between 3 and 85 years (n = 578), with a mean of 42 years. There was female predominance, with male: female (M: F) ratio = 1:8.9 (58:519).
After recategorization into TBSRTC, two (0.33%) cases were included under Bethesda I (inadequate, nondiagnostic/unsatisfactory); both of them were female patients with age between 28 and 53 years and mean age of 41 years.
The nonneoplastic thyroid lesions were reported using different terminologies such as “adenomatous goiter (AG), Hashimoto's thyroiditis (HT), Graves' disease, adenomatous goiter with secondary degeneration, and associated thyroiditis,” according to the preference of reporting pathologist. All these cases were included under Bethesda II (Benign). These accounted for 473 cases (79.8%). The age range of these patients was between 3 and 85 years, with a mean of 42 years. There was marked female predominance (M: F ratio = 1:11.4) in this category of patients.
The cases with differential of dominant nodule versus follicular neoplasm and the cases where “AG with atypical focus” was used were included under Bethesda III (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]). Most of these cases showed vague intranuclear inclusions. A total of 54 cases (9.1%) constituted Bethesda III. The age range of these patients was between 16 and 71 years, with a mean age of 42 years and M:F = 1:6.7.
The follicular neoplasms including those with mild nuclear changes and lacked true papillae and intranuclear pseudoinclusions were included under Bethesda IV (follicular neoplasm/suspicious for a follicular neoplasm). These constituted 23 cases (3.8%). The age range of these patients was between 20 and 75 years, with a mean age of 46 years and M:F = 1:10.5.
The cases diagnosed as suspicious of papillary carcinoma were included under Category V (suspicious for malignancy). These constituted three cases (0.5%). The age range was between 52 and 65 years, with a mean age of 52.5 years and M:F = 1:2.
Medullary, anaplastic, and papillary carcinomas were included under Bethesda VI (malignant). These constituted 37 cases (6.25%). The age range was between 14 and 80 years, with a mean age of 46 years and M:F = 1:2.6. Of these 37 cases, papillary carcinomas were 32, medullary carcinoma was 1, anaplastic carcinomas were 3, and squamous cell carcinoma was 1.
The histological correlation was done for 50 cases, which included 22 cases of Bethesda II, 15 cases of Bethesda III, 3 cases of Bethesda IV, and 10 cases of Bethesda VI.
The cytological diagnosis correlated with histology in 18 out of 22 cases in Bethesda II. Of these 18, in two cases, the diagnoses were revised from AG to HT in one and HT to AG in the other. Four cases showed discordance between cytological and histopathological diagnosis; of these, one turned out to be follicular adenoma, the second one turned out to be papillary carcinoma, and the other two were micropapillary carcinomas on histopathological examination.
The rate of false negativity was 9% (2/22, excluding papillary microcarcinomas). The accuracy rate was 91%.
Of 15 cases of Category III, 5 were AG, 2 were HT, 1 was follicular adenoma, 4 were papillary carcinomas, and 3 were micropapillary carcinomas on histopathology. Cases which showed focal microfollicular pattern were categorized under Bethesda III [Figure 1]a when differential diagnosis of dominant nodule in multinodular goiter versus follicular neoplasm was entertained. Few of such cases on subsequent resection showed an unencapsulated lesion of dominant nodule of AG with focal microfollicular pattern [Figure 1]b. Bethesda III was also considered when few thyrocytes showed ill-defined intranuclear inclusions [Figure 1]c. On subsequent resection, these changes were part of degenerative changes in AG [Figure 1]d. The rate of malignancy in atypical lesions was 53.3% (8/15) if microcarcinomas are included and 33.3% (5/15) if microcarcinomas are excluded.
|Figure 1: Cytology and corresponding histology of Bethesda III lesions ([a and b] – case 1 and [c and d] – case 2), (a) repetitive microfollicular pattern (H and E, ×100), (b) dominant nodule in multinodular goiter in microfollicles (H and E, ×100). (c) Thyrocytes with ill-defined nuclear inclusions (arrow) (H and E, ×200) (d) Adenomatous goiter, focal degenerative changes (arrow) (H and E, ×100)|
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Of three cases of Bethesda IV, there were one case each of follicular carcinoma, follicular variant of papillary thyroid carcinoma (FVPTC), and nodular variant of HT [Figure 2]a and b] on histopathology. The nuclear features of papillary carcinoma were not very obvious in one case of FVPTC which was diagnosed as follicular neoplasm on cytology. In the second case of nodular HT, the background showed that lymphocytes in cytology, which gave the clue to diagnosis, were however missed on cytology [Figure 2]a. The rate of false positivity was 33.33% (1/3). Since the numbers are too small, conclusions cannot be derived based on these observations.
|Figure 2: False-positive cases: ([a and b] – case 3 and [c and d] – case 4), (a) repetitive microfollicles, thyroid cytopathology IV (H and E, ×200) (b) partially encapsulated nodular Hashimoto's thyroiditis with repetitive microfollicles (H and E, ×200) (c) papillary clusters of thyrocytes with ill-defined nuclear inclusions, thyroid cytopathology VI (d) adenomatous goiter with papillary infoldings (c and d, H and E, ×100)|
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Of 10 cases of Bethesda VI, 7 were papillary carcinomas, 2 were medullary carcinomas, and 1 was AG with secondary degeneration [Figure 2]c and d]. One case, diagnosed as papillary carcinoma on cytology, turned out to be medullary carcinoma on histopathology. The rate of false positivity was 10% (1/10).
The overall rate of accuracy for FNAC of the thyroid in our study was 61.5% (4/39) (microcarcinomas and Bethesda III excluded). The true positivity was 32.5% (11/34), false positivity was 5.8% (2/34), true negativity was 52.9% (18/34), and false negativity was 8% (3/34); the rate of malignancy in atypical lesions was 33.3%; the incidence of microcarcinoma was 8% (4/50).
The sensitivity of detecting malignancy was 78.57% (95% confidence interval [CI]: 49.21%–95.09), and the specificity for detecting malignancy was 90.00% (95% CI: 68.26%–98.47%), with positive predictive value of 84.62% ([*] 95% CI: 54.54%–97.63%) and negative predictive value of 85.71% ([*] 95% CI: 63.63%–96.78%).
| Discussion|| |
The management of thyroid nodules is a multidisciplinary approach. FNAC plays a pivotal role in evaluation of thyroid nodules and in planning appropriate management. However, due to different terminologies used in FNAC which vary according to the preferences of the reporting pathologist, there is confusion in some cases. These shortcomings can be avoided by better communication among the disciplines which can be enhanced using uniform terminologies recommended by TBSRTC. In the 2017 revision of TBSRTC, the names of the six diagnostic categories remain unchanged. Each diagnostic category has an implied cancer risk which is linked to certain clinical management recommendations. Hence, we have adopted the new TBSRTC 2017 and recategorized the cases accordingly.
The overall distribution of thyroid lesions in our institute, after recategorization according to the new 2017 TBSRTC, in comparison to other studies (which are based on TBSRTC 2009 studies based on 2017 TBSRTC are not yet available) is shown in [Table 1]. Majority of thyroid swellings in our study were benign (Bethesda II) on cytological examination (79.8%) as in other studies,, [Table 1]. Bhasin et al. reclassified 80 random FNA cases according to 2009 TBSRTC and studied the interobserver variability; they have reported similar higher incidence of Bethesda II lesions (61.25%), followed by Bethesda III and IV categories (11.25% and 10%, respectively). Tepeoǧlu et al. also reported similar incidence; they have studied 1021 FNAC samples, of which majority were benign, Bethesda II (697/1021 [68.3%]), followed by Bethesda I (nondiagnostic) (122/1021 [11.9%]). Park et al. studied 1730 FNAC samples; Bethesda II lesions which were the majority constituted 40.6%, followed by Categories V and VI (19.3% and 17.3%, respectively). The incidence of benign lesions (Bethesda II) reported in literature varies between 40.6% and 87.5%. The number of inadequate samples in our study is very low (0.33%) when compared to other studies,, [Table 1]; the reported incidence varies between 1.2% and 20.1%. This might be because we routinely screen all the cases for adequacy of material during FNAC and repeat the procedure whenever required.
|Table 1: Distribution of lesions into various Bethesda categories in comparison to other studies|
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The incidence of malignancy in Bethesda II category in our study is 9% (2/22) if papillary microcarcinomas are excluded and 18.1% (4/22) if papillary microcarcinomas are included, similar to that reported in literature which varies between 0% and 11.1%.,
Rates of malignancy in atypical lesions in our study are 33.3% (5/15) if papillary microcarcinomas are excluded and 53.3% (8/15) if papillary microcarcinomas are included; these rates are higher than that recommended by Bethesda which is 5%–10%. The rate of malignancy in atypical lesions reported in literature varies between 6% and 79%,,,,,, [Table 2]. Park etal. compared there results with 11 previous studies and reported a higher rate of malignancy (69%) which they assumed to be due to lack of repeat FNA in few cases and tendency to underdiagnose malignancy in Korean cytopathologists. Lee et al. reported higher rate of malignancy in atypical lesions in their study (79%) which they suspect to be due to not following TBSRTC guidelines properly as it was relatively new for them during the study. The possible explanation for higher rates in our study is that the number of cases in Category V is less and rate of malignancy in Category III is more indicating that there is underdiagnosis of malignancies and overdiagnosis of atypical lesions. We might have been under diagnosing Category V lesions to Category III. Theoharis et al., Bohacek et al., Nayar and Ivanovic, and Faquin and Baloch reported lesser rates of malignancies in atypical lesions which ranged between 6% and 19%. As can be observed by the wide discrepancies in malignancy rates in Category III lesions, it can be stated that Category III lesions have high interobserver variability. Park etal. cited that Layfield et al. attributed these discrepancies to whether or not the cytopathologist had received cytopathology fellowship training, and similarly, Wu et al. attributed it to the differences in experience or training that cytopathologists received. Park et al. further cited that though Cibas and Ali, the authors of BSRTC paper, agreed with the poor interobserver reproducibility of atypical lesion, they still recommend using this as it enables clinically significant distinctions in some cases. Thus, we agree with Park et al. that clinicians should give special importance to cases diagnosed as atypical lesions in cytology so as to improve the management of such cases. The new TBSRTC 2017 recommends further subclassifying Category III lesions into five subcategories as (i) cytologic atypia, (ii) architectural atypia, (iii) cytologic and architectural atypia, (iv) Hurthle cell AUS/FLUS, and (v) atypia, not otherwise specified. Although the management does not changed among these subcategories, these terminologies are recommended as they are more descriptive. Earlier TBSRTC recommends that a laboratory should limit the rate of reporting Category III lesions to <7%, the new recommendations are 10%. The rate of reporting Category III lesions in our study is 9.1% (54 cases). These cases were managed by clinical correlation and repeating FNAC after appropriate interval, and in those cases with suspicious clinical and ultrasound features, surgery was done. Intraoperative frozen section was done in cases where a possibility of papillary carcinoma was entertained. However, we could do histological correlation for only 15 out of a total of 54 patients with Category III lesions; similarly, histopathological correlation was done in only 3 out of 23 Category IV patients and 10 out of 37 Category VI patients. We could not do histological correlation in any of the three Category V patients during the study period. The rest of the patients where correlation was not done were either lost to follow-up or were not willing for surgery and were under observation during the study period. The usual mode of management for Category IV lesions in our institute is hemithyroidectomy.
|Table 2: Rate of malignancy in atypia of undetermined significance in comparison to other studies|
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In light of the reclassification of the noninvasive FVPTC as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), the risk of malignancy in Category III lesions diminishes to 6%–18% from 10% to 30% because, in earlier data, NIFTP which constituted a significant number of cases was considered as malignancy.
The rates of false positivity and false negativity for malignancy in our study are 5.8% and 8%, respectively, corroborating with other studies where the rates of false positivity ranged between 0.7% and 4%,, and false negativity ranged between 0.3% and 21%.,, Sclabas et al. studied thyroid FNA results from 240 consecutive patients and compared them with histopathology after thyroidectomy; they reported a false-positive rate and false-negative rate of 4% each in their study. Lew et al. studied thyroid FNA of 797 consecutive patients with dominant nodules >1 cm; they have observed a false-positive rate of 2% and false-negative rate of 8.6%. Hambleton and Kandil reviewed thyroid FNA and stated that the rate of false negativity increases as the size of the thyroid nodule increases to 3–4 cm.
Although the sensitivity of detecting malignancy is relatively low (78.57%) in this study as compared to other studies where the sensitivity ranged between 93.5% and 100%,,, the specificity is (90%) similar to other studies where the specificity ranged between 75% and 98.5%.,, Bouvet et al. compared 54 thyroidectomy patients who had preoperative FNA with 24 thyroidectomy patients who did not have preoperative FNA and found that malignancy rate was 85.3% in patients who had a positive FNA and 33.3% in patients who did not have an FNA, with sensitivity of 93.5% and specificity of 75.0% for FNA. Yang et al. have done histopathological correlation for 4703 patients with thyroid nodules and reported sensitivity and specificity of FNA for the diagnosis of malignancy to be 94% and 98.5%, respectively. The lower rate of sensitivity in our study might be because of underdiagnosis of malignancies and overdiagnosis of atypical lesions.
In this study, one case reported as follicular neoplasm in Category IV turned out to be FVPTC on histology which would have belonged to Category V or VI according to 2009 TBSRTC but remains unchanged in Category IV according to the new 2017 TBSRTC. The 2017 TBSRTC modified the definition and diagnostic criteria of Category IV in light of NIFTP. In the 2009 BSRTC, the cases with nuclear features of papillary were excluded from this category, whereas the new TBSRTC modified the definition of these lesions so as to included NIFTP lesions into this category.
The nomenclature of “encapsulated FVPTC” has changed to “NIFTP” as it behaved more indolently, has similar RAS mutations as follicular neoplasms, and does not require completion thyroidectomy and radioactive iodine therapy, so the cytological approach to these lesions has also changed. As with follicular neoplasms where capsular invasion cannot be commented upon on the cytology, in FVPTC, also capsular invasion cannot be commented upon. Hence, the new 2017 TBSRTC had made necessary changes to address these issues. They recommend using an optional note at the end of the report so as to alert the clinical team that a possibility of FVPTC or its indolent counterpart NIFTP cannot be ruled out on cytology.
Before concluding, a special emphasis has to be given for thyroid microcarcinomas. They are usually missed on FNA as it is a blind procedure unless it is an ultrasound-guided procedure, so they are missed in FNA because of sampling error or inadequate sampling rather than difficulties in reporting and also usually FNA is done for nodules >1 cm due to lower risk of malignancy in smaller lesions. There is no universal consensus regarding appropriate management thyroid microcarcinomas. Rate of detection of microcarcinomas in present study is 8%, and it varies markedly between different studies from 1.3% to 21.6%., Hence, as of now, more data are needed to arrive at conclusions regarding its categorization.
| Conclusion|| |
The distribution of thyroid lesions in our institute is similar to that seen elsewhere.
Most of the lesions belonged to Bethesda Category II. The rate of malignancy in indeterminate lesions was 33.33%. FNA has a low false-negative rate for diagnosis of thyroid malignancy; however, controversy exists regarding the accuracy of FNA for nodules smaller than 1 cm. With nomenclature change for FVPTC to NIFTP, necessary changes are made in Bethesda diagnostic criteria as well.
Incorporation of the TBSRTC in regular cytology reporting will aid in better communication between pathologist and clinician as each Bethesda category has specified cancer risk and management protocols. Regular histological and cytological correlations by the pathologist will help in refining cytology diagnosis.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]