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Kanukuntla, Pavani, Deshpawde, and Chaitanya: Evaluation of fine needle aspiration cytology of thyroid lesions by Bethesda system and its histopathological correlation


Thyroid lesions are one of the common conditions encountered in clinical practice. With an annual incidence rate of 2-6%.1 Palpable thyroid nodules are more common in females than in men.2, 3 Fine needle aspiration has been the safest and most accurate of diagnostic tools in thyroid lesions. 2 It plays an essential role in the evaluation of the euthyroid patient with a thyroid nodule. Ultrasound guided FNA of thyroid is useful, especially in cystic and multinodular lesions harboring malignancy. Recent guidelines recommending ultrasound examination in patients with palpable nodules have led to an emerging trend of US-guided FNA. 3

The Bethesda system of reporting thyroid cytopathology was introduced in 2007.4, 5 It had established a standardized, category based reporting system. The 2017 rivision (Table 1) reaffirms that every thyroid FNA report should begin with one of the 6 diagnostic categories. It includes category Non diagnostic /Unsatisfactory(ND/US), category 2 -Benign(B), category 3 -Atypia of undetermined significance / Follicular lesion of undetermined significance(AUS/FLUS), category 4- Follicular neoplasm/ suspicious of follicular neoplasm (FN/SFN), category 5 -Suspicious of malignancy (SM)and category 6 -Malignant(M). Each category has an implied risk of malignancy. The usual management now incorporates the option of molecular testing. The purpose is to delineate patients who require surgical excision of thyroid lesions from patients who can be managed conservatively.

The objective of this study is to categorise thyroid cytology smears into various diagnostic categories, to analyze their cytopathological features and to correlate with histopathological diagnosis of surgical specimens received.

Table 1

The Bethesda System for reporting thyroid cytopathology: recommended diagnostic categories, implied risk of malignancy and recommended clinical management

Diagnostic category Risk of malignancy (%) Usual management¹
(1) Nondiagnostic or UnsatisfactoryCyst fluid onlyVirtually acellular specimenOther(obscuring blood, clotting artefact, etc.) Repeat FNA with ultrasound guidance
(2) BenignConsistent with benign follicular nodule (includes adenomatoid nodule,colloid nodule etc.)Consistent with lymphocytic thyroiditis (Hashimoto) thyroiditis in the proper clinical context.Consistent with granulomatous (sub acute) thyroiditis other 0-3 Clinical and sonographic follow-up
(3) Atypia of undetermined significance or follicular lesion of undetermined significance(AUS/FLUS) 5-15² Repeat FNA,Molecular testing or lobectomy
(4) Follicular neoplasm or suspicious for follicular neoplasm(FN/SFN)-Specify if Hurthle cell (oncocytic) type 15-30 Molecular testing or Surgical lobectomy
(5) Suspicious for malignancy (SFM)Suspicious for papillary carcinomaSuspicious for medullary carcinomaSuspicious for metastatic carcinomaSuspicious for lymphomaOther 60-75 Near-total thyroidectomy or surgical lobectomy³
(6) MalignantPapillary thyroid carcinomaPoorly differentiated carcinomaMedullary thyroid carcinomaUndifferentiated(anaplastic)carcinomaSquamous cell carcinomaCarcinoma with mixed features(specify)Metastatic carcinomaNon-Hodgkin lymphomaOther 97-99 Near-total thyroidectomy³

[i] ¹Actual management may depend on other factors (e.g., clinical and sonographic) besides the FNA interpretation.

[ii] ²Some studies have recommended molecular analysis to assess the type of surgical procedure (lobectomy versus total thyroidectomy)

[iii] ³In the case of "suspicious for metastatic tumor” or a malignant interpretation indicating metastatic tumor rather than a primary thyroid malignancy, surgery may not be indicated.

Materials and Methods

Our study includes 248 cases of clinically diagnosed thyroid nodules since august 2017 to July 2019 referred for FNA to our department. Relevant clinical history was taken, examination done. With the patient sitting upright or supine with pillow behind, the neck with hyperextension a fine needle capillary sampling was done using needle (gauge 25-27). The needle was passed quickly and gently with different directions at the point of entry. Needling was concluded before or as soon as material appeared in the hub. The smears were prepared using conventional methods and stained with MGG, routine H&E and papanicolaou (pap) stain. US-guided FNA was done in some multinodular goiters and some radiologically suspicious lesions. The cytological features evaluated and reporting was done categorised according to TBSRTC. Histopathological specimens wherever available were processed as per standard operating procedures. Sensitivity, specificity, positive predictive value, negative predictive values were calculated using histopathology diagnosis as gold standard.

After exclusion of nondiagnostic results cytological diagnoses was classified as positive


The age distribution of cases were shown in Table 2. Ranges from 16-90 years of age. Majority of cases were presented in between 4th and 5th decades of life. Of which 216 were female and 32 were male. With female to male ratio of 7.7:1.

The cytomorphologic distribution of cases were given in Table 3. Benign category was the largest and constitutes 83.87% followed by the malignant category about 6.04%. AUS/FLUS constituted 4.03% cases while FN/SFN had 2.41% cases.

The ND/UNS category includes a total of 7 cases all cases were of cyst fluid only. In benign category a total of 208 cases were consistent with benign follicular nodule. The subcategory lymphocytic thyroditis included 38 cases in the benign category. In our study category AUS/FLUS constituted 4.03% .80% of the cases showed moderately cellular smears with predominantly microfollicles and scant colloid. Two cases showed predominantly benign appearing smear with focal features of papillary thyroid carcinoma including intranuclear inclusion, enlarged nuclei with irregular nuclear margin.

There were 2.41% of cases in FN/SFN category and there were no case of FN, Hurthle cell type. In the category SFM two cases of suspicious of malignancy NOS were reported. In the malignant category constitutes 6.04%.All cases were of papillary thyroid carcinoma.

A total of 66 patients underwent surgery in our hospital for which the histopathological diagnosis was available. Among these 48 cases were benign and 18 cases were malignant. 34 of 66 cases in this study with subsequent tissue diagnosis had a definitive cytologic diagnosis of being benign or malignant.

The cyto-histomorphologic correlation were summarized in Table 4.

Sensitivity, specificity, positive predictive value, negative predictive value were found to be of 60%, 96.43%, 75%, 93.10% respectively. The diagnostic accuracy was found to be 90.91% Table 2.

Table 2

Age distribution of cases

Age group Number of cases Percentage
0-10 00 00
11-20 03 1.20%
21-30 42 16.93%
31-40 74 29.83%
41-50 56 22.58%
51-60 45 18.14%
61-70 22 8.874%
714-80 05 2.01%
81-90 01 0.40%

Table 3

Distribution of cytologic diagnosis

S. No. Category Sub category Number of cases Total number of cases (%)
1. Nondiagnostic / unsatisfactory(ND/UNS) Cyst fluid only 07 07(2.82)
Acellular smears 0
Other (obscuring blood, clotting, artifacts) 0
2. Benign Consistent with benign follicular nodule (includes adenomatoid nodule, colloid nodule) 170 208(83.87)
Consistent with lymphocytic thyroiditis (hashimoto) thyroiditis in the proper clinical context 38
Consistent with granulomatous thyroiditis 00
Other 00
3. Atypia of undetermined significance (AUS\FLUS) 10(4.03)
4. Follicular neoplasm (FN\SFN) 06(2.41)
5. Suspicious of malignancy(SFM) 02(0.8)
6 Malignant 15(6.04)
Total 248

Table 4

Cytological/Histopathological correlation

Cytologic category No of cases surgical specimens received Percent of category Histopathological diagnosis No. of cases
Non diagnostic/unsatisfactory 01 Papillary thyroid carcinoma 01
Benign 28(50) Nodular goiter 20
Follicular adenoma 05
Papillary thyroid carcinoma 02
Non invasive follicular neoplasm with papillary like features 01
AUS/FLUS 01 Nodular hyperplasia 01
Suspicious of malignancy 01 Lymphocytic thyroiditis 01
Malignancy 03 Papillary thyroid carcinoma 03

Table 5

Comparision with other studies

Study Sensitivity Specificity Positive predictive value Negative predictive value Diagnostic accuracy
Goswami et al10 85.71% 96% 85.71% 96% 93.33%
Roy PK et al.9 81.48% 95.29% 84.61% 94.18% 91.16%
Muratli et al.6 87.1% 64.6% 76.1% 79.5% 77.3%
Sheikh et al.7 83.2% 63.3% 74.3% 76.4% 74.4%
Sreemani et al.8 67.4% 99.2% 93.9% 94.2% 94.1%
Present study 60% 96.43% 75% 92.10% 90.91%

Figure 1

a): Benign follicular nodule pictomicrograph showing monolayer sheets of evernlyspaced follicular cells (inbox image show microfollicles); b): Benign follicular nodule: Pictomicrograph showing nodulargoiter

Figure 2

Pictomicrograph showing Hashimoto thyroiditis

Figure 3

a): Follicular neoplasm: Pictomicrograph showing microfollicular pattern; b) Papillary thyroid neoplasm: Pictomicrograph showingpapillary pattern; b: Papillary thyroid neoplasm: Pictomicrograph showingnuclear crowding, overlapping and intranuclear inclusions; c): Papillary thyroidneoplasm: Pictomicrograph showing nuclear crowding, overlapping andintranuclear inclusion; d): Papillary thyroid neoplasm: Pictomicrograph showingpapillary thyroid neoplasm: Benignfollicular nodule: Pictomicrograph showing follicular neoplasm

Figure 4

a): Papillary thyroid neoplasm: Pictomicrograph showingpapillary pattern; b): Papillary thyroid neoplasm: Pictomicrograph showingnuclear crowding, overlapping and intranuclear inclusions; c): Papillary thyroidneoplasm: Pictomicrograph showing nuclear crowding, overlapping andintranuclear inclusion; d): Papillary thyroid neoplasm: Pictomicrograph showingpapillary thyroid neoplasm


Thyroid malignancies constitute 1% of all cancers and are responsible for 0.5% of all cancer related deaths. Thyroid cancers are nearly three times more common in women than in men. FNA plays an essential role in evaluation of euthyroid patients with thyroid nodule. FNA combined with ultrasound is the initial approach to obtain cells for pathologic review.FNA is usually performed in patients with nodules >1cm with no associated risk factors. In patients with risk factors FNA of all nodules more than or equal to 5 mm is performed. If malignancy cannot be excluded by FNA, a lobectomy is usually performed to obtain adequate tissue for correct diagnosis.

Current study deals with 248 cases of thyroid swellings where FNA was performed in our department. Majority of the cases were presented between 3rd to 5th decades of life. Most common presenting complaint was swelling in front of neck. Majority of patients were euthyroid and most common clinical diagnosis was solitary thyroid nodule. US–guided FNA was performed wherever necessary.

Our study had 7(2.82%) cases in ND/UNS category. Other recent studies had 1.2% to 16% cases in this group.11, 12, 13, 14, 6, 9, 7, 8 Guidelines for this category are very clear in TBSRTC. The number of cases in this category is depends not only on the aspirator but also on the inherent nature of the lesion (e.g., solid vs cystic). TBSRTC provides 5-10% an implied risk of malignancy for this category.4 Also recommends nodules with an initial ND result should be re-aspirated unless the nodule is purely cystic. Ultrasound guidance with an immediate on-site adequacy evaluation is preferred for repeat aspiration especially for solid nodules in the absence of on-site evaluation for adequacy obtaining a minimum of three separate samples of the nodules can reduce the rate of unsatisfactory specimens. After two successive ND/UNS specimens, close clinical and sonographic follow-up or surgery should be considered, depending on clinical findings. In this category we had a case were the initial diagnosis was cyst fluid only. For this case an intraoperative consultation was taken, on frozen section examination it was reported as papillary thyroid carcinoma and later on histopathological examination it was consistent with papillary thyroid carcinoma

The benign category had 208 (83.87%) cases. Nodular goiter was most common thyroid lesion diagnosed on cytological examination followed by lymphocytic thyroiditis. The benign category is associated with very low risk of malignancy, and patients are usually followed conservatively with periodic clinical and radiologic examinations.

The diagnostic criteria of all the subcategories are well characterized in TBSRTC. By definition the sample is adequate for evaluation and consists of colloid and benign appearing follicular cells in varying proportions. In the subclassification a more specific benign diagnosis was given, depending on the cytomorphologic findings and associated clinical presentation.

A total of 50 cases surgical specimens were received. Clinical diagnosis was predominantly multinodular goiter followed by solitary thyroid nodule. All of them were operated for cosmetic reasons or pressure symptoms. Cyto-histo correlation was available for 28 cases, of which 20cases were nodular goiter, 05 cases were follicular adenoma and 02 cases were reported as papillary thyroid carcinoma of which one case showed a tiny focus i.e., papillary microcarcinoma

A case of noninvasive follicular thyroid neoplasm with focal papillary like nuclear features (NIFTP)15 which showed an encapsulated, follicular patterned lesion with focal nuclear features of papillary thyroid carcinoma. Cytological diagnosis for this case was nodular goiter.

Chetna J mistry et al15 and Neiki et al16 stated that presence of degenerarative changes in the monolayer sheets with abundant colloid in the background would suggest a possibility of non-neoplastic lesion. In a study of Das DK et al,17 colloid goiter, cellular adenomatoid goiter(hyperplastic goiter), hyperplastic nodule and follicular neoplasm form a continous spectrum in terms of cellularity, microfollicles in increasing order and background colloid in decreasing order. Study done by Basavaraj P Bommanahali et al18 Radhika puri et al11 showed similar findings.

Baloch ZW et al.19 stated that differential diagnosis of smears with predominanlty macronormo follicular pattern often included nodular goiter and follicular neoplasm. The cyto and histomorphologic characteristics were also described.

Our study also included 4 cases where initial cytomorphologic diagnosis was nodular goiter but later was diagnosed as follicular adenoma on histopathological examination.

FN/SFN category had 6 (2.41%) cases. TBSRTC provides a clear guidelines for this category. Aspirates were cellular with predominantly microfollicular pattern. Cellularity, nuclear size, pleomorphism of cells and amount of colloid are helpful in distinguishing neoplastic from non-neoplastic follicular lesion. A cyto-histo correlation was available for one case in this category. Patients presented with solitary thyroid nodule

The category malignant had a range of 2.9%-11% in all the recent studies.11, 12, 13, 14, 6, 9, 7, 8 The present study had 6.04% cases in malignant category. We received 3 specimens from this category diagnosed as “malignant” on cytology. All of them were diagnosed as papillary thyroid carcinoma both histopathological examination.

The total accuracy of throid FNA was reported in our study is 90.91% was comparable with other studies (Table 5).


In our study we analysed thyroid cytology smears and classified according to the bethesda system. The bethesda system for reporting thyroid cytopathology is an excellent system of reporting thyroid cytopathology. It facilitates easy sharing of data. Each category also provides clear management guidelines to clinicians and also extent of surgery.

Source of Funding


Conflict of Interest




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