XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
Acta Radiol OnlineFirst, published on October 24, 2014 as doi:10.1177/0284185114554825
Original Article
Thyroid fine needle aspiration biopsy: do nodule volume and cystic degeneration ratio affect specimen adequacy and cytological diagnosis time?
Acta Radiologica 0(0) 1–6 ! The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185114554825 acr.sagepub.com
Ismet Cengic1, Derya Tureli2, Ferhat Ozden3, Onur Bugdayci4, Hilal Aydin2 and Erkin Aribal4
Abstract Background: A fine needle aspiration biopsy (FNAB) of thyroid nodules – the least invasive and most accurate method used to investigate malignant lesions – may yield non-diagnostic specimens even under ultrasonographic guidance. Purpose: To evaluate the effects of thyroid nodule volume and extent of cystic degeneration on both the non-diagnostic specimen ratio as well as cytopathologist’s definitive cytological diagnosis time. Material and Methods: In this single center study, FNAB was performed on 505 patients with single thyroid nodules greater than 10 mm. Nodule volume was calculated prior to FNAB and cystic degeneration ratio was recorded. All biopsies were performed by a single radiologist who also prepared specimen slides. Specimen adequacy and final diagnosis were made in the pathology laboratory by a single-blinded cytopathologist based on the Bethesda system. Definitive cytological diagnosis time was recorded upon reaching a definitive diagnosis. Results: The specimen adequacy ratio was 85.3%. The mean nodule volume of adequate specimens was larger than those of non-diagnostic samples (6.00 mL vs. 3.05 mL; P ¼ 0.001). There was no correlation between nodule volume and cytopathologist’s definitive cytological diagnosis time (r ¼ 0.042). Biopsy of predominantly solid nodules yielded better specimen adequacy ratios compared to predominantly cystic nodules (87.8% vs. 75.3%; P ¼ 0.028). Definitive cytological diagnosis times were longer in predominantly cystic nodules compared to predominantly solid nodules (376 s vs. 294 s; P ¼ 0.019). Conclusion: Predominantly cystic nodules are likely to benefit from repeated nodular sampling until the specimen is declared adequate by an on-site cytopathologist. If a cytopathologist is not available, obtaining more specimens per nodule may achieve desired adequacy ratios.
Keywords Thyroid nodule, fine needle aspiration biopsy, specimen adequacy, cystic degeneration ratio, nodule size Date received: 28 July 2014; accepted: 17 September 2014
Introduction
1
Thyroid nodules are relatively common lesions, which presence is determined in 4–8% and 10–41% of the adults either by palpation or ultrasound (US), respectively. An autopsy series reported prevalence of thyroid nodules as 50% (1–6). Imaging findings of thyroid nodules are not sensitive enough to differentiate between a benign and malignant nodule. The most accurate method for determining high-risk or malignant thyroid lesions is a fine-needle aspiration biopsy (FNAB) which
Department of Van, Turkey 2 Department of 3 Department of Van, Turkey 4 Department of Istanbul, Turkey
Radiology, Van Bolge Research and Education Hospital, Radiology, Ercis State Hospital, Ercis, Van, Turkey Pathology, Van Bolge Research and Education Hospital, Radiology, Marmara University School of Medicine,
Corresponding author: Derya Tureli, Ercis State Hospital, Radyoloji Bolumu, 65400 Ercis, Van, Turkey. Email: [email protected]
Downloaded from acr.sagepub.com at UNIV CALIFORNIA SAN DIEGO on August 31, 2015
XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
2
Acta Radiologica 0(0)
is also minimally invasive. Thyroid FNAB can be performed with or without the US guidance depending on whether it is a palpable or non-palpable nodule, respectively (7–9). In our institution, thyroid FNAB is performed with US guidance by a radiologist. A cytopathologist does not accompany a radiologist to determine specimen adequacy. The purpose of this single-center study was to evaluate the effects of thyroid nodule volume and cystic degeneration ratio on both the non-diagnostic specimen ratio and cytopathologist’s definitive cytological diagnosis time. Furthermore, we wanted to determine whether the probability of a specimen being identified as an adequate sample could be achieved using these nodule characteristics. Consequently, the necessary precautions, such as more interventions per nodule or performing the biopsy in the presence of a cytopathologist, could be taken in order to acquire an adequate sample and deliver an accurate diagnosis.
Material and Methods The study included 505 patients in the period between July 2013 and January 2014. All patients had single nodules with sizes >10 mm in the maximum diameter. Nodule volumes were calculated using the formula for an ovoid (volume ¼ width depth length p/6) and recorded before the procedure. Pure cystic nodules, regardless of the size, were excluded from the study. The ‘‘Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer’’ was used as a standard for patient enrollment in this study (10). US-guided FNAB was performed on all 505 patients by a single radiologist with 8 years of experience in thyroid FNAB. The radiologist received basic training in cytopreparation from an experienced pathologist. The same radiologist performed all of the biopsies under US guidance (Aplio MX, Toshiba, Japan) using a linear 7.2–14 Mhz probe and 22G aspiration needles. The cytopathologist did not participate in any of the 505 performed FNABs. An informed consent was obtained from every patient following the ethical committee guidelines. The same biopsy technique was used for all the cases; a patient in the supine position on the examination table with a rolled towel put under the neck providing hyperextension and maximal exposure. The US probe was used to locate the nodule followed by placement of a topical lidocaine ointment 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. Each aspiration was performed by a free-hand technique using sonographic guidance and a new 22G needle. The needle tip was placed inside the
nodule. If the nodule was predominantly cystic, the needle tip was placed in contact with the cyst walls. 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 two 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 with a 95% ethanol solution. The radiologist took four samples from each nodule and prepared eight cytologic slides per patient. All obtained material was sent to the pathology laboratory, where the slides were stained with Papanicolaou dye. The specimens were evaluated for adequacy using the Bethesda System for Reporting Thyroid Cytopathology (11). The final diagnosis was made by a single-blinded cytopathologist with more than 5 years of experience. Although all eight slides from each patient were stained, the cytopathologist did not necessarily need to examine all of the slides to reach a definitive diagnosis. The term ‘‘cytological diagnosis time’’ refers to the time period in which cytopathologist made his decision and was recorded by the pathologist. Then, the cytopathologist examined the rest of the slides to confirm his original diagnosis. Cytological diagnosis was classified according to the Bethesda system (National Cancer Institute, Fourth Thyroid FNAB Guideline Committee) into six groups (11). The Mann-Whitney U test was used to analyze nonnormal distributions. The Pearson Chi-square test was used to analyze the specimen adequacy ratio. ANOVA and post hoc Bonferroni tests were used to analyze the specimen adequacy and definitive cytological diagnosis time among groups based on cystic degeneration ratios. Correlation between nodule volume and cytopathologist’s definitive cytological diagnosis time was analyzed with Spearman’s test. A P value of 0.05 or less was accepted as statistically significant.
Results Five hundred and five patients, 440 women and 65 men (age range, 18–79 years; mean age, 44 years), with single nodules underwent aspiration. The aspirated nodule volumes were in the range of 0.22– 46.17 mL (mean, 5.51 mL 8.10 mL; median, 2.33 mL) (Fig. 1). The nodule cystic degeneration ratios are presented in Table 1. Predominantly solid nodules comprised 71.7% of all cases. Based on the Bethesda system, specimen adequacy was achieved in 431 patients (85.3%), while 74 biopsies (14.7%) did not yield diagnostic samples.
Downloaded from acr.sagepub.com at UNIV CALIFORNIA SAN DIEGO on August 31, 2015
XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
Cengic et al.
3
Fig. 1. Histogram of nodule volume frequencies with a normal curve. Forty-seven percent of the nodules had volumes less than 2 mL.
Table 1. Cystic degeneration ratios vs specimen adequacy and adequacy ratios. Cystic Adequate: degeneration Frequency/ Not Adequacy inadequate ratios (%) percent (%) Adequate* adequate ratios (%) ratios 0–25
362/71.7
318
44
87.8
7.2
26–50
43/8.5
38
5
88.4
7.6
51–75
23/4.6
17
6
73.9
2.8
76–100
77/15.2
58
19
75.3
3.1
Total
505/100
431
74
85.3
5.8
*Determined using the Bethesda System for Reporting Thyroid Cytopathology.
The cytopathologist’s definitive cytological diagnosis time in the pathology laboratory was in the range of 55–1062 s (mean, 307 225 s; median, 230 s). The nodules, which yielded adequate samples for cytological diagnosis, had a mean volume of 6.00 mL 8.62 mL. Meanwhile, the nodules which did not yield diagnostic samples had a mean volume of 3.05 mL 4.04 mL (P ¼ 0.001). Therefore, the probability of obtaining adequate specimens from larger nodules is statistically higher (Fig. 2).There was no correlation between nodule volume and cytopathologist’s definitive cytological diagnosis time in the pathology laboratory (Spearman’s rho r ¼ 0.042, P ¼ 0.344). The aspirated specimen diagnostic adequacy and cystic degeneration ratios are shown in Table 1. Based on cystic degeneration ratios, the adequacy rates were
Fig. 2. Boxplot graphic representation of nodule volume distribution for adequate and non-diagnostic specimens. The Bethesda System for Reporting Thyroid Cytopathology was used to determine the specimen adequacy.
Table 2. Post hoc Bonferroni test results comparing specimen adequacy among groups based on cystic degeneration ratios. Cystic degeneration ratio (%)
0–25
26–50
51–75
76–100
0–25 26–50 51–75 76–100
NA 1.000 0.394 0.028*
1.000 NA 0.670 0.310
0.394 0.670 NA 1.000
0.028* 0.310 1.000 NA
*Biopsy of predominantly solid nodules yields more favorable specimen adequacy ratios when compared to predominantly cystic nodules (P ¼ 0.028). However, there is no statistically significant difference among other group pairs.
statistically significant between predominantly solid and predominantly cystic nodules as shown in Table 2 and Fig. 3 (87.8% vs. 75.3%; P ¼ 0.028). The cytopathologist’s definitive cytological diagnosis times for groups based on cystic degeneration ratios are
Downloaded from acr.sagepub.com at UNIV CALIFORNIA SAN DIEGO on August 31, 2015
XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
4
Acta Radiologica 0(0) Table 4. Post hoc Bonferroni test results comparing definitive cytological diagnosis time among groups based on cystic degeneration. Cystic degeneration ratio (%) 0–25
26–50 51–75 76–100
0–25 26–50 51–75 76–100
1.000 NA 1.000 0.719
NA 1.000 1.000 0.019*
1.000 1.000 NA 0.230
0.019* 0.719 0.230 NA
*Definitive cytological diagnosis times are longer in predominantly cystic nodules when compared to predominantly solid nodules (P ¼ 0.019). However there is no statistically significant difference among other group pairs.
Fig. 3. Frequencies of cases in groups based on cystic degeneration ratios and specimen adequacy.
Table 3. Descriptive statistics of definitive cytological diagnosis times (seconds) in groups based on cystic degeneration ratios. Cystic degeneration ratio (%)
n
Minimum
Maximum
Mean SD
0–25 26–50 51–75 76–100
362 43 23 77
68 55 122 93
1062 753 464 658
294 239 311 195 260 130 376 177
shown in Table 3. There was a statistically significant difference between predominantly solid and predominantly cystic nodules when cytopathologist’s definitive cytological diagnosis times in the laboratory were analyzed based on cystic degeneration ratios as summarized in Table 4 and Fig. 4 (376 177 vs. 294 239 s; P ¼ 0.019). The cytologic results were determined according to the Bethesda classification. Of the 505 specimens, 348 (68.9%) were benign, 42 (8.3%) had atypia of unknown significance, 27 (5.3%) were follicular neoplasms, 10 (2.0%) were suspicious for malignancy, four (0.8%) were malignant, and 74 (14.7%) were non-diagnostic. There were no cases where the final diagnosis differed from the initial diagnosis, after the clock was stopped and cytopathologist went through all the slides.
Fig. 4. Boxplot graphics depicting descriptive statistics of definitive cytological diagnosis times among groups based on cystic degeneration ratios.
There were no significant procedure-related complications. A small hematoma at the biopsy site developed in two patients during the FNAB procedure, which resolved spontaneously in 1 week.
Discussion Biopsy of suspicious thyroid nodules with FNAB has led to a significant decrease in the number of patients undergoing unnecessary thyroid surgery and thus a significant reduction in the economic burden on the healthcare system as well as an increase in prevalence of malignancy among pathologic specimens obtained by surgery (7,9,12–14). A more effective technique than the unguided blind biopsies, US-guided FNAB has low false negative ratios, due to lower chance of needle misplacement, and results in a significant reduction in the ratio of non-diagnostic biopsies (15–18).
Downloaded from acr.sagepub.com at UNIV CALIFORNIA SAN DIEGO on August 31, 2015
XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
Cengic et al.
5
Prior thyroid FNAB with three aspirations per patient resulted in unacceptably high inadequate specimen ratio. A previous study, without an on-site cytopathologist and radiologist performing four aspirations per nodule, showed no statistical difference between cytopathologist assisted and unassisted biopsies specimen adequacy (19). Taking already published results as well as our past experience and a consensus with the pathology department, the authors agreed to perform four interventions per patient. Our study shows that smaller nodules are statistically more likely to yield non-diagnostic specimens. Kim et al. has shown that nodules with diameters 10 mm in size (79.6% vs. 95.2%) (20). In a similar study, the likelihood of obtaining non-diagnostic specimens from nodules
(ACR)
[1–6] [PREPRINTER stage]
Acta Radiol OnlineFirst, published on October 24, 2014 as doi:10.1177/0284185114554825
Original Article
Thyroid fine needle aspiration biopsy: do nodule volume and cystic degeneration ratio affect specimen adequacy and cytological diagnosis time?
Acta Radiologica 0(0) 1–6 ! The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185114554825 acr.sagepub.com
Ismet Cengic1, Derya Tureli2, Ferhat Ozden3, Onur Bugdayci4, Hilal Aydin2 and Erkin Aribal4
Abstract Background: A fine needle aspiration biopsy (FNAB) of thyroid nodules – the least invasive and most accurate method used to investigate malignant lesions – may yield non-diagnostic specimens even under ultrasonographic guidance. Purpose: To evaluate the effects of thyroid nodule volume and extent of cystic degeneration on both the non-diagnostic specimen ratio as well as cytopathologist’s definitive cytological diagnosis time. Material and Methods: In this single center study, FNAB was performed on 505 patients with single thyroid nodules greater than 10 mm. Nodule volume was calculated prior to FNAB and cystic degeneration ratio was recorded. All biopsies were performed by a single radiologist who also prepared specimen slides. Specimen adequacy and final diagnosis were made in the pathology laboratory by a single-blinded cytopathologist based on the Bethesda system. Definitive cytological diagnosis time was recorded upon reaching a definitive diagnosis. Results: The specimen adequacy ratio was 85.3%. The mean nodule volume of adequate specimens was larger than those of non-diagnostic samples (6.00 mL vs. 3.05 mL; P ¼ 0.001). There was no correlation between nodule volume and cytopathologist’s definitive cytological diagnosis time (r ¼ 0.042). Biopsy of predominantly solid nodules yielded better specimen adequacy ratios compared to predominantly cystic nodules (87.8% vs. 75.3%; P ¼ 0.028). Definitive cytological diagnosis times were longer in predominantly cystic nodules compared to predominantly solid nodules (376 s vs. 294 s; P ¼ 0.019). Conclusion: Predominantly cystic nodules are likely to benefit from repeated nodular sampling until the specimen is declared adequate by an on-site cytopathologist. If a cytopathologist is not available, obtaining more specimens per nodule may achieve desired adequacy ratios.
Keywords Thyroid nodule, fine needle aspiration biopsy, specimen adequacy, cystic degeneration ratio, nodule size Date received: 28 July 2014; accepted: 17 September 2014
Introduction
1
Thyroid nodules are relatively common lesions, which presence is determined in 4–8% and 10–41% of the adults either by palpation or ultrasound (US), respectively. An autopsy series reported prevalence of thyroid nodules as 50% (1–6). Imaging findings of thyroid nodules are not sensitive enough to differentiate between a benign and malignant nodule. The most accurate method for determining high-risk or malignant thyroid lesions is a fine-needle aspiration biopsy (FNAB) which
Department of Van, Turkey 2 Department of 3 Department of Van, Turkey 4 Department of Istanbul, Turkey
Radiology, Van Bolge Research and Education Hospital, Radiology, Ercis State Hospital, Ercis, Van, Turkey Pathology, Van Bolge Research and Education Hospital, Radiology, Marmara University School of Medicine,
Corresponding author: Derya Tureli, Ercis State Hospital, Radyoloji Bolumu, 65400 Ercis, Van, Turkey. Email: [email protected]
Downloaded from acr.sagepub.com at UNIV CALIFORNIA SAN DIEGO on August 31, 2015
XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
2
Acta Radiologica 0(0)
is also minimally invasive. Thyroid FNAB can be performed with or without the US guidance depending on whether it is a palpable or non-palpable nodule, respectively (7–9). In our institution, thyroid FNAB is performed with US guidance by a radiologist. A cytopathologist does not accompany a radiologist to determine specimen adequacy. The purpose of this single-center study was to evaluate the effects of thyroid nodule volume and cystic degeneration ratio on both the non-diagnostic specimen ratio and cytopathologist’s definitive cytological diagnosis time. Furthermore, we wanted to determine whether the probability of a specimen being identified as an adequate sample could be achieved using these nodule characteristics. Consequently, the necessary precautions, such as more interventions per nodule or performing the biopsy in the presence of a cytopathologist, could be taken in order to acquire an adequate sample and deliver an accurate diagnosis.
Material and Methods The study included 505 patients in the period between July 2013 and January 2014. All patients had single nodules with sizes >10 mm in the maximum diameter. Nodule volumes were calculated using the formula for an ovoid (volume ¼ width depth length p/6) and recorded before the procedure. Pure cystic nodules, regardless of the size, were excluded from the study. The ‘‘Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer’’ was used as a standard for patient enrollment in this study (10). US-guided FNAB was performed on all 505 patients by a single radiologist with 8 years of experience in thyroid FNAB. The radiologist received basic training in cytopreparation from an experienced pathologist. The same radiologist performed all of the biopsies under US guidance (Aplio MX, Toshiba, Japan) using a linear 7.2–14 Mhz probe and 22G aspiration needles. The cytopathologist did not participate in any of the 505 performed FNABs. An informed consent was obtained from every patient following the ethical committee guidelines. The same biopsy technique was used for all the cases; a patient in the supine position on the examination table with a rolled towel put under the neck providing hyperextension and maximal exposure. The US probe was used to locate the nodule followed by placement of a topical lidocaine ointment 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. Each aspiration was performed by a free-hand technique using sonographic guidance and a new 22G needle. The needle tip was placed inside the
nodule. If the nodule was predominantly cystic, the needle tip was placed in contact with the cyst walls. 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 two 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 with a 95% ethanol solution. The radiologist took four samples from each nodule and prepared eight cytologic slides per patient. All obtained material was sent to the pathology laboratory, where the slides were stained with Papanicolaou dye. The specimens were evaluated for adequacy using the Bethesda System for Reporting Thyroid Cytopathology (11). The final diagnosis was made by a single-blinded cytopathologist with more than 5 years of experience. Although all eight slides from each patient were stained, the cytopathologist did not necessarily need to examine all of the slides to reach a definitive diagnosis. The term ‘‘cytological diagnosis time’’ refers to the time period in which cytopathologist made his decision and was recorded by the pathologist. Then, the cytopathologist examined the rest of the slides to confirm his original diagnosis. Cytological diagnosis was classified according to the Bethesda system (National Cancer Institute, Fourth Thyroid FNAB Guideline Committee) into six groups (11). The Mann-Whitney U test was used to analyze nonnormal distributions. The Pearson Chi-square test was used to analyze the specimen adequacy ratio. ANOVA and post hoc Bonferroni tests were used to analyze the specimen adequacy and definitive cytological diagnosis time among groups based on cystic degeneration ratios. Correlation between nodule volume and cytopathologist’s definitive cytological diagnosis time was analyzed with Spearman’s test. A P value of 0.05 or less was accepted as statistically significant.
Results Five hundred and five patients, 440 women and 65 men (age range, 18–79 years; mean age, 44 years), with single nodules underwent aspiration. The aspirated nodule volumes were in the range of 0.22– 46.17 mL (mean, 5.51 mL 8.10 mL; median, 2.33 mL) (Fig. 1). The nodule cystic degeneration ratios are presented in Table 1. Predominantly solid nodules comprised 71.7% of all cases. Based on the Bethesda system, specimen adequacy was achieved in 431 patients (85.3%), while 74 biopsies (14.7%) did not yield diagnostic samples.
Downloaded from acr.sagepub.com at UNIV CALIFORNIA SAN DIEGO on August 31, 2015
XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
Cengic et al.
3
Fig. 1. Histogram of nodule volume frequencies with a normal curve. Forty-seven percent of the nodules had volumes less than 2 mL.
Table 1. Cystic degeneration ratios vs specimen adequacy and adequacy ratios. Cystic Adequate: degeneration Frequency/ Not Adequacy inadequate ratios (%) percent (%) Adequate* adequate ratios (%) ratios 0–25
362/71.7
318
44
87.8
7.2
26–50
43/8.5
38
5
88.4
7.6
51–75
23/4.6
17
6
73.9
2.8
76–100
77/15.2
58
19
75.3
3.1
Total
505/100
431
74
85.3
5.8
*Determined using the Bethesda System for Reporting Thyroid Cytopathology.
The cytopathologist’s definitive cytological diagnosis time in the pathology laboratory was in the range of 55–1062 s (mean, 307 225 s; median, 230 s). The nodules, which yielded adequate samples for cytological diagnosis, had a mean volume of 6.00 mL 8.62 mL. Meanwhile, the nodules which did not yield diagnostic samples had a mean volume of 3.05 mL 4.04 mL (P ¼ 0.001). Therefore, the probability of obtaining adequate specimens from larger nodules is statistically higher (Fig. 2).There was no correlation between nodule volume and cytopathologist’s definitive cytological diagnosis time in the pathology laboratory (Spearman’s rho r ¼ 0.042, P ¼ 0.344). The aspirated specimen diagnostic adequacy and cystic degeneration ratios are shown in Table 1. Based on cystic degeneration ratios, the adequacy rates were
Fig. 2. Boxplot graphic representation of nodule volume distribution for adequate and non-diagnostic specimens. The Bethesda System for Reporting Thyroid Cytopathology was used to determine the specimen adequacy.
Table 2. Post hoc Bonferroni test results comparing specimen adequacy among groups based on cystic degeneration ratios. Cystic degeneration ratio (%)
0–25
26–50
51–75
76–100
0–25 26–50 51–75 76–100
NA 1.000 0.394 0.028*
1.000 NA 0.670 0.310
0.394 0.670 NA 1.000
0.028* 0.310 1.000 NA
*Biopsy of predominantly solid nodules yields more favorable specimen adequacy ratios when compared to predominantly cystic nodules (P ¼ 0.028). However, there is no statistically significant difference among other group pairs.
statistically significant between predominantly solid and predominantly cystic nodules as shown in Table 2 and Fig. 3 (87.8% vs. 75.3%; P ¼ 0.028). The cytopathologist’s definitive cytological diagnosis times for groups based on cystic degeneration ratios are
Downloaded from acr.sagepub.com at UNIV CALIFORNIA SAN DIEGO on August 31, 2015
XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
4
Acta Radiologica 0(0) Table 4. Post hoc Bonferroni test results comparing definitive cytological diagnosis time among groups based on cystic degeneration. Cystic degeneration ratio (%) 0–25
26–50 51–75 76–100
0–25 26–50 51–75 76–100
1.000 NA 1.000 0.719
NA 1.000 1.000 0.019*
1.000 1.000 NA 0.230
0.019* 0.719 0.230 NA
*Definitive cytological diagnosis times are longer in predominantly cystic nodules when compared to predominantly solid nodules (P ¼ 0.019). However there is no statistically significant difference among other group pairs.
Fig. 3. Frequencies of cases in groups based on cystic degeneration ratios and specimen adequacy.
Table 3. Descriptive statistics of definitive cytological diagnosis times (seconds) in groups based on cystic degeneration ratios. Cystic degeneration ratio (%)
n
Minimum
Maximum
Mean SD
0–25 26–50 51–75 76–100
362 43 23 77
68 55 122 93
1062 753 464 658
294 239 311 195 260 130 376 177
shown in Table 3. There was a statistically significant difference between predominantly solid and predominantly cystic nodules when cytopathologist’s definitive cytological diagnosis times in the laboratory were analyzed based on cystic degeneration ratios as summarized in Table 4 and Fig. 4 (376 177 vs. 294 239 s; P ¼ 0.019). The cytologic results were determined according to the Bethesda classification. Of the 505 specimens, 348 (68.9%) were benign, 42 (8.3%) had atypia of unknown significance, 27 (5.3%) were follicular neoplasms, 10 (2.0%) were suspicious for malignancy, four (0.8%) were malignant, and 74 (14.7%) were non-diagnostic. There were no cases where the final diagnosis differed from the initial diagnosis, after the clock was stopped and cytopathologist went through all the slides.
Fig. 4. Boxplot graphics depicting descriptive statistics of definitive cytological diagnosis times among groups based on cystic degeneration ratios.
There were no significant procedure-related complications. A small hematoma at the biopsy site developed in two patients during the FNAB procedure, which resolved spontaneously in 1 week.
Discussion Biopsy of suspicious thyroid nodules with FNAB has led to a significant decrease in the number of patients undergoing unnecessary thyroid surgery and thus a significant reduction in the economic burden on the healthcare system as well as an increase in prevalence of malignancy among pathologic specimens obtained by surgery (7,9,12–14). A more effective technique than the unguided blind biopsies, US-guided FNAB has low false negative ratios, due to lower chance of needle misplacement, and results in a significant reduction in the ratio of non-diagnostic biopsies (15–18).
Downloaded from acr.sagepub.com at UNIV CALIFORNIA SAN DIEGO on August 31, 2015
XML Template (2014) [15.10.2014–5:52pm] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140172/APPFile/SG-ACRJ140172.3d
(ACR)
[1–6] [PREPRINTER stage]
Cengic et al.
5
Prior thyroid FNAB with three aspirations per patient resulted in unacceptably high inadequate specimen ratio. A previous study, without an on-site cytopathologist and radiologist performing four aspirations per nodule, showed no statistical difference between cytopathologist assisted and unassisted biopsies specimen adequacy (19). Taking already published results as well as our past experience and a consensus with the pathology department, the authors agreed to perform four interventions per patient. Our study shows that smaller nodules are statistically more likely to yield non-diagnostic specimens. Kim et al. has shown that nodules with diameters 10 mm in size (79.6% vs. 95.2%) (20). In a similar study, the likelihood of obtaining non-diagnostic specimens from nodules
