|Year : 2020 | Volume
| Issue : 1 | Page : 13-18
Implementation of the Bethesda system of reporting thyroid cytopathology in a referral center
Kaumudee Pattnaik1, Goutami Dasnayak2, Asaranti Kar1, Smruti Swain3, Chitta Ranjan Sarangi4
1 Department of Pathology, Head and Neck Surgery, SCB Medical College, Cuttack, Odisha, India
2 Department of Pathology, KIMS, Bhubaneswar, Odisha, India
3 Department of ENT, Head and Neck Surgery, SCB Medical College, Cuttack, Odisha, India
4 Department of Endocrine Surgery, SCB Medical College, Cuttack, Odisha, India
|Date of Submission||29-Aug-2019|
|Date of Decision||27-Jan-2020|
|Date of Acceptance||09-Feb-2020|
|Date of Web Publication||20-Apr-2020|
Dr. Goutami Dasnayak
Department of Pathology, KIMS, Bhubaneswar, Odisha
Source of Support: None, Conflict of Interest: None
Introduction: The introduction of the Bethesda System of Reporting Thyroid Cytopathology (TBSRTC), following the “National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference” held in Bethesda, in 2007, offered the opportunity to establish a uniform six-tiered reporting system for thyroid fine-needle aspiration (FNA). Aim of the Study: The aim of the study was to implement and to evaluate the diagnostic accuracy and risk of malignancy (ROM) of categories of TBSRTC. Materials and Methods: FNA was taken from the thyroid swelling during the study period and smears were stained with hematoxylin and eosin, Diff-Quik, or papanicolaou stains. Nodular thyroid swelling cases were subjected to histopathological correlation. Results: Of the 1724 FNAs, a total of 223 cases of palpable nodular thyroid swelling were studied with cytohistopathological correlations. About 13.90% of the cases were diagnosed as malignant. The ROM for Bethesda Category V and VI was 100% each, whereas it was 47.62%, 10%, and 2.82% for Category III, IV, and II, respectively. The overall sensitivity, specificity, positive predictive value, negative predictive value, and the diagnostic accuracies of TBSRTC were 83.87%, 89.58%, 56.52%, 97.18%, and 88.79%, respectively. Conclusion: In our study, a more specific cytologic diagnosis was offered based on criteria laid down in the standardized nomenclature of the Bethesda System 2018 citing diagnostic accuracy and ROM in each category.
Keywords: Diagnostic accuracy, risk of malignancy, the Bethesda system of reporting thyroid cytopathology
|How to cite this article:|
Pattnaik K, Dasnayak G, Kar A, Swain S, Sarangi CR. Implementation of the Bethesda system of reporting thyroid cytopathology in a referral center. Oncol J India 2020;4:13-8
|How to cite this URL:|
Pattnaik K, Dasnayak G, Kar A, Swain S, Sarangi CR. Implementation of the Bethesda system of reporting thyroid cytopathology in a referral center. Oncol J India [serial online] 2020 [cited 2020 Aug 13];4:13-8. Available from: http://www.ojionline.org/text.asp?2020/4/1/13/282835
| Introduction|| |
Thyroid swellings are clinically significant as about 42 million people in India suffer from thyroid diseases, though majority of them are diffuse and nonneoplastic and not require surgery, and <5% of all nodular swellings of thyroid are documented as malignant., Unnecessary surgeries for patients with nonneoplastic nodules were reduced by the introduction of the Bethesda System of Reporting Thyroid Cytopathology (TBSRTC) in 2007 which appropriately triaged patients with neoplastic nodules for timely clinical intervention. The objective of our study to elucidate the usefulness of the TBSRTC by evaluating its diagnostic accuracy correlating with histopathology.
| Materials and Methods|| |
The present study was an observational descriptive analysis of the patients who presented with thyroid swelling and underwent fine-needle aspiration cytology (FNAC) from June 2016 to December 2018. Institutional Ethics Committee approval was obtained for the study. A total of 1724 patients presented with thyroid swelling during the study period and underwent FNAC. After taking aseptic precautions, a 24-gauge needle was used for the procedure and smears were made. Smears were stained with hematoxylin and eosin, Diff-Quik, and Papanicolaou stains. Repeat aspiration was done for cases with inadequate smears. FNAC diagnosis was given as per the TBSRTC guidelines mentioned in [Table 1]. All the cases were reviewed by two pathologists with expertise in thyroid/endocrine pathology.
|Table 1: The Bethesda System of Reporting Thyroid Cytopathology - diagnostic categories|
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A smear was categorized as nondiagnostic (Bethesda Category I) if it did not fulfill the adequacy criteria laid down by the Bethesda system. For a solid nodule, a cytosmear is considered adequate if it contains at least six well-preserved and well-stained follicular groups, containing at least ten cells. In contrast, abundant thick colloid, as found in a colloid nodule, did not have a requirement for a minimum number of follicular cells. Insignificant thyroid enlargement with occasional or no follicular cells or only blood elements without diagnostic cells or obscuring blood clot causing artifactual changes in follicular cells were interpreted as nondiagnostic.
A majority of cases were found to be diffuse colloid goiters. A cohort of patients with palpable thyroid nodules who underwent thyroid surgery were included in the study population and histopathological correlation was done in these cases. Of 1724 patients presented with thyroid swelling, 223 cases had nodular thyroid swelling and were subjected to excisional surgery in the form of lobectomy or subtotal/total thyroidectomy. Histologic diagnosis of the available operated samples was correlated with FNAC reports and assessed for the risk of malignancy (ROM). The cases were designated as true positive, true negative, false positive, and false negative for the diagnosis of malignancy. Based on these findings, the overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the study were calculated.
| Results|| |
The mean age of the patients included in the study population was 41.5 years (range 11–84 years), with a male-to-female ratio being 1:4.5. The duration of thyroid enlargement ranged from 3 days to 30 years.
[Table 2] depicts the thyroid lesions in cytology in accordance with the Bethesda System. The most frequently occurring thyroid swellings were noted in the Bethesda II Category, i.e., 89.67% of the cases.
|Table 2: Distribution of cytologic diagnosis of thyroid swelling as per the Bethesda category|
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The spectrum of common to rare histopathologic diagnosis was reported, and the ROM is indicated in [Table 3]. Nodular colloid goiter was the most common histological diagnosis consisting of 70.40% of the study population followed by papillary thyroid carcinoma (PTC), i.e., 8.52% and others. The most common benign diagnosis in histology was nodular colloid goiter constituting of 81.77% among all the benign lesions. The ROM was 100% in Bethesda Categories V and VI, both followed by Bethesda III Category (47.62%). We found the incidence of malignancy as 13.90% and PTC constituted 61.29% of malignancies.
|Table 3: Risk of malignancy in the Bethesda System of Reporting Thyroid Cytopathology|
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Few examples of different Bethesda categories and final histopathological correlation are depicted in [Figure 1]i, [Figure 1]ii, [Figure 1]iii, [Figure 2]i, [Figure 2]ii, [Figure 2]iii, [Figure 3]i, [Figure 3]ii, and [Figure 4]i, [Figure 4]ii, [Figure 4]iii.
|Figure 1: [i] Bethesda category II; Inset: Nodular goitre (HP); [ii] Bethesda category III: Mildly pleomorphic cells and hemosiderin laden macrophages in a hemorrhagic background. Inset: Cystic papillary carcinoma thyroid (HP); [iii] Bethesda category III: (a) Hyperplastic colloid goitre. (b) Follicular carcinoma (HP). Cyto= Cytology; HP= Histopathology|
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|Figure 2: [i] (a) Bethesda category IV: (b) Follicular adenoma (HP); [ii] (a) Bethesda category IV: (b) NIFTP= 'noninvasive follicular neoplasm of thyroid with papillary-like nuclear features' (HP); [iii] Bethesda category IV: polygonal granular cells in loose cluster , transgressing blood vessels: Inset: hurthle cell adenoma (HP). Cyto=Cytology; HP=Histopathology|
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|Figure 3: [i] Bethesda category V: Cellular smear, syntitial aggregates; Inset: follicular variant of papillary thyroid carcinoma (HP); [ii] Bethesda category V: Cellular, atypical spindloid cells, no colloid: Inset: medullary carcinoma (HP). Cyto=Cytology; HP=Histopathology|
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|Figure 4: [i] (a) Bethesda category VI: papillae, Inset: Nuclear grooving and inclusions. (b) Gross, Inset: Papillary carcinoma thyroid (HP); [ii] Bethesda category V: Spindloid cells with bizarre forms, neutrophils, necrosis, Inset: Anaplastic carcinoma (HP); [ii] Bethesda category VI: Cellular smear, trabeculae, small cells. Inset: Insular carcinoma (HP). Cyto=Cytology; HP=Histopathology|
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The statistical analysis revealed an overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 83.87%, 89.58%, 56.52%, 97.18%, and 88.79%, respectively [Table 4].
|Table 4: Diagnostic accuracy of fine-needle aspiration cytology as per the Bethesda System of Reporting Thyroid Cytopathology|
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| Discussion|| |
Thyroid FNAC is the first-line diagnostic test for evaluating thyroid swellings, both diffuse and nodular. It is a simple, rapid, and cost-effective test that can effectively distinguish between nonneoplastic, benign, and malignant lesions. Bethesda system (TBSRTC) for the first time was proposed in 2007 at the National Cancer Institute Thyroid Fine-Needle Aspiration State-of-Art and Science Conference held in Bethesda, Maryland. The aim of the Bethesda system is to address the inconsistent and sometimes confusing reporting terminologies used for thyroid FNAC throughout the world. TBSRTC consists of six diagnostic categories, each associated with an implied ROM that translates directly into a clinical management algorithm. TBSRTC not only included the diagnostic designations for the commonly encountered benign and malignant thyroid lesions in FNAC specimens but also for those who are often diagnosed as “indeterminate for malignancy (the so-called 'gray zone').” The latter was subclassified into the three diagnostic categories such as (i) atypia of undetermined significance/follicular lesion of undetermined significance; (ii) follicular neoplasm (FN)/suspicious for a FN; and (iii) suspicious for malignancy. For each of this diagnostic category also, TBSRTC defined an implied ROM. The 2010 TBSRTC Atlas More Details was created to analyze the impact of TBSRTC and to provide recommendation for its future update. The second edition of TBSRTC has covered potential impact of noninvasive follicular neoplasm of thyroid with papillary-like nuclear features (NIFTP) on the indeterminate diagnostic categories. For clarification and communication to clinicians, the FNAC report format should contain either one of the six-tiered Bethesda category. TBSRTC report can effectively triage patients with nodules who require surgery and those who do not. The clinical importance of thyroid nodules lies in the fact that although most nodules are benign, they may be the first sign of malignancy.,
Each category has an implied cancer risk ranges from 0% to 3% for the benign category to virtually 100% for the malignant category which we found congruent in our study. We found ROM of 0% for nondiagnostic, i.e., Bethesda Category I, which was similar to the finding of Arul et al. whereas Arul et al. found ROM of 0.8% for benign category. For Bethesda II Category, we found the ROM of 2.82%. One case of cystic PTC was initially suspected as nodular goiter in cystic degeneration due to cytological finding of cyst fluid with mostly cyst macrophages and occasional follicular cells without any discernable nuclear features. Another case of follicular variant of PTC (FVPTC) had cytological features of adenomatoid goiter because of follicular-patterned smear not highlighting the characteristic nuclear features of PTC. Three cases of follicular carcinoma on cytology smears showed microfollicular pattern suggesting as adenomatoid goiter or dominant nodule in nodular hyperplasia, Smears with atypia in Bethesda Category III may mimic with malignant lesions such as PTC or FC or Hürthle cell neoplasm. We found majority cases of Bethesda Category III as nodular goiter yielding a lower positive predictive value. The atypia in cytosmears was due to papilliform or three-dimensional clusters of reparative or regenerating nucleolated follicular cells of hyperplastic colloid goiter. ROM was 47.62% which showed a higher value than the risk mentioned in TBSRTC. Nearly 80% of the patients with Category III did not turn up for surgery to our center resulting such discrepancy. Arul et al. found ROM of 24.4% for Category III. For Bethesda Category IV, only 10 of 25 patients came for histopathology correlation and the value of was low, i.e., 10%. Naz et al. found ROM for Bethesda Category IV of 25% and stated that only 10 of 33 patients with cytological diagnosis of Bethesda IV–VI underwent surgical intervention and the rest were lost to follow-up resulting higher value of ROM. Furthermore, Arul et al. found ROM of 28.9% for Category IV. In our study, the lower percentage of ROM could be due to small nonpalpable nodules that had been missed in the blind clinical palpation procedure. Hence, ultrasound-guided fine-needle aspirations (FNAs) would have procured the cells from the solid neoplastic small lesions if any. Most of the cases were benign due to a lack of capsular and vascular invasion. One case was diagnosed as NIFTP. Microsection showed a well-demarcated neoplasm with follicular-patterned morphology without capsular or vascular invasion and with few nuclear features of PTC. A subset of encapsulated FVPTC has been reclassified as NIFTP recently. It is a very low-risk tumor that likely represents a preinvasive stage of invasive encapsulated FVPTC where the conservative approach is needed for management. Its cytosmears showed hypercellular, with syncytial-like fragments containing microfollicles with subtle nuclear changes of PTC, and dense colloid within follicles was suggestive of suspicious FN. Nikiforov YE and Faquin et al. have reclassified such category as neoplasm rather than carcinoma, thus lowering the ROM.,
Arul et al. found 70.8% and 100% ROM for Category V and VI, respectively. We found 100% concordance in both Bethesda V and VI Categories, which was similar to the finding of Naz et al. In Bethesda V Category, some cases categorised as the nuclear features, squamoid and histiocytoid morphology in the cellular smear was came out as PTC instead of lacking i.e., papillae, cellular swirls, and molded nuclei on cytology. Two cases diagnosed with FVPTC where we observed cellular cytosmear with microfollicles crowded enlarged clear oval nuclei without intranuclear cytoplasmic inclusions (INCIs) and grooving. A case diagnosed with medullary carcinoma was cytologically falling short of definite medullary carcinoma features such as typical dissociated plasmacytoid morphology with fine granularity, though atypical spindled cells were seen in a cellular smear lacking colloids. Another case with cytological finding of high cellularity predominantly fibroblast-like atypical spindloid cells with one focus of bizarre-appearing cells on a necroinflammatory-type background came out to be anaplastic carcinoma and due to hard fixed mass, the case was subjected for radiation and chemotherapy before the surgery. All cases among Category VI fulfilled almost all criteria of PTC variably in each case with typical nuclear features of INCI, grooving, thick outline, convolutions, enlarged clear oval shape, squamoid or histiocytoid, giant cell forms with papillary patterns, overlapping sheets, few in cellular swirls, and associated thick ropy colloids. One rare case was diagnosed with insular carcinoma, a poorly differentiated thyroid carcinoma, in a 56-year female patient. However, this case cytologically documented as malignant resembling PTC or medullary carcinoma nuclear features by noticing cellular smear in clusters, trabeculae, singles, and small uniform-sized cells with a high nuclear–cytoplasmic ratio on a background of scanty colloid. High-grade FN was a tentative cytology diagnosis given by Nguyen and Akin, seeing similar type cytomorphology in FNA.
The ROM among the various nonmalignant categories was highest in Bethesda Category III (47.62%) followed by Category IV (10%) and the least in Category II (2.82%) as documented by Naz et al. with similar type of observations (Bethesda Category III [33.3%] followed by Category IV [25%] and the least in Category II [11.1%]).
As observed in other similar studies by Choudhary et al. and Ko et al., we found that benign nonneoplastic lesions were more common than the malignant ones comprising 86.1%., Nodular colloid goiter was the most common entity among all benign lesions in our study consisting of 81.77%. In Choudhary et al.'study, 90.0% of the cases were benign nonneoplastic lesions. Baloch et al. have validated the study by showing a range of 2% to 16% malignancy in thyroid FNAs with majority being PTC. Our study also agrees to theirs with a malignancy incidence of 13.90% and PTC being the majority (70.96%) amongst all malignant lesions of thyroid.
The statistical analysis of our study revealed an overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 83.87%, 89.58%, 56.52%, 97.18%, and 88.79%, respectively. These results were comparable to other reported studies. Naz et al. in their study found sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 66.3%, 85.1%, 56.3%, 88.9%, and 80.3%, respectively. Choudhary et al. in a cross-sectional observational study found sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 75.2%, 98.2%, 90.0%, 94.7%, and 94.3%, respectively. Sinna andEzzat in a retrospective analysis of 296 diagnosed cases of thyroid nodules found sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 92.8%, 94.2%, 94.9%, 91.8%, and 93.6%, respectively. The possible explanation for such variation in results is the number of cases, subjective errors, and sampling errors.
TBSRTC is useful for a standardized system of reporting thyroid cytology, bridges the communication gap between cytopathologists and clinicians, and interlaboratory agreement, leading to more consistent management approaches and therapeutic interventions. It makes the cytology report unambiguous, clear, succinct, and clinically relevant.
| Conclusion|| |
We found high sensitivity and specificity with nearly validated accuracy of FNAC by adopting TBSRTC. Therefore, we recommend to implement TBSRTC routinely in our center with ultrasound screening as the initial workup of patients with thyroid swellings. Surgical follow-up in every indeterminate indexed cases (Bethesda Categories III and IV) is mandatory to appropriately assess the ROM.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]