European Journal of Radiology 83 (2014) 680–683
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Thyroid fine needle aspiration biopsy: Do we really need an on-site cytopathologist? Ismet Cengic a,1 , Derya Tureli a,∗ , Rengin Ahiskali b,2 , Onur Bugdayci a,3 , Hilal Aydin a,4 , Erkin Aribal a,5 a Department of Radiology, Marmara University, School of Medicine, Fevzi Cakmak Mahallesi Mimar Sinan Caddesi No: 41, 34899 Ust Kaynarca Pendik, Istanbul, Turkey b Department of Pathology, Marmara University, School of Medicine, Fevzi Cakmak Mahallesi Mimar Sinan Caddesi No: 41, 34899 Ust Kaynarca Pendik, Istanbul, Turkey
a r t i c l e
i n f o
Article history: Received 26 October 2013 Received in revised form 17 December 2013 Accepted 7 January 2014 Keywords: Thyroid nodule Fine needle aspiration biopsy Specimen adequacy Image-guided intervention
a b s t r a c t Purpose: The aim of this single center study is to evaluate the effectiveness of performing ultrasoundguided thyroid fine-needle aspiration biopsies (FNAB) performed by the radiologist alone without an on-site cytopathologist. Materials and methods: In this prospective randomized study, 203 patients with single nodules measuring 10 mm or more underwent ultrasound-guided FNAB: 102 patients underwent FNAB performed by the radiologist accompanied by a cytopathologist (control group); 101 patients underwent FNAB by the radiologist alone (study group). In both groups biopsy time, specimen adequacy ratio, total aspiration number, cytopathologist’s cytological diagnosis time (t1), cytopathologist’s total time consumption (t2) were evaluated. Results: Mean total biopsy time was 8.74 ± 2.31 min in the study group and was significantly shorter than the control group’s 11.97 ± 6.75 min (p = 0.004). The average number of aspirations per patient in the study group was 4.00 ± 0; compared to the control group’s 3.56 ± 1.23 this was significantly higher (p = 0.001). t1 of the study group was 307.48 ± 226.32 s; compared to 350.14 ± 247.64 s in the control group, there was no statistically significant difference (p = 0.137). t2 of the study group was 672.93 ± 270.45 s; compared to the control group (707.03 ± 258.78 s) there was no statistically significant difference (p = 0.360). Diagnostic adequacy of aspirated specimens was reassessed in the pathology laboratory. In the study group, 84 out of 101 aspirations and in the control group 89 out of 102 aspirations was determined as adequate with no statistically significant difference (p = 0.302). Conclusions: We believe that in centers where a cytopathologist is not available, ultrasound-guided thyroid FNAB can be adequately performed by an experienced radiologist who was effectively trained in smear preparation. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Purpose Thyroid nodules are very common, being diagnosed in 4–8% of the adult population with palpation and in 10–41% with ultrasound (US) [1–5]. In autopsy series, thyroid nodules are encountered with a prevalance of 50% [6]. When a thyroid nodule is detected, imag-
∗ Corresponding author. Tel.: +90 505 785 13 37. E-mail addresses: [email protected] (I. Cengic), [email protected] (D. Tureli), [email protected] (R. Ahiskali), [email protected] (O. Bugdayci), [email protected] (H. Aydin), [email protected] (E. Aribal). 1 Tel.: + 90 532 542 17 84. 2 Tel.: + 90 532 201 29 97. 3 Tel.: +90 532 610 73 30. 4 Tel.: +90 544 660 89 66. 5 Tel.: +90 533 202 11 53. 0720-048X/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2014.01.009
ing alone is not enough to determine if the nodule is benign or malignant. At present, thyroid fine-needle aspiration biopsy (FNAB) is the least invasive, most accurate method to determine highrisk or malignant lesions and is thus most effective [7–9]. Thyroid FNAB is performed with or without the guidance of an US for palpable nodules and with the guidance of an US for non-palpable nodules. In our institution thyroid FNAB is done by a radiologist with US guidance. A cytopathologist accompanies the radiologist during the procedure. The radiologist obtains the fine needle aspiration material from the nodule, while the cytopathologist spreads the sample and determines if the specimen is adequate for cytological diagnosis. In this single center study, we aim to evaluate the difference in the adequacy and the diagnostic process between thyroid FNAB performed by a radiologist with and without an on-site cytopathologist.
I. Cengic et al. / European Journal of Radiology 83 (2014) 680–683
2. Materials and methods Two hundred and three patients with nodules of 10 mm and larger were included in this prospective randomized study between January 2008 and May 2010. Pure cystic nodules were excluded from the study. The patients were enrolled in the study in accordance with the “Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer” of the American Thyroid Association Guidelines Taskforce [10]. US guided FNAB was performed for all 203 patients by a single radiologist with 1 year of experience in thyroid FNAB. The radiologist received basic training in cytopreparation from a pathologist. All biopsies were performed by the same radiologist under US guidance (Accuson Antares, Siemens, Germany) using a linear 9–12 Mhz probe and 22G aspiration needles. The patients were randomized using random permutated blocks and Zelen’s design. One hundred and two patients underwent FNAB performed by the radiologist accompanied by a cytopathologist for on-site evaluation of adequacy (control group), and 101 patients underwent FNAB in the absence of the cytopathologist (study group). In accordance with institutional ethical committee guidelines informed consent was obtained from every patient. The same biopsy technique was used for all cases; the patient lying in supine position on the examination table, a rolled towel was put under the neck to provide hyperextension. Before the biopsy, the nodule was localized with the US probe and a topical lidocaine ointment was salved on the skin at the level of the nodule. After allowing appropriate time for the anesthetic to take effect; the skin was cleansed with iodine solution. For every single aspiration a new 22G needle was used and aspiration was performed by free-hand technique under sonographic guidance. The needle tip was placed inside the nodule. During the procedure, curettage was performed before applying negative pressure. The curettage and the aspiration were continued until the aspiration material and a small amount of blood were observed at the hub of the syringe. After each aspiration, the aspirated material was sprayed on 4 different slides. The slides were overlapped onto one another, spreading the cells without smashing, and were gently pulled away from each other. The smears were fixed in 95% ethanol solution. The remaining material in every aspiration syringe was washed with Cytospin collection fluid (Shandon, Thermoscientific, USA) for building a cell block in the pathology lab. Four samples per patient were taken from each nodule in the study group and cytologic slides were prepared by the radiologist. In the control group, the same procedure was performed with the exception that one of the four slides prepared in every aspiration was stained by the cytopathologist using a rapid toluidine blue solution and examined under the microscope to determine the diagnostic adequacy of the specimen. In the control group this procedure was continued until the cytopathologist declared that the cytological material was adequate and the total number of aspirations was noted. Total biopsy time was noted in both groups. Biopsy time is defined as the interval that begins with the first placement of the needle inside the nodule in both groups and ends at the time when the last prepared slide was fixed in ethanol by the radiologist (study group) or at the time when the cytopathologist declared that the aspirated material was adequate for histologic diagnosis (control group). All obtained material was sent to the pathology laboratory. A total of 808 slides in the study group and 712 slides in the control group were obtained. In the pathology laboratory slides were stained with Papanicolaou dye. In both groups, the specimens were evaluated for adequacy and a final diagnosis was made by the same blinded cytopathologist who has more than 15 years of experience. In both groups, cytological diagnosis time and the
681
Table 1 The comparison of total biopsy times, cytopathologist’s definitive cytological diagnosis time (t1) and cytopathologist’s total time consumption for reviewing all specimens (t2) in the study and the control groups.
Patients (n) Total biopsy times (min) t1 (s) t2 (s)
Study group
Control group
p Value
101 8.74 ± 2.31 307.48 ± 226.32 672.93 ± 270.45
102 11.97 ± 6.75 350.14 ± 247.64 707.03 ± 258.78
.004 .137 .360
cytopathologist’s total time consumption in the laboratory were also noted. Although a definitive diagnosis can be made by the cytopathologist even after examining a single specimen, all the slides from all specimens are reviewed by the cytopathologist. Thus the diagnosis time (coined as t1) and the time required for reviewing all specimens (coined as t2) may be different from one another. There are various proposed adequacy criteria for thyroid FNAB [11,12]. In this study, we used criteria established by Kini for evaluating the adequacy of thyroid FNAB specimens [11]. Number of total aspirations and the cytopathologist’s total time consumption in the laboratory showed normal distribution and were analyzed with the Student t-test. Biopsy times and cytological diagnosis times did not show normal distribution and thus were analyzed with Mann–Whitney U test. The specimen adequacy ratio was analyzed with Pearson Chi-square test. A p value of 0.05 or less was accepted as statistically significant. Cytological adequacy was classified according to the criteria suggested by Kini et al. [11]. Cytological diagnosis was classified according to the Bethesda system (National Cancer Institute, Fourth Thyroid FNAB Guideline Commitee) into 6 groups [12]. 3. Results One hundred and one patients, 81 female and 20 male (ages 20–83, mean 49), with single nodule underwent aspiration in the study group. One hundred and two patients, 85 female and 17 male (ages 23–86, mean 50), with single nodule were sampled in the control group. Mean total biopsy time in the study group was significantly shorter than the mean total biopsy time of the control group (8.74 ± 2.31 vs. 11.97 ± 6.75 min respectively; p = 0.004) (Table 1). The average number of aspirations in the control group was significantly less than that of the study group (3.56 ± 1.23 vs. 4.00 ± 0 aspirations per patient; p = 0.001) (Table 2). The cytopathologist’s definitive cytological diagnosis time in the pathology laboratory (t1) was not significantly different between control and study groups (350.14 ± 247.64 vs. 307.48 ± 226.32 s respectively; p = 0.137) (Table 1). The cytopathologist’s total time consumption for reviewing all specimens in the pathology laboratory (t2) did not show statistically significant difference between control and study groups (707.03 ± 258.78 vs. 672.93 ± 270.45 s; p = 0.360) (Table 1). The diagnostic adequacy of aspirated specimens, which was assessed by the cytopathologist, did not show a statistically significant difference among the study and control groups (83.2% vs. 87.9%; p = 0.302) (Table 3).
Table 2 The comparison of biopsy aspiration numbers in the study and the control groups.
Study group Control group
Patient number
Average number of aspirations per patient
Standard deviation
p Value
101 102
4.00 3.55
0.00 1.23
.001 .001
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I. Cengic et al. / European Journal of Radiology 83 (2014) 680–683
Table 3 Specimen adequacy ratio of biopsy aspiration material in the study and the control groups. Study group Adequate specimen Inadequate specimen Total
Control group
84 17
89 13
101
102
p Value .302 .302
Table 4 Comparison of the cytologic results according to the Bethesda classification. Bethesda classification
Study group
Control group
Total
Benign Atypia of undetermined significance Follicular neoplasm Suspicious for malignancy Malignant Non-diagnostic
68 (67%) 6 (6%)
72 (71%) 6 (6%)
140 12
10 (10%) 0
8 (8%) 2 (2%)
18 2
0 17 (17%)
1 (1%) 13 (13%)
1 30
101
102
203
Total
The cytologic results in both groups were determined according to the Bethesda classification. The results are summarized in Table 4. There was no procedure related complications in the control group. In the study group, a hematoma in the thyroid gland developed in one patient during the FNAB procedure which resolved spontaneously in 1 week. 4. Discussion With the utilization of thyroid FNAB procedures for suspicious thyroid nodules, a significant decrease was observed in the number of patients undergoing unnecessary thyroid surgery. This also led to an increase in the prevalence of malignancy of the pathologic specimens obtained by surgery. By assessing thyroid nodules and thus obviating the need for surgery; FNAB of thyroid nodules resulted in a significant decrease of the economic burden on the health care system [7,9,13–15]. US guided FNAB is a more effective technique than the – once conventional – unguided blind biopsies. It is the first method of choice for palpable and nonpalpable lesions and considered as the second method of choice in case of inadequate biopsy results obtained by FNAB guided by palpation [11]. Thyroid FNAB is recommended to be performed with the presence of an on-site cytopathologist in order to achieve higher adequacy rate [15]. This study compared the diagnosis and procedure times, total aspiration numbers and specimen adequacy of FNAB performed with and without an on-site cytopathologist. We have demonstrated that the procedure times have shortened without affecting the adequacy rates when the radiologist performed FNAB without an on-site associating cytopathologist. In a recent study, O’Malley et al. have demonstrated that the procedure times were shorter and the adequacy of the specimens did not differ when FNAB was done without a cytopathologist which is similar to our finding [16]. In current literature, to our knowledge, there are no studies comparing diagnosis and evaluation times by the cytopathologist for thyroid FNAB which makes this study unique. One may assume that when the specimens are evaluated on-site during the procedure, the cytopathologist would have a positive effect on the quality of the specimens and that would hasten the diagnosis during further evaluation in the cytopathology laboratory. However, if the radiologist is trained in smear preparation techniques, the results of the study showed that there was not
any statistically significant difference in time of diagnosis, thus we may consider that specimen quality was similar in both groups. Although this study was not designed for assessment of the quality of the specimens; with same adequacy rates and diagnosis times in both groups, we can assume that the quality was comparable. While designing the study, the authors had certain reservations regarding the number aspirations in the study group. According to our past experience in thyroid FNAB inadequate specimen ratio was unacceptably high with 3 aspirations per patient. In a study of thyroid FNAB without an on-site cytopathologist, by O’Mellay et al., 4 aspirations per nodule were performed by the radiologist. In that study there was also no statistically significant difference between the adequacy of specimens between cytopathologist assisted and unassisted biopsies [16]. In the light of previously published study, our past experience and a consensus with the pathology department; the authors agreed on doing 4 aspirations per patient. Less number of aspirations per patient will reduce total biopsy time and means less needle intervention which results in less patient discomfort and lower risk of complications. Also, less number of slides, fixation material and dye will be used per patient. Less time will be required by the cytopathology laboratory for evaluating all specimens and reporting will be hastened. There was a statistically significant difference in the number of aspirations between the groups (mean: 3.56 vs. 4.00 per patient; p = 0.001). The difference of the mean aspirations between the groups was 0.44 per patient. We believe that this difference is considerable. A high number of aspirations may cause higher complications or patient discomfort. However, the complication rate in thyroid FNAB is very low [8,17,18]. We have observed only one minor complication which was a small hematoma (less than 0.5%) in this study. Consequently we believe that a cytopathologist’s presence does not affect the risk of procedure related complications. Procedure times of both groups were compared and the study group was significantly faster than the control group (8.74 min vs. 11.97 min). Considering that the cytopathologist’s procedure for on-site evaluation; the shorter time spent by the sole radiologist who performs the aspiration and spreads the specimen is invariably a predicted result. This was also shown by O’Malley et al. that there are numerous benefits of a faster biopsy procedure for cytopathologist, radiologist and the patient [16]. Thyroid FNAB performed solely by the radiologist will result in an average daily workload reduction of the cytopathologist by 11.9 min per patient. This reduction does not take into account the transit time to radiology lab and on site preparation time. In this study, if all 203 biopsies had been performed with an on-site cytopathologist; an additional 1202 min (20.3 h and more than 2.5 work days of 8 h) would have been required by the cytopathologist. If the radiologist had performed all 203 biopsies without an on-site cytopathologist, he would have spent 3.2 min less for each nodule and a total of 326 min (5.4 h) for all 102 patients of the control group. In this study, cost-effectiveness analysis was not performed; we believe that thyroid FNAB without an on-site cytopathologist is more efficient in terms of time and workload; thus, it is also likely to be more cost-effective. A shorter biopsy procedure is also important for the patient comfort. We have some limitations in this study. The number of suspicious lesions and malignant lesions was very low. Although we have only evaluated the cytology results that were examined by an experienced cytopathologist it was not possible to compare with histopathology which is a gold standard method. In conclusion; US guided thyroid FNAB performed solely by the radiologist results in reduction of specimen processing times without statistically significant differences in specimen adequacy ratios, cytopathologist’s definitive diagnosis time and cytopathologist’s total time consumption for evaluation of all specimens. We believe that in centers where a cytopathologist is not available, US guided
I. Cengic et al. / European Journal of Radiology 83 (2014) 680–683
thyroid FNAB can be adequately performed by an experienced radiologist who has been effectively trained in basic cytotechnology. In centers where a cytopathologist is available, performing thyroid FNAB without an on-site cytopathologist is likely to be more time efficient and cost-effective. Conflict of interest The authors declare that there are no conflicts of interest. References [1] Wiest PW, Hartshorne MF, Inskip PD, et al. Thyroid palpation versus highresolution thyroid ultrasonography in the detection of nodules. J Ultrasound Med 1998;17:487–96. [2] Carroll BA. Asymptomatic thyroid nodules: incidental sonographic detection. Am J Roentgenol 1982;138:499–501. [3] Brander A, Viikinkoski P, Nickels J, et al. Thyroid gland: US screening in a random adult population. Radiology 1991;181:683–7. [4] Bruneton JN, Balu-Maestro C, Marcy PY, et al. Very high frequency (13 MHz) ultrasonographic examination of the normal neck: detection of normal lymph nodes and thyroid nodules. J Ultrasound Med 1994;13:87–90. [5] Horlocker TT, Hay ID. Prevalence of incidental nodular thyroid disease detected during high-resolution parathyroid sonography. In: Medeiros-Neto G, Gaitan E, editors. Frontiers in thyroidology, vol. 2. New York: Plenum; 1985. p. 1309–12. [6] Mortensen JD, Woolner LB, Bennett WA. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955;15: 1270–80.
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[7] Rojeski MT, Gharib H. Nodular thyroid disease: evaluation and management. N Engl J Med 1985;313:428–36. [8] Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997;126:226–31. [9] Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med 1993;118:282–9. [10] Cooper DS, Doherty GM, Haugen BR, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006;16(2):109–42. [11] Kini SR. Thyroid. In: Kline TS, editor. Guides to clinical aspiration biopsy. 2nd ed. New York: Igaku-Shoin Medical Publishers; 1996. p. 176–88. [12] Baloch ZW, Cibas ES, Clark DP, et al. The National cancer institute thyroid fine needle aspiration state of the science conference: a summation. Cytojournal 2008;5:6. [13] Hamberger JI, Husain M. Semiquantitative criteria for fine-needle biopsy diagnosis: reduced false-negative diagnoses. Diagn Cytopathol 1988;4: 14–7. [14] Caplan RH, Strutt PJ, Kisken WA, Wester SM. Fine needle aspiration biopsy of thyroid nodules. Wis Med J 1991;90:285–8. [15] Miller DA, Carrasco CH, Katz RL, et al. Fine needle aspiration biopsy: the role of immediate cytologic assessment. Am J Roentgenol 1986;147:155–8. [16] O’Malley ME, Weir MM, Hahn PF, et al. US-guided fine-needle aspiration biopsy of thyroid nodules: adequacy of cytologic material and procedure time with and without immediate cytologic analysis. Radiology 2002;222(2): 383–7. [17] Gharib H. Thyroid nodules: clinical importance, assessment, and treatment. Endocrinol Metab Clin North Am 2007;36(3):707–35. [18] Braga M, Cavalcanti TC, Collaco LM. Efficacy of US-guided fine-needle aspiration biopsy in the diagnosis of complex thyroid nodules. J Clin Endocrinol Metab 2001;86(9):4089–91.
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Thyroid fine needle aspiration biopsy: Do we really need an on-site cytopathologist? Ismet Cengic a,1 , Derya Tureli a,∗ , Rengin Ahiskali b,2 , Onur Bugdayci a,3 , Hilal Aydin a,4 , Erkin Aribal a,5 a Department of Radiology, Marmara University, School of Medicine, Fevzi Cakmak Mahallesi Mimar Sinan Caddesi No: 41, 34899 Ust Kaynarca Pendik, Istanbul, Turkey b Department of Pathology, Marmara University, School of Medicine, Fevzi Cakmak Mahallesi Mimar Sinan Caddesi No: 41, 34899 Ust Kaynarca Pendik, Istanbul, Turkey
a r t i c l e
i n f o
Article history: Received 26 October 2013 Received in revised form 17 December 2013 Accepted 7 January 2014 Keywords: Thyroid nodule Fine needle aspiration biopsy Specimen adequacy Image-guided intervention
a b s t r a c t Purpose: The aim of this single center study is to evaluate the effectiveness of performing ultrasoundguided thyroid fine-needle aspiration biopsies (FNAB) performed by the radiologist alone without an on-site cytopathologist. Materials and methods: In this prospective randomized study, 203 patients with single nodules measuring 10 mm or more underwent ultrasound-guided FNAB: 102 patients underwent FNAB performed by the radiologist accompanied by a cytopathologist (control group); 101 patients underwent FNAB by the radiologist alone (study group). In both groups biopsy time, specimen adequacy ratio, total aspiration number, cytopathologist’s cytological diagnosis time (t1), cytopathologist’s total time consumption (t2) were evaluated. Results: Mean total biopsy time was 8.74 ± 2.31 min in the study group and was significantly shorter than the control group’s 11.97 ± 6.75 min (p = 0.004). The average number of aspirations per patient in the study group was 4.00 ± 0; compared to the control group’s 3.56 ± 1.23 this was significantly higher (p = 0.001). t1 of the study group was 307.48 ± 226.32 s; compared to 350.14 ± 247.64 s in the control group, there was no statistically significant difference (p = 0.137). t2 of the study group was 672.93 ± 270.45 s; compared to the control group (707.03 ± 258.78 s) there was no statistically significant difference (p = 0.360). Diagnostic adequacy of aspirated specimens was reassessed in the pathology laboratory. In the study group, 84 out of 101 aspirations and in the control group 89 out of 102 aspirations was determined as adequate with no statistically significant difference (p = 0.302). Conclusions: We believe that in centers where a cytopathologist is not available, ultrasound-guided thyroid FNAB can be adequately performed by an experienced radiologist who was effectively trained in smear preparation. © 2014 Elsevier Ireland Ltd. All rights reserved.
1. Purpose Thyroid nodules are very common, being diagnosed in 4–8% of the adult population with palpation and in 10–41% with ultrasound (US) [1–5]. In autopsy series, thyroid nodules are encountered with a prevalance of 50% [6]. When a thyroid nodule is detected, imag-
∗ Corresponding author. Tel.: +90 505 785 13 37. E-mail addresses: [email protected] (I. Cengic), [email protected] (D. Tureli), [email protected] (R. Ahiskali), [email protected] (O. Bugdayci), [email protected] (H. Aydin), [email protected] (E. Aribal). 1 Tel.: + 90 532 542 17 84. 2 Tel.: + 90 532 201 29 97. 3 Tel.: +90 532 610 73 30. 4 Tel.: +90 544 660 89 66. 5 Tel.: +90 533 202 11 53. 0720-048X/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejrad.2014.01.009
ing alone is not enough to determine if the nodule is benign or malignant. At present, thyroid fine-needle aspiration biopsy (FNAB) is the least invasive, most accurate method to determine highrisk or malignant lesions and is thus most effective [7–9]. Thyroid FNAB is performed with or without the guidance of an US for palpable nodules and with the guidance of an US for non-palpable nodules. In our institution thyroid FNAB is done by a radiologist with US guidance. A cytopathologist accompanies the radiologist during the procedure. The radiologist obtains the fine needle aspiration material from the nodule, while the cytopathologist spreads the sample and determines if the specimen is adequate for cytological diagnosis. In this single center study, we aim to evaluate the difference in the adequacy and the diagnostic process between thyroid FNAB performed by a radiologist with and without an on-site cytopathologist.
I. Cengic et al. / European Journal of Radiology 83 (2014) 680–683
2. Materials and methods Two hundred and three patients with nodules of 10 mm and larger were included in this prospective randomized study between January 2008 and May 2010. Pure cystic nodules were excluded from the study. The patients were enrolled in the study in accordance with the “Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer” of the American Thyroid Association Guidelines Taskforce [10]. US guided FNAB was performed for all 203 patients by a single radiologist with 1 year of experience in thyroid FNAB. The radiologist received basic training in cytopreparation from a pathologist. All biopsies were performed by the same radiologist under US guidance (Accuson Antares, Siemens, Germany) using a linear 9–12 Mhz probe and 22G aspiration needles. The patients were randomized using random permutated blocks and Zelen’s design. One hundred and two patients underwent FNAB performed by the radiologist accompanied by a cytopathologist for on-site evaluation of adequacy (control group), and 101 patients underwent FNAB in the absence of the cytopathologist (study group). In accordance with institutional ethical committee guidelines informed consent was obtained from every patient. The same biopsy technique was used for all cases; the patient lying in supine position on the examination table, a rolled towel was put under the neck to provide hyperextension. Before the biopsy, the nodule was localized with the US probe and a topical lidocaine ointment was salved on the skin at the level of the nodule. After allowing appropriate time for the anesthetic to take effect; the skin was cleansed with iodine solution. For every single aspiration a new 22G needle was used and aspiration was performed by free-hand technique under sonographic guidance. The needle tip was placed inside the nodule. During the procedure, curettage was performed before applying negative pressure. The curettage and the aspiration were continued until the aspiration material and a small amount of blood were observed at the hub of the syringe. After each aspiration, the aspirated material was sprayed on 4 different slides. The slides were overlapped onto one another, spreading the cells without smashing, and were gently pulled away from each other. The smears were fixed in 95% ethanol solution. The remaining material in every aspiration syringe was washed with Cytospin collection fluid (Shandon, Thermoscientific, USA) for building a cell block in the pathology lab. Four samples per patient were taken from each nodule in the study group and cytologic slides were prepared by the radiologist. In the control group, the same procedure was performed with the exception that one of the four slides prepared in every aspiration was stained by the cytopathologist using a rapid toluidine blue solution and examined under the microscope to determine the diagnostic adequacy of the specimen. In the control group this procedure was continued until the cytopathologist declared that the cytological material was adequate and the total number of aspirations was noted. Total biopsy time was noted in both groups. Biopsy time is defined as the interval that begins with the first placement of the needle inside the nodule in both groups and ends at the time when the last prepared slide was fixed in ethanol by the radiologist (study group) or at the time when the cytopathologist declared that the aspirated material was adequate for histologic diagnosis (control group). All obtained material was sent to the pathology laboratory. A total of 808 slides in the study group and 712 slides in the control group were obtained. In the pathology laboratory slides were stained with Papanicolaou dye. In both groups, the specimens were evaluated for adequacy and a final diagnosis was made by the same blinded cytopathologist who has more than 15 years of experience. In both groups, cytological diagnosis time and the
681
Table 1 The comparison of total biopsy times, cytopathologist’s definitive cytological diagnosis time (t1) and cytopathologist’s total time consumption for reviewing all specimens (t2) in the study and the control groups.
Patients (n) Total biopsy times (min) t1 (s) t2 (s)
Study group
Control group
p Value
101 8.74 ± 2.31 307.48 ± 226.32 672.93 ± 270.45
102 11.97 ± 6.75 350.14 ± 247.64 707.03 ± 258.78
.004 .137 .360
cytopathologist’s total time consumption in the laboratory were also noted. Although a definitive diagnosis can be made by the cytopathologist even after examining a single specimen, all the slides from all specimens are reviewed by the cytopathologist. Thus the diagnosis time (coined as t1) and the time required for reviewing all specimens (coined as t2) may be different from one another. There are various proposed adequacy criteria for thyroid FNAB [11,12]. In this study, we used criteria established by Kini for evaluating the adequacy of thyroid FNAB specimens [11]. Number of total aspirations and the cytopathologist’s total time consumption in the laboratory showed normal distribution and were analyzed with the Student t-test. Biopsy times and cytological diagnosis times did not show normal distribution and thus were analyzed with Mann–Whitney U test. The specimen adequacy ratio was analyzed with Pearson Chi-square test. A p value of 0.05 or less was accepted as statistically significant. Cytological adequacy was classified according to the criteria suggested by Kini et al. [11]. Cytological diagnosis was classified according to the Bethesda system (National Cancer Institute, Fourth Thyroid FNAB Guideline Commitee) into 6 groups [12]. 3. Results One hundred and one patients, 81 female and 20 male (ages 20–83, mean 49), with single nodule underwent aspiration in the study group. One hundred and two patients, 85 female and 17 male (ages 23–86, mean 50), with single nodule were sampled in the control group. Mean total biopsy time in the study group was significantly shorter than the mean total biopsy time of the control group (8.74 ± 2.31 vs. 11.97 ± 6.75 min respectively; p = 0.004) (Table 1). The average number of aspirations in the control group was significantly less than that of the study group (3.56 ± 1.23 vs. 4.00 ± 0 aspirations per patient; p = 0.001) (Table 2). The cytopathologist’s definitive cytological diagnosis time in the pathology laboratory (t1) was not significantly different between control and study groups (350.14 ± 247.64 vs. 307.48 ± 226.32 s respectively; p = 0.137) (Table 1). The cytopathologist’s total time consumption for reviewing all specimens in the pathology laboratory (t2) did not show statistically significant difference between control and study groups (707.03 ± 258.78 vs. 672.93 ± 270.45 s; p = 0.360) (Table 1). The diagnostic adequacy of aspirated specimens, which was assessed by the cytopathologist, did not show a statistically significant difference among the study and control groups (83.2% vs. 87.9%; p = 0.302) (Table 3).
Table 2 The comparison of biopsy aspiration numbers in the study and the control groups.
Study group Control group
Patient number
Average number of aspirations per patient
Standard deviation
p Value
101 102
4.00 3.55
0.00 1.23
.001 .001
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Table 3 Specimen adequacy ratio of biopsy aspiration material in the study and the control groups. Study group Adequate specimen Inadequate specimen Total
Control group
84 17
89 13
101
102
p Value .302 .302
Table 4 Comparison of the cytologic results according to the Bethesda classification. Bethesda classification
Study group
Control group
Total
Benign Atypia of undetermined significance Follicular neoplasm Suspicious for malignancy Malignant Non-diagnostic
68 (67%) 6 (6%)
72 (71%) 6 (6%)
140 12
10 (10%) 0
8 (8%) 2 (2%)
18 2
0 17 (17%)
1 (1%) 13 (13%)
1 30
101
102
203
Total
The cytologic results in both groups were determined according to the Bethesda classification. The results are summarized in Table 4. There was no procedure related complications in the control group. In the study group, a hematoma in the thyroid gland developed in one patient during the FNAB procedure which resolved spontaneously in 1 week. 4. Discussion With the utilization of thyroid FNAB procedures for suspicious thyroid nodules, a significant decrease was observed in the number of patients undergoing unnecessary thyroid surgery. This also led to an increase in the prevalence of malignancy of the pathologic specimens obtained by surgery. By assessing thyroid nodules and thus obviating the need for surgery; FNAB of thyroid nodules resulted in a significant decrease of the economic burden on the health care system [7,9,13–15]. US guided FNAB is a more effective technique than the – once conventional – unguided blind biopsies. It is the first method of choice for palpable and nonpalpable lesions and considered as the second method of choice in case of inadequate biopsy results obtained by FNAB guided by palpation [11]. Thyroid FNAB is recommended to be performed with the presence of an on-site cytopathologist in order to achieve higher adequacy rate [15]. This study compared the diagnosis and procedure times, total aspiration numbers and specimen adequacy of FNAB performed with and without an on-site cytopathologist. We have demonstrated that the procedure times have shortened without affecting the adequacy rates when the radiologist performed FNAB without an on-site associating cytopathologist. In a recent study, O’Malley et al. have demonstrated that the procedure times were shorter and the adequacy of the specimens did not differ when FNAB was done without a cytopathologist which is similar to our finding [16]. In current literature, to our knowledge, there are no studies comparing diagnosis and evaluation times by the cytopathologist for thyroid FNAB which makes this study unique. One may assume that when the specimens are evaluated on-site during the procedure, the cytopathologist would have a positive effect on the quality of the specimens and that would hasten the diagnosis during further evaluation in the cytopathology laboratory. However, if the radiologist is trained in smear preparation techniques, the results of the study showed that there was not
any statistically significant difference in time of diagnosis, thus we may consider that specimen quality was similar in both groups. Although this study was not designed for assessment of the quality of the specimens; with same adequacy rates and diagnosis times in both groups, we can assume that the quality was comparable. While designing the study, the authors had certain reservations regarding the number aspirations in the study group. According to our past experience in thyroid FNAB inadequate specimen ratio was unacceptably high with 3 aspirations per patient. In a study of thyroid FNAB without an on-site cytopathologist, by O’Mellay et al., 4 aspirations per nodule were performed by the radiologist. In that study there was also no statistically significant difference between the adequacy of specimens between cytopathologist assisted and unassisted biopsies [16]. In the light of previously published study, our past experience and a consensus with the pathology department; the authors agreed on doing 4 aspirations per patient. Less number of aspirations per patient will reduce total biopsy time and means less needle intervention which results in less patient discomfort and lower risk of complications. Also, less number of slides, fixation material and dye will be used per patient. Less time will be required by the cytopathology laboratory for evaluating all specimens and reporting will be hastened. There was a statistically significant difference in the number of aspirations between the groups (mean: 3.56 vs. 4.00 per patient; p = 0.001). The difference of the mean aspirations between the groups was 0.44 per patient. We believe that this difference is considerable. A high number of aspirations may cause higher complications or patient discomfort. However, the complication rate in thyroid FNAB is very low [8,17,18]. We have observed only one minor complication which was a small hematoma (less than 0.5%) in this study. Consequently we believe that a cytopathologist’s presence does not affect the risk of procedure related complications. Procedure times of both groups were compared and the study group was significantly faster than the control group (8.74 min vs. 11.97 min). Considering that the cytopathologist’s procedure for on-site evaluation; the shorter time spent by the sole radiologist who performs the aspiration and spreads the specimen is invariably a predicted result. This was also shown by O’Malley et al. that there are numerous benefits of a faster biopsy procedure for cytopathologist, radiologist and the patient [16]. Thyroid FNAB performed solely by the radiologist will result in an average daily workload reduction of the cytopathologist by 11.9 min per patient. This reduction does not take into account the transit time to radiology lab and on site preparation time. In this study, if all 203 biopsies had been performed with an on-site cytopathologist; an additional 1202 min (20.3 h and more than 2.5 work days of 8 h) would have been required by the cytopathologist. If the radiologist had performed all 203 biopsies without an on-site cytopathologist, he would have spent 3.2 min less for each nodule and a total of 326 min (5.4 h) for all 102 patients of the control group. In this study, cost-effectiveness analysis was not performed; we believe that thyroid FNAB without an on-site cytopathologist is more efficient in terms of time and workload; thus, it is also likely to be more cost-effective. A shorter biopsy procedure is also important for the patient comfort. We have some limitations in this study. The number of suspicious lesions and malignant lesions was very low. Although we have only evaluated the cytology results that were examined by an experienced cytopathologist it was not possible to compare with histopathology which is a gold standard method. In conclusion; US guided thyroid FNAB performed solely by the radiologist results in reduction of specimen processing times without statistically significant differences in specimen adequacy ratios, cytopathologist’s definitive diagnosis time and cytopathologist’s total time consumption for evaluation of all specimens. We believe that in centers where a cytopathologist is not available, US guided
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thyroid FNAB can be adequately performed by an experienced radiologist who has been effectively trained in basic cytotechnology. In centers where a cytopathologist is available, performing thyroid FNAB without an on-site cytopathologist is likely to be more time efficient and cost-effective. Conflict of interest The authors declare that there are no conflicts of interest. References [1] Wiest PW, Hartshorne MF, Inskip PD, et al. Thyroid palpation versus highresolution thyroid ultrasonography in the detection of nodules. J Ultrasound Med 1998;17:487–96. [2] Carroll BA. Asymptomatic thyroid nodules: incidental sonographic detection. Am J Roentgenol 1982;138:499–501. [3] Brander A, Viikinkoski P, Nickels J, et al. Thyroid gland: US screening in a random adult population. Radiology 1991;181:683–7. [4] Bruneton JN, Balu-Maestro C, Marcy PY, et al. Very high frequency (13 MHz) ultrasonographic examination of the normal neck: detection of normal lymph nodes and thyroid nodules. J Ultrasound Med 1994;13:87–90. [5] Horlocker TT, Hay ID. Prevalence of incidental nodular thyroid disease detected during high-resolution parathyroid sonography. In: Medeiros-Neto G, Gaitan E, editors. Frontiers in thyroidology, vol. 2. New York: Plenum; 1985. p. 1309–12. [6] Mortensen JD, Woolner LB, Bennett WA. Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955;15: 1270–80.
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