Should we perform fine needle aspiration cytology of subcentimetre thyroid nodules? A retrospective review of local practice

Introduction

Thyroid nodules are ubiquitous with an incidence of almost 70% in adults. Although thyroid malignancy is relatively rare with a 5–10% risk in clinically detected nodules,^1,2 a review article by Pellegriti et al. ³ has revealed that the incidence of thyroid cancer has increased across all tumour sizes and stages. Approximately 50% of the increase in incidence of thyroid cancer in the USA from 1992 to 1995 is attributed to tumour detected within subcentimetre nodules (≤1 cm). ⁴

Although fine needle aspiration cytology (FNAC) is the cornerstone of thyroid nodule evaluation, there is still much controversy about its clinical value and diagnostic accuracy in subcentimetre nodules. The current American Thyroid Association (ATA) guidelines of 2015 do not recommend routine FNAC for subcentimetre nodules (<1 cm) due to their low risk of malignancy and high rate of non-diagnostic FNAC. ² The British Thyroid Association (BTA) guidelines of 2014 recommend that small (<1 cm) nodules be subjected to FNAC in the following clinical scenarios: extrathyroidal extension and associated metastatic lymphadenopathy, high-risk clinical history. ⁵ In spite of higher non-diagnostic results, a Korean study by Bo et al. ⁶ revealed significantly higher malignancy rate in subcentimetre nodules (6.9% versus 2.9%, p < 0.001).

In light of the rising rate of incidentally detected subcentimetre thyroid nodules due to improved surveillance and diagnostic imaging, the decision of whether to perform FNAC is increasingly pertinent.

Aim

Our aim was to assess amongst subcentimetre thyroid nodules: (1) the rate of sampling adequacy (i.e. non-diagnostic) of ultrasound (US)-guided FNAC, (2) the malignancy rate, (3) the thyroidectomy rate and (4) the correlation of histological findings with initial cytology in patients with Bethesda IV–VI diagnoses (diagnostic accuracy).

Methods and materials

This retrospective study was approved by our Institutional Review Board, with waiver of informed consent from our patients.

A total of 245 subcentimetre nodules in 220 patients underwent FNAC between December 2011 and December 2014. The nodule size was defined according to the largest diameter on US. Based on 2015 ATA guidelines, ² those nodules demonstrating suspicious sonographic features were recommended for FNAC by the reporting radiologists. The medical records of the identified patients were reviewed for retrieval of the following data: cytology results, subsequent management and histopathological results in the event the patient underwent thyroidectomy (total or hemi).

Cytopathological evaluation was based on the Bethesda System for Reporting Thyroid Cytology, stratifying the results according to risk of malignancy. Sampling adequacy was calculated as the percentage of diagnostic results (Bethesda II–VI). Malignancy rate was defined as the percentage of Bethesda IV–VI diagnoses, as the established risk of malignancy in these groups ranges from 15 to 99% with concomitant recommendation of surgical intervention. ⁷

For patients with Bethesda IV–VI cytological results, their follow-up management was reviewed for subsequent surgical excision. In cases where the patient underwent thyroidectomy, their pre-operative cytological results were correlated with the post-operative histopathological findings to determine the diagnostic accuracy of FNAC.

Results

Of 220 patients, 186 were female (84.5%) and 34 were male (15.5%). The mean age was 57 years (range 15–84).

Malignancy rate

The distribution of cytological diagnosis as classified by the Bethesda system is shown in Table 1. Malignancy rate (Bethesda IV–VI) was 9.7%. The respective malignancy rates in the < 5 mm nodule group and ≥ 5 mm nodule group were 6.67 and 10.0%.

OPEN IN VIEWER

Table 1.

FNAC results of 245 subcentimetre nodules classified by Bethesda score.

Bethesda classification	Number of nodules (%)
I. Non-diagnostic	56 (22.9)
II. Benign	162 (66.1)
III. Atypical	3 (1.2)
IV. Suspicious for follicular neoplasm	3 (1.2)
V. Suspicious for malignancy	6 (2.4)
VI. Malignant	15 (6.1)

FNAC: fine needle aspiration cytology.

Rates of thyroidectomy

The percentage and number of nodules in each Bethesda category that were surgically excised are presented in Table 2. In total, 79.2% (19/24) of the malignant (Bethesda IV–VI) nodules underwent surgical excision during the study period. Amongst the remaining five patients, two were lost to follow-up whilst the other three were not keen for surgery and subsequently also defaulted follow-up. This was in spite of multiple attempts to recall these patients for clinic consults. A total of 19 nodules in 19 patients were operated. The average age of these patients was 52 years (range 20–71, SD 11.9).

OPEN IN VIEWER

Table 2.

Rates of surgery.

Bethesda score	Number of nodules (%)
I	9/56 (16.1)
II	15/162 (9.3)
III	1/3 (33.3)
IV	2/3 (66.7)
V	5/6 (83.3)
VI	12/15 (80.0)

In Bethesda I–III groups, 11.3% (25/221) of the nodules were treated with thyroidectomy or hemithyroidectomy for various indications including multinodular goitre and/or symptomatic goitre, and the rest due to history of prior thyroidectomy. Interestingly, 40% of these excised cases had papillary thyroid carcinoma/microcarcinoma on histology. However, the histology may not correspond to the nodule that was initially sampled with FNAC (i.e. incidentally detected malignant nodule on surgical specimen).

Diagnostic accuracy of Bethesda IV–VI nodules

The distribution of pathological diagnoses amongst patients who underwent surgical excision of thyroid nodules (total or hemithyroidectomy) is presented in Table 3. Amongst the operated subcentimetre nodules with cytological diagnoses of Bethesda IV–VI, 84.2% (16/19) had definitive malignant histology. Five of these patients demonstrated multifocal carcinoma and/or extrathyroidal extension of carcinoma on histology. Initial cytological and subsequent histopathological diagnoses matched in all cases except for three whom had false-positive cytological results.

OPEN IN VIEWER

Table 3.

Post-operative histology of 18 patients with Bethesda IV–VI subcentimetre nodules.

Histopathological diagnosis	No. (%)
Papillary thyroid microcarcinoma	16 (88.9)
Nodular goitre	2 (11.1)

Compared to the nodules ≥ 5 mm, nodules < 5 mm had lower rates in both diagnostic yield of FNAC (66.7% versus 77.8%) and malignancy rate. The group of nodules < 5 mm is a small subset, limiting the validity of statistical comparison. In spite of this, the risk of inadequate cytology, additional costs and resources challenge the clinical value of FNAC.

Discussion

Our institution’s rate of sampling inadequacy in the group of subcentimetre nodules is 22.9% compared to 10% amongst all nodules regardless of size. It largely reflects the technical difficulties in accurately targeting smaller nodules, as highlighted by Leenhardt et al. ⁸ This is comparable to published rates ranging from 16.6 to 24.3%.^9–11

Interestingly, the malignancy rate in subcentimetre nodules is higher (9.7%) than that of all thyroid nodules regardless of size (7.0%). The studies by Bo et al. ⁶ and Berker et al. ⁹ showed similar trend of higher malignancy rate in subcentimetre nodules compared to nodules sized 1 cm or more with statistically significant difference. In our centre, we postulate that this stems from a relatively higher threshold to proceed with FNAC of subcentimetre nodules.

The emergence of thyroid microcarcinoma raises the question of thyroidectomy versus US surveillance in our management strategy. Although papillary thyroid microcarcinoma (PTMC) without extrathyroidal extension or metastatic lymphadenopathy can be observed without emergent surgery, there is no way to confidently predict which tumour may be the precursor to a more aggressive process. Guidelines, including those from the ATA, BTA, Korean Thyroid Association and National Comprehensive Cancer Network, are controversial regarding the management of PTMC. Older studies by Ito and co-workers^12–15 have suggested that microcarcinomas generally demonstrate an indolent nature and that immediate surgery is not mandatory. More recently, Ito et al. ¹⁶ and Oda et al. ¹⁷ recommend active surveillance in low-risk PTMC, based on similarly excellent oncological outcomes and the potential complications of surgery. In our series, we observed that majority (76.6%) of patients with Bethesda IV–VI nodules underwent surgery, notwithstanding the current guidelines ² and expert consensus ¹⁸ not recommending aggressive treatment of subcentimetre nodules. Similar to previous reports,^12,13 we observed that patient’s preference was a significant contributory factor in their decision to undergo definitive surgery even when offered observation without intervention.

The surgically excised thyroid nodules demonstrated a strong concordance between their FNAC findings and pathological diagnoses, with 84.2% (16/19) of them proving to be malignant on histopathology. Three patients had discordant cytological and histopathological results (false-positive cytology). Two of them had Bethesda IV cytology results suspicious for follicular neoplasm. Their surgical histopathology revealed follicular adenoma. This is a recognised grey zone in FNAC diagnosis of ‘follicular neoplasm’ with majority being benign. ¹⁹ The third patient is a 61-year-old male who had positive cytology findings of ‘follicular cells with nuclear grooves and intranuclear pseudoinclusions’ suggestive of papillary thyroid carcinoma (Bethesda V). He underwent left hemithyroidectomy with left tracheoesophageal groove clearance. His surgical histopathology revealed lymphocytic thyroiditis with focal Hurthle cell change. It is not an unexpected diagnostic challenge. The reactive nuclear changes observed in follicular cell or Hurthle cell groups infiltrated by lymphocytes can mimic papillary thyroid carcinoma. ²⁰

Amongst our patients, papillary thyroid carcinoma was not associated with any mortality during our study period in spite of nearly one-third of them proving to be aggressive on histopathology (multifocal nodules, extrathyroidal invasion or nodal disease). They were followed up with radioactive iodine uptake scan.

The limitations of this retrospective study are the variability in sonographic technique, reporting radiologist’s threshold to refer for FNAC, interventional radiologist’s experience, FNAC techniques (use of 21G/23G needles or 21G Surecut needle) and presence/absence of on-site cytotechnician.

Contrary to the ATA guidelines, we note that in our local practice, the FNAC results of the subcentimetre nodules appear to heavily influence the clinical management of this patient group. This is reflected by the high surgical rate in Bethesda category IV–VI subcentimetre nodules, which may be contributed by patient’s preference. Ito et al. ²¹ have shown that although sonographically suspicious subcentimetre thyroid nodule without evidence of extrathyroidal extension or sonographically suspicious lymph nodes may be observed with close sonographic follow-up of the nodule and cervical lymph nodes rather than pursuing immediate FNA, patient’s age and preference may modify decision-making. The costs and implications of prolonged surveillance for PTMC in comparison to initial thyroidectomy are being assessed at our centre.

Conclusion

Despite the relatively lower diagnostic accuracy of FNAC in subcentimetre thyroid nodules, it appears to remain relevant in our local clinical practice by influencing the subsequent management of patients with suspicious cytology results.