Thyroid nodules are detected in 19–67% of asymptomatic adults on high-resolution ultrasonography, but only about 7–16% are malignant [1]. Accurate risk stratification is therefore essential to identify patients who require surgery while avoiding unnecessary intervention in those with benign disease. Ultrasound-guided fine-needle aspiration cytology (FNAC) has been the first-line diagnostic test for more than four decades because it is simple, safe, inexpensive, and highly accurate. Most international guidelines recommend FNAC as the next step in the evaluation of sonographically detected thyroid nodules [1,2].

Despite its established role, FNAC has important limitations. Non-diagnostic and indeterminate results—including atypia or follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm, and suspicious-for-malignancy categories—account for a substantial proportion of aspirates [3]. Although repeat aspiration resolves many of these cases, some remain inconclusive, leading to additional investigations, increased cost, patient anxiety, and sometimes unnecessary diagnostic surgery [1,3]. FNAC is also limited in lesions where tissue architecture is critical. It cannot reliably distinguish follicular adenoma from follicular carcinoma and has limited value in subtyping lymphoma, anaplastic carcinoma, and medullary carcinoma, conditions with markedly different treatment strategies.

Ultrasound-guided core-needle biopsy (CNB) addresses many of these limitations. Using a spring-activated cutting (trucut) needle, CNB provides intact tissue cores that preserve histological architecture, include the nodule–parenchyma interface, and yield sufficient material for immunohistochemistry and, when indicated, molecular analysis [2,4]. Published studies and the 2016 consensus statement of the Korean Society of Thyroid Radiology (KSThR) support CNB as a safe and effective adjunct to FNAC, particularly for nodules with previous non-diagnostic or indeterminate cytology, heavily calcified nodules, and lesions suspected to represent uncommon malignancies [2,4]. Reported non-diagnostic rates are generally 1–7%, substantially lower than those of repeat FNAC, while pooled meta-analyses have shown higher sensitivity for CNB (approximately 74% versus 50%) with similarly high specificity [2,5]. Despite these advantages, CNB has been adopted cautiously in the Indo-Pakistan region, largely because of concerns about bleeding associated with a larger-bore needle in the highly vascular thyroid gland.

This study evaluated the feasibility of ultrasound-guided thyroid CNB in a tertiary interventional radiology practice by assessing specimen adequacy, procedural safety, and the diagnostic contribution of core histology beyond cytology, with the aim of defining the role of CNB in local clinical practice.

Study design and setting

This single-centre retrospective observational study included all ultrasound-guided thyroid and thyroid-region biopsy and aspiration procedures performed by the interventional radiology service at Lady Reading Hospital, Peshawar, a tertiary-care teaching hospital. Tissue specimens were submitted to two reference laboratories—Shaukat Khanum Memorial Cancer Hospital, Lahore, and Shifa International Hospital, Islamabad—for histopathological and cytological evaluation. Consecutive core-needle (trucut) biopsy and FNAC reports issued between 2021 and 2024 were retrieved and reviewed. The study was approved by the institutional ethics committee. Written informed consent for biopsy or aspiration had been obtained from all patients before the procedure.

Participants

Patients referred for image-guided sampling of a thyroid nodule or thyroid-region mass were eligible for inclusion. In accordance with routine safety practice, core biopsy was not performed in patients with uncorrected coagulopathy, purely cystic lesions unsuitable for tissue sampling, or those who did not provide consent. The decision to perform CNB or FNAC was based on the operator's clinical judgement. Consequently, the two techniques were used in largely different patient groups rather than on the same nodules (see Limitations).

Procedures

All procedures were performed under ultrasound guidance by a single experienced operator. Core biopsies were carried out under local anaesthesia using an 18–20-gauge spring-activated cutting needle with a freehand technique. The needle was maintained in-plane throughout the procedure, and the specimen notch was positioned to include the lesion and, where possible, the adjacent normal parenchyma. One or more core samples were obtained based on the operator's assessment of specimen adequacy. Manual compression was applied after the procedure to achieve haemostasis. Ultrasound-guided FNAC was performed using standard fine needles, with direct smears prepared for all cases and cell-block material obtained from selected cystic lesions. Core specimens were fixed in neutral-buffered formalin, while cytology smears were processed according to each laboratory's standard protocol. Immunohistochemistry and other ancillary studies were performed on core specimens when considered necessary by the reporting pathologist.

Definitions and outcomes

The primary outcomes were specimen adequacy and documented procedure-related complications. Core biopsy specimens were considered adequate when they contained representative tissue sufficient for histological interpretation and diagnosis. Specimens containing only non-representative tissue, such as fibrosis without thyroid parenchyma, were classified as inadequate or non-diagnostic. FNAC adequacy was assessed according to the Bethesda System for Reporting Thyroid Cytopathology, with Bethesda categories II–VI regarded as adequate and category I (non-diagnostic/unsatisfactory) classified as inadequate [3]. Secondary outcomes included the final diagnostic category assigned to each specimen—benign, malignant, suspicious, indeterminate (atypia/follicular lesion requiring excision), or non-diagnostic—and, for FNAC, the corresponding Bethesda category. Complications included any adverse event documented in the procedure report or request record.

Statistical analysis

Categorical variables are presented as counts and percentages with 95% Wilson score confidence intervals. Continuous variables are summarised as mean (standard deviation) and median (range). Group proportions were compared using Fisher's exact test, and continuous variables using Welch's t-test. All statistical tests were two-sided, with p < 0.05 considered statistically significant. As CNB and FNAC were performed in largely different patient groups, comparisons are descriptive and should be interpreted cautiously. Statistical analyses were performed in Python using the pandas and SciPy libraries. Owing to the small sample size, selection differences between groups, and the absence of surgical confirmation as a reference standard, neither multivariable analysis nor estimates of diagnostic accuracy (sensitivity and specificity) were undertaken.

Cohort characteristics

A total of 60 ultrasound-guided thyroid procedures were analysed, comprising 22 core (trucut) biopsies and 38 FNAC specimens. Most patients were female (50/60, 83%), giving a female-to-male ratio of 5:1. The mean age was 43.8 years (range 4–81). The two groups differed substantially at baseline. Patients undergoing core biopsy were older than those undergoing FNAC (mean age 54.7 vs 37.5 years; p < 0.001) and were typically referred for clinically suspicious, rapidly enlarging, or aggressive-appearing lesions. In contrast, the FNAC group was younger and consisted predominantly of patients with benign nodular goitre. Sex distribution did not differ significantly between the groups (p = 1.0). Baseline characteristics are summarised in Table 1.

Table 1. Baseline characteristics of the core-biopsy and FNAC groups. SD, standard deviation; FNAC, fine-needle aspiration cytology. The significant age difference reflects operator selection of older patients with suspicious disease for core biopsy.

Specimen adequacy

Core biopsy provided an adequate, interpretable specimen in 21 of 22 cases (95.5%; 95% CI 78–99). FNAC was adequate (Bethesda II–VI) in 34 of 38 cases (89.5%; 95% CI 76–96). Although adequacy was higher with core biopsy, the difference was not statistically significant (p = 0.64), reflecting the small sample size. The causes of inadequate sampling differed between the two techniques. All four non-diagnostic FNAC specimens (Bethesda I) were obtained from cystic or fluid-filled lesions and contained acellular or sparsely cellular material. The single inadequate core biopsy contained only post-aspiration fibrocollagenous tissue without residual thyroid parenchyma. Specimen adequacy and diagnostic category distributions are summarised in Table 2.

Table 2. Specimen adequacy and final diagnostic category by technique. FNAC categories map to the Bethesda System; 'indeterminate' for FNAC corresponds to Bethesda III (AUS/FLUS). The core-biopsy caseload was enriched for malignancy by referral selection and is not directly comparable to the FNAC caseload.

Diagnostic yield and the role of core histology

The principal advantage of core biopsy in this series was not a higher specimen adequacy rate but the diagnostic information it provided. Twelve of 22 core biopsies (54.5%) established a definitive malignant diagnosis, with many representing tumour types for which FNAC has recognised limitations. These included diffuse large B-cell lymphoma (n = 4), anaplastic/undifferentiated carcinoma (n = 2), medullary carcinoma (n = 2, including one nodal metastasis), squamous cell carcinoma, metastatic carcinoma, and poorly differentiated carcinoma. Immunohistochemistry was performed in 19 of 22 core specimens and was essential for tumour classification, including CD20, Ki-67, and Bcl-2 staining for lymphoma, and calcitonin and chromogranin for medullary carcinoma. In one case, core biopsy established a definitive diagnosis of lymphoma after a previous FNAC had been reported as atypical/non-diagnostic.

The FNAC cohort reflected routine evaluation of thyroid nodules. Twenty-six of 38 aspirates (68.4%) were benign colloid or adenomatous nodules (Bethesda II), five were classified as AUS/FLUS (Bethesda III), two were suspicious for malignancy (Bethesda V), and four were non-diagnostic (Bethesda I). No FNAC specimen was reported as malignant (Bethesda VI) or follicular neoplasm (Bethesda IV). The Bethesda category distribution is presented in Table 3.

Table 3. Distribution of FNAC results by Bethesda category. AUS/FLUS, atypia of undetermined significance / follicular lesion of undetermined significance. Later specimens were reported under the 2023 Bethesda revision; numbering is unchanged.

Complications

Documented complications were uncommon, minor, and self-limiting in both groups. Three of 22 core biopsies (13.6%) were associated with a recorded complication: two small contained haematomas (one accompanied by pain and the other by swelling) and one episode of procedural pain. Four of 38 FNAC procedures (10.5%) had a recorded complication, including pain in two cases, pain with swelling in one, and a small haematoma in one. No major complications, including airway compromise, major haemorrhage, nerve injury, or infection requiring hospital admission, occurred with either technique. The difference in complication rates between the two groups was not statistically significant (p = 0.70). Details of the recorded complications are summarised in Table 4.

Table 4. Documented complications by technique (p = 0.70, Fisher exact). *Pain and swelling co-occurred with haematoma in some cases; counts reflect individual symptoms recorded, so category totals may exceed the number of affected patients. All events were minor and managed conservatively.

This single-centre study found ultrasound-guided core-needle biopsy of the thyroid to be both feasible and safe. Specimen adequacy was high (95.5%), and all recorded complications were minor and self-limiting, with no significant difference from FNAC. These findings are consistent with published data showing high adequacy rates, non-diagnostic rates of 1–7% in experienced hands, and low complication rates (0–4.1%), with major complications reported in only 0–1.9% of cases and small haematomas accounting for most adverse events [2,4,5]. The single inadequate core biopsy in this series contained only post-aspiration fibrotic tissue without thyroid parenchyma, a recognised sampling failure in previously biopsied fibrotic nodules rather than an inherent limitation of the technique [2,4].

The main value of core biopsy in this series lay in the diagnoses it enabled rather than in specimen adequacy alone. Most malignant lesions diagnosed by CNB were tumour types in which histology and immunohistochemistry are essential, including lymphoma, anaplastic carcinoma, and medullary carcinoma. Current international recommendations support the use of CNB as an alternative or adjunct to FNAC in these settings [2,6]. Thyroid lymphoma and anaplastic carcinoma often present as rapidly enlarging neck masses in older patients, require markedly different treatment strategies, and can be difficult to distinguish on cytology alone. Previous studies have shown that CNB can reduce unnecessary diagnostic surgery in such cases [2]. The older age and more suspicious clinical features of the CNB group in this study reflect deliberate case selection, with CNB used as a targeted diagnostic tool rather than a routine first-line investigation.

FNAC fulfilled its expected role by providing a rapid and reliable diagnosis in the majority of patients with benign colloid nodular disease. The principal cause of non-diagnostic FNAC results was aspiration of predominantly cystic lesions, a well-recognised limitation of the technique rather than an indicator of operator performance [1,3]. Together, these findings support current recommendations that CNB should complement rather than replace FNAC, particularly for nodules with previous inconclusive cytology, heavily calcified lesions, and suspected uncommon thyroid malignancies [2,4,6].

The overall conclusiveness rates observed in this study (73% for CNB and 76% for FNAC) should be interpreted with caution because the two techniques were applied to different patient populations. Meta-analyses from the Korean Society of Thyroid Radiology (KSThR), demonstrating lower non-diagnostic and inconclusive rates and higher pooled sensitivity for CNB, are based largely on paired or matched study designs that minimise differences in lesion characteristics [2,5]. Our retrospective, selection-based comparison does not permit the same inference, and no claim of diagnostic superiority is made on the basis of specimen adequacy alone.

Limitations

This study has several limitations. The sample size was small (22 CNB and 38 FNAC cases), limiting statistical power. None of the between-group comparisons reached statistical significance, and the findings should be regarded as descriptive and hypothesis-generating. More importantly, the CNB and FNAC groups were not paired. The two techniques were applied to largely different patient populations, with significant differences in age and, by design, clinical presentation. Consequently, direct comparisons of diagnostic performance are not appropriate. Surgical or long-term clinical confirmation was unavailable for most cases, preventing calculation of sensitivity, specificity, and diagnostic accuracy; specimen adequacy and procedural complications were therefore selected as the primary outcome measures. As a retrospective study based on issued reports, complication rates depended on documented events and likely underestimate minor transient complications. Histopathological reporting was performed by two laboratories, and later cases were classified according to the updated 2023 Bethesda system, introducing a degree of reporting heterogeneity. Finally, indeterminate core biopsy results, particularly follicular lesions requiring surgical excision, reflect a fundamental limitation shared by CNB and FNAC, as neither technique can distinguish follicular adenoma from follicular carcinoma without assessment of the complete tumour capsule [2].

Implications and future directions

Despite these limitations, the findings have clear clinical relevance. In experienced hands and with continuous ultrasound guidance, thyroid CNB is a safe, high-yield procedure that is most valuable when used selectively for nodules in which FNAC is likely to be inconclusive or when lymphoma, anaplastic carcinoma, or medullary carcinoma is suspected. A prospective, adequately powered study comparing FNAC and CNB in the same nodules, with surgical pathology or robust clinical follow-up as the reference standard, would provide a more reliable assessment of specimen adequacy, inconclusive rates, and diagnostic accuracy. Such a design would also better define the incremental value of CNB for nodules with previous non-diagnostic or AUS/FLUS cytology in this population.

In this single-centre experience, ultrasound-guided core-needle (trucut) biopsy of the thyroid was feasible, well tolerated, and achieved a high specimen adequacy rate. The frequency of minor complications was comparable to FNAC, and no major complications occurred. Its greatest value was in the evaluation of aggressive and uncommon thyroid malignancies, as well as nodules likely to produce inconclusive cytology, where core histology combined with immunohistochemistry provided definitive diagnoses that directly influenced patient management. These findings support current international recommendations that CNB should complement, rather than replace, FNAC. Larger paired studies incorporating surgical confirmation are needed to better define the additional diagnostic value of CNB in this region.

1. Yoon JH, Kim EK, Kwak JY, Moon HJ. Effectiveness and limitations of core needle biopsy in the diagnosis of thyroid nodules: review of current literature. J Pathol Transl Med. 2015;49:230–235.
2. Na DG, Baek JH, Jung SL, et al. Core needle biopsy of the thyroid: 2016 consensus statement and recommendations from Korean Society of Thyroid Radiology. Korean J Radiol. 2017;18:217–237.
3. Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2009;19:1159–1165.
4. Jung CK, Baek JH. Recent advances in core needle biopsy for thyroid nodules. Endocrinol Metab. 2017;32:407–412.
5. Suh CH, Baek JH, Lee JH, et al. The role of core-needle biopsy in the diagnosis of thyroid malignancy in 4580 patients with 4746 thyroid nodules: a systematic review and meta-analysis. Endocrine. 2016;54:315–328.
6. Renshaw AA, Pinnar N. Comparison of thyroid fine-needle aspiration and core needle biopsy. Am J Clin Pathol. 2007;128:370–374.
7. Screaton NJ, Berman LH, Grant JW. US-guided core-needle biopsy of the thyroid gland. Radiology. 2003;226:827–832.
8. Na DG, Kim JH, Sung JY, Kim KS. Core-needle biopsy is more useful than repeat fine-needle aspiration in thyroid nodules read as nondiagnostic or atypia of undetermined significance by the Bethesda system for reporting thyroid cytopathology. Thyroid. 2012;22:468–475.
9. Sung JY, Na DG, Kim KS, Kim JH. Diagnostic accuracy of fine-needle aspiration versus core-needle biopsy for the diagnosis of thyroid malignancy in a clinical cohort. Eur Radiol. 2012;22:1564–1572.
10. Ha EJ, Baek JH, Lee JH, Kim JK. Core needle biopsy could reduce diagnostic surgery in patients with anaplastic thyroid cancer or thyroid lymphoma. Eur Radiol. 2016;26:1031–1036.
11. Ha EJ, Baek JH, Na DG, et al. The role of core needle biopsy and its impact on surgical management in patients with medullary thyroid cancer: clinical experience at 3 medical institutions. AJNR Am J Neuroradiol. 2015;36:1512–1517.
12. Jung CK, Min HS, Park HJ, et al. Pathology reporting of thyroid core needle biopsy: a proposal. J Pathol Transl Med. 2015;49:288–299.