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A comparative study between conventional and the Bethesda System for Reporting Thyroid Cytology of 240 cases


1 Department of Pathology, Uttar Pradesh University of Medical Sciences, Etawah, Uttar Pradesh, India
2 Department of Clinical Pharmacology, Uttar Pradesh University of Medical Sciences, Etawah, Uttar Pradesh, India
3 Department of Dentistry, Maharaja Suhel Dev Autonomous State Medical College and Mahrishi Balark Hospital, Bahraich, Uttar Pradesh, India
4 Department of Pathology, Maharaja Suhel Dev Autonomous State Medical College and Mahrishi Balark Hospital, Bahraich, Uttar Pradesh, India
5 Department of ENT, Uttar Pradesh University of Medical Sciences, Etawah, Uttar Pradesh, India
6 Insurance Medical Officer, ESI Hospital, Lucknow, Uttar Pradesh, India

Date of Submission10-Apr-2020
Date of Decision01-Jun-2020
Date of Acceptance10-Sep-2020
Date of Web Publication23-Oct-2021

Correspondence Address:
Megha Ralli,
Department of Pathology, Maharaja Suhel Dev Autonomous State Medical College and Mahrishi Balark Hospital, Bahraich - 271 801, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_447_20

 > Abstract 


Introduction: Thyroid nodule is a common disorder of thyroid. Despite their benign nature, they can be associated with multiple pathologic conditions including thyroid cancer. Fine-needle aspiration plays an essential role in evaluating thyroid nodules. The Bethesda System for Reporting Thyroid Cytology (TBSRTC) has attempted to standardize reporting and cytological criteria in aspiration smears.
Aim: The aim of this study is to compare the conventional and TBSRTC and to compare and correlate the cases with histological findings wherever available.
Materials and Methods: The present study was a retrospective study undertaken in the department of pathology from January 2018 to December 2018 to access the validity of TBSRTC considering histopathology as the gold standard. May Grünwald Giemsa and Papanicolaou stained thyroid FNA smears of 240 patients were collected which were reported by the conventional system for reporting thyroid cytology and also categorized as per current Bethesda nomenclature for thyroid cytology. Diagnosis of both the reporting systems was then compared and correlated with the histological diagnosis wherever possible.
Results: A total of 240 cases were examined on cytology, out of which histopathological correlation was possible in 110 cases. For benign thyroid lesions, sensitivity and specificity with conventional system were 69.91% and 40.25%, respectively, while with TBSRTC, sensitivity and specificity were 84.04% and 29.94%, respectively. Sensitivity and specificity of conventional system for malignant thyroid lesions were 58.56% and 69.91%, respectively, while with TBSRTC, sensitivity and specificity were 73.69% and 95.12%, respectively. The Bethesda system found to be highly sensitive for benign thyroid lesions and highly specific for malignant thyroid lesions as compared to the conventional method of reporting of thyroid cytology.
Conclusion: Bethesda system was found to be superior for reporting thyroid cytology over the conventional system of reporting for thyroid cytology.

Keywords: Fine-needle aspiration cytology, The Bethesda System for Reporting Thyroid, Thyroid



How to cite this URL:
Pandey P, Dixit A, Sawhney A, Ralli M, Chaturvedi V, Agarwal S, Singh JP, Gupta S. A comparative study between conventional and the Bethesda System for Reporting Thyroid Cytology of 240 cases. J Can Res Ther [Epub ahead of print] [cited 2021 Dec 7]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=329054




 > Introduction Top


Palpable thyroid nodules may be found in 4%–7% of the general population, and this prevalence may approach 60% when high-resolution ultrasonography (USG) is used.[1],[2],[3] Fine-needle aspiration cytology (FNAC) is considered the first-line investigation apart from other investigations such as USG, thyroid function tests, thyroid scan, and antibody levels for the primary evaluation of the patients.[4] The technique is a safe, minimally invasive, easily performed with minimal patient discomfort, is efficient, and an excellent cost-effective method of evaluating thyroid lesions.[5],[6]

FNAC effectively distinguishes thyroid lesions suitable for surgical resection with those that can be managed conservatively. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) emerged from a conference held at the National Institute of Health in 2007 and leads to the standardization of FNA reports. It alleviates interobserver variability. TBSRTC categorizes the FNAC diagnosis into six groups with well-defined cancer risk and clear indications for further clinical management.[7]

Many studies have compared conventional reporting with TBSRTC and have concluded that about 70% to 80% of FNAC specimens from the thyroid can be classified as benign or malignant with a negative predictive value for a benign diagnosis of 92% and a positive predictive value for a malignant diagnosis of up to 100% in some series.[8] The aim of our study was to compare sensitivity and specificity of the conventional and TBSRTC along with histological findings.


 > Materials and Methods Top


The present study was conducted in the department of pathology from January 2018 to December 2018. It was a retrospective study taking all cases who underwent thyroid FNAC on an outpatient department basis in 1-year duration. Our sample size was of 240 cases. Clinically, the patients presented with swelling in any or both lobes of thyroid on palpation. Informed consent was taken before performing the procedure. Age, gender, and diagnosis were recorded. Some patients underwent thyroid scan. The patients who were already diagnosed thyroid lesions were not included in this study.

Thyroid nodules were aspirated by performing 2–3 passes using a 22G needle, 1–3 smears were prepared and fixed in alcohol for Papanicolaou staining, and air dried for May Grünwald Giemsa staining as per standard protocol. Histopathological specimens, wherever available, were processed and stained with hematoxylin and eosin as per standard methods. Thyroid FNA smears of 240 cases were observed and cytological features were evaluated as per current recommended conventional and TBSRTC categories. Histological follow-up was available in 110 cases. Histopathology was used as a gold standard to compare the sensitivity of both systems. The reporting of cases was done by conventional method, TBSRTC method, and histopathology by the same pathologist.

Conventional method

As per the conventional method of reporting, the cases were diagnosed and placed under the following categories:[9],[10]

  • Non diagnostic/unsatisfactory: when smears were hemorrhagic or containing <6 groups of well-preserved follicular cells on each of at least two slides
  • Colloid cyst: when follicular cells, thin or thick colloid in the background and hemosiderin-laden macrophages were seen in the smears
  • Colloid goiter: when smears contained follicular cells with abundant thick colloid in the background
  • Thyroiditis: acute, graves, Hashimoto, De Quervain's, and Riedel's thyroiditis
  • Follicular lesions/neoplasm: When smears contained many follicular cells without or scanty colloid in the background or when smears contain a predominant population of Hurthle cells, the differential diagnosis would include hyperplasic adenomatoid nodule with Hurthle cell change, Hurthle cell adenoma, and Hurthle cell carcinoma
  • Indeterminate smears: When smears containing cells with findings that were not clearly benign but were not diagnostic of a neoplasm or malignant lesions
  • Suspicious for malignancy: When aspirates suggested a follicular neoplasm, i.e., hypercellular sample with scant colloid and a significant proportion of microfollicles, trabeculae, or crowded overlapping clusters of follicular cells (also includes lesions consisting of oncocytic [Hurthle cell] neoplasm). When there is suspicion of papillary carcinoma, medullary carcinoma, or lymphoma
  • Malignant lesions:


    • Papillary carcinoma
    • Medullary carcinoma
    • Anaplastic carcinoma
    • Lymphoma
    • Metastatic carcinoma


The Bethesda System for Reporting Thyroid Cytopathology

The same cases were rescreened and reported as per the Bethesda system of reporting having the following six categories.[7]

1. Nondiagnostic or unsatisfactory

  • Cyst fluid only
  • Virtually acellular specimen
  • Other (obscuring blood, clotting artifact, etc.).


2. Benign

  • Consistent with a benign follicular nodule (includes adenomatoid nodule, colloid nodule, etc.)
  • Consistent with lymphocytic (Hashimoto) thyroiditis in the proper clinical context
  • Consistent with granulomatous (subacute) thyroiditis
  • Other.


3. Atypia of undetermined significance or follicular lesion of undetermined significance

  • Follicular neoplasm or suspicious for a follicular neoplasm
  • Specify if Hurthle cell (oncocytic) type.


4. Suspicious for malignancy

  • Suspicious for papillary carcinoma
  • Suspicious for medullary carcinoma
  • Suspicious for metastatic carcinoma
  • Suspicious for lymphoma
  • Other.


5. Malignant

  • Papillary thyroid carcinoma
  • Poorly differentiated carcinoma
  • Medullary thyroid carcinoma
  • Undifferentiated (anaplastic) carcinoma
  • Squamous cell carcinoma
  • Carcinoma with mixed features (specify)
  • Metastatic carcinoma
  • Non-Hodgkin lymphoma
  • Other.



 > Results Top


Out of total 240 cases, 196 were females and 44 were males with female:male ratio of 4.5:1. Age ranged between 14 and 72 years. Most of the cases belonged to 30–40 age group. Histological correlation was done in 110 cases.

Thyroid FNA smears of 240 cases were observed, and cytological features were evaluated as per the current recommended conventional and TBSRTC categories. Histological follow-up was available in 110 cases. Histopathology was used as a gold standard to compare the sensitivity of both systems [Table 1] and [Table 2].
Table 1: Distribution of cases as perconventional method of reporting and their histopathological correlation

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Table 2: Distribution of cases as per the Bethesda system of reporting and their histopathological correlation

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On histopathological correlation, 0% of nondiagnostic or unsatisfactory (2 cases), 8.57% of benign (35 cases), 22.22% of indeterminate (9 cases), 22.72% of follicular lesion/neoplasm (44 cases), 57.14% of suspicious for malignancy (7 cases) as per the conventional method of reporting were malignant [Table 1].

On histopathological correlation, 0% of nondiagnostic or unsatisfactory (2 cases), 5.88% of benign (34 cases), 27.27% of atypia of undetermined significance or follicular lesion of undetermined significance (11 cases), 25.53% of follicular neoplasm or suspicious for a follicular neoplasm (47 cases), and 80% of suspicious for malignancy (5 cases) as per the Bethesda system of reporting were malignant [Table 2].

Data show high sensitivity for benign thyroid lesions and high specificity for malignant thyroid lesions with the Bethesda system as compared to the conventional method [Table 3].
Table 3: Comparison of sensitivity and specificity for diagnosing benign and malignant thyroid lesions by Conventional and Bethesda system of reporting

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Statistical analysis

The sensitivity, specificity, and diagnostic accuracy using Statistical Package for Social Sciences (SPSS) version 20 software were calculated considering thyroid FNA as a “screening test.” FNA specimens interpreted as benign were considered to be true negative samples, and the remaining categories were considered to be true positive samples because they led to a recommendation of surgery. The false-positive category included cases that were diagnosed as malignant but which were confirmed as benign on histopathological evaluation. The false-negative case included those diagnosed as benign on FNA but confirmed as malignant on histopathology.


 > Discussion Top


Nodules of thyroid are a common clinical problem, and FNAC of the thyroid is often the key preoperative test usually preceded by imaging examination. An assessment regarding the need to exclude malignancy using FNA must be performed. FNAC helps to determine whether surgical removal of a detected nodule is recommended or not. The previous data show that the introduction of the new simplified Bethesda thyroid reporting system into six categories logically relates to the prognosis of thyroid diseases and increases the reproducibility of diagnosis.[11]

Before TBSRTC was introduced, reports were largely descriptive, with a multiplicity of category names, descriptive reports (no categories), or the use of surgical pathology terminology. Each diagnostic category, according to Bethesda conveys specific risks of malignancy, which offers guidance for patient management.[12]

The percentage distribution in our cases in the Bethesda System was in accordance with the results of other study conducted by Mondal et al. and Gupta et al.[13],[14]

In the present study, female:male ratio is 4.5:1 showing thyroid lesions are more common in females. This is in concordance to a study conducted by Bongiovanni et al., Laishram et al., and Misiakos et al.[15],[16],[17]

In our study, one case was classified as benign by conventional method on the basis of the presence of sheets of Hurthle cells and few macrofollicles, while by TBSRTC, it was classified as follicular neoplasm or suspicious for a follicular Neoplasm (Cat-IV) because of the presence of few microfollicles and nuclear atypia. This case was further diagnosed as Hurthle cell adenoma on histopathological examination [Figure 1] and [Figure 2].
Figure 1: Sheet of Hurthle cells having abundant eosinophilic granular cytoplasm with large nuclei and prominent nucleoli categorized benign by conventional method and follicular neoplasm or suspicious for a follicular neoplasm (Cat-IV) by The Bethesda System for Reporting Thyroid Cytology (May Grünwald Giemsa, ×400)

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Figure 2: Hurthle cell adenoma showing sheet of Hurthle cells with pools of colloid (H and E, ×400)

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In another case, there was the presence of microfollicles, nuclear crowding, nuclear overlapping, and atypia, which was categorized as follicular lesion by conventional method and suspicious for follicular neoplasm/follicular neoplasm (Cat-IV) by TBSRTC. On Histopathology, it was diagnosed as follicular variant of papillary carcinoma [Figure 3] and [Figure 4].
Figure 3: Many microfollicles categorized as follicular lesion by conventional method and suspicious for follicular neoplasm/follicular neoplasm (Cat.IV) by The Bethesda System for Reporting Thyroid Cytology (May Grunwald Giemsa stain, ×200)

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Figure 4: Follicular variant of papillary carcinoma showing follicles along with optical clearing of nucleus, intranuclear cytoplasmic inclusion, and nuclear grooving (H and E, ×400)

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There was a case of Hashimoto's thyroiditis which was reported as suspicious for malignancy because of good cellularity, high proportion of follicular cells along with the presence of intranuclear cytoplasmic inclusions in few cells. As intranuclear cytoplasmic inclusions are not specific for papillary carcinoma thyroid and may be seen in benign thyroid lesions, this case was reported as suspicious of malignancy so that malignancy may not be missed. Further on histopathology, this case was reported as papillary carcinoma thyroid.

During our study according to conventional system, ten cases found to be suspicious for malignancy, histopathological follow-up was possible in seven cases, of which only 57.14% of cases (4 cases) confirmed to be malignant by histopathology, and according to TBSRTC 5, cases were diagnosed as suspicious for malignancy, histopathological follow-up was possible in all these five cases, of which only 80% of cases (4 cases) diagnosed malignant on histopathological examination.

For benign thyroid lesions, sensitivity and specificity with the conventional system were 69.91% and 40.25%, respectively, while with TBSRTC sensitivity and specificity were 84.04% and 29.94%, respectively. Sensitivity and specificity of conventional system for malignant thyroid lesions were 58.56% and 69.91%, respectively, while with TBSRTC, sensitivity and specificity were 73.69% and 95.12%, respectively.

In our study, The Bethesda system showed a high sensitivity for benign thyroid lesions and high specificity for malignant thyroid lesions as compared to the conventional method. Thus, TBSRTC is more accurate in diagnosing malignancy.

The sensitivity and specificity of our study with the Bethesda system proved to be 73.68% and 95.12%, respectively. When compared with similar studies [Table 4], we found that our findings were consistent with other studies such as Gupta et al. and Himakham et al. and which was conducted on 75 and 469 cases, respectively.[14],[19]
Table 4: Comparison of sensitivity and specificity for Bethesda system with other studies

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There is a difference in sensitivity and specificity between the present study and other previous studies because of the difference in epidemiology of thyroid lesion in different geographic areas. For example, iodine deficiency disorders and colloid goiter are known to be endemic in India with a greater prevalence as compared to the Western countries. This may have led to more proportion of cases being diagnosed as benign with a consequent decrease in the other categories.

The other reason may be less often use of the atypia of undetermined significance and the suspicious for malignancy category during reporting, probably because of newness of the category.

Frank benign and malignant cases do not pose diagnostic difficulties, and majority of the cases can be reported without difficulty.[14] However, there is a gray zone area consisting of overlapping entities such as adenomatous goiter, follicular adenoma, and follicular carcinoma referred collectively as follicular patterned lesions, for which not only cytology, even the histological diagnosis is at times difficult.

Besides histopathology, immunohistochemistry (IHC) and molecular marker studies are also helpful in diagnosing cases of medullary carcinoma, anaplastic carcinoma, and lymphoma in thyroid specimens. IHC panels can be implicated for cases of suspicious malignancies which include calcitonin, thyroglobulin, CEA, and chromogranin for medullary carcinoma; pan-cytokeratin for anaplastic; and TTF-1 to differentiate metastatic carcinoma. Molecular studies for BRAF mutation or rearranged during transfection /papillary thyroid carcinoma chromosomal rearrangements are very helpful for the diagnosing papillary carcinoma thyroid.[23],[24]

The main limitation of our study was that it was a single-center study, so the data of this study may not accurately reflect the prevalence of thyroid lesions in the general population. Along with it, as it was a retrospective study, the correlation with clinical, biochemical, and radiology findings was not available for many cases, and histological specimen was not available in all cases for histopathological correlation. Hence, more research is required to overcome the limitations of the study.


 > Conclusion Top


The Bethesda System was found to be superior for reporting thyroid cytology over conventional system of reporting and more beneficial to clinician for accurately planning surgery of thyroid lesions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
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