Should we perform fine needle aspiration cytology of subcentimetre thyroid nodules? A retrospective review of local practice
Show less
Jasmine ME Chua, Jonathan YM Tang, Desmond SW Lim, Nanda Venkatanarasimha, Sivanathan Chandramohan, Chow Wei Too, Sarat K Sanamandra, Parag R Salkade, Bien Soo Tan, Karthikeyan DamodharanFirst Published January 9, 2019 Research Article
https://doi.org/10.1177/1742271X18820556
Article information
Article has an altmetric score of 6 Free Access
Abstract
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 fine needle aspiration cytology is increasingly pertinent. We aim to assess (1) the sampling adequacy of fine needle aspiration cytology, (2) malignancy rate, (3) thyroidectomy rate and (4) diagnostic accuracy of fine needle aspiration cytology. A total of 245 subcentimetre nodules in 220 patients underwent fine needle aspiration cytology between 2011 and 2014. Medical records were reviewed for cytology results, subsequent management and histopathological results in the event the patient underwent thyroidectomy. 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. Amongst patients with Bethesda IV–VI diagnoses who underwent thyroidectomy, their cytology reports were correlated with post-operative histopathological findings. The sampling adequacy of fine needle aspiration cytology was 77.1%. 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%. In total, 79.2% (19/24) of the malignant nodules underwent surgical excision. The rest declined surgery and/or were lost to follow-up. Amongst the malignant nodules which were surgically resected, 84.2% (16/19) had definitive malignant histology. Five of these demonstrated multifocal carcinoma and/or extrathyroidal extension of carcinoma on histology. Initial fine needle aspiration cytology and subsequent histopathological diagnoses matched in all cases except for three that had false-positive fine needle aspiration cytology results. Majority of our patients with suspicious cytology results subsequently underwent thyroidectomy, notwithstanding the relatively lower diagnostic accuracy of fine needle aspiration cytology in subcentimetre thyroid nodules.
Keywords Fine needle aspiration cytology, subcentimetre thyroid nodules, ultrasound guided
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).
Sampling adequacy
The FNAC was performed for a total of 245 subcentimetre nodules, of which 77.1% yielded samples that were adequate for diagnosis. Diagnostic cytology findings were recorded more frequently in nodules ≥ 5 mm in size (77.8%, 179/230) compared to nodules < 5 mm (66.7%, 10/15).
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%.
Table
Table 1. FNAC results of 245 subcentimetre nodules classified by Bethesda score.
Table 1. FNAC results of 245 subcentimetre nodules classified by Bethesda score.
View larger version
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).
Table
Table 2. Rates of surgery.
Table 2. Rates of surgery.
View larger version
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.
Table
Table 3. Post-operative histology of 18 patients with Bethesda IV–VI subcentimetre nodules.
Table 3. Post-operative histology of 18 patients with Bethesda IV–VI subcentimetre nodules.
View larger version
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-workers12–15 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 guidelines2 and expert consensus18 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.
Acknowledgements
We are grateful to the interventional radiologists from Singapore General Hospital for performing the thyroid FNAC.
Contributors
JMEC and KD researched literature and conceived the study. JYMT, DSWL and KD designed the audit. JMEC and KD did the data analysis. JMEC wrote the first draft of the manuscript. JMEC, NV, and KD wrote the final version of the manuscript. All authors reviewed and approved the final version of the manuscript.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethics Approval
SingHealth Centralised Institutional Review Board (Institution: SingHealth, reference number: 2014/238/C).
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Guarantor
JMEC.
References
1. Gharib, H, Papini, E, Paschke, R American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. J Endocrinol Invest 2010; 33: 1–50.
Google Scholar | Medline | ISI
2. Haugen, BR, Alexander, EK, Bible, KC 2015 American Thyroid Association Management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016; 26: 1–133.
Google Scholar | Medline | ISI
3. Pellegriti, G, Frasca, F, Regalbuto, C Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol, ▪▪, 2013, pp. 965212–965212.
Google Scholar | Medline
4. Enewold, L, Zhu, K, Ron, E Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev 2009; 18: 784–91.
Google Scholar | Medline | ISI
5. Perros P, Boelaert K, Colley S, et al. British Thyroid Association guidelines for the management of thyroid cancer. Clin Endocrinol 2014, 81: 1–122.
Google Scholar
6. Bo, YH, Ahn, HY, Lee, YH Malignancy rate in sonographically suspicious thyroid nodules of less than a centimeter in size does not decrease with decreasing size. J Korean Med Sci 2011; 26: 237–242.
Google Scholar | Medline
7. Cibas, ES, Ali, SZ. NCI Thyroid FNA State of the Science Conference. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 2009; 132: 658–665.
Google Scholar | Medline | ISI
8. Leenhardt, L, Hejblum, G, Franc, B Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules. J Clin Endocrinol Metab 1999; 84: 24–28.
Google Scholar | Medline
9. Berker, D, Aydin, Y, Ustun, I The value of fine-needle aspiration biopsy in subcentimeter thyroid nodules. Thyroid 2008; 18: 603–608.
Google Scholar | Medline
10. Naïm, C, Karam, R, Eddé, D. Ultrasound-guided fine-needle aspiration biopsy of the thyroid: methods to decrease the rate of unsatisfactory biopsies in the absence of an on-site pathologist. Can Assoc Radiol J 2013; 64: 220–225.
Google Scholar | Medline
11. Moon, HJ, Son, E, Kim, E-K The diagnostic values of ultrasound and ultrasound-guided fine needle aspiration in subcentimeter-sized thyroid nodules. Ann Surg Oncol 2012; 19: 52–59.
Google Scholar | Medline | ISI
12. Ito, Y, Miyauchi, A. Is surgery necessary for papillary thyroid microcarcinomas? Nat Rev Endocrinol 2011; 8: 1–1.
Google Scholar | Medline
13. Ito, Y, Uruno, T, Nakano, K An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003; 13: 381–387.
Google Scholar | Medline | ISI
14. Ito, Y, Miyauchi, A, Inoue, H An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg 2010; 34: 28–35.
Google Scholar | Medline | ISI
15. Ito, Y, Miyauchi, A. Nonoperative management of low-risk differentiated thyroid carcinoma. Curr Opin Oncol 2015; 27: 15–20.
Google Scholar | Medline
16. Ito, Y, Miyauchi, A, Oda, H. Low-risk papillary microcarcinoma of the thyroid: a review of active surveillance trials. Eur J Surg Oncol 2018; 44: 307–315.
Google Scholar | Medline
17. Oda, H, Miyauchi, A, Ito, Y Incidences of unfavorable events in the management of low-risk papillary microcarcinoma of the thyroid by active surveillance versus immediate surgery. Thyroid 2016; 26: 150–155.
Google Scholar | Medline
18. Pacini, F, Schlumberger, M, Dralle, H European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006; 154: 787–803.
Google Scholar | Medline | ISI
19. Baloch, ZW, Fleisher, S, LiVolsi, VA Diagnosis of “follicular neoplasm”: a gray zone in thyroid fine-needle aspiration cytology. Diagn Cytopathol 2002; 26: 41–44.
Google Scholar | Medline | ISI
20. Baloch, ZW, LiVolsi, VA. Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. Am J Clin Pathol 2006; 125: 135–144.
Google Scholar | Medline
21. Ito, Y, Miyauchi, A, Kihara, M Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid 2014; 24: 27–34.
Google Scholar | Medline
Show less
Jasmine ME Chua, Jonathan YM Tang, Desmond SW Lim, Nanda Venkatanarasimha, Sivanathan Chandramohan, Chow Wei Too, Sarat K Sanamandra, Parag R Salkade, Bien Soo Tan, Karthikeyan DamodharanFirst Published January 9, 2019 Research Article
https://doi.org/10.1177/1742271X18820556
Article information
Article has an altmetric score of 6 Free Access
Abstract
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 fine needle aspiration cytology is increasingly pertinent. We aim to assess (1) the sampling adequacy of fine needle aspiration cytology, (2) malignancy rate, (3) thyroidectomy rate and (4) diagnostic accuracy of fine needle aspiration cytology. A total of 245 subcentimetre nodules in 220 patients underwent fine needle aspiration cytology between 2011 and 2014. Medical records were reviewed for cytology results, subsequent management and histopathological results in the event the patient underwent thyroidectomy. 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. Amongst patients with Bethesda IV–VI diagnoses who underwent thyroidectomy, their cytology reports were correlated with post-operative histopathological findings. The sampling adequacy of fine needle aspiration cytology was 77.1%. 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%. In total, 79.2% (19/24) of the malignant nodules underwent surgical excision. The rest declined surgery and/or were lost to follow-up. Amongst the malignant nodules which were surgically resected, 84.2% (16/19) had definitive malignant histology. Five of these demonstrated multifocal carcinoma and/or extrathyroidal extension of carcinoma on histology. Initial fine needle aspiration cytology and subsequent histopathological diagnoses matched in all cases except for three that had false-positive fine needle aspiration cytology results. Majority of our patients with suspicious cytology results subsequently underwent thyroidectomy, notwithstanding the relatively lower diagnostic accuracy of fine needle aspiration cytology in subcentimetre thyroid nodules.
Keywords Fine needle aspiration cytology, subcentimetre thyroid nodules, ultrasound guided
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).
Sampling adequacy
The FNAC was performed for a total of 245 subcentimetre nodules, of which 77.1% yielded samples that were adequate for diagnosis. Diagnostic cytology findings were recorded more frequently in nodules ≥ 5 mm in size (77.8%, 179/230) compared to nodules < 5 mm (66.7%, 10/15).
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%.
Table
Table 1. FNAC results of 245 subcentimetre nodules classified by Bethesda score.
Table 1. FNAC results of 245 subcentimetre nodules classified by Bethesda score.
View larger version
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).
Table
Table 2. Rates of surgery.
Table 2. Rates of surgery.
View larger version
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.
Table
Table 3. Post-operative histology of 18 patients with Bethesda IV–VI subcentimetre nodules.
Table 3. Post-operative histology of 18 patients with Bethesda IV–VI subcentimetre nodules.
View larger version
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-workers12–15 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 guidelines2 and expert consensus18 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.
Acknowledgements
We are grateful to the interventional radiologists from Singapore General Hospital for performing the thyroid FNAC.
Contributors
JMEC and KD researched literature and conceived the study. JYMT, DSWL and KD designed the audit. JMEC and KD did the data analysis. JMEC wrote the first draft of the manuscript. JMEC, NV, and KD wrote the final version of the manuscript. All authors reviewed and approved the final version of the manuscript.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethics Approval
SingHealth Centralised Institutional Review Board (Institution: SingHealth, reference number: 2014/238/C).
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Guarantor
JMEC.
References
1. Gharib, H, Papini, E, Paschke, R American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. J Endocrinol Invest 2010; 33: 1–50.
Google Scholar | Medline | ISI
2. Haugen, BR, Alexander, EK, Bible, KC 2015 American Thyroid Association Management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016; 26: 1–133.
Google Scholar | Medline | ISI
3. Pellegriti, G, Frasca, F, Regalbuto, C Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J Cancer Epidemiol, ▪▪, 2013, pp. 965212–965212.
Google Scholar | Medline
4. Enewold, L, Zhu, K, Ron, E Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev 2009; 18: 784–91.
Google Scholar | Medline | ISI
5. Perros P, Boelaert K, Colley S, et al. British Thyroid Association guidelines for the management of thyroid cancer. Clin Endocrinol 2014, 81: 1–122.
Google Scholar
6. Bo, YH, Ahn, HY, Lee, YH Malignancy rate in sonographically suspicious thyroid nodules of less than a centimeter in size does not decrease with decreasing size. J Korean Med Sci 2011; 26: 237–242.
Google Scholar | Medline
7. Cibas, ES, Ali, SZ. NCI Thyroid FNA State of the Science Conference. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 2009; 132: 658–665.
Google Scholar | Medline | ISI
8. Leenhardt, L, Hejblum, G, Franc, B Indications and limits of ultrasound-guided cytology in the management of nonpalpable thyroid nodules. J Clin Endocrinol Metab 1999; 84: 24–28.
Google Scholar | Medline
9. Berker, D, Aydin, Y, Ustun, I The value of fine-needle aspiration biopsy in subcentimeter thyroid nodules. Thyroid 2008; 18: 603–608.
Google Scholar | Medline
10. Naïm, C, Karam, R, Eddé, D. Ultrasound-guided fine-needle aspiration biopsy of the thyroid: methods to decrease the rate of unsatisfactory biopsies in the absence of an on-site pathologist. Can Assoc Radiol J 2013; 64: 220–225.
Google Scholar | Medline
11. Moon, HJ, Son, E, Kim, E-K The diagnostic values of ultrasound and ultrasound-guided fine needle aspiration in subcentimeter-sized thyroid nodules. Ann Surg Oncol 2012; 19: 52–59.
Google Scholar | Medline | ISI
12. Ito, Y, Miyauchi, A. Is surgery necessary for papillary thyroid microcarcinomas? Nat Rev Endocrinol 2011; 8: 1–1.
Google Scholar | Medline
13. Ito, Y, Uruno, T, Nakano, K An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003; 13: 381–387.
Google Scholar | Medline | ISI
14. Ito, Y, Miyauchi, A, Inoue, H An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg 2010; 34: 28–35.
Google Scholar | Medline | ISI
15. Ito, Y, Miyauchi, A. Nonoperative management of low-risk differentiated thyroid carcinoma. Curr Opin Oncol 2015; 27: 15–20.
Google Scholar | Medline
16. Ito, Y, Miyauchi, A, Oda, H. Low-risk papillary microcarcinoma of the thyroid: a review of active surveillance trials. Eur J Surg Oncol 2018; 44: 307–315.
Google Scholar | Medline
17. Oda, H, Miyauchi, A, Ito, Y Incidences of unfavorable events in the management of low-risk papillary microcarcinoma of the thyroid by active surveillance versus immediate surgery. Thyroid 2016; 26: 150–155.
Google Scholar | Medline
18. Pacini, F, Schlumberger, M, Dralle, H European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006; 154: 787–803.
Google Scholar | Medline | ISI
19. Baloch, ZW, Fleisher, S, LiVolsi, VA Diagnosis of “follicular neoplasm”: a gray zone in thyroid fine-needle aspiration cytology. Diagn Cytopathol 2002; 26: 41–44.
Google Scholar | Medline | ISI
20. Baloch, ZW, LiVolsi, VA. Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. Am J Clin Pathol 2006; 125: 135–144.
Google Scholar | Medline
21. Ito, Y, Miyauchi, A, Kihara, M Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid 2014; 24: 27–34.
Google Scholar | Medline
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου