Comparative utility of fine-needle aspiration biopsy vs. ultrasound in detecting residual disease after radiofrequency ablation for papillary thyroid microcarcinoma: a retrospective case series

Introduction

Papillary thyroid microcarcinoma (PTMC), defined as a thyroid tumor measuring ≤10 mm, has shown a marked increase in incidence and currently accounts for more than 50% of newly diagnosed thyroid cancers (1). Despite its typically indolent behavior and excellent disease-specific prognosis (2), the optimal management of PTMC remains controversial. Current strategies range from active surveillance to surgical resection, with treatment decisions influenced by patient preference, tumor characteristics, and institutional expertise (3).

In recent years, thermal ablation techniques, particularly radiofrequency ablation (RFA), have emerged as minimally invasive alternatives for selected low-risk PTMC patients (4). RFA induces localized coagulative necrosis, resulting in progressive reduction in tumor volume while preserving the surrounding thyroid parenchyma. Multiple studies have demonstrated that RFA can be a safe and effective treatment option in carefully selected patients with PTMC, with favorable oncologic and functional outcomes (5,6).

Post-RFA surveillance of PTMC is currently based primarily on serial ultrasound examinations, which allow assessment of nodule size, echogenicity, and vascularity (7). Accordingly, major international guidelines, including those from the Korean Society of Thyroid Radiology (KSThR) (8) and the European Thyroid Association (ETA) (9), do not recommend routine biopsy after thermal ablation. This recommendation reflects the well-recognized difficulty of interpreting post-ablation cytology, as thermal injury can induce coagulative necrosis, cellular degeneration, and reparative atypia that may mimic malignancy and lead to false-positive or indeterminate results.

Nevertheless, reliance on imaging alone may be insufficient to identify residual viable tumor in selected cases, particularly when post-ablation changes obscure lesion margins or when tumor regrowth occurs at the periphery of the ablation zone. Histopathologic evaluation using fine-needle aspiration (FNA) or core needle biopsy (CNB) could theoretically provide complementary information, particularly when targeted to biologically relevant regions. However, the use of tissue sampling in the post-RFA setting remains limited. To date, only one study has evaluated CNB after RFA in PTMC, reporting peripheral-zone positivity in a small subset of cases despite imaging response (10). In contrast, no studies have systematically evaluated FNA biopsy (FNAB) for PTMC during post-RFA follow-up, likely due to concerns regarding inadequate cellularity and cytologic artifacts related to thermal injury.

Against this background, the present study explores the feasibility and safety of FNAB as an adjunctive follow-up tool after RFA in patients with low-risk PTMC. Rather than challenging current guideline recommendations, this retrospective case series aims to assess FNAB findings in the post-ablation setting descriptively and to examine their concordance with ultrasound-based surveillance, thereby contributing preliminary data to an area with limited clinical evidence. We present this article in accordance with the CARE and AME Case Series reporting checklists (available at https://aot.amegroups.com/article/view/10.21037/aot-2025-14/rc).

Case presentation

Study design and setting

This study is a retrospective case series conducted at the Instituto de la Tiroides y Enfermedades de Cabeza y Cuello (ITECC), a private referral center in Quito, Ecuador. Consecutive patients treated between May 2021 and December 2023 were reviewed. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics board of the Universidad San Francisco de Quito (No. 161-2023-CA-23030M-CEISH-USFQ). Publication of this case series and accompanying images was waived from patients’ consent according to the ethics board.

Case selection

Eligible cases included adult patients with low-risk PTMC who underwent RFA and completed FNAB at 12 months post-ablation.

Low-risk PTMC was defined as a single intrathyroidal tumor ≤10 mm without ultrasound evidence of capsular infiltration, extrathyroidal extension, or cervical lymph node metastasis. Patients were excluded if they had tumors >10 mm, sonographic features suggestive of capsular or extrathyroidal invasion, nodal disease, incomplete follow-up data, or declined participation.

Preprocedural assessment

All patients underwent comprehensive ultrasound evaluation and routine laboratory testing, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), free thyroxine (fT4), serum thyroglobulin (Tg), anti-Tg antibodies, platelet count, and coagulation profile. Before RFA, each patient had undergone at least two diagnostic FNABs confirming PTMC.

RFA procedure

A single experienced operator performed all RFA procedures in an outpatient setting. A VIVA RF System (STARmed, Korea) with an internally cooled 18-gauge electrode was used under continuous ultrasound guidance with a linear transducer. The moving-shot technique was applied, delivering 20–40 W of power.

Ablation was continued until transient hyperechoic zones replaced the entire nodule on ultrasound. Hydrodissection with cold dextrose solution was routinely employed to separate the target lesion from adjacent critical structures and minimize thermal injury.

Follow-up and surveillance protocol

Post-ablation follow-up included serial ultrasound examinations and laboratory assessment (TSH, Tg, and anti-Tg antibodies) at 1, 3, 6, and 12 months. After 12 months, patients were followed every 6 months for up to 2 years and annually thereafter.

FNAB protocol

All patients underwent scheduled ultrasound-guided FNAB at 12 months post-RFA. FNAB was performed by a single operator (C.G.) using a cito-aspirator and a 20-gauge needle. Samples were systematically obtained from the ablation zone and mapped into central and peripheral regions.

Cytologic specimens were prepared using Papanicolaou and Giemsa staining and interpreted by a single dedicated pathologist (D.O.) according to the Bethesda System for Reporting Thyroid Cytopathology, who was blinded to ultrasound findings.

Outcome measures

The primary outcome was the cytologic classification of FNAB performed 12 months after RFA.

The secondary outcome was tumor volume reduction (VR) over time.

Tumor volume was calculated using ultrasound measurements of three orthogonal diameters and the ellipsoid formula: (length × width × height) × π/6.

Additional descriptive variables included patient demographics, procedural parameters, thyroid function, and procedure-related complications.

Data handling and analysis

Given the descriptive nature of this case series, data were analyzed using descriptive statistics only. Continuous variables are reported as median and interquartile range (IQR) or mean and standard deviation, as appropriate. Categorical variables are presented as counts and percentages. No hypothesis testing or inferential statistical comparisons were performed.

Data availability

The datasets supporting the findings of this study are publicly available at: https://github.com/paosolis/RFA-and-FNAB-in-the-follow-up.git.

Case characteristics

Fifteen consecutive patients with low-risk PTMC were included (Figure 1). Fourteen patients (93.3%) were female. The median age at diagnosis was 44.5 years (standard deviation: 11.2). All patients presented with a single PTMC nodule.

Figure 1 Patients included in the analysis. FNAB, fine needle aspiration biopsy; PTMC, papillary thyroid microcarcinoma.

At baseline, 60.0% (n=9) had a normal body mass index, and 40.0% (n=6) were overweight. A family history of thyroid cancer and active smoking were each reported by 13.3% (n=2). Most patients were euthyroid at baseline (86.7%, n=13). Baseline characteristics are summarized in Table 1.

RFA characteristics

All RFA procedures were performed under local anesthesia and completed in a single session. Median ablation power was 2.50 kJ/mL (IQR: 0.20–21.86 kJ/mL), median energy delivery was 35 W (IQR: 35.0–50.0 W), and median ablation time was 2.32 minutes (IQR: 1.22–15.1 minutes).

Intraoperative tolerance was favorable. Mild transient pain was reported in 16.7% (n=2) of patients, while no complications were observed in the remaining cases (Table 2).

Tumor volume reduction

Baseline mean tumor volume was 0.17±0.15 mL. Progressive volume reduction was observed on serial ultrasound examinations, with volumes of 0.40±0.38 mL at 1 month, 0.09±0.11 mL at 3 months, 0.03±0.06 mL at 6 months, and 0.01±0.03 mL at 12 months.

By 12 months, the median volume reduction exceeded 99%, with near-complete ablation in most cases (Table 3, Figure 2). TSH levels remained stable throughout follow-up, and no recurrent or suspicious cervical lymph nodes were detected.

Figure 2 Papillary thyroid microcarcinoma pre- and post-RFA (1, 3, and 6 months). RFA, radiofrequency ablation.

FNAB findings

All patients underwent FNAB at a mean follow-up of 12 months (range, 9–15 months). Cytologic evaluation demonstrated benign findings (Bethesda II) in 14 cases.

One patient exhibited indeterminate cytology (Bethesda III) despite the absence of suspicious ultrasound features. This patient remains under close surveillance, and the need for further intervention will be determined based on longitudinal imaging and cytologic evolution (Figure 3).

Figure 3 Post-radiofrequency follow-up cytology of thyroid nodules (Papanicolaou stain; ×40). (A) Bethesda II: benign. (B) Bethesda III: atypia of undetermined significance. (C) Bethesda IV: follicular neoplasm. (D) Bethesda V: suspicious for malignancy.

Discussion

In this retrospective case series, we evaluated the feasibility of FNA as an adjunct to post-RFA surveillance in patients with low-risk PTMC. Systematic FNAB sampling of the ablation zone, stratified into central and peripheral regions, was feasible and well tolerated. Nearly complete tumor volume reduction was observed at 12 months, and no suspicious cervical lymph nodes were identified on serial ultrasound. Cytologic evaluation demonstrated benign findings in the majority of cases, while one patient exhibited indeterminate cytology (Bethesda III) on FNAB.

The finding of Bethesda III cytology in a single patient warrants cautious interpretation. Thermal ablation is known to induce coagulative necrosis, inflammatory infiltration, and reparative changes, which may result in nuclear elongation, cytoplasmic vacuolization, and architectural distortion that can mimic malignancy on cytology (11). These post-ablation changes have been widely described as a source of false-positive or indeterminate cytologic results (12). In the present study, molecular testing (e.g., BRAF mutation analysis) was not performed; therefore, the Bethesda III result cannot be interpreted as definitively indicating residual viable carcinoma. This diagnostic ambiguity underscores the principal challenge in applying FNAB in the post-ablation setting and reinforces the need for cautious, context-aware cytologic interpretation. In this study, one patient with Bethesda III did not demonstrate suspicious findings on conventional ultrasound surveillance and therefore did not undergo immediate reintervention. Instead, the patient remains under close clinical, imaging, and cytologic follow-up, with further intervention determined by longitudinal evolution rather than FNAB findings alone.

The biological rationale for mapping FNAB samples into central and peripheral zones deserves particular emphasis (13). The central ablation zone is expected to consist predominantly of necrotic and carbonized tissue, whereas the peripheral margin represents the most plausible site for residual viable tumor cells due to potential heat-sink effects and nonuniform thermal distribution (14). This distinction has been highlighted in a prior study using CNB after RFA (10), where malignant cells were detected almost exclusively in peripheral sampling zones. Our approach was informed by this biological framework, aiming to maximize diagnostic yield while acknowledging the inherent limitations of post-ablation cytology.

Management strategies for PTMC continue to evolve, with increasing emphasis on active surveillance and minimally invasive therapies (15,16). Although active surveillance is endorsed by major guidelines, patient anxiety regarding untreated malignancy remains a significant barrier to its widespread adoption. A systematic review and meta-analysis by Cho et al. (17) reported surgical conversion rates of 8.7% to 32% during active surveillance, compared with only 1.1% following RFA, highlighting the potential role of ablation in reducing the need for surgery in selected patients. Multiple studies have demonstrated that RFA offers favorable oncologic control, preservation of thyroid function, and cosmetic advantages in low-risk PTMC (7,18,19). However, these benefits must be coupled with robust and reliable post-treatment surveillance strategies (20,21).

Currently, ultrasound-based assessment of tumor volume reduction remains the cornerstone of post-RFA monitoring (19). While expert consensus statements, including those from China, have suggested that early biopsy may be useful in selected cases, routine tissue sampling is not widely recommended due to concerns regarding interpretative reliability (22). Yan et al. (10), in a retrospective study of 211 patients with PTMC who underwent RFA, used the CNB at 3 and 6 months post-RFA. A total of 208 were Bethesda II (Bening), and just 3 were positive for malignancy; those patients had additional RFA. Also, the experience of FNAB on laser ablation is reported in two studies. Zhou et al. (23), in a retrospective study of 30 patients with PTMC, reported that FNAB was performed on the ablation area at 1, 6 and 12 months after laser ablation (LA). On the last follow-up, all samples were Bethesda II (Bening). Moreover, Zhang et al. (18), in a retrospective study of 64 low-risk PTMCs, FNAB of the ablated zones demonstrated inflammatory cells, necrotic and carbonized material without viable neoplastic cells (Bethesda II). In this context, our findings align with existing literature while adding novel data on FNAB specifically after RFA.

Finally, from a health economics perspective, the routine incorporation of FNAB into post-RFA surveillance may increase follow-up costs and resource utilization. While FNAB is less costly than surgical intervention or repeat ablation, its routine use may not be cost-effective in patients with an unequivocal imaging response. Formal cost-effectiveness analyses are needed to define its role in post-ablation surveillance algorithms.

Strengths and limitations

This study has several limitations inherent to its retrospective, single-center, case series design. The absence of a control group and the limited sample size preclude causal inference and limit generalizability. The relatively short follow-up period restricts conclusions regarding long-term recurrence. Additionally, the lack of molecular testing limits definitive interpretation of indeterminate cytology.

Despite these limitations, this study has notable strengths. To our knowledge, it represents the first report from Latin America evaluating FNAB as a complementary surveillance tool following RFA for PTMC. All procedures were performed by a single experienced operator using standardized protocols, and cytologic analyses were conducted by a dedicated pathologist blinded to imaging findings. Systematic FNAB at 12 months provided additional descriptive information beyond ultrasound alone and highlighted both the potential value and interpretative challenges of cytology in the post-ablation setting.

Conclusions

FNAB after RFA is feasible and safe, but must be interpreted cautiously due to the well-recognized effects of thermal injury on cytologic morphology. While FNAB may offer complementary information in selected cases, its role in routine post-RFA surveillance remains to be defined. Larger prospective studies incorporating longer follow-up and molecular testing are needed to clarify the clinical utility of FNAB and to refine surveillance strategies after thermal ablation for PTMC.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE and AME Case Series reporting checklists. Available at https://aot.amegroups.com/article/view/10.21037/aot-2025-14/rc

Peer Review File: Available at https://aot.amegroups.com/article/view/10.21037/aot-2025-14/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aot.amegroups.com/article/view/10.21037/aot-2025-14/coif). P.S.P. serves as an unpaid editorial board member of Annals of Thyroid from August 2025 to December 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the ethics board of the Universidad San Francisco de Quito (No. 161-2023-CA-23030M-CEISH-USFQ). Publication of this case series and accompanying images was waived from patients’ consent according to the ethics board.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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