Thyroid Research and Practice

: 2018  |  Volume : 15  |  Issue : 2  |  Page : 84--88

Cytomorphological analysis of categories in the Bethesda system and its accuracy in predicting thyroid neoplasms

Navkirti Mittal, Pavneet Selhi, Harpreet Kaur, Ankur Mittal, Anita Nagiraj, Aminder Singh, Neena Sood 
 Department of Pathology, DMCH, Ludhiana, Punjab, India

Correspondence Address:
Navkirti Mittal
102, Good Earth Colony, B/S Moti Palace, Patiala - 147 001, Punjab


Background: Fine-needle aspiration (FNA) cytology is a keynote modality in diagnosis and screening of thyroid nodules. The management of thyroid nodules largely depends on FNA; thus, it is challenging for the pathologist to distinguish the neoplastic nodule from benign ones and further, categorize the malignant tumors wherever possible. Due to the lack of uniform criteria for specimen adequacy and terminology, “The Bethesda System for Reporting Thyroid Cytopathology (BSRTC)” was designed. Objective: The objective of this study was to review the Bethesda thyroid FNA classification system in evaluation of thyroid nodules. Materials and Methods: This study was conducted over 4½ years. Fine-needle aspiration was done by palpation or ultrasound-guided, using a fine (25 or 27G) needle, and cytological smears were prepared using Giemsa, hematoxylin and eosin, and Papanicolaou stain. These smears were then examined and classified according to the BSRTC. Results: Of the 504 cases analyzed, benign lesions were the most common (78.9%), followed by malignant (4.2%), suspicious for follicular neoplasm/follicular neoplasm (4.2%), atypia/follicular lesion of undetermined significance (3.9%), and suspicious for malignancy (3.6%). Good cytohistological correlation (94.4%) was observed. Only 5.2% smears were nondiagnostic. Limitations: Small sample size for which histopathological follow-up was available. Conclusions: The BSRTC is a systematized 6-tier classification system for thyroid nodule aspirates. It is based on a complete literature analysis and is a unified risk-based reporting system.

How to cite this article:
Mittal N, Selhi P, Kaur H, Mittal A, Nagiraj A, Singh A, Sood N. Cytomorphological analysis of categories in the Bethesda system and its accuracy in predicting thyroid neoplasms.Thyroid Res Pract 2018;15:84-88

How to cite this URL:
Mittal N, Selhi P, Kaur H, Mittal A, Nagiraj A, Singh A, Sood N. Cytomorphological analysis of categories in the Bethesda system and its accuracy in predicting thyroid neoplasms. Thyroid Res Pract [serial online] 2018 [cited 2022 Dec 8 ];15:84-88
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Full Text


Fine-needle aspiration (FNA) of the thyroid is a rapid and cost-effective screening and diagnostic test with minimal patient discomfort, which has been recommended for the evaluation of thyroid nodules.[1],[2]

A lack of unified risk-based reporting system with the prevalence of many confusing classification schemes, wide variation in diagnostic thresholds and varied terminologies used by pathologist led to the increase in a number of thyroid nodules being biopsied, which was the harbinger of the Bethesda system of reporting thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) resulted from a conference held at the National Institute of Health in 2007.[3] The system led to standardization of FNA reports based on six diagnostic categories as follows: DC I – nondiagnostic/unsatisfactory (ND/UNS), DC II – Benign, DC III – atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), DC IV – follicular neoplasm/suspicious for a FN, (FN/SFN) DC V – suspicious for malignancy (SM), and DC VI – malignant.[4] The present study classified thyroid nodules according to the BSRTC based on cellularity, cytomorphology, architectural patterns, and colloid. It also suggested implied risk of malignancy in various Bethesda system-based diagnostic categories.

 Materials and Methods

This was a 3½-year prospective and 1-year retrospective study and included all patients who presented with thyroid nodules to the Department of Pathology. Fine-needle aspiration was performed guided either by palpation or ultrasound using a fine (25 or 27G) needle and cytological smears were prepared and stained using the standard techniques for Giemsa, hematoxylin and eosin, and Papanicolaou stains. Imaging studies were utilized wherever possible to localize the lesions. Two different pathologists then examined these smears and classified the findings according to the BSRTC. All patients were followed up for at least 2 years and histopathology of all the patients who subsequently underwent total/partial thyroidectomy was studied. Finally, the risk of malignancy for each Bethesda category was calculated and compared to the specified range according to the BSRTC.


Of the total 504 cases, 414 were female and 90 were male. The male to female ratio was 1:4.6 and majority of the females were in the age group of 31–40 years. The cytological smears were placed in one of the six diagnostic categories as follows: ND/UNS, Benign, AUS/FLUS, FN/SFN, SM, and malignant as per the BSRTC. The most frequent were the benign lesions constituting 78.9% (n = 398), whereas malignant was seen to the tune of 4.2% (n = 21). Smears were categorized into ND/UNS were 5.2% (n = 26), AUS/FLUS 3.9% (n = 20), FN/SFN 4.2% (n = 21), and SM 3.6% (n = 18). A good cytohistological correlation (94.4%) was observed and the calculated risk of malignancy for each category was found comparable with the specified range by the BSRTC. A comparative analysis of percentages of distribution of diagnostic cytological categories of thyroid lesions with published studies revealed a maximum number of cases in Category II, i.e., benign lesions [Table 1].{Table 1}


The BSRTC categorizes thyroid nodules in six categories; hence, appropriately triaging patients with malignant nodules for timely surgical intervention.[8] In the BSRTC, surgery is not recommended for ND/UNS, benign, and AUS/FLUS category. In this study, many benign cases underwent surgery primarily for cosmetic reasons and to reduced pressure symptoms on the neck. In cases with FN/SFN, SFM, and malignant categories, and excision of nodules or partial/complete thyroidectomy was performed as per the BSRTC recommendations.

DC-1, nondiagnostic/unsatisfactory

Of the FNA samples, 26 were nondiagnostic with no concomitant diagnosis constituting 5.2% of all cases. This category included cases diagnosed as predominantly blood (n = 2) or characterized by the absence of colloid/insufficient number of cells (n = 21) or poor fixation quality of follicular cells (n = 3).

To be adequate the smears contained a minimum of six groups of well-visualized follicular cells, with at least 10 cells per group, preferably on a single slide.[4]

DC-II, benign

This category included maximum number of cases comprising Nodular goiter (24.8%), Hashimoto's thyroiditis (16.3%), colloid nodule (17.1%), de Quervain's thyroiditis (0.5%), acute thyroiditis (0.25%), and benign follicular nodule, NOS (40.8%). Cellularity was variable spanning from marked in dominant nodule of a nodular goiter and two cases of Hashimoto's thyroiditis to scanty in the colloid nodule.

Various architectural patterns were noted with common patterns being cell clusters and sheets. Papillae and papillaroid structures were seen in four cases of multinodular goiter.

The abundant colloid was seen in 100% of cases of the colloid nodule with scanty/absent colloid in 50% nodular goiters and all cases of Hashimoto's thyroiditis. Numerous neutrophils with scant follicular epithelial cells and colloid were seen in a solitary case of acute thyroiditis.

Multinucleated giant cells were a feature of de Quervain's thyroiditis (100%), Hashimoto's thyroiditis (31.4%), and multinodular goiter (2.8%). Pseudofollicular giant cells were seen exclusively in Multinodular goiter (38.9%). Hurthle cell change was noted in 245 cases (61.5%) out of total benign cases. Intraepithelial lymphoid cell infiltration was noted in 100% of cases of Hashimoto's thyroiditis with epithelioid cell granulomas (25%) and multinucleated giant cells (21.9%). De Quervain's thyroiditis showed epithelioid cell granulomas in 100% and multinucleated giant cells in 66.6% of cases with no evidence of intraepithelial lymphoid cells. Therefore, the presence of intraepithelial lymphoid cells was the definite feature distinguishing Hashimoto's thyroiditis from de Quervain's thyroiditis, as the other features are overlapping. Follow-up histology [Table 2] was available for 13.5% (54 cases) of cases in category II yielding a 94.4% cytohistological concordance. Two cases of follicular adenoma with cystic change were diagnosed as benign on cytology owing to the presence of abundant cystic fluid which was misinterpreted as colloid.{Table 2}

DC-III, atypia of undetermined significance/follicular lesion of undetermined significance

The indeterminate category, a gray zone between benign and malignant included cases where cytological findings were not convincingly benign, yet the degree of cellular or architectural atypia was not sufficient for an interpretation of “FN” or “SM.” These have a lower risk of malignancy and thus are separated from SM.[10] A total of 20 cases included in this category exhibited a heterogeneous morphology. Although 15 of these exhibited architectural atypia seen as microfollicular pattern, it was focal in nine cases, whereas four showed low overall cellularity, and two had abundant colloid in the background. Hürthle cells only with scant colloid were seen in only one case, but the cellularity was not sufficient for the diagnosis of Hurtle cell adenoma. The last four cases had moderate cellularity with focal nuclear atypia seen as nuclear grooves and enlarged nuclei with intranuclear cytoplasmic inclusions. Forty-five percent (nine cases) were followed by surgical resection, with the following diagnoses such as Nodular hyperplasia, 4; Follicular adenoma, 2; Hürthle cell adenoma, 1; and one case each of follicular variant of papillary carcinoma (FVPC) and Medullary carcinoma. The three cases diagnosed with Follicular adenoma and Hürthle cell adenoma had specific features on cytology such as prominent microfollicular pattern and Hürthle cells only respectively, but due to insufficient cellularity and the presence of colloid these were diagnosed as FLUS. The other four cases diagnosed with nodular goiter on histopathology were put in FLUS category due to marked cellularity with focal nuclear features such as nuclear membrane irregularities, nuclear grooves, and occasional nucleoli. One case of FVPC had few microfollicles with occasional pseudoinclusion. This outcome highlights the overlapping morphologic features among reactive follicular cells, Hürthle cell lesions, and malignancies due to the presence of nuclear grooves and even pseudoinclusions. Contributing authors to the Bethesda system recommend limited use of this diagnostic category with approximately 7% or fewer of the total cases to be diagnosed as atypical FLUS; which is 3.6% in our case study.[4]

DC-IV, follicular neoplasm, or suspicious for follicular neoplasm

In all the 21 cases of FN/SFN, architectural atypia was evident as microfollicles along with cell clusters and sheets with scant or absent colloid [Figure 1]. All cases of FN (14) exhibited significant nuclear overlapping and crowding, whereas those labeled SFN, this feature was focal. Moreover, cellularity in SFN was moderate as compared to marked in FN. Histopathology was performed in 52% of cases. Follicular adenoma was diagnosed in seven cases and follicular carcinoma in two and one cases of hurtle cell carcinoma. Follicular adenomas outnumber follicular carcinomas in the population as is evident in this study. A single case of multinodular goiter was falsely diagnosed with class IV on cytology. As there are inherent diagnostic limitations to further characterize follicular lesions (based on capsular invasion) on thyroid FNA alone; hence, the goal of DC-IV is to identify all potential follicular carcinomas and refer them for a diagnostic lobectomy, thus making Thyroid FNA an effective screening test for these lesions.{Figure 1}

DC-V, suspicious for malignancy

Although the cytological features of papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), and lymphoma are well-established, in any given specimen they may be quantitatively and/or qualitatively insufficient for a definitive diagnosis, and hence, categorized as SM. Reasons for diagnostic uncertainty include suboptimal sampling or preservation, an unusual variant of PTC and MTC, and overlapping cytomorphological (particularly nuclear) features with other thyroid conditions.

Of the 18 cases, 16 were suspicious of papillary carcinoma and were Pattern A or Pattern B type, i.e., either the nuclear features were patchy or incomplete. In one case, clusters of large cells having high N: C ratio, marked nuclear pleomorphism, and scanty cytoplasm, i.e., suspicious for metastatic carcinoma (patient was a known case of carcinoma esophagus) was observed. The aspirate of one of the cases constituted a monomorphic population of dyscohesive small–medium-sized cell with a high N/C ratio and was reported as suspicious for lymphoma. About 77% of cases in SM underwent surgical excision; two cases were reported as nodular goiter on histopathology, therefore, recorded as false-positive. This was attributed to papillaroid clusters of cells and occasional nuclear grooves. Another case, suspicious for papillary carcinoma on cytology was diagnosed histologically with FVPC. In FVPC, nuclear enlargement and chromatin clearing are common, but nuclear grooves and INCIs are less common.[11] Thus, many follicular variant of papillary thyroid carcinomas were interpreted as “suspicious for papillary carcinoma” rather than unequivocally malignant.

DC-VI, malignant lesions

This category, constituting 21 cases, included all the cytology samples interpreted as unequivocally malignant with cytological interpretations as follows: papillary carcinoma 16, medullary carcinoma four, and one case of nonHodgkin lymphoma.

The smears with marked cellularity were observed in majority (19 cases) and moderate cellularity in only two cases. It was further observed that colloid was either scant or nil in all cases. Chewing gum colloid was observed in 50% of cases of the papillary carcinoma. Papillae and papillaroid structures were seen mainly in papillary carcinoma. Intranuclear grooves were noted in 66.7% of cases and intranuclear cytoplasmic inclusions in 100% aspirates of papillary carcinoma. An altered architectural pattern such as cell overlapping and crowding was seen in all cases of papillary carcinoma [Figure 2]. All the cases of medullary carcinoma had cell arrangement in the form of syncytial clusters, singly scattered cells which were plasmacytoid, polygonal, and spindle-shaped cells [Figure 3]. One case of nonHodgkin lymphoma reported in this study was composed of markedly cellular smears having noncohesive round medium-sized cells, vesicular chromatin, and prominent nucleoli. Numerous lymphoglandular bodies were present in the background; however, no follicular epithelial cells, oncocytes, and plasma cells were seen. Fifty-two percentages of cases underwent surgical excision with 100% cytohistological correlation.{Figure 2}{Figure 3}


This study shows high concordance in malignancy rates with those defined by the Bethesda system in each category. This predefined risk of malignancy according to BSRTC helps to triage patients with thyroid nodules. Universal application of the 6-tiered BSRTC will improve communication not only between the various pathologists but also the pathologist and surgeon. Moreover, it will facilitate research into the epidemiology, molecular biology, pathology, and diagnosis of thyroid diseases with better cytological-histological correlation and more consistent management approaches. This study was, however, limited by the small sample size of histopathological follow-ups and needs to be validated in further studies.

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Conflicts of interest

There are no conflicts of interest.


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