US-guided Fine-Needle Aspiration Biopsy of Thyroid Nodules: Adequacy of Cytologic Material and Procedure Time with and without Immediate Cytologic Analysis

¹ From the Departments of Radiology (M.E.O., P.F.H., B.J.W., P.R.M.) and Pathology (M.M.W., J.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass. From the 1999 RSNA scientific assembly. Received December 29, 2000; revision requested February 8, 2001; revision received and accepted August 28. 

	ABSTRACT

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PURPOSE: To compare the adequacy of aspirated material and procedure time when performing ultrasonography-guided fine-needle aspiration biopsy of thyroid nodules with and without immediate cytologic analysis of the aspirated sample.

MATERIALS AND METHODS: One hundred twenty-one thyroid nodules were sampled for biopsy in 109 patients. In group A, results of 50 biopsies in which immediate cytologic analysis was performed were retrospectively reviewed for cytologic adequacy. In group B, 50 biopsies were performed without immediate cytologic analysis, and the procedure time was recorded. In group C, 21 biopsies were performed with immediate cytologic analysis, and the procedure time was recorded. Cytologic adequacy rates were compared by using the proportional odds model, and procedure times were compared by using linear regression to adjust for differences in the character of the nodules.

RESULTS: For groups A and C (immediate cytologic analysis performed), the adequacy categories included the following results: 39 (55%) satisfactory, 15 (21%) limited, and 17 (24%) unsatisfactory. For group B (immediate cytologic analysis not performed), the adequacy categories included the following results: 25 (50%) satisfactory, 15 (30%) limited, and 10 (20%) unsatisfactory (Wald test, P = .815). The average procedure time was 12.5 minutes for group B and 44.4 minutes for group C (P < .001).

CONCLUSION: There was no significant difference in cytologic adequacy whether immediate cytologic analysis of aspirated material was performed or not. The procedure time was significantly shorter when immediate cytologic analysis was not performed.

　

Index terms: Thyroid, biopsy, 273.1261 • Thyroid, neoplasms, 273.36, 273.37

	INTRODUCTION

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Thyroid nodules are common in North American adults, and most are benign (1,2). When a thyroid nodule is discovered, imaging alone is not usually sufficient to characterize the nodule as benign or malignant (3,4). Fine-needle aspiration biopsy (FNAB) is currently the least invasive and most accurate method of identifying a high-risk or malignant lesion within the thyroid gland (3,4). FNAB of the thyroid gland is effective because it is a safe, accurate, and minimally invasive procedure (5). At our institution, ultrasonography (US)-guided FNAB of the thyroid gland is most commonly performed if a patient has nonpalpable nodules or if the result of FNAB obtained without image guidance is unsatisfactory.

Before undertaking the current study, we routinely performed US-guided FNAB of thyroid nodules with a cytopathologist present to immediately assess the adequacy of the aspirated material. Additional specimens were obtained if there was insufficient material in the initial aspirates. Although this method was time consuming, we believed that it would increase our ability to provide satisfactory material for cytologic analysis, as opposed to performing FNAB without immediate cytologic analysis. We had no scientific data to support this approach, however.

We therefore undertook this study to compare the adequacy of aspirated material and procedure time when performing US-guided FNAB of thyroid nodules with and without immediate cytologic analysis of the aspirated samples.

	MATERIALS AND METHODS

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A total of 121 thyroid nodules in 109 patients were included in this study, which was approved by our institutional review board. The nodules selected for biopsy were divided into three groups (groups A, B, and C). Group A consisted of 50 sequential US-guided thyroid nodule FNABs (in 41 patients) that were performed with immediate adequacy assessment by a cytopathologist. The procedure time was not recorded because the data in group A were obtained retrospectively. Group B was composed of the next 50 sequential US-guided thyroid nodule FNABs (in 47 patients). In group B, biopsy was performed without immediate assessment by a cytopathologist, and the procedure time was recorded. In group C, the next 21 FNABs (in 21 patients) were performed with immediate assessment by a cytopathologist, and the procedure time was recorded.

The size of each nodule was recorded on the basis of its largest diameter. Nodules were characterized as solid, predominantly solid (more than half of the nodule was solid), or predominantly cystic (more than half of the nodule was cystic). The number of needle passes and the number of slides reviewed for each nodule were recorded. The number and age of patients and the female/male distribution were also recorded. For group A, the data were retrospective, and the size and character of each nodule and the number of needle passes for each biopsy were not available. The results for each group are summarized in .

fig.ommitted  TABLE 1. Summary of Nodules and FNAB Study

 
For all nodules, the same biopsy technique was used, and informed consent was obtained from each patient. The patient was placed in a supine position with a rolled towel behind the lower cervical spine to extend the neck. The nodule was localized with a 10-MHz transducer prior to biopsy. The overlying skin was cleansed with iodine, and 1% lidocaine (Xylocaine; Astra USA, Westborough, Mass) was administered for local anesthesia.

A 22- or 25-gauge needle was attached to a 10-mL plastic syringe. With a freehand technique and direct US visualization, the needle tip was placed in the nodule, the syringe plunger was pulled back by 2–3 mL, and multiple excursions were made through the nodule. When an aspirate was bloody, the next needle pass was performed without suction. The aspirated material was placed on appropriately labeled glass slides, smeared, fixed in 95% ethyl alcohol, and either stained with hematoxylin-eosin for immediate interpretation or retained in alcohol for Papanicolaou staining later. Material flushed from the needle was placed in sterile, normal saline for Thin Prep (Cytyc, Boxborough, Mass) slide preparation.

When a cytopathologist was present (groups A and C), the aspirated material was placed on labeled slides, smeared, and stained (with hematoxylin-eosin) by a cytotechnologist and immediately examined with a microscope. A "rapid interpretation" was provided immediately by a cytopathologist. A final diagnosis was rendered within 24–48 hours on review of the material prepared for rapid interpretation and the remainder of the slides. Aspirates were obtained until the cytopathologist determined that adequate cellular material had been collected or until the procedure was terminated at the discretion of the radiologist performing the biopsy. In group C, the procedure time was defined as the time from placement of the first needle in the nodule until adequate cellular material had been obtained or until the procedure was terminated by the radiologist. When a cytopathologist was present (groups A and C), the maximum number of passes for each nodule was 12.

Without a cytopathologist present (group B), biopsy was performed according to a set protocol. A total of four aspirates were obtained with a 22- or 25-gauge needle according to the technique described above. The aspirates were expressed onto labeled glass slides, smeared, and placed in 95% ethyl alcohol by the radiologist. The needle and syringe were rinsed in normal saline for Thin Prep slide preparation. The slides and material flushed from the needle were sent to the cytopathology laboratory for analysis. The procedure time in group B (50 biopsies) was defined as the time from placement of the first needle in the nodule until removal of the fourth needle from the nodule.

All biopsies were performed or supervised by the same pool of staff radiologists throughout the study. All biopsies were performed in the same room, with the same US equipment and the same biopsy tray setup. There were no biopsy-related complications in our study population.

The adequacy criteria for thyroid nodule FNABs are not standardized, and they vary according to author and institutional preference (5–9). We chose our adequacy criteria  for FNAB of thyroid nodules on the basis of the Guidelines of the Papanicolaou Society of Cytopathology, and we assigned them in a retrospective manner (6).

fig.ommitted   TABLE 2. Adequacy Criteria for Thyroid Nodule FNAB

 
Retrospective review of all of the FNAB material was performed by one cytopathologist (J.M.), who assigned one of three adequacy categories (satisfactory, evaluation limited, or unsatisfactory) to each biopsy result. The adequacy categories were assigned on the basis of the criteria given in . The diagnosis for each nodule with a satisfactory or limited interpretation was recorded and is summarized in . The nodules that resulted in an unsatisfactory cytopathologic interpretation were reviewed to determine their outcome .

fig.ommitted  TABLE 3. Diagnostic Categories for Thyroid Nodule FNAB Groups

 

fig.ommitted  TABLE 4. Follow-up of Unsatisfactory FNAB Results

 
The thyroid nodule, rather than the patient, was used as the unit of analysis for this study. This was justified by analysis that showed no evidence for lack of independence on the adequacy assessment between multiple nodules in the same patient. The cytologic adequacy of the aspirated material in groups A and C (cytopathologist present, retrospective and prospective data) was compared with the adequacy in group B (cytopathologist not present, prospective data) by using the proportional odds model. The procedure time for group B was compared with that of group C by using linear regression to adjust for differences in nodule character between groups B and C. A P value of less than .05 was considered to indicate a statistically significant difference.

	RESULTS

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In groups A and C (cytopathologist present), 71 nodules were sampled for biopsy in 62 patients (eight patients underwent two biopsies, one patient underwent three biopsies). There were 43 women and 19 men, ranging in age from 20 to 81 years (mean, 52 years). A total of 875 slides were reviewed retrospectively (range, 5–29 slides; mean, 12 slides per nodule) . The assigned adequacy categories from the 71 aspirates included the following results: 39 satisfactory (55%), 15 limited (21%), and 17 unsatisfactory (24%). The procedure time in group C (21 biopsies) ranged from 20 to 90 minutes, with an average of 44.4 minutes .

fig.ommitted TABLE 5. Adequacy Categories and Procedure Time for Thyroid Nodule FNAB Groups

 
In group B (without a cytopathologist present), 50 nodules were sampled for biopsy in 47 patients (three patients underwent two biopsies). There were 41 women and six men, ranging in age from 18 to 78 years (mean, 46 years). A total of 429 slides were reviewed retrospectively (range, 7–9 slides; mean, nine slides per nodule) . The assigned adequacy categories from the 50 nodule aspirates included the following results: 25 satisfactory (50%), 15 limited (30%), and 10 unsatisfactory (20%). The procedure time ranged from 6 to 25 minutes, with an average of 12.5 minutes .

Comparison of groups A and C (cytopathologist present) with group B (cytopathologist not present) reveals that there was no significant difference in the adequacy of the aspirated material (Wald test, P = .815). Results of the Wald test in the comparison of groups A and C justified their pooling for adequacy analysis (P = .85). After adjusting for nodule character, the difference in mean procedure time for groups B and C was statistically significant (P < .001). The adjusted procedure time for group B was 31.7 minutes less (standard error, 2.9 minutes) than that for group C. This result is essentially the same as the unadjusted difference of 31.9 minutes.

Nodules assigned to the satisfactory or limited diagnostic categories were most commonly benign thyroid nodules, or they were associated with thyroiditis or cystic lesions . Nodules were comparable between groups.

The follow-up of nodules with unsatisfactory biopsy results is summarized in . In group A, there were 14 unsatisfactory biopsy results. Three nodules underwent repeat biopsy: Two were benign, and one was a papillary cancer. Six nodules were followed up with US: Three remained stable in size, and three decreased in size. One patient with two nodules underwent thyroidectomy, which revealed adenomatous hyperplasia. In three nodules, no follow-up imaging or biopsy was performed.

In group B, there were 10 unsatisfactory biopsy results. Repeat biopsy was performed in three nodules, and all three were benign. Three nodules were followed up with US, and all three remained stable in size. One benign nodule was excised. In three nodules, no follow-up imaging or biopsy was performed.

In group C, there were three unsatisfactory biopsy results. At follow-up, two nodules underwent repeat biopsy, and both were benign. One nodule underwent repeat biopsy twice, and the results were unsatisfactory on both occasions.

	DISCUSSION

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Since the introduction of FNAB in the assessment of thyroid nodules, there has been a demonstrable reduction in the number of patients undergoing surgery for benign thyroid nodules, an increase in the prevalence of malignancy in pathologic thyroid specimens obtained at surgery, and a demonstrable savings to the health care system (3,5,10,11). US-guided FNAB of the thyroid is often performed when attempts to obtain diagnostic material with direct-palpation needle-aspiration biopsy have failed. The use of US-guided FNAB may therefore reduce the number of open surgical procedures required to exclude thyroid nodule malignancy (12).

Our study showed no statistically significant difference in adequacy rates for US-guided thyroid nodule FNAB with and without immediate cytopathologic analysis. We did demonstrate a statistically significant difference between the procedure times of the two groups, with an average faster procedure time occurring with FNAB without immediate cytologic analysis (12.5 minutes vs 44.4 minutes). This may be an expected finding, given that intuitively, by involving a cytopathologist, there will be additional time spent on the procedure.

Other studies have examined the usefulness of having a cytopathologist present for immediate interpretation when performing image-guided biopsy. In the case of FNAB of the lung, biopsy findings tended to be more accurate when a cytopathologist was present during the procedure, but the study results were not always statistically significant (13–15). Results of some studies indicate that the presence of a cytopathologist may decrease the frequency of complications related to biopsy. For example, Johnsrude et al showed a decrease in the rate of pneumothorax when a cytopathologist was present because of a decrease in the number of needle passes required for diagnosis (16). When performing image-guided splenic biopsy, the presence of a cytopathologist has been advocated to reduce the risk of bleeding (17).

In the case of FNAB of the thyroid, complications are extremely rare (5). There were no complications in our study group, nor are we aware of a complication in any patient who has undergone US-guided FNAB of the thyroid at our institution in the past 10 years. Because the procedure is of such low risk, it is unlikely that the presence or absence of a cytopathologist would influence the rate of complications.

The number of unsatisfactory FNAB results in our study was similar between groups, regardless of whether immediate cytologic analysis was performed (groups A and C, 24%; group B, 20%). The unsatisfactory FNAB rate in this study is comparable to the nondiagnostic rates reported in the literature for FNAB performed without image guidance (18,19). The follow-up of nodules with unsatisfactory biopsy results at our institution is determined by the referring physician. In our study, 21 of the 27 nodules with unsatisfactory results underwent repeat biopsy, excision, or US follow-up. Of the nine nodules that underwent repeat biopsy, seven received a benign diagnosis, one yielded papillary cancer, and the results of one remained unsatisfactory despite a third biopsy. From these results, we believe that it is prudent and useful to perform repeat biopsy on nodules that initially yielded an unsatisfactory specimen. This is consistent with the recommendation of other authors, who have found malignancy in approximately 10% of excised nodules that had nondiagnostic aspirates (20).

Nodules that are predominantly cystic or small can yield unsatisfactory cytologic results because of sampling error (20). In the prospective portion of our study (groups B and C), results of 13 of 71 (18%) nodule biopsies were unsatisfactory. There were 61 nodules that were solid or predominantly solid, of which 10 (16%) yielded an unsatisfactory result. Of the 10 nodules that were predominantly cystic, three (30%) yielded an unsatisfactory result. Although these numbers are small, the results imply that a cystic nodule, rather than a solid nodule, is more likely to yield an unsatisfactory result.

There were 30 nodules less than 1.0 cm in size, and five (17%) yielded unsatisfactory results. Of the 41 nodules 1.0 cm or larger, eight yielded unsatisfactory results (20%). Thus, the size of the nodule did not appear to influence the adequacy of the aspirated material in our study.

In conclusion, our study demonstrated no significant difference in adequacy rate between US-guided thyroid nodule FNAB performed with and without immediate cytologic assessment; however, the procedure time was significantly shorter when FNAB was performed without immediate cytologic analysis. A shorter procedure time would result in a more comfortable procedure for the patient and a reduction in the use of valuable cytologic and radiologic resources. As a result of this study, we have changed our procedure for US-guided thyroid nodule FNAB: We no longer routinely request immediate cytopathologic analysis when performing thyroid FNAB. Immediate cytopathologic analysis is requested when results of a prior biopsy were unsatisfactory or when material needs to be prepared for special studies, such as in cases in which lymphoma is suspected or when there is a history of thyroid malignancy.

　

	ACKNOWLEDGMENTS

 
The authors thank George Tomlinson, PhD, for his assistance with the statistical review.

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