Radiol med DOI 10.1007/s11547-016-0624-7
HEAD, NECK AND DENTAL RADIOLOGY
Potential causes for obtaining non‑diagnostic results from fine needle aspiration biopsy of thyroid nodules Deniz Özel1 · Betül Duran Özel2 · Fuat Özkan1
Received: 1 December 2015 / Accepted: 19 January 2016 © Italian Society of Medical Radiology 2016
Abstract Purpose The aim of this prospective study was to evaluate factors that could affect the diagnostic result success ratio of fine needle aspiration biopsy of thyroid nodules. Materials and methods 664 patients and 696 nodules were included in this study. Demographic features of age and gender and nodule features of macrocalcification (MC) and internal content (cystic or solid predominance) were evaluated. All biopsies were performed from 1 cm or larger nodules. Three different size needles were used for comparison (22, 23 and 25 G). The patients in each group had a similar number of nodules with MC, and cystic predominance to obtain comparable results. All procedures were performed by the same radiologist, who had 4 years of experience. Histologically adequate material criteria were identified. All pathological specimens were evaluated as diagnostic or non-diagnostic by the same pathology technician. Chi-square, student’s t test and univariate analysis were used for statistical analysis. Results There were no statistically significant differences in demographic features and nodule properties from diagnostic results of fine needle aspiration biopsy of thyroid nodules. On the other hand, 23 G needles offered a better potential for obtaining adequate samples with a statistically significant difference.
* Deniz Özel
[email protected] 1
Okmeydani Education and Research Hospital, Radiology Clinic, Kaptanpasa Mah. Darülaceze Cad. No:27, Okmeydan ı‑S¸is¸liIstanbul, 34384 Istanbul, Turkey
2
Sisli Hamidiye Etfal Education and Research Hospital, Radiology Clinic, Istanbul, Turkey
Conclusion Obtaining adequate material in fine needle aspiration biopsy from thyroid nodules is a challenging issue and the results are controversial. Since we obtained the best ratio with 23 G needles, we recommend interventional radiologists to use 23 G needles as far as possible and not to consider needles thicker needles than 22 G or thinner than 25 G. Nodule features and demographic features did not have an effect on obtaining adequate cytological material. Keywords Inadequate material · Thyroid nodules · Fine needle aspiration biopsy
Introduction Thyroid nodules are common and present difficulties in clinical diagnosis. Most glands are normal in palpation. Ultrasonography (USG) reveals the real prevalence and importance of nodules, which cannot be determined by physical examination. Although thyroid nodules are often seen, thyroid malignancies are rare and represent only 1 % of all malignant neoplasms [1]. Thyroid malignancies usually show an indolent nature and life expectancy is long after diagnosis, though early diagnosis is still important. USG sensitivity is very high for nodules undetectable in physical examination due to their small size or deep placement. As a result of the widespread use of USG, the number of thyroid nodules detected in asymptomatic patients is increasing [2]. The main problem of detected nodules in the thyroid gland is making a distinction whether nodule is benign or malignant. Thyroid function tests, scintigraphy and USG are routinely used in the diagnosis of thyroid nodules [3]. But, benign/malignant differentiation is not sufficiently precise
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Table 1 Baseline characteristics of study subjects Age (years), mean Internal content of nodules Solid predominance Cystic predominance Calcifications Macrocalcification No macrocalcification
Group 22 G (n = 232)
Group 23 G (n = 232)
Group 25 G (n = 232)
50.9
50.76
50.71
208 24
209 23
209 23
15
15
14
217
217
218
n number of biopsies, G gauge
with these methods. Fine needle aspiration biopsy (FNAB) provides more accurate information for obtaining histopathology of thyroid nodules, when considered in conjunction with other diagnostic methods. Today FNAB is the most valuable method used in the diagnosis of thyroid nodules [4–6]. FNAB’s most important limiting feature is the possibility of obtaining inadequate target cells from the sample material and even when there is sample material, the cells may be masked by other cells especially by red blood cells. In summary, FNAB is not the gold standard, but is a good screening method for diagnosis. The main causes of insufficient material can be summarized as follows: lack of sufficient cells from cystic, necrotic and calcified areas, small and inaccessible nodules, nodules showing compact architecture and blood cells masking target cells as a result of the traumatic effect of the procedure [7]. On the other hand, onsite adequacy assessment of thyroid FNAs significantly reduces the number of nondiagnostic aspirates [8]. There are controversial results in the literature on the size of needle that can provide the best specimens in terms of adequate cytopathology [8–13]. To our knowledge, our study represents the largest series in evaluating three different sizes of needles (22, 23 and 25 G). The aim of this prospective study was to evaluate factors that can affect the diagnostic result ratio in fine needle aspiration biopsy of thyroid nodules.
Patients and methods Patients A total of 664 patients and 696 thyroid nodules were prospectively reviewed by performing USG guided biopsy in institute between February and November 2015. The age and gender of all patients were noted. All thyroid nodules were evaluated with USG. They were divided into two groups according to their dominant component as solid or
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cystic. Evidence of macrocalcification (MC) was noted. Table 1 summarizes the baseline characteristics of the study. Only nodules larger than or equal to 1 cm in size were evaluated to exclude the effect of nodule size. FNAB procedure Before the procedure, all patients were questioned for contraindications such as anticoagulant medications or overanxiety preventing the procedure. Informed consents were acquired. After necessary sterilization was provided, topical 10 % lidocaine solution (Vemcaine Pump Spray 10 %, Nobel Farma, Turkey) was used as preanesthetic to reduce pain at the procedure site. The USG device was Qsonics (Ultrasonics Medical Co. Canada) and probe chosen was a 7.5 MHz linear probe. The probe was covered with a sterile instrument. All procedures were performed by the same interventional radiologist with 4 years of experience. Three types of needles were used for FNAB according to their thickness. They were 22, 23 and 25 G needles. Evidence of bleeding under the skin was controlled with USG after homeostasis. All patients were observed for a short period of time. Pathological results as diagnostic and non-diagnostic were calculated as frequency in percent. Diagnostic and non-diagnostic result frequencies were calculated according to patient age and gender. As nodule features; evidence of MC and solid or cystic dominance diagnostic ratios was calculated as well for comparison. Each needle thickness diagnostic frequency was calculated. Three different needle thicknesses were used: 22, 23 and 25 G needles. Patient mean age for each group was similar and each group had a similar number of MC and internal content to obtain comparable results. Histological evaluations were performed by the same pathology technician to prevent different diagnostic result ratios from different pathologists. Diagnostic adequacy criteria: If the specimen had at least one of these criteria below, it was considered as adequate.
Radiol med Table 2 Comparison of the study groups for adequacy rate according to ultrasonographic features Diagnostic results (n = 576) (% 82.8)
Non-diagnostic results (n = 120) (% 17.2)
p
50.48 ± 12.83
51.76 ± 14.16
0.17
Female (n = 565) (81.1 %)
467 (82.7 %)
98 (17.3 %)
0.80
Male (n = 131) (18.9 %)
109 (83.2 %)
22 (16.8 %)
Macrocalcification (n = 44)
34 (77.3 %)
10 (22.7 %)
No macrocalcification (n = 652)
542 (83.1 %)
110 (16.9 %)
Solid predominance (n = 626)
520 (83.1 %)
106 (16.9 %)
Cystic predominance (n = 70)
56 (80 %)
14 (20 %)
22 (n = 232)
183 (78.9 %)
49 (21.1 %)
23 (n = 232)
203 (85.8 %)
29 (14.2 %)
25 (n = 232)
190 (83.6 %)
42 (16.4 %)
Mean age (years) ± SD Gender
Calcifications 0.42
Internal content of nodules 0.54
Needle thickness (G) 0.045
n number of biopsies, G gauge, SD standard deviation
1. Evidence of 6 follicular cell groups each containing at least 10 cells in any slice. 2. Evidence of follicular cells showing cellular atypia regardless of their count. 3. Evidence of many inflammatory cells. 4. Evidence of intense colloid. Statistical analysis Continuous variables are expressed as mean ± SD, and categorical variables as percentages. Patients were categorized into two groups as having adequate cytological material (CM) or inadequate CM. Comparisons between groups of patients were done using χ2 test for categorical variables and independent samples t test for normally distributed continuous variables. Univariate analysis was used to quantify the association of variables with inadequate CM. All statistical procedures were performed using a Microsoft updated Excel program. A p value of equal to or less than 0.05 was considered as statistically significant.
Results The number of patients and biopsies were 664 and 696, respectively. 540 (81.3 %) of the patients were female and 124 (18.7 %) were male. 565 samples were obtained from females (81.1 %) and 131 (18.9 %) from male patients. The mean age of the patients was 50.79 ranging from 18 to 83 years. Each group contained similar numbers of nodules with MC and cystic predominance (CP). Patient mean age was similar for each group (Table 1).
The number of diagnostic results for all patients was 576 (82.8 %) and for non-diagnostic results it was 120 (17.2 %). There was not statistically significant difference in the mean age of patients with diagnostic material versus those with non-diagnostic material (p = 0.17). The difference in diagnostic results between female and male patients was not statistically significant (p = 0.8). The difference in ratios of diagnostic results from nodules containing MC and those not containing MC, was not statistically significant (p = 0.42). The difference between ratios of diagnostic results from nodules showing CP and solid predominance (SP) was not statistically significant (p = 0.54). The difference between ratios of diagnostic results from the three size of needles was statistically significant (p = 0.045) (Table 2). Figure 1 summarizes the whole study.
Discussion Many factors defined as causes for obtaining inadequate (or non-diagnostic) material from fine needle aspiration biopsy of thyroid nodules are suggested in the literature. These include demographic features, nodule size, nodule composition, vascularity, MC and needle thickness [7]. Patient dependent causes are limitation of throat motion and patient unexpected activity as a result of anxiety during the operation [8]. In previous studies, researchers have evaluated needles with sizes from 21 to 25 G. In evaluation of their results we realized that thinner size needles offer better results so we
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Radiol med 22 G 50
25 G
45 40 35
23 G
30
49
25 42
20 15 10 5 0
Male
29
No 22,7
17,3 16,8
Needle
Yes
Female
Gender
16,9
MC
CP SP
20
16,9
Architecture
Fig. 1 Non diagnostic results. Needles section as count and rest as percent
excluded 21 G needles from our study. After facing some problems obtaining 24 G needles from the medical market we finally decided to compare 22, 23 and 25 G needles. In our study, 565 of 696 (81.1 %) samples obtained from female patients. This ratio is consistent with the literature. Thyroid disease including nodules is 3–4 times more common in females [9–11]. In comparing the diagnostic result ratio for both genders, it was found to be higher for male patients (82.7–83.2 %). As expected, the difference was not statistically significant. Ucler et al. [12] also did not find a significant difference between the two genders in their study that included 140 patients. In comparing patient age, there was no statistically significant difference for different ages. On the other hand Inci et al. [13] found the inadequate material ratio to be higher in older patients. The mean age of diagnostic results was lower in our study as well, but the difference was not statistically significant. In our experience older patients tend to be anxious because they expect poor results of biopsy evaluation. Patient anxiety affects the procedure in a negative way. They tend to breathe rapidly and move more often, etc. Such that results are not obtained. To evaluate nodule dependent factors two features were included. They were the existence of MC and internal content. MC was chosen because this tends to be found in dead and degenerative tissues. Forty of the thyroid nodules had MC and the frequency was 6.3 %. In this study those nodules were relatively rare. The diagnostic result frequency from those nodules was 77.3 %. When comparing the mean diagnostic frequency it was lower, but the difference was not statistically significant. Ucler et al. [12] found the same result and stated that, evidence of MC does not influence obtaining diagnostic material. If nodules with a size of 1 cm were included in the study, non-diagnostic results
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would be higher since the area with MC would increase proportionally. As a second feature internal content was evaluated. Two groups of nodules were formed as SP and CP. If the nodule was pure solid it was assigned to the first group and if it was pure cystic, it was assigned to the second group. In the comparison, the majority of nodules were SP (around 90 %). SP nodule diagnostic results were higher than for CP (83.1–80 %), but the difference was not statistically significant. Ucler et al. [12] evaluated internal content in their groups as pure solid, SP and CP. They found statistically significant differences in obtaining diagnostic CM only for SP nodules with 22 and 27 G needles. Since the pathology technician was in the procedure room and was aware that those nodules had a cystic component. She took this into account when making her decision. This can be an important reason why the CP nodule diagnostic results were not lower. Nodules smaller than 1 cm were already excluded to obtain comparable results with respect to their size. The patient population was chosen with a similar mean age, including the same number of MC and internal content for each needle thickness. When comparing diagnostic results, the best ratio was obtained with the 23 G needle (85.8 %) and the worst with the 22 G needle (78.9 %), while the 25 G needle ratio was in between (83.6 %). There are controversial results on this issue in the literature. Gumus et al. [14] compared 21 and 27 G needles and did not find a significant difference in obtaining adequate CM in their study with 100 patients. Inci et al. [13] compared 20, 22 and 24 G needles and did not find a significant difference in their study with 270 patients. On the other hand, Tangpricha et al. [15] compared 21 G and 25 G needles in their study with 50 patients and declared that 21 G needles provided more cellular samples than 25 G needles in fine needle aspiration biopsy of the thyroid, but may not provide increased diagnostic accuracy. Degirmenci et al. [16] found significant differences in obtaining adequate CM when using 20, 22 and 24 G needles in their study with 232 thyroid nodules. Aslaner et al. [17] also found a statistically significant difference in obtaining adequate CM in comparison of 21 and 25 G needles in their study including 252 thyroid nodules. In our experience, using needles as thick as 22 G may provide more specimen, but traumatic effects will increase. As a result, blood cells mask the other cells we aim to observe and greatly decrease the diagnostic ratio. The lowest ratio was obtained from the thickest needle and this should be the reason. On the other hand using thin needles is less traumatic, but of course the observer cannot obtain as much specimen. Especially when using needles thinner than 25 G, the specimen containing needle can be clogged easily, causing
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another problem. With this background the 25 G needle was chosen as the thinnest choice. To take the middle course, the best ratio was obtained with 23 G needles. Obtaining adequate material in fine needle aspiration biopsy from thyroid nodules is a challenging issue and the results from it are controversial. In conclusion using around 23 G needles as far as possible and not considering to use thicker needles than 22 G or thinner needles than 25 G can be recommended to interventional radiologists. Compliance with ethical standards Conflict of interest The authors declare that they have no conflict of interest. Ethical statement All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.
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