Ann Surg Oncol DOI 10.1245/s10434-013-3365-z
ORIGINAL ARTICLE – ENDOCRINE TUMORS
Clinical Outcomes in Patients with Non-Diagnostic Thyroid Fine Needle Aspiration Cytology: Usefulness of the Thyroid Core Needle Biopsy Sung Hak Lee, MD, PhD1, Min Hee Kim, MD2, Ja Seong Bae, MD, PhD3, Dong Jun Lim, MD, PhD2, So Lyung Jung, MD, PhD4, and Chan Kwon Jung, MD, PhD1 1
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3 Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 4Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea 2
ABSTRACT Background. Patients with non-diagnostic thyroid fine needle aspiration cytology (FNAC) results undergo repeat FNAC or core needle biopsy (CNB) for definite diagnosis or surgical resection, or are followed up by clinical and ultrasound surveillance. We aimed at evaluating the risk of malignancy in patients with non-diagnostic FNACs and their clinical outcomes according to the follow-up modality. Methods. We retrospectively reviewed 1,496 (8.8 %) cases with a non-diagnostic result on a first aspiration among 17,045 thyroid FNACs performed between October 2008 and August 2012. Of the non-diagnostic FNACs, 389 patients underwent a second FNAC; 125, CNB; and 89, thyroidectomy by clinical indication. The remaining patients were clinically followed up. Results. The rate of a second non-diagnostic result was significantly higher on repeat FNAC than on CNB (33.2 vs. 2.4 %; p \ 0.001). There was no significant difference in the malignancy risk among patients initially non-diagnostic, twice non-diagnostic, and thrice or more nondiagnostic, nor did this differ from the rate following CNB. No further malignancy was found in cases with C2 nondiagnostic CNBs. The malignancy risk was 51 % in those who underwent thyroidectomy. The sensitivity for detecting malignancy was 65 and 70 % for repeat FNACs and
Ó Society of Surgical Oncology 2014 First Received: 9 August 2013 C. K. Jung, MD, PhD e-mail: [email protected]
first CNBs, respectively, with no false positives seen in either test. Conclusions. Approximately one-third of repeat FNACs after an initial non-diagnostic aspirate are non-diagnostic on repeat examination, and the malignancy risk may not reduce following repetitively non-diagnostic FNACs. However, a single CNB may be enough to exclude malignancy risk for patients with a non-diagnostic aspirate.
Ultrasound-guided fine needle aspiration cytology (FNAC) is accepted as a cost effective, efficient, and safe method for the initial screening of thyroid nodules.1 The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has a six-tier diagnostic scheme: non-diagnostic or unsatisfactory, benign, atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), suspicious for a follicular neoplasm/follicular neoplasm, suspicious for malignancy, and malignant.2 The non-diagnostic rate for thyroid FNAC is *13.8 %.2–5 In both conventional smear and liquid-based cytology, a thyroid FNAC specimen is considered adequate for evaluation when it contains a minimum of six groups of wellpreserved follicular cells, with at least ten cells/group, preferably on a single slide.6,7 The risk of malignancy after a non-diagnostic FNAC is estimated to be 1.7–6.6 %.8 The recommended clinical management for a case of non-diagnostic aspirate is repeat FNAC with ultrasound guidance, which produces satisfactory results in most cases.6 However, non-diagnostic results are obtained again in as many as 50 % of second repeat FNACs.9,10
S. H. Lee et al.
17,045 thyroid FNACs
ND 1,636 (9.6%)
1,496 Nondiagnostic on 1st FNAC
89 (5.9%) Thyroidectomy • Due to clinical suspicion for a malignancy (63) • Due to other suspicious thyroid lesson (26)
AUS, 4.9% FN/SFN, 0.3% SM, 1.8% M, 3.9% ND, 33.2% Benign, 56.0%
514 (34.4%) Repeat testing
389 (75.7%) 2nd FNACs
893 (59.7%) Clinically benign
125 (24.3%) CNBs
AUS, 4.0% FN/SFN, 8.8% SM, 0.0% M, 5.6% ND, 2.4% Benign, 79.2%
357 final results Refer to Table 1
121 final results Refer to Table 1
FIG. 1 Study design and follow-up results of thyroid nodules with a non-diagnostic aspirate. FNAC fine needle aspiration cytology, CNB core needle biopsy, ND non-diagnostic, AUS atypia of undetermined
significance, FN/SFN follicular neoplasm/suspicious for a follicular neoplasm, SM suspicious for malignancy, M malignancy
Core needle biopsy (CNB) preserves cellular architecture and facilitates precise histopathologic assessment.11 Although concerns of possible complications, patient discomfort, and technical difficulties exist, recent studies have revealed that ultrasound-guided CNB of the thyroid gland is safe.12,13 Furthermore, few studies support the clinical value of CNB in the evaluation of thyroid nodules.13–15 Several studies suggest that ultrasound-guided CNB can reduce the number of non-diagnostic or AUS/FLUS results compared with FNAC, especially in cases of nodules with previous non-diagnostic FNAC readings.14,16 However, whether CNB is valuable in terms of sample and diagnostic accuracy in the evaluation of thyroid nodules remains unclear.14–17 In this study, we investigated the expected risk of malignancy in patients with an initial non-diagnostic thyroid FNAC result according to the follow-up modality in a large series of thyroid FNAC cases. We also evaluated the role of CNB follow-up after an initial non-diagnostic FNAC.
MATERIALS AND METHODS Patients and Study Design From October 2008 to August 2012, 17,045 thyroid FNACs from 12,567 patients from the pathology database at the Catholic University of Korea, Seoul St. Mary’s Hospital, were retrospectively retrieved. Of these, 1,636 (9.6 %) were non-diagnostic, and of which we excluded 140 FNACs that were repeated C2 times (Fig. 1). Therefore, the remaining 1,496 thyroid FNACs non-diagnostic at the first FNAC constituted the study population. The cytopathologic and histologic slides were reviewed by two experienced pathologists (CKJ and SHL). Of the 1,496 cases of thyroid nodules with initial nondiagnostic FNAC results, 514 (34.4 %) underwent repeat testing with FNAC (75.7 %, 389/514) or CNB (24.3 %, 125/514) for definite diagnosis, 89 (5.9 %) were resected instead of repeat testing by clinical indication (clinical suspicion for a malignancy or presence of other suspicious
Outcome of Non-Diagnostic Thyroid Aspirates
thyroid nodule), and 893 were followed up by clinical and ultrasound surveillance (Fig. 1). CNB was preferred for thyroid nodules with macrocalcification or hypervascularity, arousing the concern of repetitively non-diagnostic FNAC results. We retrospectively reviewed ultrasound findings of 514 thyroid nodules in a repeat testing group. The size and location of each thyroid nodule was evaluated by ultrasound imaging. The ultrasound features of internal contents were recorded based on the ratio of the cystic portion to the solid portion of the nodule as solid ([90 %), predominantly solid (50–90 %), predominantly cystic (50–90 %), or cystic ([90 %).18 Calcifications (micro-, macro-, and rim calcifications) known to be associated with non-diagnostic aspiration were also recorded.16,19 A minimum of 12 months of clinical follow-up was available for each case. For malignant cases, the final diagnosis was performed on histopathologic findings with CNB procedures and/or after surgical resection. For benign cases, the final diagnosis was confirmed on histopathologic findings after surgical resection, benign results at FNAC that had been repeated at least twice, or benign ultrasonographic interpretations as remaining stable or decreasing in size at follow-up.16,20,21
gland, as well as tissues containing few follicular cells insufficient for proper diagnosis.15,20 CNB histopathologic diagnoses were categorized into the same six categories as in the TBSRTC used for the thyroid FNAC.
Fine Needle Aspiration Cytology
Of the 514 patients who underwent repeat testing, 405 (78.8 %) were women and 109 (21.2 %) were men. In total, 268 nodules (52.1 %) were located in the right lobe, 225 nodules (43.8 %) in the left lobe, and 21 nodules (4.1 %) in the isthmic portion of the thyroid. There was no difference in the mean patient age between the repeat FNAC (57.3 years; range 22–86 years) and CNB groups (56.9 years; range 18–87 years) (p = 0.751). The mean nodule size in the CNB group was larger than in the repeat FNAC group (15.5 vs. 11.2 mm; p \ 0.001). There was no difference in the portion of nodules with [50 % cystic component between the repeat FNAC and CNB groups (10.8 vs. 5.6 %; p = 0.084). There was also no difference in the portion of nodules with macrocalcification and/or microcalcification between the two groups (42.4 % for FNAC vs. 48.8 % for CNB; p = 0.211).
All FNACs were performed by experienced radiologists under ultrasound guidance and processed using liquidbased preparations (SurePathTM, BD Diagnostics-TriPath, Burlington, NC, USA, or ThinPrepTM, Cytyc Co., Boxborough, MA, USA). For the diagnosis of FNAC specimens, we used Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).2 To be adequate for evaluation, at least six groups of follicular cells were required, with at least ten cells/group. Cases consisting of overwhelmingly cyst contents (macrophages) were classified as a ‘cystic fluid only’ and were included in the nondiagnostic category. Core Needle Biopsy All CNB procedures were performed by three experienced radiologists under ultrasound guidance. A disposable 18-gauge, double-action, spring-activated needle (1.1 or 1.6 cm excursion; TSK Ace-cut; Create Medic, Yokohama, Japan) was used for CNB. After CNB, patients were observed with self-manual compression of the biopsy site for 20–30 min. No major complications related to CNB were noted in any patients. For the purpose of this study, we considered the specimen as non-diagnostic when it had no identifiable thyroid tissue or only a normal thyroid
Statistical Analysis We investigated the diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of repeat FNAC and CNB for diagnosing malignancy. For statistical analysis, we considered non-diagnostic, benign, AUS, and FN/SFN categories as negative results, and suspicious for malignancy and malignant categories as positive results. The 95 % confidence intervals (CI) were calculated using MedCalc (www.medcalc.org). SPSS software (version 21.0, Chicago, IL, USA) was used to perform the Chi square test for comparison and evaluation of variables. Statistical significance was defined by p \ 0.05. RESULTS Characteristics of the Repeat Fine Needle Aspiration Cytology and Core Needle Biopsy Groups
Diagnostic Rate of Repeat Testing The rate of persistent non-diagnosis for thyroid nodules with initially non-diagnostic results on FNAC was significantly higher on repeat FNAC than on CNB (33.2 vs. 2.4 %; p \ 0.001) (Table 1). The diagnostic rate of AUS between the repeat FNAC and CNB groups did not differ significantly (4.9 vs. 4.0 %; p = 0.684). The rate of FN/ SFN was significantly higher on CNB than on repeat FNAC (8.8 vs. 0.3 %; p \ 0.001) (Fig. 1).
S. H. Lee et al. TABLE 1 Final results of the second aspirates and core needle biopsy after an initial non-diagnostic FNAC n (%)
No. of Final results follow-up Benign Malignant
Second FNAC diagnosis Non-diagnostic
129 (33.2) 104
218 (56.0) 218
Suspicious for malignancy 7 (1.8)
CNB diagnosis Non-diagnostic
Suspicious for malignancy 0 Malignancy
follicular variant of papillary carcinoma, all AUS results were benign, and two (25 %) of eight follicular neoplasm results were malignancies (one minimally invasive follicular carcinoma and one follicular variant of papillary carcinoma) (Table 1). The risk of malignancy was 51 % (32/63) for thyroid nodules with an initial non-diagnostic FNAC result that underwent thyroidectomy without repeat testing due to the clinical suspicion of malignancy. The malignancy risk was 7.7 % (2/26) when the non-diagnostic nodules were incidentally resected by surgery for other suspicious thyroid lesions. We subclassified the initially non-diagnostic FNAC specimens into the paucicellular group and cyst fluid-only group (Table 2). The risk of malignancy between these two subgroups did not differ significantly (5.6 vs. 3.2 %) (p = 0.220). Regardless of the number of FNAC repetitions performed, the risk of malignancy between paucicellular and cyst fluid-only FNACs did not differ significantly.
FNAC fine needle aspiration cytology, CNB core needle biopsy, AUS atypia of undetermined significance
Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value for Predicting Malignancy
We further analyzed ultrasonographic findings of 389 nodules with second FNAC results. The non-diagnostic results of second FNAC correlated with the cystic component of nodules (p = 0.001), but were not associated with the size and location of nodules, or the presence of calcification within nodules (p = 0.532, 0.458, and 0.171, respectively).
Repeat FNAC (n = 357) had a sensitivity, specificity, PPV, and NPV of 65 % (95 % CI 45.4–80.8), 100 % (95 % CI 98.9–100), 100 % (95 % CI 83.0–100), and 96.7 % (95 % CI 94.2–98.4), respectively, for predicting malignancy. CNB (n = 121) had a sensitivity, specificity, PPV, and NPV of 70 % (95 % CI 34.8–93.0), 100 % (95 % CI 96.6–100), 100 % (95 % CI 58.9–100), and 97.3 % (95 % CI 92.3–99.4), respectively, for detecting malignancy.
Risk of Malignancy According to the Follow-Up Modality DISCUSSION Final results of the surgical or clinical follow-up were available for 1,460 cases (Table 1). The overall risk of malignancy for an initial non-diagnostic FNAC was 5.3 % (77/1,460). Malignancy was histologically identified in 10.3 % (26/253) and 8.5 % (10/118) of cases after the first repeat FNAC and CNB, respectively (Table 1). The risk of malignancy for persistently non-diagnostic aspirates after second FNAC was 4.8 % (5/104) and was not significantly different from that of the initial non-diagnostic aspirate (p = 0.103) (Table 1). After the second FNAC, 1 (0.5 %) of 218 benign aspirates was diagnosed as minimally invasive follicular carcinoma and 5 (36 %) of 14 cases of AUS results were diagnosed as papillary carcinomas. There were ten malignancies (eight papillary carcinomas, one minimally invasive follicular carcinoma, and one medullary carcinoma) in 121 CNB cases. All repetitively non-diagnostic CNBs were surgically identified as benign. One (1 %) of the 99 benign CNB specimens was a
Sample adequacy of the thyroid FNAC depends on the skill and experience of surgeons and pathologists, sample preparation techniques, and the nature of lesions. The rate of non-diagnostic FNAC specimens in our study was 9.6 %, which is within the 1.8–40.7 % range reported previously (Table 3).4,5,12,16,22–31 Non-diagnostic aspirates are the main factor for false negative results of FNAC in the diagnosis of thyroid malignancy, as non-diagnostic results do not exclude the likelihood of malignancy.32–35 Up to 70.3 % of non-diagnostic FNAC cases undergo a surgical excision, with an average malignancy rate of 27.7 % (range 2.7–51.6 %) (Table 3).4,5,12,16,22–31 In our cohort, the overall risk of malignancy was 5.3 % (77/ 1,460), 8.7 % (3/357), and 4.8 % (5/104) after the first, second, and third or more successive non-diagnostic FNACs, respectively. There was no significant difference in the risk of malignancy between a single non-diagnostic
Outcome of Non-Diagnostic Thyroid Aspirates TABLE 2 Final results of the non-diagnostic aspirates by causable scenarios and number of FNAC repetitions Non-diagnostic Initial non-diagnostic FNACs (n = 1,460)
Third or more non-diagnostic FNACs (n = 104)
Cyst fluid only Total
Second non-diagnostic FNACs (n = 357)
0 5 (4.8)
FNAC fine needle aspiration cytology TABLE 3 Cytohistological correlations on non-diagnostic thyroid FNAC in the literature Authors
Oertel et al.
Histologic follow-up results No. of follow-up among ND
Renshaw and Pinnar
Orija et al.9
Nayar and Ivanovic4
Theoharis et al.29
Jo et al.25
Yoon et al.31
Deandrea et al.23
Kim et al.27 Jo et al.26
Bongiovanni et al.
Bohacek et al.45
Choi et al.22
Na et al.16
Wu et al.30 44
Samir et al.12 24
Hryhorczuk et al.
FNAC fine needle aspiration cytology, ND non-diagnostic, N/A not applicable, CNB core needle biopsy a
Data are based on the final diagnosis from histopathologic findings with CNB procedures and/or after surgical resection, FNAC results that had been repeated at least twice, and benign ultrasonographic interpretations with a stable or decreased size at follow-up of at least 1 year
FNAC and repeat non-diagnostic aspirates. These results agree with those of Jo et al.26 It has been reported that the main cause for a non-diagnostic thyroid FNAC result is that the aspirate arises from a cystic lesion.36,37 Alexander et al.10 revealed that the yield of repeat FNAC decreased with multiple prior non-diagnostic FNACs and [50 % of cystic component was the only predictor of non-diagnostic FNAC. Samir et al.12 also reported that the diagnostic rate of repeat FNAC was proportional to the cystic content in the nodule, although the data in that study was limited in terms of statistical significance. In our study, the diagnostic rate of FNAC correlated with the solid
content of thyroid nodules. However, the diagnostic rate of CNB was constant regardless of the solid or cystic component of thyroid nodules (Fig. 2). The proportion of lesions of the ‘cyst fluid only’ subcategory among non-diagnostic FNACs was 12.8 % on the initial FNAC, 7.6 % on the second FNAC, and 6.7 % on the third or more FNAC (Table 2). We found no significant difference in the risk of malignancy between the paucicellular and cyst fluid-only FNACs. CNBs contain larger amounts of tissue sample than FNACs and provide histopathological information about intra- and extra-nodules.16 The non-diagnostic rate of CNB for the evaluation of thyroid nodules is 1.6–23 %, which is
S. H. Lee et al. FIG. 2 Diagnostic rates of repeat testing among solid and cystic thyroid nodules with initial non-diagnostic FNACs. FNAC fine needle aspiration cytology, CNB core needle biopsy
significantly lower than that of FNAC.12–14,16 In our study, the rate of non-diagnosis for CNB was 2.4 %. A recent study on thyroid CNB revealed that conclusive diagnoses could be achieved for a large number of patients (87.1 %), thereby reducing the need for further biopsies or unnecessary diagnostic surgery for patients with a repeat nondiagnostic FNAC result.20 In our study, CNB significantly reduced the rate of non-diagnostic results and the clinical necessity for additional biopsies, suggesting that it is a reliable method for diagnosing thyroid nodules following a non-diagnostic FNAC result. However, CNB can be technically unsuitable or challenging in some cases and has the disadvantages of more potential complications, patient discomfort, and the necessity of local anesthesia and immediate compression of the biopsy site after each biopsy procedure.38 Nevertheless, thyroid gland CNB is a relatively safe technique with a very low rate of complications. In studies on clinical complications following thyroid FNAC, the rate of major complications was reported to be 0.036–1 %.39,40 In our study, there were no major complications associated with a CNB procedure. Recent guidelines on the evaluation of thyroid nodules do not provide a specific recommendation for the use of CNB.1 CNB has a limited role in distinguishing a cellular hyperplastic nodule from a follicular adenoma or carcinoma. Thus, CNB should be used as a complementary diagnostic tool, and not as an alternative to FNAC.41
There are some limitations in our study, including its retrospective design, possibility of selection bias, incomplete post-procedural follow-up, and radiologists’ variability on the performance of FNAC and CNB. The number of patients who did not undergo repeat biopsy (either FNAC or CNB) after initial non-diagnostic FNA was over 50 % of the initial study population. However, nodules in these patients were left alone because nodule size remained stable or decreased throughout follow-up and their ultrasonographic interpretations were benign. CNB following a previous nondiagnostic FNAC resulted in a higher diagnostic rate than a repeat FNAC. However, patients undergoing a repeat FNAC due to an initial non-diagnostic FNAC result did not show significant differences in age or the degree of cystic change and calcification compared with those having a CNB, although nodule size was larger in the CNB group. When we analyzed the relationship between the diagnostic rate of repeat FNAC and mean nodule size, no significant difference was found (p = 0.909). These results contradict the notion that the low non-diagnostic rate of CNB is primarily due to case selection bias in our study. The rates of AUS for repeat FNAC and CNB were similar. A previous study by Na et al.16 demonstrated that repeat AUS was significantly lower in CNB than in repeat FNAC (23.6 vs. 39.8 %, respectively) in patients with an initial AUS result of FNAC. This discrepancy may be attributed to differences in enrolled patient groups between the two studies.
Outcome of Non-Diagnostic Thyroid Aspirates
CONCLUSIONS About one-third of repeat FNACs after an initial nondiagnostic aspirate can repeatedly be non-diagnostic, and the risk of malignancy may not reduce following several non-diagnostic FNACs. CNB is more useful for achieving a diagnosis than a repeat FNAC. We suggest that a single CNB may be enough to exclude the risk of malignancy after an initial non-diagnostic aspirate, suggesting CNB as a useful alternative for the management of thyroid nodules with a non-diagnostic FNAC result. ACKNOWLEDGMENT The authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2013. DISCLOSURES
REFERENCES 1. Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167–214. 2. Cibas ES, Ali SZ. The Bethesda System for reporting thyroid cytopathology. Am J Clin Pathol. 2009;132:658–65. 3. Yassa L, Cibas ES, Benson CB, et al. Long-term assessment of a multidisciplinary approach to thyroid nodule diagnostic evaluation. Cancer. 2007;111:508–16. 4. Nayar R, Ivanovic M. The indeterminate thyroid fine-needle aspiration: experience from an academic center using terminology similar to that proposed in the 2007 National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Cancer. 2009;117:195–202. 5. Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda System for reporting thyroid cytopathology: a meta-analysis. Acta Cytol. 2012;56:333–9. 6. Ali SZ. Thyroid cytopathology: Bethesda and beyond. Acta Cytol. 2011;55:4–12. 7. Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid. 2009;19:1159–65. 8. Al Maqbali T, Tedla M, Weickert MO, Mehanna H. Malignancy risk analysis in patients with inadequate fine needle aspiration cytology (FNAC) of the thyroid. PLoS One. 2012;7:e49078. 9. Orija IB, Pineyro M, Biscotti C, Reddy SS, Hamrahian AH. Value of repeating a nondiagnostic thyroid fine-needle aspiration biopsy. Endocr Pract. 2007;13:735–42. 10. Alexander EK, Heering JP, Benson CB, Frates MC, Doubilet PM, Cibas ES, et al. Assessment of nondiagnostic ultrasound-guided fine needle aspirations of thyroid nodules. J Clin Endocrinol Metab. 2002;87:4924–7. 11. Lo Gerfo P, Colacchio T, Caushaj F, Weber C, Feind C. Comparison of fine-needle and coarse-needle biopsies in evaluating thyroid nodules. Surgery. 1982;92:835–8. 12. Samir AE, Vij A, Seale MK, et al. Ultrasound-guided percutaneous thyroid nodule core biopsy: clinical utility in patients with prior nondiagnostic fine-needle aspirate. Thyroid. 2012;22:461–7. 13. Screaton NJ, Berman LH, Grant JW. US-guided core-needle biopsy of the thyroid gland. Radiology. 2003;226:827–32. 14. Harvey JN, Parker D, De P, Shrimali RK, Otter M. Sonographically guided core biopsy in the assessment of thyroid nodules. J Clin Ultrasound. 2005;33:57–62.
15. Renshaw AA, Pinnar N. Comparison of thyroid fine-needle aspiration and core needle biopsy. Am J Clin Pathol. 2007;128:370–4. 16. Na DG, Kim JH, Sung JY, Baek JH, Jung KC, Lee H, et al. Coreneedle 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;22:468–75. 17. Khoo TK, Baker CH, Hallanger-Johnson J, et al. Comparison of ultrasound-guided fine-needle aspiration biopsy with core-needle biopsy in the evaluation of thyroid nodules. Endocr Pract. 2008;14:426–31. 18. Moon WJ, Baek JH, Jung SL, et al. Ultrasonography and the ultrasound-based management of thyroid nodules: consensus statement and recommendations. Korean J Radiol. 2011;12:1–14. 19. Lee J, Lee SY, Cha SH, Cho BS, Kang MH, Lee OJ. Fine-needle aspiration of thyroid nodules with macrocalcification. Thyroid. 2013;23(9):1106–12. 20. Yeon JS, Baek JH, Lim HK, et al. Thyroid nodules with initially nondiagnostic cytologic results: the role of core-needle biopsy. Radiology. 2013;268:274–80. 21. Lim DJ, Kim JY, Baek KH, et al. Natural course of cytologically benign thyroid nodules: observation of ultrasonographic changes. Endocrinol Metab. 2013;28:110–118. 22. Choi YS, Hong SW, Kwak JY, Moon HJ, Kim EK. Clinical and ultrasonographic findings affecting nondiagnostic results upon the second fine needle aspiration for thyroid nodules. Ann Surg Oncol. 2012;19:2304–9. 23. Deandrea M, Ragazzoni F, Motta M, et al. Diagnostic value of a cytomorphological subclassification of follicular patterned thyroid lesions: a study of 927 consecutive cases with histological correlation. Thyroid. 2010;20:1077–83. 24. Hryhorczuk AL, Stephens T, Bude RO, et al. Prevalence of malignancy in thyroid nodules with an initial nondiagnostic result after ultrasound guided fine needle aspiration. Ultrasound Med Biol. 2012;38:561–7. 25. Jo VY, Stelow EB, Dustin SM, Hanley KZ. Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol. 2010;134:450–6. 26. Jo VY, Vanderlaan PA, Marqusee E, Krane JF. Repeatedly nondiagnostic thyroid fine-needle aspirations do not modify malignancy risk. Acta Cytol. 2011;55:539–43. 27. Kim SK, Hwang TS, Yoo YB, et al. Surgical results of thyroid nodules according to a management guideline based on the BRAF (V600E) mutation status. J Clin Endocrinol Metab. 2011;96:658–64. 28. Renshaw AA. Sensitivity of fine-needle aspiration for papillary carcinoma of the thyroid correlates with tumor size. Diagn Cytopathol. 2011;39:471–4. 29. Theoharis CG, Schofield KM, Hammers L, Udelsman R, Chhieng DC. The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Thyroid. 2009; 9:1215–23. 30. Wu HH, Rose C, Elsheikh TM. The Bethesda system for reporting thyroid cytopathology: An experience of 1,382 cases in a community practice setting with the implication for risk of neoplasm and risk of malignancy. Diagn Cytopathol. 2012;40:399–403. 31. Yoon JH, Kwak JY, Kim EK, et al. How to approach thyroid nodules with indeterminate cytology. Ann Surg Oncol. 2010;17:2147–55. 32. Grani G, Calvanese A, Carbotta G, et al. Intrinsic factors affecting adequacy of thyroid nodule fine-needle aspiration cytology. Clin Endocrinol (Oxf). 2013;78:141–4. 33. Gharib H. Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and effect. Mayo Clin Proc. 1994;69:44–9. 34. Degirmenci B, Haktanir A, Albayrak R, et al. Sonographically guided fine-needle biopsy of thyroid nodules: the effects of nodule characteristics, sampling technique, and needle size on the adequacy of cytological material. Clin Radiol. 2007;62:798–803.
S. H. Lee et al. 35. Chow LS, Gharib H, Goellner JR, van Heerden JA. Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas. Thyroid. 2001;11:1147–51. 36. Cappelli C, Pirola I, Castellano M, et al. Fine needle cytology of complex thyroid nodules. Eur J Endocrinol. 2007;157:529–32. 37. Redman R, Zalaznick H, Mazzaferri EL, Massoll NA. The impact of assessing specimen adequacy and number of needle passes for fine-needle aspiration biopsy of thyroid nodules. Thyroid. 2006;16:55–60. 38. Sung JY, Na DG, Kim KS, Yoo H, Lee H, Kim JH, et al. Diagnostic accuracy of fine-needle aspiration versus core-needle biopsy for the diagnosis of thyroid malignancy in a clinical cohort. Eur Radiol. 2012; 22:1564–72. 39. Taki S, Kakuda K, Kakuma K, et al. Thyroid nodules: evaluation with US-guided core biopsy with an automated biopsy gun. Radiology. 1997;202:874–7. 40. Polyzos SA, Anastasilakis AD. Clinical complications following thyroid fine-needle biopsy: a systematic review. Clin Endocrinol (Oxf). 2009;71:157–65.
41. Gharib H, Papini E, Paschke R, et al. 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: executive summary of recommendations. J Endocrinol Invest. 2010;33:51–6. 42. Oertel YC, Miyahara-Felipe L, Mendoza MG, Yu K. Value of repeated fine needle aspirations of the thyroid: an analysis of over ten thousand FNAs. Thyroid. 2007;17:1061–6. 43. Renshaw AA. Should ‘‘atypical follicular cells’’ in thyroid fineneedle aspirates be subclassified? Cancer Cytopathol. 2010;118: 186–9. 44. Bongiovanni M, Crippa S, Baloch Z, et al. Comparison of 5tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology: a multi-institutional study. Cancer Cytopathol. 2012;120:117–25. 45. Bohacek L, Milas M, Mitchell J, Siperstein A, Berber E. Diagnostic accuracy of surgeon-performed ultrasound-guided fine-needle aspiration of thyroid nodules. Ann Surg Oncol. 2012;19:45–51.