Diagnostic Role of The Bethesda System of Reporting Thyroid Cytopathology and Immunohistochemistry as an Adjunct to Fine Needle Aspiration Cytology in Differentiating Benign and Malignant Thyroid Lesions: A Cross-sectional Study

1. Senior Resident, Department of Pathology, ABVIMS and Dr. RML Hospital, New Delhi, India. 2. Professor, Department of Pathology, ABVIMS and Dr. RML Hospital, New Delhi, India. 3. Professor, Department of Ear, Nose and Throat, ABVIMS and Dr. RML Hospital, New Delhi, India. 4. Professor, Department of Pathology, ABVIMS and Dr. RML Hospital, New Delhi, India.

Abstract

Introduction: Fine Needle Aspiration Cytology (FNAC) plays a crucial role in the preoperative assessment of thyroid nodules. The Bethesda System of Reporting Thyroid Cytopathology (TBSRTC; 2023) is a standardised system for reporting thyroid FNAC. However, diagnostic challenges can occur in each category of TBSRTC.

Aim: To categorise thyroid FNAC according to TBSRTC and revisit the challenges of cytological diagnosis in each category.

Materials and Methods: A cross-sectional, observational study was conducted from November 2018 to April 2020 (18 months) in the Department of Pathology at ABVIMS and Dr. RML Hospital in New Delhi, India. The study included all 470 thyroid FNA cases received in the department from patients presenting with palpable thyroid nodules or ultrasonographically detected solid thyroid lesions, regardless of their age or sex. The cases were classified according to TBSRTC. Diagnostic tests were used to calculate sensitivity, specificity, Negative Predictive Value (NPV), Positive Predictive Value (PPV), and diagnostic accuracy of TBSRTC. Immunoexpression for Human Bone Marrow Endothelium marker-1 (HBME-1) and p63 was studied in Bethesda III to VI category cases, i.e., atypia of undetermined significance (AUS), Suspicious for Malignancy (SFM) and malignant cases only, and not in categories I and II.

Results: The study included 470 thyroid FNA cases with a mean age of 39.72 years. Cytohistological follow-up was available for 50 cases, of which six cases were discordant and the remaining 44 cases were concordant. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of TBSRTC were calculated as 50%, 97.06%, 32%, 80.49%, and 82%, respectively. Three cases with diagnostic challenges were revisited and discussed. Immunohistochemistry was performed on a total of 33 FNAC cases. However, histological follow-up was available for only 18 cases, of which seven cases were diagnosed as Papillary Thyroid Carcinoma (PTC) on histological follow-up. HBME-1 and p63 were positive in 57.14% and 42.86% of these cases, respectively.

Conclusion: The TBSRTC, 2023, is an excellent reporting system for thyroid FNA and serves as an initial investigative tool for thyroid lesions. Present study findings reveal that it has high specificity and diagnostic accuracy. The Risk of Malignancy (ROM) was comparable to other studies, except for the Bethesda II category. Immunoexpression of HBME-1 and p63 was useful in isolated cases; however, it is not sufficient for cytological diagnosis.

Cytological diagnosis, Cytohistological correlation, Thyroid carcinoma

Thyroid malignancy comprises 0.1-0.2% of all cancers in India, with an age-adjusted incidence of 1 and 1.8 per 100,000 in males and females, respectively (1). The majority of malignant thyroid tumours are non medullary, primarily PTC (80%) or Follicular Carcinoma (FC) (15%) (2). FNAC is an important, widely accepted, safe, and cost-effective method for triaging patients with thyroid nodules. Currently, FNAC is the preferred diagnostic method for the initial evaluation of thyroid nodules (1). The primary objective is to distinguish benign nodules from malignant ones and to manage patients by identifying those who require surgical resection and those who do not require further intervention. Recently, the role of FNAC in detecting malignant thyroid nodules has been increasing. Early diagnosis is important for aiming for a higher life expectancy because thyroid carcinomas have low malignant potential and progress slowly (3).

The Bethesda System of Reporting Thyroid Cytopathology (TBSRTC 2023) recommends using six reporting category names: Non Diagnostic (ND), benign, Atypia of Undetermined Significance (AUS), Follicular Neoplasm (FN), Suspicious For Malignancy (SFM), and malignant. TBSRTC 2023 continues to recommend using category names rather than just numerical designations when reporting results to avoid confusion with Thyroid Imaging and Reporting Data System (TIRADS) and other primarily numeral-based reporting systems. To effectively and clearly communicate the cytopathologic interpretation, the use of numerical designations alone (e.g., Bethesda IV) is discouraged for FNA reporting and scientific publication purposes, although numerical designations can be used in conjunction with the category name, such as FN (Bethesda IV) (4). The widespread adoption of TBSRTC 2023 demonstrates that it is built on a reporting framework with a probabilistic approach (i.e., implicit ROM) for each category. It provides each category with an implied cancer risk (4). While the majority of thyroid malignancies can be readily diagnosed using TBSRTC, in some cases, such as diagnosing specific variants of carcinomas, this distinction becomes subtle. Similarly, the diagnosis of benign lesions can be established cytologically (5). However, each category presents certain diagnostic challenges in rendering a correct cytological diagnosis. Ancillary techniques such as Immunohistochemistry (IHC) and Immunocytochemistry (ICC) can be applied to cell block sections or Liquid-based Cytology (LBC) smears, respectively. Sections were subsequently cut from the cell block for Haematoxylin and Eosin (H&E) staining and poly-L-lysine-coated slides for ICC staining.

Rossi ED et al., concluded that a panel of antibodies must always be considered in the diagnosis of thyroid nodules (6). The antibody panel serves as a crucial step in achieving a correct preoperative diagnosis of thyroid nodules, as it improves the accuracy of conventional cytological evaluation, enabling a better selection of candidates for surgery. p63 serves as a useful marker in distinguishing PTC from other thyroid lesions, and when used along with other markers like HBME-1 and Galectin-3, it can improve diagnostic accuracy (7). The expression of HBME-1 is significantly higher in PTC compared to FC and Follicular Adenoma (FA). HBME-1 is the best-balanced marker in terms of sensitivity (71.3%) and specificity (85%) for malignancy (8). Some studies have shown higher expression of HBME-1 in FC than in FA [9,10]. Palo S and Biligi DS observed that HBME-1 positivity was noted in 86.1% of malignant cases, while most benign lesions were negative for HBME-1 (11). The diagnostic accuracy of HBME-1 was further increased when a panel comprising CK 19 and S-100 was used. CK 19 positivity was more often seen with papillary differentiation, while S-100 had minimal utility. With the recent recognition of Non Invasive Follicular Thyroid neoplasm with Papillary-like nuclear features (NIFTP), it has become crucial to differentiate benign tumours (FA) from low-risk thyroid lesions (NIFTP) and the follicular patterned variant of PTC (infiltrative FVPTC). Tastekin E et al., used a panel of IHC markers comprising HBME-1, CK 19, Galectin-3, CD 56, CD 57, and p63 (12). They concluded that p63 is a useful marker in FVPTC, CD 57 and CK 19 in FVPTC, classical variant PTC, and NIFTP, while HBME1 is a useful marker in classical variant PTC (12).

The study aimed to assess the diagnostic role of TBSRTC and to revisit the challenges of cytological diagnosis in each category. The primary objective of the present study was to study the role of TBSRTC. Cytological cases that were discrepant on histopathological follow-up were revisited. The secondary objective was to assess whether HBME-1 and p63 immunocytochemical markers have a role in differentiating benign and malignant thyroid lesions.

Material and Methods

A cross-sectional observational study was conducted in the Department of Pathology at ABVIMS and DR. RML Hospital in New Delhi from November 2018 to April 2020, spanning a period of 18 months. The clearance from ethical committee [TP(MD/MS) (105/2018)/IEC/PGIMER/RMLH-1941] was obtained.

Inclusion criteria: The study included a total of 470 cases of FNAC for palpable or ultrasonographically detected diffuse solid thyroid nodules; regardless of age or sex.

Exclusion criteria: Patients with haemorrhagic diathesis and skin infections at the aspiration site were excluded from the study.

Study Procedure

The clinical history, physical findings, and provisional clinical diagnosis were recorded. Local examination of thyroid swelling was performed, noting the location, size, consistency, mobility with deglutition, and protrusion of the tongue. Additionally, cervical lymphadenopathy or any other palpable swellings elsewhere were examined. Thyroid function test results-serum T3, serum T4, and serum TSH levels were available for 154 patients (Table/Fig 1)a, and neck ultrasonographic findings were also noted in 274 patients (Table/Fig 1)b. The normal reference ranges for TSH, T3, and T4 are 0.64 to 5.94 lU/mL, 0.91 to 2.47 ng/dL, and 5.53 to 12.48 g/dL, respectively (13).

FNAC was performed using a disposable 24-gauge needle and a 10 mL syringe with the patient in the supine position and the neck hyperextended. A minimum of two passes of FNAC were conducted. The first pass was used to make conventional smears, which were air-dried, fixed in 95% ethanol, and stained with Giemsa and Papanicolaou stains, respectively. The second pass was divided to collect samples for cell block preparation and +/- LBC. LBC smears were prepared unstained to be used for ICC. For LBC processing, the aspirate was collected in an ethanol-based solution (CytoRichTM), centrifuged twice, and slowly sedimented onto a poly-L-lysine-coated slide. The slides were stained with a specific Papanicolaou stain, and one slide was left unstained for subsequent ICC. For the cell block, the aspirate was collected in 50% ethanol, centrifuged at 4000 rpm for six minutes, and then fixed in a combination of 100% ethanol and 40% formaldehyde in a ratio of 9:1 for 45 minutes (14). After centrifugation, the remaining sediment was processed for histopathology. Sections were cut from the cell block for Haematoxylin and Eosin (H&E) staining and on poly-L-lysine-coated slides for IHC staining.

FNAC smears were evaluated according to the TBSRTC 2023 guidelines (4). IHC was performed on cell block sections or LBC unstained smears for cases falling under Bethesda categories III, IV, V, and VI, which are diagnostically significant in cytology and include the grey zone and malignant thyroid lesions. HBME-1 (HBME-1, Bio SB) was used in a ready-to-use dilution with the tonsil as a Positive control for follicular cells. p63 (p63, Biocare Medical) was also used in a ready-to-use dilution with the prostate as a positive control for the nuclei of basal epithelium. Cytoplasmic staining with membranous accentuation in 10% or more of neoplastic cells and any nuclear staining were considered positive expressions of HBME-1 and p63, respectively. Negative cases showed no staining of p63 in neoplastic cells (15),(16).

LBC samples and cell blocks were specifically prepared for cases with discrepancies in cytohistopathological follow-up and those with discordance between cytological diagnosis and ultrasonography findings only. Conservative follow-up, including periodic clinical and radiological examinations of benign cases, was conducted as recommended by TBSRTC whenever possible. For categories IV, V, and VI, diagnostic lobectomy or near-total thyroidectomy was advised, as recommended. For AUS category cases, repeat FNA was performed. ROM was calculated by dividing the number of patients who were found to have malignancy in histopathological follow-up by the total number of cases in each Bethesda category.

Statistical Analysis

For statistical analysis, Bethesda categories were broadly divided into benign, malignant, and grey-zone lesions:

- Benign lesions included categories I and II.
- Grey zone lesions included categories III and IV.
- Malignant lesions included the grey-zone lesions (categories III, IV) and categories V, VI True positive, true negative, false positive, and false negative results were obtained. From these values, sensitivity, specificity, PPV, and NPV were calculated as follows:

1. Sensitivity=True Positive (TP) / (True Positive+False Negative (FN))
2. Specificity=True Negative (TN) / (True Negative+False Positive (FP))
3. PPV=True Positive / (True Positive+False Positive)
4. NPV=True Negative / (True Negative+False Negative)
5. Diagnostic accuracy=(TP+TN) / (TP+TN+FP+FN).

Results

In the present study, a total of 470 cases of thyroid FNAC were performed. Patients with thyroid nodules ranged from 8 to 82 years. The major bulk of patients 120 (25.53%) belonged to the 21-30 years age group (Table/Fig 2). There were 265 (56.4%) females and 205 (43.6%) males. The adequate FNA smears were broadly categorised according to TBSRTC. Among the 470 cases, the distribution of various categories in TBSRTC was noted (Table/Fig 3).

Out of 470 FNA smears, 8 (1.8%) aspirates were ND for cytological evaluation. The total number of cases in category II was 409 (87.02%). The majority (268, 65.55%) of cases presented as Colloid Goitre (CG) and 72 (17.60%) presented as chronic lymphocytic thyroiditis. Out of the total 470 FNA cases, 50 cases were available for cytohistological follow-up, and ROM was calculated for TBSRTC categories (Table/Fig 4).

Three cases with diagnostic challenges were revisited and discussed. These were two cases diagnosed as Bethesda category II on cytology and diagnosed as PTC with CG and NIFTP on histopathology. Another case was diagnosed as Bethesda category V on cytology and diagnosed as adenomatous goitre on histology (Table/Fig 5): Bethesda category V(g-i). Histopathological follow-up was available in 30 (60.00%) cases in Bethesda category II: 18 cases were diagnosed as CG, 3 as Hashimoto thyroiditis, 2 as Riedle’s thyroiditis, 5 as PTC with CG (Table/Fig 5)a-c, one each as FA and NIFTP (Table/Fig 5)d-f on histopathology. Sixty benign category cases were correlated with clinicoradiological findings and had no surgical intervention. Neoplastic lesions comprised TBSRTC categories III to VI.

There were a total of 06 cases in the AUS category, and only 01 (2%) case was followed-up with histological confirmation as FA. Out of the total 24 cases in category (IV) of FN, histological follow-up was available in 10 (20%) cases. 05 cases were diagnosed as FA, 02 as Hurthle cell adenoma, 02 cases as FC, and 01 case as PTC on histology. In the category V reported as SFM, out of 2 (4%) cases, one case was PTC, and the other was benign (adenomatous goitre) (Table/Fig 5)g-i on histological follow-up. There were a total of 21 cases reported malignant on cytology (TBSRTC category VI). However, 07 (14%) cases were available for histological follow-up: 06 cases were PTC, and 01 case of Medullary Thyroid Carcinoma (MTC) on histopathological examination. For statistical analysis, AUS (III) and FN (IV) cases were included with benign (II) cases. Malignant cases included category SFM (V) and malignant (VI). Sensitivity and specificity of FNAC using TBSRTC were calculated as 50% and 97.06%, respectively. The diagnostic accuracy of the TBSRTC reporting system was 82%, calculated as the proportion of true positive and true negative in all the evaluated cases. Out of the total 50 cases with cytohistological correlation, there were six discordant cases and the remaining were concordant cases (Table/Fig 4). Five cases diagnosed as benign on cytology were diagnosed as PTC with CG on histology. One case diagnosed as SFM on cytology was diagnosed as adenomatous goitre on histology. When AUS (III) and FN (IV) were included in the malignant group, the sensitivity and specificity of FNAC using TBSRTC were 68.5% and 73.53%, respectively (Table/Fig 6).

IHC for HBME-1 and p63 were performed on cell block sections/LBC smears on a total of 33 FNAC cases. However, out of these 33 cases, histological follow-up was available only in 18 (54.5%) cases (Table/Fig 7). Out of these 18 cases, seven cases were diagnosed as PTC on histological follow-up. In these seven cases, HBME-1 and p63 were positive in 4 (57.14%) and 3 (42.86%) of cases, respectively. However, p63 was positive in one case diagnosed as FN on cytology, which on histopathology was diagnosed as FA [Table/Fig 8]a-d. One case was diagnosed as FN on FNAC comprising a classical repetitive microfollicle pattern and high cellularity (Table/Fig 8)e,f. It showed strong positivity for HBME-1 (Table/Fig 8)g. However, histological follow-up was lacking. Six cases were diagnosed as PTC on FNA smears and had no histopathological follow-up. However, HBME-1 was positive in five cases and p63 in one case (Table/Fig 8)h-l.

Discussion

The FNAC is considered a standard diagnostic test in the initial evaluation of thyroid nodules. FNAC helps to identify nodules that require surgery from benign nodules that can be clinically followed and observed (17). It is a remarkable procedure in the management of thyroid lesions with a high degree of accuracy and is performed with good patient compliance. It has high sensitivity and specificity and exhibits an adequate diagnostic correlation with the final histopathological examination. FNAC provides a definite diagnosis of thyroid lesions as either benign or malignant, thereby avoiding unnecessary surgeries (3).

TBSRTC is a standardised cytology reporting system that improves communication between clinicians and cytopathologists, as well as provides a uniform inter-laboratory reporting system (18).

Highlights of the 2023 TBSRTC (4) include:

(i) Assignment of a single name for each of the following diagnostic categories: (i) ND; (ii) benign; (iii) atypia of AUS; (iv) FN; (v) SFM; and (vi) malignant.
(ii) Revised nomenclature for certain thyroid lesions in alignment with the recently published 2022 World Health Organisation classification of thyroid neoplasms.
(iii) Refined ROM estimates.
(iv) More formalised subcategorisation of AUS based on ROM and molecular profiling.
(v) The addition of two new dedicated chapters, recognising the importance of clinical perspectives and imaging findings, and the expanding landscape of molecular testing in thyroid disease.
(vi) An expanded discussion on reporting and management of paediatric thyroid disease. TBSRTC can be adequately applied for reporting paediatric thyroid cytopathology. ROMs have been calculated for six reporting categories for this age group based on published studies and linked with commonly practiced guidelines.

Similar to the previous edition, the effect of NIFTP on ROM estimates has been considered. Although NIFTP is a surgical disease and a definitive diagnosis cannot be made using FNA, the cytological features of this indolent tumour have led to classification on FNA as either AUS (Bethesda III), FN (Bethesda IV), or SFM (Bethesda V), thereby affecting resultant ROM calculation (4).

In thyroid ultrasonography, nodules with a diameter <1 cm do not require FNA and can be followed-up with ultrasonography (19). TBSRTC categorisation on FNAC further guides patient management.

The number of ND FNA cases reflects the skill and experience of the person performing the FNA. Thus, lower the proportion of Category-I cases, the higher the skill level of the person conducting the FNA (20). In the present study, repeat USG-guided FNA might have reduced the number of non diagnostic aspirates (1.8%), which was done only on patients with a high index of clinical and radiological features suspicious of malignancy.

The maximum number of cases in the present study were in category II, as seen in other studies. 1.3% of cases were reported as AUS, which was much lower compared to studies by Mehra P and Verma AK, and Reuters KB et al. TBSRTC recommends that the overall frequency of AUS should be limited to 7% of total thyroid cytology interpretations. Upadhyaya P et al., interpreted that TBSRTC results in a decreased percentage of indeterminate cases and improves the ability to diagnose FN (21),(22),(23),(24).

In category II, upon histological follow-up of 30 cases, the false-negative cytological diagnosis of CG with cystic degeneration was rendered in five cases, which were diagnosed as PTC with CG on histopathology. This inadvertently increased the ROM for category II (16.67%) in the present study due to inadvertent sampling of the adjoining benign tissue. Authors reiterate that possibly a routine practice of multiple-site sampling in thyroid FNAC may help obviate the error or a routine practice of USG guided FNA for thyroid swellings.

Two cases with a cytological diagnosis of hyperplastic goitre were diagnosed as PTC; Hurthle variant and PTC; classic type (Table/Fig 5): Bethesda category II (a-c); respectively on histology. Since FNAC smears lacked papillary or papillaroid fragments, a possibility or suspicion of PTC was not possible on the examined smears. Further, there were no definitive nuclear features of PTC on the examined smears. Poor cellularity of aspirated samples in cystic lesions and suboptimal preparations are often misinterpreted as benign lesions (25). A suspicious ultrasonographic finding may warrant repeat FNAC under ultrasonography guidance from the solid area.

Based on the findings in the present study, it can be concluded that the reason for false-negative reporting on FNAC was inadequate or inappropriate sampling from thyroid nodules rather than the inadequacy of the TBSRTC reporting system itself.

One case with a cytological diagnosis of hyperplastic CG was diagnosed as NIFTP on histology (Table/Fig 5): Bethesda category II (d-f). On reviewing the slides, it was noted that FNA smears were cellular with monotonous-looking follicular cells seen in sheets and groups with focal colloid in a haemorrhagic background. However, occasional discrete microfollicle formation was noted, which was overlooked at the initial point of diagnosis. Possibly, in such cellular smears, a differential diagnosis of a follicular lesion of neoplastic origin (Category IV) could also have been considered. Based on the relaxation of morphologic criteria in TBSRTC second edition to possibly include all cases suspected to be NIFTP, the third edition provides a detailed description of diagnostic clues for potential cases of this entity.

It increases awareness of NIFTP in cytologic diagnosis. When NIFTP is suspected, the lesion should be categorised in the FN category and not the SFM/malignant category to avoid overtreatment with aggressive surgery (4). In the present study, there were only 1.3% of cases in the AUS category, which was similar to a study by Anand B et al., (20). The smaller number of cases was due to a rigid adherence to the Bethesda diagnostic criteria. In the present study, cases were categorised under categories IV and V, and indiscriminate use of the waste basket category III was avoided. Also, it is difficult to calculate the ROM for category III precisely because histological follow-up was available in only one case, as only a few patients with suspicious clinical or ultrasonographic features are selected for surgery. In addition, these patients do not even undergo repeat FNA prior to surgery. In category III, repeat FNA, along with clinicoradiological correlation, should be done to avoid unnecessary surgery of benign cases and to avoid underdiagnosis and false-negative diagnosis.

Under category V, a false-positive cytological diagnosis of suspicious of PTC was rendered in one case, which was adenomatous goitre on histology. Features diagnostic of PTC, like nuclear grooves, nuclear pseudo-inclusions, etc., can be present even in benign thyroid conditions (adenomatous goitre, Hashimoto’s thyroiditis, FN, etc.); although this is much less common in benign lesions compared to PTC (26). Also, papillary hyperplasia, which is well known to occur in adenomatous goitre, can reveal an excess of cellularity with many sheets of benign follicular cells (27). In the present case, aspiration was probably done from the hypercellular area of adenomatous goitre, revealing a papillaroid fragment and focal Intranuclear Cytoplasmic Inclusion (INCI), which led to overdiagnosis. Multiple aspirations from different parts of the lesion can provide more representative cytological features (in absence of USG guided thyroid FNA) and thus reduce overinterpretation or underinterpretation, helping in reaching the correct diagnosis.

Under category VI, all seven cases on cytology had a 100% histological correlation. Similar to the study by Anand B et al., the ROM for categories V and VI were calculated precisely due to the correlation of cytological features with clinical, ultrasonographic, and biochemical findings while reporting the case (20). The results were comparable to the above-mentioned studies, except in the case of the benign category with a ROM of 16.67%. The present study reported a higher ROM in the benign category due to five false-positive diagnosis because of sampling of adjoining benign areas with cystic changes rather than cellular (solid) areas of PTC (25).

Aggarwal S and Jain D conducted a meta-analysis to obtain a precise assessment of ROM in different categories (1). The AUS category comprises cases that cannot be categorised as benign, nor in categories IV and V. The efficacy of FNAC using the TBSRTC was evaluated. Specificity and PPV in the current study were found to be 97.06% and 32%, respectively. Mehra P and Verma AK interpreted that when FN is included in the malignant group, sensitivity increases while specificity decreases (21). In the present study, when AUS and FN were included in the malignant group, there was an increase in sensitivity from 50% to 68.5% and a decrease in specificity from 97.06% to 73.53%.

The role of commonly used IHC stains like HBME-1, CK-19, Galectin-3, along with new ones CD56, CD57, and p63 in thyroid pathology has been extensively studied (12). HBME-1 can prove to be a useful marker in discriminating between malignant and benign thyroid lesions, particularly for PTC cases (11),(28). p63 is more specific in PTC and can help in discriminating PTC from other thyroid lesions (29),(30). Rossi ED et al., interpreted that the antibody panel improves the accuracy of conventional cytological evaluation (6). Preto A et al., reported that 33.3% of PTC cases were positive for p63 (31). In the present study, HBME-1 and p63 were positive in 57% and 43% of cases, respectively, which were PTC on histological follow-up. However, due to the small number of cases, the further diagnostic accuracy of IHC couldn’t be calculated.

Kim YW et al., concluded that p63 is usually expressed late in the course of thyroid tumour progression (32). p63 was positive from least to most frequent in follicular tumour (1.3%), PTC (14.7%), and undifferentiated carcinoma (22.2%). In a study by Jeong JY et al., a single case of FA was positive for p63 (7). In the present study, p63 was positive in one case diagnosed as FN on cytology and FA on histology. Since it showed only focal weak positivity, it might be related to progression to a worse state.

One case diagnosed as classical PTC on cytology had HBME-1 positivity and was negative for p63. However, patient succumbed and did not have histopathological follow up. The clinical course suggest that a reliable diagnosis of PTC can be considered on cytology combined with ancillary use of IHC.

The FNAC has a sensitivity of 50%, specificity of 97.06%, PPV of 32%, NPV of 80.49%, and diagnostic accuracy of 82%. In detecting thyroid cancer, the implied ROM (Table/Fig 9) in Bethesda II, III, IV, V, and VI is 16.66%, 0%, 30%, 50%, and 100%, respectively, comparable to other studies (22),(33),(34),(35).

Limitation(s)

Many patients with thyroid nodules reported as benign on cytology did not undergo surgery. Therefore, assessing the final histological diagnosis in such cases was not possible. A reliable false negative rate can only be determined if all patients, regardless of FNA results, undergo surgery. The low sample size for cytohistological correlation is a probable bias due to more malignant lesions than those seen in other studies.

Conclusion

This study reported thyroid aspiration smears using TBSRTC, 2023. It is a reliable investigation with high specificity for diagnostic evaluation and distinguishing between benign and malignant lesions. FNAC is useful in diagnosing category VI (malignant) lesions, but it is challenging to assess its usefulness in AUS (category III), which had only a limited number of cases for histopathological follow-up. This study emphasises that the diagnosis of NIFTP on cytology is not possible, and if discrete microfollicle formation is sparse, it can be mistaken for a hyperplastic nodule (Benign category II). However, a differential diagnosis of FN (category IV) in such cases may prevent delay in further management. Thus, determining the appropriate clinical/surgical management protocol is crucial and TBSRTC is a dependable initial investigation for thyroid lesions.

DOI and Others

DOI: 10.7860/JCDR/2024/67344.19794

Date of Submission: Sep 02, 2023
Date of Peer Review: Nov 09, 2023
Date of Acceptance: Jul 04, 2024
Date of Publishing: Aug 01, 2024

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

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EMENDATIONS: 7