Comparison of palpation-versus ultrasound-guided fine-needle aspiration biopsies in the evaluation of thyroid nodules

Thyroid nodules are commonly encountered in clinical practice. There are only two recent practice guidelines for the management of thyroid nodules, both published in 2006. American Association of Clinical Endocrinologists (AACE) recommends ultrasound (USG)-guided fine-needle aspiration (FNA), universally for all thyroid nodules that are ≥ 10 mm in diameter in euthyroid subjects [1]. In contrast, American Thyroid Association (ATA) recommends either palpation- or ultrasound-guided FNA biopsy [2]. As established guidelines differ on the utility of ultrasound guidance, we aimed to compare the results of palpation-guided and ultrasound-guided thyroid fine-needle aspiration biopsies in our clinical case series.

We prospectively recorded the clinical information and cytology results of all consecutive patients who underwent FNA biopsy of thyroid nodules in the outpatient endocrinology clinic of our hospital in a computerized database. This prospectively-maintained database was retrospectively analyzed. All patients were examined by ASC, an endocrinologist who also performed all thyroid FNA biopsies between January 1998 and April 2003. Thyroid function tests and thyroid ultrasonography were routinely obtained. Free thyroxine (kit: FT4), free triiodothyronine (kit: FT3) and TSH (kit: TSH) were measured with electrochemiluminescence immunoassay in an Elecsys autoanalyzer. Kits and the autoanalyzer were supplied by the Turkish distributor of Roche Diagnostics, Indianapolis, IN, USA. Subjects were classified into euthyroid, hypothyroid and hyperthyroid categories according to the results of thyroid function tests. Thyroid scintigraphy with Technetium-99m was routinely obtained for all subjects who had low TSH levels and in some euthyroid subjects. Five patients had hyperactive nodules in thyroid scintigraphy and were excluded from this analysis. There were 299 subjects with thyroid nodules. Two hundred and twenty patients had a solitary thyroid nodule and 79 patients had a multinodular goiter. An ultrasound system (Ultramark 4+, Advanced Technology Laboratories, Washington, USA) with a 7.5 MHz linear array transducer was acquired by our outpatient endocrinology clinic in August 1999 and was used for all USG-guided biopsies since then. Seventy percent of palpation-guided biopsies were performed between January 1998 and August 1999 and 30% (n = 60) afterwards, at times when ultrasound system was temporarily unavailable. A published standard technique was used for palpation-guided FNA biopsies, performed by the investigator ASC [3]. All of the ultrasound-guided biopsies were performed between August 1999 and April 2003. The same investigator (ASC) performed all USG-guided biopsies with 22 or 26 G needles according to a previously published technique [4]. Local anesthesia with 2% lidocaine was routinely administered for both palpation- and USG-guided FNAs. Two needle aspirations were carried out for each nodule. If the material was judged macroscopically insufficient, up to four aspirations were performed to obtain additional material. On-site microscopic adequacy was not evaluated. Half of the slides were air-dried and stained with May-Grünwald-Giemsa and the other half were alcohol-fixed and stained with Hematoxylene-Eosine or Papanicolaou. The same investigator (KP) has evaluated all cytological smears. Cytological diagnoses were classified as recommended by existing guidelines into malignant, benign, indeterminate and inadequate for evaluation categories [2, 3]. Six clusters of benign cells in at least two slides constituted adequate material for cytological diagnosis. Each cluster was composed of at least 15 cells. The smears that do not meet these criteria were assigned into inadequate category. Indeterminate samples included a pattern of follicular or Hurthle cell neoplasm or aspects of atypia suggestive, but not conclusive of the presence of a malignant neoplasm [3].

Baseline characteristics and FNA results of ultrasound-guided and palpation-guided groups were compared. Parametric variables were presented as mean ± standard deviation and Student's t test was used for comparison. Because of its positively skewed distribution, logarithmic transformation of nodule diameter was used in Student's t test. Categorical variables were presented as percentages and chi-square test was used for comparison. Because the expected frequencies of malignant results were less than five in both groups, each cytology category in palpation- and USG-guided groups was compared by chi-square test after collapsing the rest of the categories. Fisher's exact test was employed when the expected frequencies were less than five. Malignant and indeterminate FNA cytology results were categorized into positive tests in construction of 2 × 2 tables in the calculation of sensitivity and specificity, as surgery is recommended to patients with such results. Benign and inadequate cytology results were categorized into negative tests, as surgery is not recommended in these circumstances. In 2 × 2 tables, benign and malignant surgical histopathology results were categorized as negative and positive disease, respectively. The study was approved by the Scientific Research Review Board of Vehbi Koc Foundation American Hospital. As this analysis was based on a clinical case series and the subjects were patients who seek medical care, the informed consent was for the performance of thyroid FNA biopsy. Informed consent to perform thyroid FNA was obtained from all subjects in accordance with the hospital bylaws and Turkish Ministry of Health rules. The study was in compliance with the Helsinki Declaration.

We have demonstrated that utilization of ultrasound guidance for thyroid FNA biopsies significantly decreases inadequate for evaluation category. We also confirm the high sensitivity and specificity of thyroid FNA biopsy in the diagnosis of thyroid cancer. In view of our results, where available, we recommend universal application of ultrasound guidance for thyroid fine-needle aspiration biopsy, as a standard component of this diagnostic technique.