Do They Do Needle Biopsys Based On The Size Of A Thyroid Nodule

Fine-needle aspiration biopsy (FNAB) is considered the most reliable diagnostic test for evaluation of thyroid nodules and has a low rate of complications, especially when ultrasound guidance is used. Use of FNAB increases the rate of detection of thyroid cancer and reduces the number of unnecessary surgical procedures and overall cost of medical intendance [ane–3]. However, performing FNAB on every thyroid nodule detected with ultrasound is non cost-effective because of the loftier prevalence of nodules. Studies have been conducted to identify sonographic features suggestive of malignancy. These findings include hypoechogenicity, irregular or microlobulated margins, calcifications, greater length than width, intranodular vascularity, solitary presence, and solid components [iv–11]. No single ultrasound feature, however, has a high positive predictive value (PPV) for cancer that tin be used to identify nodules that should exist subjected to FNAB. For this reason, guidelines with various combinations of ultrasound features that are both sensitive and specific for predicting the presence of cancer have been defined in several studies, but debate continues about which guidelines are the most accurate and effective [4, five, vii–nine, 12, 13]. It is difficult to compare the accuracy of sets of guidelines, however, because of the differing samples in the studies in which the guidelines were established. In this report, we calculated the take a chance of malignancy of thyroid nodules with known suspicious sonographic features. We practical three sets of sonographic criteria from previous reports to the same sample to assess the diagnostic performance of the criteria in prediction of the presence of histologically confirmed malignancy.

The institutional review board of our university approved this study, and informed consent was not required. Informed consent for FNAB had been obtained from all patients before biopsy.

Study Sample

From September 2002 through July 2004, one,583 nodules in ane,491 patients (one,371 women and girls [91.9%], 120 men [8%]; mean historic period, 49.0 years; range, nine–82 years) were biopsied under ultrasound guidance. Multiple nodules were present in 626 patients (42%). FNAB was performed on the largest of nodules with like ultrasound features merely on each nodule when multiple nodules had several different ultrasound features.

Ane of five cytopathologists specializing in thyroid cytology interpreted the ultrasound-guided FNAB findings. The cytopathologist knew the ultrasound diagnosis made by the radiologist. At our institution, cytologic reports from ultrasound-guided FNAB indicate whether a specimen is adequate or inadequate. A specimen was considered adequate if a minimum of 6 groupings of well-preserved thyroid cells consisting of at least ten cells per group was present [8]. The acceptable specimens were farther divided into the four subgroups benign, indeterminate, suspicious for papillary carcinoma, and malignancy. A benign cytologic finding included colloid nodules, nodular hyperplasia, lymphocytic thyroiditis, Graves illness, and postpartum thyroiditis. Indeterminate cytologic findings included follicular and Hürthle cell neoplasia. The finding suspicious for papillary carcinoma was used when the specimen exhibited cytologic atypia (nuclei crowded and overlapping, enlarged, and pleomorphic) only insufficient cellularity for a definite diagnosis of papillary carcinoma. Cytologic results were classified as malignancy when the specimen exhibited abundant cells with unequivocal cytologic features of cancer. Cytopathologic results obtained upward to 2008 were reviewed retrospectively; the results of repeated biopsy were included in the data analysis.

Among ane,583 nodules, thyroidectomy was performed for 455 nodules, including 33 with nondiagnostic cytologic findings, 111 benign nodules, 27 follicular neoplasms, 78 nodules suspicious for papillary carcinoma, and 206 malignant nodules (Fig. i ). Surgery was performed on nodules with benign cytologic findings for the post-obit miscellaneous reasons: suspicious ultrasound findings in v patients, thyroid nodules showing substantial growth in 19, and compression symptoms or corrective problem due to large goiter (> 3 cm) in 40 patients. The other patients with thyroid nodules with benign cytologic findings underwent thyroid resection because they elected this method of treatment. Because surgery was not performed after FNAB, 128 of 161 nodules with nondiagnostic cytology, 25 of 52 nodules with cytologic findings of follicular neoplasm, and 32 of 110 nodules suspicious for papillary carcinoma were excluded from this study. Nodules with benign (n = 1,016) or malignant (n = 244) cytologic findings were included whether or not the patient underwent surgery.

Sonographic Evaluation and Ultrasound-Guided FNAB

Thyroid ultrasound (HDI 3000 or 5000 unit, Philips Healthcare) was performed with a vii- to 12-MHz transducer. All images were sent to the local PACS for review. Ane experienced radiologist who performed FNAB prospectively described the sonographic characteristics of thyroid nodules with respect to the following parameters: size, multiplicity, composition, echogenicity, margin, calcification, shape, and abnormal cervical lymph nodes.

Size was measured at the maximum dimension. Substantial growth was retrospectively assessed in 287 nodules examined with ultrasound at least 6 months before FNAB. The composition of the nodule was classified as purely cystic, mixed, or solid on the basis of the ratio of the cystic portion to the solid portion in the nodule. A purely cystic nodule was completely anechoic with or without a comet-tail artifact. A nodule having both a cystic and solid portion was defined as a mixed echoic nodule. Echogenicity of a mixed echoic nodule was assessed on the basis of the solid portion. The echogenicity of the nodule was compared with that of the surrounding parenchyma and was classified as hypoechogenic, isoechogenic, or hyperechogenic. Marked hypoechogenicity was defined as lower echogenicity than the cervical strap musculus.

The margin of a nodule was described besides confining or not well circumscribed, which included irregular or microlobulated margins. Microcalcifications were defined equally tiny (< two mm diameter), punctuate, and hyperechoic foci with or without audio-visual shadows. Macrocalcifications or coarse calcifications were defined as larger than 2 mm. Mixed calcifications were defined as a combination of microcalcifications and macrocalcifications, which were reclassified as the presence of microcalcifications. Shape was assessed equally the ratio of anteroposterior to transverse diameter (≥ 1 or < i). Abnormal lymph nodes were defined as lymph nodes with heterogeneous echotexture, calcifications, cystic areas, and round shape.

Ultrasound-guided FNAB was performed past ane experienced radiologist using a 23-guess needle fastened to a 20-mL dispensable plastic syringe and aspirator. Each lesion was aspirated at least twice. Materials obtained at aspiration biopsy were expelled onto glass slides and smeared. All smears were placed immediately in 95% alcohol for Papanicolaou staining. The rest of the fabric was rinsed in saline solution for processing every bit a cell block. The cytopathologist was not on site during the biopsy. Additional special staining was made on a example-past-case basis co-ordinate to the requirements of the cytopathologist.

Comparison of Guidelines

3 sonographic criteria were applied to our data to compare the accuracies of the various guidelines in prediction of cancer. In improver, we regrouped the study sample with nodules i cm or more in bore and analyzed them in the same way.

Kim criteria—According to the Kim criteria [iv], FNAB of nodules with any single suspicious ultrasound feature, regardless of nodule size, is recommended. Suspicious sonographic features are divers every bit marked hypoechogenicity, irregular or microlobulated margins, microcalcifications, and anteroposterior to transverse diameter ratio of 1 or greater (Fig. 2 ).

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Fig. two —42-year-old adult female with thyroid nodule. Transverse ultrasound image of left lobe of thyroid shows 10-mm wider than long (anteroposterior diameter, 7 mm; transverse bore, 10 mm) hypoechoic nodule with irregular margin (arrow). These ultrasound findings would atomic number 82 to fine-needle aspiration biopsy on basis of Kim and American Clan of Clinical Endocrinologists criteria. Nodule was confirmed papillary carcinoma with extrathyroidal invasion.

Society of Radiologists in Ultrasound criteria—The Society of Radiologists in Ultrasound criteria [vii] are based on the size and ultrasound characteristics of thyroid nodules. The recommendations for FNAB are as follows: nodule 1.0 cm or more in diameter if microcalcifications are present; nodule one.5 cm or more in diameter if completely or almost entirely solid or if coarse calcifications (classified as macrocalcifications) are present; nodule 2.0 cm or more in diameter if mixed solid and cystic components are present or nodule is most entirely cystic with a solid mural component; and nodule has grown substantially since previous ultrasound examination (Figs. 3 and four ). Because there was no consensus on the definition of substantial growth that would necessitate biopsy, we included nodules with an increase in maximal diameter of 3 mm or more [14]. This guideline also calls for FNAB when abnormal lymph nodes are present regardless of the ultrasound features of thyroid nodules. Ultrasound features associated with loftier risk of cancer are defined as lymph nodes with heterogeneous echotexture, calcifications, cystic areas, circular shape, and mass effect. Because lymph node size is not mentioned, nosotros included morphologically abnormal lymph nodes regardless of size.

American Association of Clinical Endocrinologists criteria—According to the American Association of Clinical Endocrinologists guidelines [8], FNAB should be performed on all hypoechoic nodules with at least i of the following boosted ultrasound features: irregular margins, intranodular vascular spots, longer than broad shape, or microcalcifications (Fig. ii ). The parameter intranodular vascularity was excluded from our written report because color Doppler sonography was not performed.

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Fig. iii —47-year-old woman with thyroid nodule. Transverse ultrasound image of thyroid shows 7-mm well-defined, longer than wide (anteroposterior diameter, 7 mm; transverse diameter, iv mm) isoechoic nodule (arrow). Fine-needle aspiration biopsy was recommended but on basis of Kim criteria, and nodule was confirmed papillary carcinoma with extrathyroidal invasion.

Statistical Analyses

Statistical assay was performed with statistical software (SAS version 9.1.3, SAS; MedCalc version 9.three.vi.0, MedCalc). The odds ratio of malignancy for each ultrasound feature was calculated with logistic regression assay. We calculated sensitivity, specificity, PPV, negative predictive value (NPV), and accuracy for individual sonographic characteristics and various combinations of sonographic features. The diagnostic accuracy of predictions of malignancy was calculated with receiver operating feature assay of each set of guidelines. The number of nodules recommended for FNAB and the rate of missed carcinoma were assessed on the basis of the criteria, and statistical significances was evaluated with Yates correction for continuity.

A total of 1,398 nodules in ane,318 patients (1,217 women, 101 men; hateful age, 46.3 years) were included in this report. The final diagnosis was based on surgical pathologic findings or on cytologic findings if the patient did not undergo surgery. At that place were i,071 benign (76.6%) and 327 malignant (23.4%) nodules (Table 1). The diagnosis of malignancy included papillary carcinoma (n = 319), follicular carcinoma (n = 3), lymphoma (n = 1), medullary carcinoma (north = 1), anaplastic carcinoma (n = 1), metastasis from breast cancer (north = 1), and poorly differentiated carcinoma (n = 1). The hateful size of the nodules was 16.half dozen mm (range, 3–100 mm); 402 nodules (28.viii%) were smaller than ane cm in bore. The hateful size of benign nodules was 17.9 mm (range, 3–100 mm) and of cancerous nodules was 12.1 mm (range, 3–80 mm). Among 287 nodules that had been examined with ultrasound at least 6 months before FNAB, 36 nodules (12.5%) had an increase in maximal diameter of 3 mm or more.

Table 1: Size and Pathologic Features of Thyroid Nodules in Study Sample (n = 1,398)

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Fig. 4 —32-twelvemonth-old woman with thyroid nodule. Transverse ultrasound image of thyroid shows 4-cm well-defined mixed solid and cystic nodule. Fine-needle aspiration biopsy would be recommended merely with Order of Radiologists in Ultrasound criteria. Surgical finding was adenomatous hyperplasia.

Ultrasound Findings

Contained predictors of the presence of cancerous thyroid nodules at ultrasound examination are irregular or microlobulated margins, microcalcifications, marked hypoechogenicity, hypoechogenicity, longer than wide shape, solidity, and presence of calcifications (Tabular array 2). These seven ultrasound findings had meaning associations with the presence of malignancy (p < 0.001). Morphologically abnormal lymph nodes were plant merely in cases of malignancy (17/327). Solitary or multiple nature was not associated with chance of malignancy (odds ratio, 1.i). The frequency of each suspicious ultrasound feature based on nodule size is shown in Table 3. All suspicious findings, except abnormal lymph node, were made significantly more than oftentimes in nodules smaller than i cm.

Tabular array 2: Diagnostic Accuracy of Ultrasound Findings for Presence of Malignant Nodules

Table 3: Frequency of Suspicious Ultrasound Features Co-ordinate to Nodule Size

Diagnostic Performance According to the Three Sets of Guidelines

The sensitivity, specificity, PPV, and NPV of the Kim criteria were estimated to be 92.7%, lxxx.9%, 59.vi%, and 97.iii%. The area under the receiver operating characteristic curve (A _z ) based on the Kim criteria was 0.868. The A _z value based on the Society of Radiologists in Ultrasound criteria was 0.551 (p < 0.001), and the A_z based on the American Association of Clinical Endocrinologists criteria was 0.850 (p = 0.179) (Fig. 5 ). The sensitivity, specificity, PPV, and NPV of each gear up of criteria are shown in Table 4.

Tabular array 4: Diagnostic Accuracy of Each Fix of Criteria

In a comparison of the A _z of the Kim criteria with that of the other criteria for nodules 1 cm or more in diameter (Table four), the A _z of the Kim criteria was 0.872, significantly greater than that of the Society of Radiologists in Ultrasound criteria (0.567; p < 0.001). The Kim criteria appeared to exist more than accurate than the American Association of Clinical Endocrinologists criteria for nodules 1 cm in bore or larger (A _z = 0.872 vs 0.842; p = 0.117), merely the divergence was not significant.

The three sets of guidelines were compared to determine the number of biopsies that would have been performed and the number of cases of cancer that would accept been missed had the criteria been applied (Table 5). For all nodules, the percent of nodules recommended for FNAB on the basis of the American Clan of Clinical Endocrinologists criteria could have been reduced to 25.6% (358/ane,398), significantly lower than that based on the other criteria (p < 0.001). All the same, the percentage of malignant tumors missed with employ of the Kim criteria (7.3%) was the everyman (p < 0.001). When we applied the criteria to thyroid nodules 1 cm in diameter or larger, employ of the American Association of Clinical Endocrinologists criteria would have decreased the number of nodules for which FNAB is recommended to xvi.5%, and the Kim criteria showed low risk of missing carcinoma (x.8%).

TABLE v: Biopsies That Would Have Been Performed and Cases of Thyroid Carcinoma That Would Have Been Missed With Each Set of Criteria

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Fig. 5 —Graph shows receiver operator characteristic curves for Kim criteria (solid curve), Society of Radiologists in Ultrasound criteria (dashed bend), and American Association of Clinical Endocrinologists criteria (dotted bend).

Detection of thyroid nodules has increased with the wide use of ultrasound, and it is important to exclude the presence of malignancy, which is found in approximately 5% of all thyroid nodules regardless of size [8]. Because of the high prevalence of thyroid nodules, it is essential to decide a reliable and cost-effective guideline for basing the direction of thyroid nodules on the ultrasound features. In a multicenter retrospective study, spiculated margins, microcalcifications, marked hypoechogenicity, longer than wide shape, and macrocalcifications had a pregnant association with the presence of malignancy [15]. These suspicious features had relatively high specificity (fourscore.8–96.1%) and PPV (64.8–81.3%) even though the sensitivity was low (9.seven–48.3%). No unmarried sonographic feature, however, is accurate plenty for a recommendation of FNAB; therefore, several guidelines with various combinations of suspicious ultrasound findings take been suggested [4, 7, 8].

In this study, the A _z of the Kim and American Association of Clinical Endocrinologists criteria were comparable (0.868 and 0.850). Both of these values were superior to that of the Society of Radiologists in Ultrasound criteria (A _z = 0.551). The Kim criteria were originally suggested for recommendations of FNAB of nonpalpable solid nodules of the thyroid and had high sensitivity (93.eight%) and NPV (95.9%). Tae et al. [16] applied the same FNAB criteria to palpable or nonpalpable thyroid nodules and besides found a high NPV (97.8%) and diagnostic accuracy (86.five%). These results advise that the Kim criteria can be applied not simply to nonpalpable nodules only also palpable nodules.

The Lodge of Radiologists in Ultrasound recommendations are based on the size and ultrasound characteristics of thyroid nodules measuring i cm or more than in largest diameter. They do not call for FNAB of a nodule smaller than 1 cm because it is assumed that thyroid surgery for microcarcinoma may not amend life expectancy owing to the indolent clinical grade of this tumor. Nevertheless, the prevalence of thyroid cancer does non differ between nodules larger or smaller than 1 cm [five, 6]. Furthermore, microcarcinoma can have an aggressive course, including extracapsular growth and nodal metastasis [five, half dozen, 17–21].

The overall malignancy charge per unit in our study was 23.4% (327/1,398). This high rate was due to the high prevalence of cancer in nodules smaller than one cm (169/402, 42%). The malignancy charge per unit as well may accept been loftier considering many patients with small suspicious thyroid nodules had been referred to our tertiary care hospital for FNAB. In other words, patients with small nodules with obviously beneficial ultrasound findings might not have been referred for FNAB. Other authors [half-dozen, 22] also have reported a high prevalence of malignancy of subcentimeter nodules compared with larger nodules. In this serial, suspicious findings were more than prevalent in nodules smaller than 1 cm than in nodules larger than ane cm (Table 3). This observation suggests that the size of nodules may be a poor predictor of malignancy.

The Social club of Radiologists in Ultrasound suggests that FNAB be considered for nodules exhibiting substantial growth on serial ultrasound images. However, only 2 of 36 nodules that grew more than 3 mm proved to be cancerous and consequently had a low PPV (5.six%). Our findings support previous results suggesting that the presence or absenteeism of growth is non a reliable marker of the cancerous or benign nature of a nodule [8, nine, 23–26].

According to the American Association of Clinical Endocrinologists criteria, boosted suspicious ultrasound features include intranodular vascular spots. Nosotros did not apply this benchmark because our data did not include color Doppler findings. Color Doppler ultrasound is useful for evaluating intranodular and perinodular vascularity in the thyroid, merely its utility for differentiating benign from malignant nodules continues to be debated [v, 27–30]. Results of several previous studies [5, 28, 29] have suggested that intranodular vascularity is a significant indicator of malignancy and that the sensitivity of intranodular vascularity is relatively loftier, ranging from 66.7% to 91.7%. In those studies, however, specificity varied (range, 34.7–80.eight%) and PPV was low (range, 23.2–34.5%), possibly because intranodular vascularity was identified in many benign nodules. If we had included color Doppler sonographic data, the false-positive charge per unit likely would have been higher and the specificity and PPV of the American Association of Clinical Endocrinologists criteria lower, merely sensitivity would take increased. Further written report that includes data on the type of vascularity is needed for direct comparison of the diagnostic accuracies of the various criteria.

The American Thyroid Association (ATA) recommends routine FNAB of nodules 1 cm in diameter or larger unless the serum level of thyroid-stimulating hormone is low [9]. According to the ATA, nodules smaller than 1 cm may have to exist evaluated if the ultrasound findings are suspicious. Nonetheless, considering the suspicious ultrasound findings were not specified [nine], we did not include the ATA guideline in this assay. If we had performed FNAB on nodules measuring 1 cm or larger, co-ordinate to the ATA guidelines, 996 nodules would take been biopsied to place 158 malignant lesions.

Several guidelines, including those of the Society of Radiologists in Ultrasound, the American Association of Clinical Endocrinologists, and the ATA, and routine observation take been evaluated in terms of relative desirability [31]. The investigators reported that apply of all of the guidelines except those of the ATA had similar outcomes and that performance of FNAB on the basis of the ATA guidelines appeared to be the to the lowest degree desirable class. The baseline model assumptions in that written report, withal, were based on the likelihood suggested in previous studies, and the investigators calculated the probability of every potential outcome statistically instead of estimating it in real patients. Therefore, the findings may non necessarily exist applied to the full general population. In dissimilarity, we applied ultrasound criteria to a large gear up of real nodules in patients.

Our written report had limitations. Start, although many patients had multiple nodules, we did not perform FNAB on all nodules, which might accept caused option bias. However, considering nosotros do not perform FNAB on all thyroid nodules detected with ultrasound in clinical do, this limitation may be inevitable. 2d, all sonographic evaluations were performed by one experienced radiologist, so we did not include interobserver variation data. Moon et al. [15] reported that reviewers had fair to high understanding on the ultrasound characteristics of thyroid nodules (κ > 0.5). A large-scale prospective written report would exist warranted to confirm these results. Third, nosotros did non include color Doppler findings as part of the sonographic evaluation. Last, nosotros did non take clinical data, such as previous head and neck irradiation, family history of thyroid cancer, or serum thyroid-stimulating hormone or thyroglobulin level, that might have afflicted the conclusion to perform FNAB. This lack of data, however, might not necessarily have affected the results considering all of the criteria were practical to the aforementioned nodules under the same conditions with blinding to clinical history.

We conclude that the Kim and American Association of Clinical Endocrinologists criteria are more accurate than the Society of Radiologists in Ultrasound criteria. The American Association of Clinical Endocrinologists guidelines are recommended for achieving loftier specificity and the Kim criteria for achieving loftier sensitivity.

Address correspondence to E. K. Kim ([email protected]).

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