Abstract
Introduction
High false-negative results have been reported for fine-needle aspiration (FNA) cytology in thyroid nodules. Fine-needle capillary (FNC) cytology is an alternative technique that prevents aspiration, reducing tissue damage. This study aimed to compare FNA and FNC in assessing thyroid nodules and in terms of their predictive role in the appropriate diagnosis of malignancy.
Methods
This is a comparative prospective study conducted on 486 patients. FNA was performed in 235 patients during 2016 and 2017 and FNC in 251 patients during 2018 and 2019. The quality of cytological specimens was compared and then correlated with the final histopathological findings of 39 patients who underwent thyroidectomy.
Results
Both groups were statistically similar regarding age and sex distribution. The FNA technique yielded significantly higher adequate specimens compared with FNC (p<0.001). Abundant blood in the background was found more frequently in the FNA technique (p<0.001). The sensitivity and specificity of FNA for malignancy diagnosis were both 100%, compared with 83.3% and 57.7% for FNC, respectively.
Conclusions
The two methods, FNA and FNC, did not differ in terms of overall quality. FNA was superior regarding consistency with the histopathological results and the ability to diagnose malignancy.
Keywords: Bethesda, Cytology, Fine-needle aspiration, Fine-needle capillary, Thyroid nodule
Introduction
Although thyroid nodules are common and affect 4–7% of the adult population, only 5% of all diagnoses are malignant.1 Fine-needle aspiration (FNA) cytology is the most recommended diagnostic technique. In 1930, Martin and Ellis2 proposed this technique as a reliable, easy, and convenient technique for the primary diagnosis of thyroid nodules.3,4
Studies have shown limitations of this technique, namely insufficient or nondiagnostic specimens and nondifferentiation between benign and malignant lesions in patients with follicular neoplasms.5,6 High false-negative results have been reported in FNA specimens of large thyroid nodules.7–9 However, FNA is an efficient tool for cytological evaluation of a nodular thyroid, with 89% to 98% diagnostic sensitivity, and 92% specificity.10
A growing technique for thyroid nodules biopsy, fine-needle capillary (FNC) cytology, was first developed in France in 1982.11 FNC avoids the negative pressure of aspiration as done in FNA. It can reduce tissue damage and blood contamination of specimens.12 It is less traumatic, less painful and allows better control of the needle in the lesion.13 Although the superior diagnostic potential of FNC for malignant lesions has been demonstrated,12,14,15 few studies have been performed to compare FNA and FNC.14,16 These studies showed no agreement on the best technique because it is still not clear which technique can lead to better specimens for cytological diagnosis.17
The aim of this study was to compare FNA and FNC in the evaluation of thyroid nodules and in terms of their predictive role in the proper diagnosis of malignant and benign thyroid lesions according to postoperative histopathological findings.
Methods
This was a prospective study comparing FNC and FNA in 486 patients suffering from thyroid nodules, from 2016 to 2019. Patients suffering from thyrotoxicosis or patients with previous surgery or irradiation were excluded from the study. The study protocol was reviewed and approved by the local ethics committee. Written informed consent was obtained from all patients. All procedures were conducted by the same operator. An exact clinical evaluation was performed to examine the suspicious areas of the thyroid gland for which a needle biopsy was performed. The order of FNC and FNA sampling was planned sequentially every 2 years. FNA was performed in 235 patients during 2016 and 2017 and FNC in 251 patients during 2018 and 2019. Both techniques were employed at the same centre by the same investigator.
The patients underwent needle biopsies (not ultrasound-guided) using a 23-gauge needle for both techniques, with an average of four slides for every specimen. FNA was performed using a 10ml syringe, while the FNC technique used a single needle. The same blinded pathologist provided the cytological reports. Thyroidectomy was done by the same surgeon in 45 patients, and postoperative histopathology reports were available for 39 patients.
The collected data were analysed using SPSS version 19 (IBM; Armonk, NY, USA). The mean values of continuous variables were compared using the Student t-test. Categorical data were compared by chi-square and Fisher tests. The statistical significance level was considered p≤0.001.
Results
In this study, 235 patients (mean age 49±14.5 years) were subjected to the FNA technique and 251 (mean age 48.6±13.6 years) to the FNC technique (p=0.77); 61.1% (n=296) of these specimens belonged to women and 28.9% (n=190) to men. Sex distribution among the FNA group did not differ from that of the FNC group (p=0.45).
Table 1 categorises the patients in each of the FNA/FNC groups, based on the Bethesda reporting system. Nondiagnostic cases (Bethesda I) were significantly more frequent in the FNC group (p=0.002). Also, the frequency of Bethesda III in the FNC group was higher than in the FNA group, though not statistically significant (p=0.2). The total number of cases with benign, suspected and malignant diagnosis based on cytology (Bethesda II, V and VI) in the FNA group was significantly more than in the FNC group (p=0.001) (Table 2).
Table 1 .
Comparison of the frequency of different diagnostic groups in the cytology report based on Bethesda classification in two sampling techniques
| Bethesda groups | FNA (%) | FNC (%) | Total (%) | p-value |
|---|---|---|---|---|
| Nondiagnostic (I) | 40 (17.0) | 72 (28.7) | 112 (23) | 0.013 |
| Benign (II) | 185 (78.7) | 162 (64.5) | 347 (71.4) | |
| Atypia of undetermined Sig. (III) | 1 (0.4) | 4 (1.6) | 5 (1) | |
| Follicular neoplasm (IV) | 5 (2.1) | 5 (2) | 10 (2.1) | |
| Suspicious (V) | 4 (1.7) | 6 (2.4) | 10 (2.1) | |
| Malignant (VI) | 0 (0) | 2 (0.8) | 2 (0.4) |
FNA = fine needle aspiration; FNC = fine needle capillary
Table 2 .
Comparison of quality, background and follicular cells between FNA and FNC
| FNA (%) | FNC (%) | Total (%) | p-value | |
|---|---|---|---|---|
| Sampling quality | ||||
| Inadequate | 38 (16.2) | 71 (27.3) | 109 (22.4) | >0.001 |
| Adequate | 50 (21.3) | 2 (0.8) | 52 (10.7) | |
| Superior | 147 (62.6) | 178 (70.9) | 325 (66.2) | |
| Blood/clot background | ||||
| Abundant | 88 (37.4) | 40 (15.9) | 128 (26.3) | >0.001 |
| Medium | 114 (48.5) | 187 (74.5) | 301 (61.9) | |
| Slight | 33 (14) | 24 (9.6) | 57 (11.7) | |
| Follicular cells | ||||
| Abundant | 43 (18.3) | 73 (29.1) | 116 (23.9) | 0.017 |
| Medium | 93 (39.6) | 77 (30.7) | 301 (35) | |
| Slight | 99 (42.1) | 101 (40.2) | 57 (41.1) | |
FNA = fine needle aspiration; FNC = fine needle capillary
Comparison of sample quality between the two groups, based on accuracy score (superior/adequate/inadequate), showed that the frequency of inadequate cases with the FNC technique was significantly higher than with the FNA technique (28.3% vs 16.2%, p<0.001). On the other hand, the frequency of superior and optimal quality cases in the FNC group was significantly higher than those of the FNA technique (70.9% vs 62.6%, p<0.001). Comparison of smear field between the two sampling techniques indicated that cases with abundant blood in the background were significantly higher in the FNA technique than with the FNC technique (p<0.001). The frequency of insufficient cell clusters for diagnosis was significantly higher with the FNC technique than with the FNA technique (p=0.017) (Table 2).
Out of 486 patients studied, 45 underwent thyroidectomy, and histopathologic reports were available for 39 patients. Non-neoplastic lesions were reported in 66.7% of cases (26 patients). Non-neoplastic cases included colloid goiter (12 cases), benign adenomatous nodules (12 cases) and lymphocytic thyroiditis (two cases). Among 12 neoplastic lesions, 2 were follicular adenoma and 3 were follicular carcinoma, 1 was Hürthle cell carcinoma and 9 were papillary thyroid carcinoma.
Kappa’s agreement coefficient for cytologic–pathologic correlation was very good (0.87) in the FNC group and good (0.63) in the FNA group. Excluding Bethesda group IV, the sensitivity and specificity of the FNA for malignancy diagnosis was 100%, compared with 83.3% and 57.7% for the FNC, respectively. In the FNC technique, the diagnosis of subsequently resected thyroid tissue was in agreement with that of the cytologic report in 86.4% of cases. However, in the FNA technique, cytologic–pathologic agreement was seen in 94.1% of cases.
Discussion
This study showed more insufficient cell clusters for diagnosis in the FNC than in the FNA group. Furthermore, the number of nondiagnostic and inadequate specimens with the FNC technique was more than with FNA. However, the FNC technique produces less blood in backgrounds and therefore allows easier diagnosis for the cytopathologist compared with the FNA technique. There was no significant difference between the two techniques regarding other slide quality criteria such as the degree of cell degeneration and trauma.
FNA is an available technique that yields reliable results in examining the nodular thyroids.18 In 2017, a survey was performed across many countries, according to which the Bethesda system for reporting thyroid cytopathology was used in roughly 31% of all laboratories.19 Many of these laboratories reported being unsatisfied (24.04%). Some reported the low rates of indeterminate diagnoses, including atypia of undetermined significance/follicular lesions of undetermined significance (4.87%) and follicular neoplasm/suspicious for a follicular neoplasm (0.35%).19 It is suggested that the presence of blood cannot be prevented completely in thyroid gland cytology specimens but its effects can be reduced as much as possible by the capillary action in FNC rather than the active high suction pressure of FNA.
In the study by Kamal et al, the FNC technique had a significant advantage over the FNA technique in terms of cell count. They found that there was no significant difference between the two techniques in terms of other characteristics such as basal blood, degree of cell degeneration and degree of cell trauma.12 Pinki et al found that FNC performed better than FNA in three criteria: basal blood, cellular matter and tissue structure maintenance (p<0.001).20
In a study by Ramachandra et al, which compared FNA and FNNA (fine-needle nonaspiration), the results suggested that FNNA findings were superior to FNA in terms of less blood in the field and higher cell quality, which is in line with the results of the present study.21 In the study by Buzduga et al on 309 patients, no difference was found between the smear quality of these two techniques (FNA and FNC) in terms of blood contamination, cell trauma rate, cellularity and degree. No cell degeneration was observed.22
In the study of Braun et al, 21.7% of cases were FNC and 32.5% of FNA cases were nondiagnostic cytology. Poor smear quality was reported in 24.1% of FNC cases and 36.1% of FNA cases.23 In the study of Wang et al, nondiagnostic results were reported in 7.66% of FNNA cases and in 7.99% of cases of FNA (p>0.05).24 Based on their results, the frequency of superior and optimal quality cases was 70.9% in the FNC group and 62.6% in the FNA technique. In the study of Braun et al, the frequency of cases with very good quality of cytological smear was 24.7% in FNC and 12.1% in FNA.
In a study conducted by Guo et al in 2018, the accuracy of acupuncture (FNA) and nonacupuncture (FNNA) techniques was evaluated and compared. No difference was observed in high-quality, medium and low-quality smears in the two techniques.25 In a meta-analysis by Song et al in 2015 that included 16 studies and the results of 1,842 patients with 2,221 samples, no significant difference was observed between FNA and FNNA in thyroid nodules.26 Tublin et al proved that the FNA technique in 11% and the FNC technique in 13% of cases were nondiagnostic, and that the accuracy of the cytological diagnosis of both techniques in imaging-guided sampling was considerable and the same.27 In the study of Wang et al, nondiagnostic results were reported in 7.66% of FNNA cases and in 7.99% of FNA cases (p>0.05).24
However, the results of the present study manifested that the slide quality in the two techniques of FNA and FNC with a considerable overall score (accuracy score) was not significantly different, which was due to insufficient cases in the FNC technique and, at the same time, the high number of superior cases (optimal quality). In the same way, the results showed that, in 94.1% of cases in the FNA technique and 86.4% of cases in the FNC technique, cytological results were consistent with the pathological results. In the study by Braun et al, the results of biopsy and surgery matched FNC in 95.7% and FNA in 90.5% of cases.23
In this study, the sensitivity and specificity of cytology (in terms of determining benign and malignant) in the FNA technique were 100% and 100%, respectively, and in the FNC technique these values were 83.3% and 57.7%, respectively. In De Carvelho's study, the diagnostic accuracy of FNA and FNC techniques was compared and the sensitivity rate was 85.7% for FNA and 100% for FNC, with a specificity rate in both techniques of 100%.28 Tauro and colleagues performed both sampling techniques on 50 patients for 2 years, and found that the diagnostic power, technique sensitivity, technique specificity and accuracy coefficient for the FNA and FNC techniques were not significantly different between the two techniques.
In sum, FNC and otherwise FNA were recommended for per cell samples.13 In the study of Wang et al, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNA and FNNA techniques were reported as 96.67% versus 100%, 89.74% versus 96.5%, 87.88% versus 96.97%, 97.22% versus 100%, 92.75% versus 98.36% (in all cases p>0.05).18
On the other hand, in Georgescu's study, a sensitivity of 76.47% and a specificity of 83.1% were reported, yielding 82.3% overall accuracy, 35.1% positive predictive value, 96.7% negative predictive value, 16.9% false-positive rate and 23% false-negative rate.29 These findings were partially compatible with other studies that report a sensitivity ranging from 65% to 98%, 72-100% specificity and 75-90% overall accuracy. One such study by Pinchot et al discovered that the FNA had a sensitivity between 89% and 98%, with a sensitivity of 92%.7 Previous research has proposed 57-98% sensitivity and 72-100% specificity for FNA.30 The sensitivity and specificity in our study were 64.96% and 62.76%, respectively.
The author who performed biopsies in this study had several years of experience in performing FNA, while FNC was conducted for the first time in our center for this investigation, although the FNC technique was studied for some time to gain experience and promote the skill of the operator in performing this technique. Less experienced operators may fail in performing the FNC compared with the usual FNA technique, which may lead to a high number of nondiagnostic and insufficient specimens using this technique. Therefore, results can vary according to the experience of the operator;13 this was the most important limitation of this study. For a more accurate comparison of the FNA method with FNC, more studies with sufficient sample size and after gaining sufficient experience in performing both methods are needed.
Conclusions
According to the results of this study, the FNA technique results in a lower number of nondiagnostic/insufficient cytology specimens compared with the FNC technique, although the FNC was superior regarding the frequency of superior cases with optimal quality and slide field quality. The consistency of cytology results with the results of tissue sample pathology and the sensitivity and specificity of malignancy determination in FNA was better than with the FNC technique. Therefore, it can be concluded that FNA is the technique of choice in cases of suspected malignancy.
Acknowledgement
This research is taken from the dissertation of Mohammad Movahedinia's MPH course (Master of Public Health) under the supervision of Hossein Hatami.
References
- 1.Gharib H. Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and effect. Mayo Clinic Proc 1994; 69: 44–49. [DOI] [PubMed] [Google Scholar]
- 2.Zajdela A, Zillhardt P, Voillemot N. Cytological diagnosis by fine needle sampling without aspiration. Cancer 1987; 59: 1201–1205. [DOI] [PubMed] [Google Scholar]
- 3.Ha EJ, Na DG, Baek JHet al. US fine-needle aspiration biopsy for thyroid malignancy: diagnostic performance of seven society guidelines applied to 2000 thyroid nodules. Radiology 2018; 287: 893–900. [DOI] [PubMed] [Google Scholar]
- 4.Choong KC, Khiyami A, Tamarkin SW, McHenry CR. Fine-needle aspiration biopsy of thyroid nodules: is routine ultrasound-guidance necessary? Surgery 2018; 164: 789–794. [DOI] [PubMed] [Google Scholar]
- 5.Carpi A, Di Coscio G, Iervasi Get al. Thyroid fine needle aspiration: how to improve clinicians’ confidence and performance with the technique. Cancer Lett 2008; 264: 163–171. [DOI] [PubMed] [Google Scholar]
- 6.Deveci MS, Deveci G, LiVolsi VA, Baloch ZW. Fine-needle aspiration of follicular lesions of the thyroid. diagnosis and follow-Up. Cytojournal 2006; 3: 9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Pinchot SN, Al-Wagih H, Schaefer Set al. Accuracy of fine-needle aspiration biopsy for predicting neoplasm or carcinoma in thyroid nodules 4cm or larger. Arch Surg 2009; 144: 649–655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Stang MT, Carty SE. Recent developments in predicting thyroid malignancy. Curr Opin Oncol 2009; 21: 11–17. [DOI] [PubMed] [Google Scholar]
- 9.Rizvi SA, Husain M, Khan S, Mohsin M. A comparative study of fine needle aspiration cytology versus non-aspiration technique in thyroid lesions. Surgeon 2005; 3: 273–276. [DOI] [PubMed] [Google Scholar]
- 10.Alolayan H, Alyahya Y, Altuaysi Aet al. Accuracy of fine needle aspiration cytology of thyroid compared to final histopathology in total thyroidectomy. IJMDC 2020; 4: 179–184. [Google Scholar]
- 11.Briffod M, Gentile A, Hebert H. Cytopuncture in the follow-up of breast carcinoma. Acta Cytol 1982; 26: 195–200. [PubMed] [Google Scholar]
- 12.Kamal MM, Arjune DG, Kulkarni HR. Comparative study of fine needle aspiration and fine needle capillary sampling of thyroid lesions. Acta Cytol 2002; 46: 30–34. [DOI] [PubMed] [Google Scholar]
- 13.Tauro LF, Lobo GJ, Fernandes Het al. A comparative study on fine needle aspiration cytology versus fine needle capillary cytology in thyroid nodules. Oman Med J 2012; 27: 151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Pothier DD, Narula A. Should we apply suction during fine needle cytology of thyroid lesions? A systematic review and meta-analysis. Ann R Coll Surg Engl 2006; 88: 643–645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Raghuveer C, Leekha I, Pai M, Adhikari P. Fine needle aspiration cytology versus fine needle sampling without aspiration. A prospective study of 200 cases. Indian J Med Sci 2002; 56: 431–439. [PubMed] [Google Scholar]
- 16.Haddadi-Nezhad S, Larijani B, Tavangar SM, Nouraei SM. Comparison of fine-needle-nonaspiration with fine-needle-aspiration technique in the cytologic studies of thyroid nodules. Endocr Pathol 2003; 14: 369–373. [DOI] [PubMed] [Google Scholar]
- 17.Romitelli F, Di Stasio E, Santoro Cet al. A comparative study of fine needle aspiration and fine needle non-aspiration biopsy on suspected thyroid nodules. Endocr Pathol 2009; 20: 108–113. [DOI] [PubMed] [Google Scholar]
- 18.Wong C, Liu X, Lang B. Cost-effectiveness of fine-needle aspiration cytology (FNAC) and watchful observation for incidental thyroid nodules. J Endocrinol Invest 2020; 43: 1645–1654. [DOI] [PubMed] [Google Scholar]
- 19.Chen C-C, Hang J-F, Liu C-Yet al. Thyroid fine-needle aspiration cytology in Taiwan: a nationwide survey and literature update. J Pathol Transl Med 2020; 54: 361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Pinki P, Alok D, Ranjan A, Chand MN. Fine needle aspiration cytology versus fine needle capillary sampling in cytological diagnosis of thyroid lesions. Iran J Pathol 2015; 10: 47. [PMC free article] [PubMed] [Google Scholar]
- 21.Ramachandra L, Kudva R, Rao BA, Agrawal S. A comparative study of fine needle aspiration cytology (FNAC) and fine needle non-aspiration cytology (FNNAC) technique in lesions of thyroid gland. Indian J Surg 2011; 73: 287–290. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Buzduga C, Galesanu C, Vulpoi Cet al. Thyroid fine-needle biopsy: aspiration versus capillary. Medsurg Nurs 2015; 119: 45–50. [PubMed] [Google Scholar]
- 23.Braun H, Walch C, Beham A, Moinfar F. Fine needle capillary cytology versus fine needle aspiration cytology–a comparison of quality between puncture techniques in the ENT area. Laryngo-Rhino-Otol 1997; 76: 358–363. [DOI] [PubMed] [Google Scholar]
- 24.Wang D, Fu H-J, Xu H-Xet al. Comparison of fine needle aspiration and non-aspiration cytology for diagnosis of thyroid nodules: a prospective, randomized, and controlled trial. Clin Hemorheol Microcirc 2017; 66: 67–81. [DOI] [PubMed] [Google Scholar]
- 25.Guo Y, Huo J, Qu Ret al. A comparison of fine needle nonaspiration cytology versus fine needle aspiration for thyroid nodules: a meta-analysis. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018; 32: 868–872. [DOI] [PubMed] [Google Scholar]
- 26.Song H, Wei C, Li Det al. Comparison of fine needle aspiration and fine needle nonaspiration cytology of thyroid nodules: a meta-analysis. Biomed Res Int 2015; 2015: 796120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Tublin ME, Martin JA, Rollin LJet al. Ultrasound-guided fine-needle aspiration versus fine-needle capillary sampling biopsy of thyroid nodules: does technique matter? J Ultrasound Med 2007; 26: 1697–1701. [DOI] [PubMed] [Google Scholar]
- 28.de Carvalho GA, Paz-Filho G, Cavalcanti TC, Graf H. Adequacy and diagnostic accuracy of aspiration vs. capillary fine needle thyroid biopsies. Endocr Pathol 2009; 20: 204. [DOI] [PubMed] [Google Scholar]
- 29.Georgescu R, Oprea AL, Contra Aet al. The sensitivity and specificity of fine-needle aspiration in thyroid neoplasia. J Interdiscip Med 2017; 2: 127–131. [Google Scholar]
- 30.Eng CY, Quraishi MS, Bradley PJ. Management of thyroid nodules in adult patients. Head Neck Oncol 2010; 2: 11. [DOI] [PMC free article] [PubMed] [Google Scholar]