Introduction
Approximately 4000 new thyroid cancer cases are diagnosed annually in the UK.Reference Cancer Research1 The incidence has almost tripled over the last three decades and is projected to rise a further 74 per cent by the year 2035.Reference Cancer Research1 Fine needle aspiration cytology (FNAC) is the mainstay of initial thyroid nodule assessment, owing to its relative speed, ease, and high safety profile. Cytopathological classification follows the Royal College of Pathologists’ thyroid classification (Thy grading 1–5).Reference Cross, Chanda, Giles, Johnson and Poller2 However, FNAC is limited by a significantly high rate of inadequate (13.4 per cent) or indeterminate (15–30 per cent) results.Reference Poller, Doyle, Trimboli and Bongiovanni3, Reference Vignali, Macerola, Poma, Sparavelli and Basolo4 As a result, repeat sampling is often required to inform the multidisciplinary team (MDT) outcome and determine further management.
In December 2022, the National Institute for Health and Care Excellence (NICE) made new recommendations in relation to further investigations following initial FNAC results.5 The change in practice most significantly relates to nodules graded as Thy1 (non-diagnostic) and Thy3a (neoplasm possible, atypical features). Conventionally, Thy1 and Thy3a nodules would typically be reassessed with repeat FNAC. The updated NICE guidelines now recommend that Thy1 nodules undergo further evaluation with ultrasound-guided FNAC with rapid on-site evaluation or core needle biopsy, with progression to diagnostic hemithyroidectomy if the repeat sample is also Thy1.5 Ultrasound-guided core needle biopsy alone is suggested for Thy3a nodules, with consideration for diagnostic hemithyroidectomy or active surveillance if the repeat sample remains Thy3a.5 These recommendations were made based on health economic models and a diagnostic accuracy review, finding that core needle biopsy or FNAC with rapid on-site evaluation is more accurate and less likely to yield unsatisfactory results than a repeat FNAC. The recently published national head and neck cancer multidisciplinary guidelines makes brief mention of the new NICE recommendations, stating that “when a repeat sample is required, the 2022 NICE guidelines advocate core needle biopsy as an alternative to repeat FNAC, particularly for Thy3a lesion,” but does not elaborate further on the change in guidelines or its potential benefit.Reference Homer, Winter, Abbey, Aga, Agrawal and Ap6 Further, the most recent Royal College of Pathologists dataset for histopathological reporting of thyroid cancer recommends against using core needle biopsy as a substitute for FNA as the first line investigation for thyroid nodules, but outlines specific clinical scenarios where it can be beneficial.Reference Poller, Johnson, Moonim and Smart7
Since introduction of the updated NICE guidance, our UK-based head and neck tertiary centre has implemented the recommended changes with the use of core needle biopsy for further thyroid nodule assessment. The aim of this study was to evaluate the role of core needle biopsy in the assessment of thyroid nodules and its benefit in the diagnostic pathway. We aimed to determine if core needle biopsy was effective in providing more clinically definitive results than initial FNAC and reducing the need for diagnostic hemithyroidectomy.
Materials and methods
The National Health Service (NHS) Research Ethics Committee tool provided by the Medical Research Council deemed that ethics was not required for this study. This study was conducted at the University Hospitals Coventry and Warwickshire NHS Trust, a large tertiary head and neck centre based in the UK. Patients aged 18 years and above referred with thyroid nodules to the host institution’s thyroid multidisciplinary team (MDT) assessed with core needle biopsy between 1 January 2023 and 27April 2024 were screened for inclusion. Patients who did not undergo initial FNAC but proceeded directly to core needle biopsy based on high clinical and radiological suspicion of malignancy (undifferentiated thyroid cancer or lymphoma) were excluded from final analysis. Data collection was performed retrospectively using electronic patient records, MDT outcomes, and pathology reports. This included patient age and sex, initial FNAC results, Thy grading (and results of repeated FNAC prior to core needle biopsy where applicable), core needle biopsy results, MDT outcomes, progress to diagnostic hemithyroidectomy, and final diagnosis. Specific dates for each stage in the diagnostic pathway were also documented to determine timing between initial FNAC and each stage in the diagnostic pathway.
Results and analysis
Fifty-three patients underwent core needle biopsy as part of their diagnostic workup at the host institution’s thyroid MDT within the specified timeframe. Three patients were excluded from final analysis having not had FNA prior to core needle biopsy; two patients were diagnosed with high-grade non-Hodgkin’s lymphoma and one patient with anaplastic thyroid carcinoma, leaving 50 patients eligible for analysis. In this cohort, there were 37 females and 13 males, and the median age was 55.5 years.
The majority of initial FNAC results were reported as Thy1 (n = 25, 50.0 per cent), followed by Thy3a (n = 21, 42.0 per cent), and the remainder Thy2 (n = 3) and one Thy3f (Figure 1). Of the 50 patients, 15 had two FNAs prior to core needle biopsy (see Table 1 for comparison of first and second FNAC results).
Initial FNAC results according to Thy grading.
Cases where FNAC repeated before proceeding to core needle biopsy
Core needle biopsy results are outlined in Figure 2. Most core biopsies were reported as follicular patterned lesions of undetermined significance (n = 41). This category included all core needle biopsies where reporting indicated that benign pathology was suspected (e.g. thyroid follicular nodular disease), but benign or malignant follicular neoplasia (follicular adenoma or follicular carcinoma) could not be fully excluded. A definitive diagnosis of malignancy was made in three core biopsies, two of which were medullary thyroid carcinomas and one case of B cell non-Hodgkin’s lymphoma. Two core needle biopsies were reported as suspicious for malignancy (papillary lesion and epithelial tumour suspicious for carcinoma). Three samples were non-diagnostic due to insufficient sampling and in one case no sample was obtained as the core needle biopsy was not tolerated by the patient.
Summary of core needle biopsy results as per histopathology reporting.
Figure 3 shows the same core needle biopsy results in conjunction with concurrent Thy grading from initial FNACs. Of those reported as follicular patterned lesions of undetermined significance, 18 initial FNACs were graded Thy1 and 20 were graded Thy3a. A further three were graded as Thy2 but were deemed as requiring further assessment by the MDT. The three malignant cases were initially graded as Thy1 (B cell non-Hodgkin’s lymphoma), Thy3a and Thy3f (both medullary thyroid carcinomas). The two samples reported as suspicious for malignancy were initially graded Thy1, as were the remaining three insufficient samples and one sample in which core needle biopsy was not tolerated.
Core needle biopsy results in conjunction with initial FNAC Thy grading.
Most patients were subsequently offered a diagnostic hemithyroidectomy (n = 39, 79.6 per cent). This is summarised in Table 2, which also details the outcome regarding diagnostic hemithyroidectomy alongside initial FNAC results. Table 2 shows that 76.0 per cent initially graded Thy1 nodules and 85.7 per cent (18 of 21) initially graded Thy3a nodules proceeded to being offered diagnostic hemithyroidectomy following FNAC and core needle biopsy, with an overall total of 79.6 per cent.
Summary of cases offered diagnostic hemithyroidectomy after core needle biopsy with initial FNAC results
The average time in cumulative days between initial FNAC (day zero) and key stages in the diagnostic pathway leading up to diagnostic hemithyroidectomy is represented in Figure 4. There was an average of approximately 40 days (22.9–63.0) between MDT decision to perform core needle biopsy and decision to offer diagnostic hemithyroidectomy.
Timeline showing average cumulative days from initial FNAC to diagnostic hemithyroidectomy.
Discussion
Ultrasound-guided FNAC is the preferred first line investigation for thyroid nodules, owing to its relative ease, speed, low-cost and high safety profile. However, the main limitation of FNAC is its high rate of non-diagnostic and indeterminate results, 13.4 per cent and 15–30 per cent respectively.Reference Poller, Doyle, Trimboli and Bongiovanni3, Reference Vignali, Macerola, Poma, Sparavelli and Basolo4 NICE recently updated guidelines favouring core needle biopsy to conventional repeat FNAC for Thy1 and Thy3a nodules, based on a diagnostic clinical review concluding that core needle biopsy is more accurate and associated with a lower rate of unsatisfactory results.5
It should be emphasised that thyroid MDT decision-making is complex, considering the overall clinical assessment, radiological findings, and histopathological reporting concurrently, rather than any single investigation or tissue sampling in isolation. However, consideration must be given as to whether repeat sampling with core needle biopsy is more meaningful in the pursuit of diagnosis compared to conventional repeat FNAC. The new NICE guideline acknowledges that the recommendation to offer core needle biopsy after Thy1 and Thy3a cytology is a significant change from current practice.5 However, the guideline also states that following adequate training and implementation, it would reduce unnecessary diagnostic surgeries and improve efficiency.5 This implies that fewer patients would require diagnostic hemithyroidectomy and infers that core needle biopsy is more likely to provide a definitive diagnosis than repeat FNACs.
In the current study, most patients were offered diagnostic hemithyroidectomy following core needle biopsy (n = 39, 79.6 per cent) (Table 2), indicating that core needle biopsy did not sufficiently negate the need for diagnostic surgery in most cases. Our data indicate that patients initially graded as Thy1 or Thy3a had a high likelihood of being offered diagnostic hemithyroidectomy despite repeat sampling with core needle biopsy, with a rate of 76.0 per cent and 85.7 per cent, respectively. Further, an approximate average of 40 days was added to the diagnostic pathway between the MDT decision to perform core needle biopsy and the decision to undertake diagnostic hemithyroidectomy, representing a potentially significant delay in achieving definitive diagnosis (Figure 4).
Previous reports have shown core needle biopsy to increase diagnostic accuracy and effectively reduce the rate of non-diagnostic results for thyroid nodules with initially indeterminate FNAC.Reference Su, Yue, Yang and Ma8–Reference Yoon, Kwaik, Moon and Kim11 A comparative analysis of 471 patients with initially inconclusive FNAC, compared 242 core needle biopsies to 229 repeat FNACs.Reference Su, Yue, Yang and Ma8 The study reported that for nodules measuring between 5 and 20 mm, core needle biopsy resulted in a significantly higher rate of diagnosis (70.7 per cent vs 35.8 per cent, p < 0.001). Additionally, a retrospective study including 195 core needle biopsies in 178 patients reported definitive diagnosis in 91.7 per cent of nodules.Reference Cortazar-Garcia, Martin-Escalante, Robles-Cabeza and Martinez-Santos9 However, this study included a wide category of cytopathological reporting as diagnostic, including indeterminate results such as follicular proliferation and Hürthle cell proliferation.
Another study involved 235 thyroid nodules (≥ 1 cm) initially diagnosed as atypical/follicular lesions of undetermined significance according to the Bethesda thyroid classification system (equivalent to Thy3a/Thy3f).Reference Joo, Na, Kim and Seo10, Reference Bongiovanni, Spitale, Faquin, Mazzucchelli and Baloch12 All cases subsequently underwent both repeat FNAC and core needle biopsy to allow for diagnostic comparison. The authors determined the need for diagnostic surgery prospectively according to the repeat FNAC and core needle biopsy results and determined that core needle biopsy was superior to repeat FNAC in reducing the need for diagnostic surgery.Reference Joo, Na, Kim and Seo10 A similar study also compared core needle biopsy and repeat FNAC in nodules previously classified as atypical/follicular lesions of undetermined significance but yielded a different conclusion.Reference Yoon, Kwaik, Moon and Kim11 In this study of 149 thyroid nodules, repeat FNAC had significantly higher rates of inconclusive diagnosis compared to core needle biopsy (33.7 per cent vs 11.1 per cent, p = 0.003). However, rates of cytopathologic candidates for diagnostic hemithyroidectomy between repeat FNAC and core needle biopsy did not differ significantly amongst any of the categorised groups.
Whilst core needle biopsy may be more accurate than FNAC, it may still be limited in suitably negating the need for diagnostic hemithyroidectomy when applied pragmatically to MDT practice. Yoon et al. noted that whilst several studies focus on the higher malignancy detection rate and lower rate of inconclusive results of core needle biopsy compared with FNAC, few reported on the effect on clinical decision making with regards to diagnostic surgery.Reference Yoon, Kwaik, Moon and Kim11 Further, not all studies comparing core needle biopsy and repeat FNAC have shown the former to be superior. A retrospective study of 320 thyroid nodules analysed all patients who underwent both FNAC and core needle biopsy for thyroid nodule assessment prior to surgery and concluded core needle biopsy did not show diagnostic superiority compared to FNAC.Reference Shin, Kim, Moon, Yoon, Park and Lee13
In the evidence review attached to the NICE guideline, under the heading of ‘Thy3a – neoplasm possible,’ the following statement was made: For any indeterminate result an additional sample should be offered to establish whether the nodule was malignant or not.14 This statement may be interpreted to suggest that a core needle biopsy is always able to differentiate between benign and malignant pathology. As demonstrated in this study, this level of definitive reporting is often not possible in the majority of initially graded Thy3a nodules (Figure 2). In the current study, whilst histopathological reporting was often able to provide a favoured differential, it could not exclude entirely between completely benign indolent follicular changes and a follicular neoplasia, encompassing the possibility of a malignant follicular carcinoma.
At present, the Royal College of Pathologists have produced detailed guidance on reporting thyroid nodule FNAC specimens, stating that standardised categorical systems for FNA reporting can make the results easier for aspirators to understand, and can suggest therapeutic action.Reference Cross, Chanda, Giles, Johnson and Poller2 This guidance is specific to FNAC reporting only and does not directly encompass reporting of core needle biopsy results. Rather the Royal College of Pathologists dataset for thyroid cancer histopathological reporting recommends the selective use of core needle biopsy in cases of suspected anaplastic carcinoma, lymphoma, and/or metastases.Reference Poller, Johnson, Moonim and Smart7 It highlights the inability of core needle biopsy to differentiate between hyperplastic nodules, follicular adenoma and follicular carcinoma as well as its limitations in smaller, deeper located nodules and the potential for compromising pathological evaluation of subsequently surgically excised specimens.
Further, core needle biopsy remains a more time-consuming investigation than FNAC both in terms of procedure and results interpretation.14 The NICE guideline does acknowledge that this change of practice will involve further training of required pathologists and radiologists but suggests that it will be more cost-effective in the long term.5 In the studied cohort, there was a significant time delay between MDT decision to perform core needle biopsy and a subsequent decision to proceed with diagnostic hemithyroidectomy. On the basis that 79.6 per cent of patients were still offered diagnostic hemithyroidectomy despite having a core needle biopsy, one may argue that the addition of core needle biopsy delayed definitive diagnostic in most patients.
Pitt et al. noted the state of heightened anxiety and fear that patients experience when faced with a diagnosis of an indeterminate thyroid nodule.Reference Pitt, Saucke, Wendt, Schneider, Orne and Macdonald15 In this qualitative study involving structured interviews of 85 participants with a diagnosis of papillary thyroid carcinoma or indeterminate nodules, the prevailing reaction in both subgroups was the strong desire to ‘get it out.’ This study also identified the psychological stress that patients experience whilst waiting for surgery, with some describing this as the most difficult or worst aspect of the process. Thus, any delay in attaining a definitive diagnosis is likely to adversely affect patients’ mental well-being.
On the other hand, the three cases of confirmed malignancy through core needle biopsy in our cohort avoided unnecessary diagnostic surgery. These patients benefited from a fast-track referral to the appropriate speciality for ongoing management. Thus, in instances of biopsy-proven malignancy, core needle biopsy is advantageous compared to repeat FNAC.
Regarding economic impact, a lifetime health economic model comparing cost effectiveness of different diagnostic pathways was used to inform the NICE recommendations.14 The model compared repeat FNAC and selective use of diagnostic hemithyroidectomy with core needle biopsy and selective use of diagnostic hemithyroidectomy for Thy1, Thy3a, and Thy3f populations separately. The analysis found core needle biopsy and selective use of diagnostic hemithyroidectomy to be more cost-effective for Thy1 and Thy3a categories in their simulated population groups. The authors were unable to identify any UK-based studies comparing the cost-effectiveness of core needle biopsy and FNA in the assessment of thyroid nodules to date. However, studies have shown core needle biopsy to be more costly than FNAC in the field of breast oncology,Reference Nagar, Iacco, Riggs, Kestenberg and Keidan16, Reference Vimpeli, Saarenmaa, Huhtala and Soimakallio17 thus the assertion of core needle biopsy being more cost-effective than repeat FNAC in thyroid nodule assessment remains equivocal.
• Recent changes to National Institute for Health and Care Excellence guidelines advocate the use of core needle biopsy in the assessment of thyroid nodules
• Whilst most of the literature suggests that core needle biopsy is more accurate compared to fine needle aspiration cytology, there is little focus on the effect in daily multidisciplinary team practice
• This study aimed to analyse if core needle biopsies effectively informed the thyroid multidisciplinary team in a busy tertiary referral centre and averted the need for diagnostic surgery
• Most patients were still recommended for diagnostic hemithyroidectomy despite undergoing core needle biopsy, potentially delaying definitive diagnosis
• This study highlights the need for further guidance and homogeneity in reporting thyroid nodule core needle biopsies to inform specific multidisciplinary team recommendations
Conclusion
This study highlighted important considerations around the application of core needle biopsy assessment in the thyroid MDT of a busy tertiary head and neck centre. Whereas core needle biopsy is useful in progressing the care of a small cohort of patients who have malignancy confirmed on biopsy, its benefit remains less clear in the majority where the possibility of malignancy cannot be fully excluded. Our local experience suggests there is limited value in offering core needle biopsy in all cases of initially graded Thy3a FNA biopsies and its use should be assessed on a case-by-case basis following MDT consensus. Further UK-based studies assessing the effect of core needle biopsy in thyroid nodule assessment, specifically in relation to diagnostic hemithyroidectomy, will help to establish its use in facilitating decision-making and whether it is justifiably superior to repeat FNAC in pragmatic thyroid MDT practice.
Contribution statement
All listed authors made significant contributions to the content, production, and review of this article.
