Clinicopathological Correlation of Core-Needle Biopsy in Thyroid Nodule Assessment: Insights from a Tertiary Care Center

Abstract

Background:

Fine-needle aspiration cytology (FNAC) is the mainstay for thyroid nodule assessment, boasting excellent specificity and cost-effectiveness. However, its diagnostic limitations often yield nondiagnostic or indeterminate results, especially in complex thyroid cases. Core-needle biopsy (CNB) has emerged as a complementary technique that preserves tissue architecture, enabling improved morphological and molecular analysis. This study compares the diagnostic performance and clinical utility of FNAC and CNB in a tertiary care setting.

Materials and Methods:

In this retrospective analysis at Sanjay Gandhi Postgraduate Institute of Medical Sciences, 116 patients with thyroid masses underwent both FNAC and CNB between 2014 and 2024. Clinicopathological features, imaging, and cytological/histological data were reviewed. Diagnoses were correlated with final surgical outcomes where available.

Results:

FNAC adequacy was 96.6%, and CNB adequacy was 99.1%. FNAC’s sensitivity, negative predictive value, and diagnostic accuracy were 81.8%, 50%, and 81.5%, respectively, whereas CNB achieved 95.7%, 80%, and 96.2%, respectively. All four nondiagnostic FNAC cases were accurately diagnosed by CNB, with precise subtyping of poorly differentiated, medullary, and anaplastic carcinomas and lymphomas.

Conclusion:

FNAC is a valuable first-line investigation, but its limitations—especially in indeterminate or high-risk thyroid lesions in tertiary centers—justify early use of CNB. CNB complements FNAC by improving diagnostic yield, subtype accuracy, and suitability for ancillary studies, thus optimizing clinical management and reducing unnecessary surgeries in complex thyroid pathology.

INTRODUCTION

Fine-needle aspiration cytology (FNAC) has traditionally served as the first-line diagnostic modality for thyroid masses, offering excellent specificity (85.1%–100%) and cost-effectiveness in resource-limited settings.[1] However, despite its widespread adoption in clinical practice, FNAC demonstrates significant limitations that increasingly challenge its adequacy as a standalone diagnostic technique. According to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), 6%–36% of thyroid nodules yield nondiagnostic results and 10%–30% yield indeterminate results.[2,3] These diagnostic gaps necessitate repeat procedures, delay definitive treatment, and often result in unnecessary surgical interventions. Diagnostic accuracy remains paramount in contemporary pathology practice, particularly in tertiary care centers where complex cases demand precise tissue characterization.

Core-needle biopsy (CNB) overcomes fundamental FNAC limitations by preserving tissue architecture, enabling histopathological diagnosis, immunohistochemical profiling, and molecular testing—capabilities particularly critical for large thyroid masses requiring definite characterization.[4,5] Unlike FNAC, CNB specimens provide adequate tissue for comprehensive molecular evaluation, extending diagnostic utility beyond malignancy detection to encompass the molecular characterization increasingly demanded by contemporary thyroid pathology practice.[6,7]

This institutional experience evaluates the comparative diagnostic performance of both techniques in a tertiary care setting, with the aim of providing evidence-based recommendations for optimal CNB utilization in thyroid nodules requiring tissue characterization.

MATERIALS AND METHODS

This was a retrospective study, conducted at the Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences. All fine-needle aspirate samples of thyroid lesions with corresponding CNBs received in the department from January 2014 to December 2024 were included in this study. In this study, all histology specimens of thyroid lesions received at the Department of Pathology of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, between January 2014 and December 2024 were identified through a data search. We excluded surgical specimens (total thyroidectomy, hemithyroidectomy, lobectomy, and completion thyroidectomy) from a total of 6336 thyroid tissue specimens. We examined 117 CNB specimens from solid and cystic thyroid mass lesions. One specimen revealed only fibrocollagenous tissue and muscle bundles and was therefore excluded from this study, leaving 116 specimens for final analysis. CNBs were performed for the unresectable, rapidly growing diffuse masses, subtyping of the malignancy, and excluding the possibility of lymphoma. The histopathology slides of these cases were retrieved and reviewed.

The FNAC samples of the corresponding CNB cases were studied. The archival FNAC smears stained with May–Grunwald–Giemsa stain and Papanicolaou stain were retrieved and reviewed for adequacy and confirmation of diagnosis. For each case, clinical data, laboratory tests, imaging reports, and surgical follow-up data were retrieved from the hospital information system. Imaging reports, including sonography and computed tomography, were reviewed to assess the location, size, and characteristics of the thyroid lesions. A summary of the selected cases and their distribution is given in Figure 1.

Figure 1.

Consort of the selected cases and their distribution

In our institute, FNAC of the thyroid nodule was performed under ultrasound guidance, and a pathologist assessed adequacy on-site. CNB was performed under ultrasound-guided puncture with a core needle (18–21 gauge).[5] Two experienced cytopathologists (NN and RS) independently evaluated all FNAC smears and CNB specimens, blinded to clinical history, radiology findings, and each other’s interpretations. Discrepancies were resolved by consensus review. Pathological diagnoses were compared with surgical histopathology, supported by immunohistochemistry (gold standard) and/or clinico-radiological follow-up without knowledge of biopsy outcomes.

Statistical analysis

A statistical analysis was conducted using the Statistical Package for the Social Sciences software (SPSS, Chicago, IL). Quantitative variables are presented as means ± standard deviations, and categorical variables are presented as frequencies (%). Categorical variables were compared between groups using appropriate chi-square or Fisher’s exact tests. The results of surgical histopathological examination were used to calculate the accuracy of FNAC, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic precision. Pearson’s correlation analysis was used to evaluate the correlation between variables. Significance was defined at a P value of <0.05.

RESULTS

This study enrolled 116 patients with thyroid masses who had undergone both CNB and FNAC. Out of these 116 patients, 27 underwent thyroidectomy, and histological follow-up was available. The median age of patients in this study was 57 years (range: 5–84), and the female-to-male ratio was 2.1:1. Lesions measured a mean diameter of 6.8 ± 3.3 cm. Ultrasound risk stratification according to the “Thyroid Imaging and Reporting System” classified 63 as thyroid imaging reporting and data system (TIRADS) 5, 24 as TIRADS 4, 10 as TIRADS 3, and 19 as TIRADS 2. Retrosternal extension was present in 34 patients. One patient had bleeding following the CNB procedure, which was controlled after 10 min of firm pressure. The clinicopathological parameters are summarized in Table 1.

Table 1.

Epidemiological and radiological features of the study group (n = 116)

Variables	Value
Age, median (range)	57 years (5–84)
Gender	Male: 37
	Female: 79
M:F ratio	1:2.1
Size (mean ± SD)	6.8 ± 3.3 cm
TIRADS	TIRADS 2–19
	TIRADS 3–10
	TIRADS 4–24
	TIRADS 5–63
Retrosternal extension	No: 82
	Yes: 34
Complications of CNB	1 (Bleeding)

CNB = core needle biopsy, SD = standard deviation, TIRADS = thyroid imaging reporting and data system

Adequacy of the FNAC for thyroid masses was 96.6% (n = 112/116), and that of CNB was 99.1% (n = 116/117). Comparison of FNAC and CNB revealed that FNAC yielded nondiagnostic (TBSRTC I) results in four (3.4%) cases, all of which were definitively characterized on CNBs, including one case each of follicular neoplasm and medullary carcinoma and two cases of thyroid lymphoma. Among 22 (19%) lesions classified as benign on FNAC (TBSRTC II), CNB identified eight malignancies—two papillary thyroid carcinomas, two poorly differentiated carcinoma, and four lymphomas. Atypia of undetermined significance (TBSRTC III) had one (0.9%) case, which on CNB was anaplastic thyroid carcinoma. FNAC assigned 83 (71.6%) cases to TBSRTC V/VI categories, detecting 11 papillary carcinomas, 8 medullary thyroid carcinomas, 5 poorly differentiated carcinomas, 34 anaplastic carcinomas, 17 lymphomas, and 8 metastatic lesions, collectively confirmed by CNBs. Details are given in Table 2.

Table 2.

Comparison of the results of FNAC and CNB in thyroid masses (n = 116)

FNAC		Diagnosis on CNB								Total
TBSRTC		Benign	PTC	FC/FA	MTC	ATC	PDTC	TL	TGM
TBS I	Nondiagnostic		–	1	–	1	–	2	–	4
TBS II	Benign	14	2	1	–	–	1	4	–	22
TBS III	AUS			–	–	1	–	–	–	1
TBS IV	Follicular neoplasm	1	–	3	–	1	1	–	–	6
TBS V	Suspicious for malignancy	–	3	–	–	5		3	–	11
TBS VI	Malignant		8	–	8	29	5	14	8	72
	Total	15	13	5	8	37	7	23	8	116

FNAC = fine-needle aspiration cytology, CNB = core-needle biopsy, PTC = papillary thyroid carcinoma, FC/FN = follicular carcinoma/follicular adenoma, MTC = medullary thyroid carcinoma, ATC = anaplastic thyroid carcinoma, PDTC = poorly differentiated thyroid carcinoma, TL = thyroid lymphoma, TGM = thyroid gland metastases

Of 116 cases, surgical excision was performed in 27. Details are given in Table 3. The sensitivity of cytology was 81.8%, specificity was 100%, PPV was 81.8%, and NPV was 50.0%. Diagnostic accuracy was 81.5%. Although cytology had high diagnostic accuracy, its NPV was low. The sensitivity of the CNBs was 95.65%, specificity was 100%, PPV was 100%, and NPV was 80% [Table 4].

Table 3.

Diagnostic performance of FNAC and CNB compared with histology in patients treated with surgery (n = 27)

S. No.	Age (years)	Sex	FNAC	CNB	Surgical histology	Concordance of cytology with surgical histology	Concordance of CNB with surgical histology
1	59	F	TBSRTC VI	MTC	MTC	Yes	Yes
2	62	F	TBSRTC I	FN	FTC	No	Yes
3	56	M	TBSRTC II	FND	FND	Yes	Yes
4	74	M	TBSRTC V	PTC	PTC	Yes	Yes
5	60	M	TBSRTC VI	PTC	PTC	Yes	Yes
6	35	F	TBSRTC VI	PTC	PTC	Yes	Yes
7	35	M	TBSRTC VI	MTC	MTC	Yes	Yes
8	45	F	TBSRTC II	PDTC	PDTC	No	Yes
9	84	M	TBSRTC VI	ATC	ATC	Yes	Yes
10	61	F	TBSRTC VI	MTC	MTC	Yes	Yes
11	49	F	TBSRTC II	FN	FTC	No	Yes
12	67	M	TBSRTC IV	FTC	FTC	Yes	Yes
13	69	F	TBSRTC VI	MTC	MTC	Yes	Yes
14	70	F	TBSRTC V	PTC	PTC	Yes	Yes
15	65	M	TBSRTC VI	PTC	PTC	Yes	Yes
16	57	M	TBSRTC II	LT	LT	Yes	Yes
17	57	F	TBSRTC II	PTC	PTC	No	Yes
18	54	F	TBSRTC VI	PTC	PTC	Yes	Yes
19	44	F	TBSRTC IV	FN	FTC	Yes	Yes
20	48	F	TBSRTC II	LT	LT	Yes	Yes
21	35	F	TBSRTC II	LT	LT	Yes	Yes
22	78	F	TBSRTC IV	FTC	FTC	Yes	Yes
23	47	F	TBSRTC VI	MTC	MTC	Yes	Yes
24	47	F	TBSRTC VI	MTC	MTC	Yes	Yes
25	30	F	TBSRTC II	FND	FTC	No	No
26	49	F	TBSRTC VI	PTC	PTC	Yes	Yes
27	57	F	TBSRTC VI	MTC	MTC	Yes	Yes

FNAC = fine-needle aspiration cytology, CNB = core-needle biopsy, TBSRTC = the Bethesda System of Reporting Thyroid Cytology, PTC = papillary thyroid carcinoma, FC/FN = follicular carcinoma/follicular adenoma, MTC = medullary thyroid carcinoma, ATC = anaplastic thyroid carcinoma, PDTC = poorly differentiated thyroid carcinoma, TL = thyroid lymphoma, TGM = thyroid gland metastases, FTC = follicular thyroid carcinoma

Table 4.

Diagnostic capability of core-needle biopsies (CNBs) and ultrasound-guided fine-needle aspiration cytology (FNAC) in thyroid mass lesions

Diagnostic modality	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Diagnostic accuracy (%)
FNAC	81.8	100	81.8	50	81.5
CNB	95.7	100	100	80	96.2

PPV = positive predictive value, NPV = negative predictive value

FNAC concordance or diagnostic accuracy with histology was 81.5% (22/27). Diagnostic accuracy of the CNBs was 96.2% (n = 26/27). Many of the cases were misdiagnosed on cytology. One case of inadequate cytology and four cases of benign cytology turned out to be malignancy on the surgical specimens (3: follicular thyroid carcinoma, 1: poorly differentiated thyroid carcinoma, and 1: papillary thyroid carcinoma). CNB correctly identified all but one follicular neoplasm. The case of follicular neoplasm does not show any evidence of capsular invasion on CNB and was not correctly diagnosed by CNB. The surgical resection specimen shows minimally invasive follicular carcinoma with capsular and vascular invasion. These findings underscore CNB’s superior diagnostic yield, particularly in indeterminate or nondiagnostic FNAC cases, and its high accuracy in guiding surgical management [Figure 2].

Figure 2.

Axial contrast-enhanced computed tomography (CECT) image (a) shows a heterogeneously enhancing mass lesion with a cystic component (13 cm × 8 cm × 4.7 cm). Cytology smear (b; 100×; May–Grunwald–Giemsa [MGG]) shows papillary clusters with nuclear grooving, overlapping, and intranuclear inclusions (inset). Core-needle biopsy (CNB) shows papillary thyroid carcinoma with nuclear features [hematoxylin and eosin (H&E)]. Surgical specimen shows similar histomorphology (e; 100×; H&E). Axial CECT image (f) shows a heterogeneous solid-cystic lesion in the right lobe of the thyroid gland. Cytology shows microfollicles arranged in a repetitive pattern (g; 100×; MGG). CNB cores show follicular neoplasm (h and i; 100× and 200×; H&E). The surgical specimen reveals a vascular invasion (j; 100×; H&E). Sagittal CECT image (k) showing a predominantly cystic mass replacing the thyroid gland (white arrows) with a mildly enhancing solid component at the periphery. Cytology reveals a cellular tumor of C-cell differentiation (l; 200×; MGG). CNB shows infiltration by medullary carcinoma of the thyroid (m; 200×; H&E), and the cells are positive for calcitonin (n) and chromogranin (o) and negative for thyroglobulin (p). Axial CT image (q) showing a large partly cystic/necrotic soft-tissue mass lesion replacing the right lobe of the thyroid gland (red arrow) and another hypoenhancing nodule in the left lobe (blue arrow). The right lobe mass had ill-defined planes and invaded the right internal jugular vein (IJV). Cytology smears have necrosis and anaplastic cells (r; 400×; MGG). CNB reveals necrosis (star) and anaplastic thyroid carcinoma (s and t; 200× and 400×; H&E). The surgical specimen shows similar histomorphology (u; 200×; H&E). Axial CECT image (v) showing a predominantly cystic mass replacing the thyroid gland (white arrows) with a mildly enhancing solid component at the periphery (red arrow). Cytology smear (w; 200×; MGG) reveals a poorly differentiated malignancy. CNB shows infiltrating sheets and an insular pattern of tumor with high nuclear grade (x and y; 200× and 400×; H&E). On immunohistochemistry, tumor cells are positive for PAX8 (z) and TTF1 (a1) and negative for thyroglobulin (inset). Axial CECT image (b1) showing a large heterogeneously enhancing predominantly solid/soft-tissue mass replacing the left lobe and isthmus of the thyroid gland, with ill-defined planes with surrounding structures (red arrow). The left IJV was invaded, and the left common carotid artery (black oval) was displaced posteriorly. The residual right lobe of the thyroid gland is shown (blue arrow). Cytology shows a dispersed population of atypical lymphoid cells (c1; 200×; MGG). CNB shows infiltration by tumor cells, which are large-sized with round to oval nuclei, coarse chromatin, conspicuous nucleoli, and scant cytoplasm. Frequent mitotic figures are also evident. (d1 and e1; 200× and oil immersion [inset]; H&E). Immunohistochemistry slides showing diffuse CD20 positivity (f1; 200×) in tumor cells and Ki67 index of ~80%–90%

DISCUSSION

This comparative analysis of FNAC and CNB in evaluating thyroid masses in a tertiary care setting provides meaningful insights for modern diagnostic pathology. FNAC is a historical cornerstone in thyroid nodule diagnosis, due to its minimally invasive nature, affordability, and high specificity rates of 85%–100% across various clinical settings.[8,9]

This study reaffirms the high sample adequacy of FNAC (96.6%) and its usefulness in screening and initial triage. FNAC, however, still poses a major clinical challenge due to nondiagnostic results (3.4%) and indeterminate or false-negative results, especially in larger or heterogeneous nodules.[10,11]

According to TBSRTC, 10%–30% of thyroid nodules yield indeterminate findings. We have low rates of atypia of undetermined significance (AUS) in thyroid cytology (n = 1; 0.9%). This is due to strict adherence to the Bethesda System criteria, accurate sample preparation, on-site adequacy assessment, and correlation with clinical and radiological findings that reduce subjective interpretation.[12]

However, our findings also highlight well-documented limitations of FNAC, particularly in rapidly enlarging thyroid masses—a cohort enriched with diagnostically complex and high-risk cases typical of tertiary practice. Nondiagnostic (TBSRTC I) and indeterminate results (TBSRTC III) occurred in 3.4% and 0.9% of cases, respectively. Importantly, among the 22 cases cytologically classified as benign (TBSRTC II), eight were ultimately diagnosed as malignant by CNB and/or surgical histopathology—including papillary thyroid carcinoma, poorly differentiated carcinoma, and several lymphomas. Such discrepancies align with meta-analyses reporting nondiagnostic FNAC rates as high as 36% and underscore the challenges posed by follicular and nonepithelial/neuroendocrine lesions, which often lack overt cytological distinction.[13] The low NPV observed in our cohort (50%) indicates that benign FNAC results cannot entirely exclude malignancies.[14,15]

As a complementary tool, CNB provided not only a higher adequacy rate (99.1%) but also superior diagnostic granularity, offering a more accurate classification of follicular, medullary, poorly differentiated, and anaplastic carcinomas and lymphomas.[16,17]

CNB successfully subtyped all four nondiagnostic FNAC cases, and in all but one case, the CNB diagnosis matched the final surgical histology. These results replicate global evidence that CNB is especially valuable for large, rapidly progressing, or ambiguous thyroid nodules and when cytology is indeterminate or discordant. CNB’s preserved tissue architecture enables the diagnosis of follicular neoplasms (which require architectural evaluation for capsular/vascular invasion) and the reliable detection of lymphoid and metastatic malignancies. This study also confirms the enhanced sensitivity of CNB (95.65%) compared with FNAC (81.8%), a finding reported in recent meta-analyses.[13,15,18,19] The use of thyroid CNBs reduces the need for unnecessary surgery in AUS cases.[20] According to some studies, CNBs are associated with significantly fewer cases in the indeterminate and AUS categories.[21]

Statistically, the difference between modalities is substantial. In our cohort, FNAC’s sensitivity (81.8%), NPV (50%), and diagnostic accuracy (81.5%) were clearly outperformed by CNB, which yielded a sensitivity of 95.7%, an NPV of 80%, and an accuracy of 96.2% against the surgical gold standard. These figures mirror those of other tertiary care center studies and multi-institutional reviews, which document improved diagnostic confidence, fewer false negatives, and greater concordance with surgical outcomes when CNB is used as a second-line or adjunct diagnostic tool.[22,23,24,25]

The clinical impact of CNB’s superior diagnostic yield is profound, especially in cases where management decisions hinge on precise subtyping. Anaplastic carcinoma, thyroid lymphoma, and metastatic tumors not only have highly divergent prognoses but also require radically different treatment algorithms.[11,13]

Several studies have shown that CNBs can reduce the need for diagnostic surgery in cases of anaplastic carcinoma, owing to their higher specificity and PPV.[26] There were, however, a few cases in which cytology could not accurately diagnose the type of malignancy. Additionally, the development of lymphoma in lymphocytic thyroiditis can also be challenging to diagnose on cytology. Such cases can benefit from CNBs as an adjuvant diagnostic approach. This method has the added benefit of providing tissue for both immunohistochemistry and molecular analysis in complex cases, where ancillary techniques are crucial to the diagnosis.[6] A potential diagnostic limitation of CNB in this study is the inability to differentiate between follicular adenoma and carcinoma in the absence of unequivocal capsular and vascular invasion.[27] Immunohistochemical and molecular ancillary testing are increasingly vital in the contemporary assessment of thyroid nodules. FNAC, while cytologically informative, often yields insufficient material for advanced analyses, whereas CNB consistently provides tissue suitable for immunohistochemistry and molecular classifiers [B-Raf (v-Raf murine sarcoma viral oncogene homolog B1) and rat sarcoma (viral oncogene family: HRAS, KRAS, NRAS)], which may aid in diagnosis in such cases.[28,29]

Safety is an essential consideration for widespread adoption of CNB. In this study, only a single patient experienced a mild, self-limited bleeding complication. This finding is in keeping with a survey by Ha et al.,[30] which demonstrated major complication rates of <1% for CNB with experienced operators and ultrasound guidance. Ha et al.[30] reported a 1% complication rate in their meta-analysis, whereas the significant complication rate was 0.06%. Major complications include permanent voice change, damage to the recurrent laryngeal nerve, local hematoma, infections, and pseudoaneurysm.[30] There were no significant complications in this study, except for minor bleeding. Proper coagulation work-up before the procedure and adequate pressure afterward can help minimize the risk of thyroid bleeding.[30]

Limitations of this study include its retrospective, single-center design, limited surgical follow-up cohort, and the absence of molecular profiling. This study focused on masses where clinico-radiological suspicion of malignancy was high. Therefore, the high diagnostic yield observed may not be generalizable to low-suspicion, incidentally discovered nodules. Despite these limitations, our results remain robust and comparable to larger multicenter investigations.[24,25,31] Future prospective, algorithm-based randomized trials incorporating conventional cytology, CNB, and molecular testing are warranted to optimize individualized thyroid nodule management.

CONCLUSION

FNAC remains the effective first-line test for thyroid nodules; however, in complex cases where FNA often yields “atypical” or “nondiagnostic” results, the architectural preservation of CNB provides superior diagnostic clarity, preventing delayed treatment in aggressive cases. The CNB complements FNAC for high-risk nodules, overcomes its limitations, provides detailed histology and material for immunohistochemistry, and thus reduces unnecessary surgery and diagnostic delays.

Author contributions

Conception and design: NN. Provision of study materials or patients: AS, AM, and SM. Collection and assembly of data: NN and NK. Data analysis and interpretation: NN, RS, OG, PM, and AR. Manuscript writing: NN and RS. Final approval of manuscript: all authors.

Data availability statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

Ethical policy and Institutional Review Board statement

This retrospective study was conducted solely on archival smears and slides.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.