Abstract
Purpose
To compare the diagnostic performances of fine-needle aspiration (FNA) and core-needle biopsy (CNB) for thyroid nodules according to nodule size.
Materials and Methods
This retrospective study included 320 thyroid nodules from 320 patients who underwent both FNA and CNB at outside clinics and proceeded with surgery in our institution between July 2012 and May 2019. According to nodule size, the diagnostic performances of FNA and CNB were calculated using various combinations of test-negatives and test-positives defined by the Bethesda categories and were compared using the generalized estimated equation and the Delong method.
Results
There were 279 malignant nodules in 279 patients and 41 benign nodules in 41 patients. The diagnostic performance of FNA was mostly not different from CNB regardless of nodule size, except for negative predictive value, which was better for FNA than CNB when applying Criteria 1 and 2. When applying Criteria 3, the specificity and positive predictive value of FNA were superior to CNB regardless of size. When applying Criteria 4, diagnostic performance did not differ between FNA and CNB regardless of size. After applying Criteria 5, diagnostic performance did not differ between FNA and CNB in nodules ≥2 cm. However, in nodules ≥1 cm and all nodules, the sensitivity, accuracy, and negative predictive value of CNB were better than those of FNA.
Conclusion
CNB did not show superior diagnostic performance to FNA for diagnosing thyroid nodules.
Keywords: Ultrasonography; biopsy, fine-needle; thyroid neoplasms; biopsy, large-core needle
INTRODUCTION
Ultrasonography (US) guided-fine-needle aspiration (FNA) has been used as the primary diagnostic tool for thyroid nodules, owing to its safety, simplicity, cost-effectiveness, and reliability.1 Since early 2010, several articles have demonstrated the safety and tolerability of core-needle biopsy (CNB) for the evaluation of thyroid nodules, as well as its diagnostic efficacy.2,3,4,5,6,7,8 Unlike FNA, which has been validated as a standard diagnostic method for over half a century, the value of CNB has not yet been fully evaluated for diagnosing thyroid nodules.9,10,11
The main limitation of FNA is nondiagnostic and indeterminate results, corresponding to categories I, III, and IV of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC).12 To overcome this weakness, some investigators have suggested CNB as alternative or complementary diagnostic tool for thyroid nodules,5,8,13,14,15,16 even though CNB does not show superior diagnostic performance to FNA for diagnosing thyroid cancer and poses a higher rate of post-biopsy hematoma than FNA.1,17 Many favorable results for CNB have been found in studies conducted by experienced radiologists and CNB has even been used to diagnose small nodules,5,8,15,16,18 even micronodules not indicated for FNA in prestigious guidelines.19,20 Considering the thickness of the core needle, the potential risks of CNB might be greater than the expected benefits in patients with thyroid nodules, especially in those with small nodules, even though CNB shows better diagnostic accuracy than FNA.
The purpose of our study was to compare the diagnostic performances of FNA and CNB performed simultaneously at outside clinics for thyroid nodules according to nodule size.
MATERIALS AND METHODS
Our Yonsei University Institutional Review Board approved this retrospective study (IRB No. 4-2019-0745), and the requirement for informed consent was waived for review of images and medical records.
Study population
Between July 2012 and May 2019, patients who underwent both FNA and CNB for a thyroid nodule from one of 71 outside clinics were included. Among these patients, 320 patients who underwent surgery in our institution were finally included in our study. The median age of patients was 42 years (range, 19–74 years), and the median size of nodules was 10 mm (range, 3–62 mm). There were 250 female patients and 70 male patients (Table 1).
Table 1. Demographic Data of 320 Nodules in 320 Patients.
| Total (n=320) | Benign (n=41) | Malignant (n=279 ) | p value | |
|---|---|---|---|---|
| Median age (yr) | 42 (19–74) | 39 (22–68) | 42 (19–74) | 0.783 |
| Median nodule size (mm) | 10 (3–62) | 23 (5–62) | 10 (3–47) | <0.001 |
| Male sex | 70 (21.9) | 11 (26.8) | 59 (21.2) | 0.411 |
| FNA results | <0.001 | |||
| Nondiagnostic | 23 (7.2) | 8 (19.5) | 15 (5.4) | |
| Benign | 18 (5.6) | 12 (29.3) | 6 (2.2) | |
| AUS/FLUS | 75 (23.4) | 18 (43.9) | 57 (20.4) | |
| FN/SFN | 2 (0.6) | 2 (4.9) | 0 (0) | |
| SUSP | 88 (27.5) | 0 (0) | 88 (31.5) | |
| Malignancy | 114 (35.6) | 1 (2.4) | 113 (40.5) | |
| CNB results | <0.001 | |||
| Nondiagnostic | 18 (5.6) | 2 (4.9) | 16 (5.7) | |
| Benign | 8 (2.5) | 1 (2.4) | 7 (2.5) | |
| AUS/FLUS | 59 (18.4) | 23 (56.1) | 36 (12.9) | |
| FN/SFN | 18 (5.6) | 15 (36.6) | 3 (1.1) | |
| SUSP | 32 (10.0) | 0 (0) | 32 (11.5) | |
| Malignancy | 185 (57.8) | 0 (0) | 185 (66.3) |
FNA, fine-needle aspiration; CNB, core-needle biopsy; AUS/FLUS, atypia of undetermined significance or follicular lesion of undetermined significance; FN/SFN, follicular neoplasm or suspicious for follicular neoplasm; SUSP, suspicious for malignancy.
Values are number (%) or number (range).
Staging US and cytopathology reports
Preoperative staging US was performed by one of 33 radiologists with 1–22 years of experience in thyroid imaging. The radiologists prospectively recorded the size and US features of thyroid nodules that had undergone FNA or CNB at outside clinics into our institutional database. The recorded US features were composition, echogenicity, margin, calcifications, and shape.21
In our institution, all cytopathologic slides from outside clinics were reviewed by one of the 15 cytopathologists in our institution according to the review schedule before surgery. Cytology reports were based on the six categories of the BSRTC.12 The CNB pathologic reports were categorized into the same six categories of the Bethesda System according to a recently proposed guideline by a radiologist (K.J.Y.), because the diagnostic categories of CNB have yet to be standardized for thyroid nodules (Fig. 1).22
Fig. 1. US images of a 35-year-old female with a papillary thyroid carcinoma, conventional type, which was diagnosed as “malignancy” on fine-needle aspiration and “nondiagnostic” on core-needle biopsy detected at an outside clinic. A 1.3-cm solid hypoechoic nodule (arrows) with microlobulated margins and mixed calcifications was seen on the axial (A) and longitudinal (B) scans of US. US, ultrasonography.
Data and statistical analysis
Surgical pathologic diagnosis was defined as the standard reference. One nodule was interpreted as “malignancy” on FNA and “suspicious for malignancy (SUSP)” on CNB, although no residual cancer was noted in the surgical specimen. In this study, the nodule was considered as a cancer because central lymph node metastases were seen on the pathologic samples. We compared demographics between benign and malignant nodules, using the chi-square or Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables.
To calculate the diagnostic performances of both FNA and CNB, we defined various combinations of test-negatives and test-positives according to the Bethesda categories to assess malignancy and designated these combinations as Criteria 1 to 5 (Table 2).4,8,14,16,23,24 In Criteria 1, “benign” was considered as test-negative, and “SUSP” and “malignancy” were considered as test-positive. In Criteria 2, “benign” was considered as test-negative, and “follicular neoplasm or suspicious for follicular neoplasm (FN/SFN),” “SUSP,” and “malignancy” were considered as test-positive. In Criteria 3, “nondiagnostic,” “benign,” and “atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS)” were considered as test-negative, and the remaining categories were considered as test-positive. In Criteria 4, “SUSP” and “malignancy” were considered as test-positive, and the remaining categories were considered as test-negative. In Criteria 5, “malignancy” was considered as test-positive, and the remaining categories were considered as test-negative. We calculated the sensitivites, specificities, accuracies, positive predictive values (PPVs), negative predictive values (NPVs), and areas under the receiver operating characteristic curve (AUCs) along with 95% confidence intervals (CIs) of FNA and CNB to diagnose thyroid malignancy. These variables were compared using the generalized estimated equation and the AUCs using the Delong method. All diagnostic performances of FNA and CNB were calculated and compared separately for all nodules, nodules ≥10 mm, and nodules ≥20 mm, respectively. All analyses were performed with SPSS version 25 (IBM Corp., Armonk, NY, USA) and SAS (version 9.4, SAS Institute Inc., Cary, NC, USA). A p value of less than 0.05 was considered to indicate a significant difference.
Table 2. Diagnostic Criteria.
| Criteria | Test-negative | Test-positive |
|---|---|---|
| Criteria 11,23,24 | Benign | SUSP, malignancy |
| Criteria 21,24 | Benign | FN/SFN, SUSP, malignancy |
| Criteria 31,8,24 | Nondiagnostic, benign, AUS/FLUS | FN/SFN, SUSP, malignancy |
| Criteria 41,4,14 | Nondiagnostic, benign, AUS/FLUS, FN/SFN | SUSP, malignancy |
| Criteria 58,16 | Nondiagnostic, benign, AUS/FLUS, FN/SFN, SUSP | Malignancy |
AUS/FLUS, atypia of undetermined significance or follicular lesion of undetermined significance; FN/SFN, follicular neoplasm or suspicious for follicular neoplasm; SUSP, suspicious for malignancy.
RESULTS
Baseline clinicopathological characteristics
There were 279 malignant nodules in 279 patients and 41 benign nodules in 41 patients (Tables 1 and 3). The median age (42 years, range; 19–74 years) of the patients with malignant nodules was not significantly different from that (39 years, range; 22–68 years) of patients with benign nodules. The median size of benign nodules was 23 mm, which was significantly larger than that of malignant nodules (10 mm) (p<0.001). There was no statistical association between malignancy risk and gender. Significant differences were evident between benign and malignant nodules for the FNA and CNB results (p<0.001).
Table 3. Final Surgical Diagnosis According to FNA and CNB Results.
| FNA | CNB | Final diagnosis | |
|---|---|---|---|
| Malignant (n=279) | Benign (n=41) | ||
| Nondiagnostic (23) | Nondiagnostic (1) | AH (1) | |
| Benign (1) | PTC FV (1) | ||
| AUS/FLUS (9) | PTC conv (3), FC MI (1) | FA (2), AH (3) | |
| FN/SFN (2) | AH (1), HCA (1) | ||
| SUSP (1) | PTC FV (1) | ||
| Malignancy (9) | PTC conv (7), PTC FV (1), anaplastic carcinoma (1) | ||
| Benign (18) | AUS/FLUS (6) | AH (3), FA (1), HCA (1), NIFTP (1) | |
| FN/SFN (7) | FC MI (1) | AH (1), FA (5) | |
| SUSP (1) | PTC conv (1) | ||
| Malignancy (4) | PTC conv (3), PTC FV (1) | ||
| AUS/FLUS (75) | Nondiagnostic (8) | PTC conv (4), PTC FV (3) | FA (1) |
| Benign (1) | AH (1) | ||
| AUS/FLUS (25) | PTC conv (5), PTC FV (5), FC MI (5) | AH (5), FA (4), SAT (1) | |
| FN/SFN (8) | FC MI (1), PTC FV (1) | AH (1), FA (4), HCA (1) | |
| SUSP (8) | PTC conv (8) | ||
| Malignancy (25) | PTC conv (22), PTC FV (3) | ||
| FN/SFN (2) | AUS/FLUS (1) | FA (1) | |
| FN/SFN (1) | AH (1) | ||
| SUSP (88) | Nondiagnostic (7) | PTC conv (7) | |
| Benign (3) | PTC conv (3) | ||
| AUS/FLUS (8) | PTC conv (6), PTC FV (2) | ||
| SUSP (11) | PTC conv (9), PTC FV (2) | ||
| Malignancy (59) | PTC conv (56), PTC FV (2), MTC (1) | ||
| Malignancy (114) | Nondiagnostic (2) | PTC conv (2) | |
| Benign (3) | PTC conv (3) | ||
| AUS/FLUS (10) | PTC conv (9) | AH (1) | |
| SUSP (11) | PTC conv (9), PTC FV (1), no residual carcinoma (1)* | ||
| Malignancy (88) | PTC conv (86), PTC FV (1), PTC solid variant (1) | ||
FNA, fine-needle aspiration; CNB, core-needle biopsy; AUS/FLUS, atypia of undetermined significance or follicular lesion of undetermined significance, FN/SFN, follicular neoplasm or suspicious for follicular neoplasm; AH, adenomatous hyperplasia; FA, follicular adenoma; HCA, Hürthle cell adenoma; MTC, medullary thyroid carcinoma; NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC FV, papillary thyroid carcinoma, follicular variant; PTC conv, papillary thyroid carcinoma, conventional; SAT, subacute granulomatous thyroiditis; SUSP, suspicious for malignancy; FC MI, follicular carcinoma, minimally invasive.
Data in parentheses are number of nodules.
*One nodule was “malignancy” on FNA and “SUSP” on CNB. On the pathologic sample, there was no residual cancer. However, central lymph node metastases were seen on the pathologic samples. Therefore, the nodule was considered as a cancer in this study.
The proportions of the “benign” and “SUSP” categories were higher in FNA than in CNB (p=0.049 and p<0.001, respectively). In contrast, the proportions of the “FN/SFN” and “malignancy” categories were higher in CNB than in FNA (p<0.001).
Diagnostic performances of FNA and CNB
Table 4 demonstrates the diagnostic performances of FNA and CNB according to nodule size using Criteria 1–5.
Table 4. Diagnostic Performance of FNA versus CNB According to Nodule Size.
| FNA | Criteria 1 | Criteria 2 | Criteria 3 | Criteria 4 | Criteria 5 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| FNA | CNB | p value | FNA | CNB | p value | FNA | CNB | p value | FNA | CNB | p value | FNA | CNB | p value | |
| All data (n=320) | |||||||||||||||
| TP | 201 | 217 | 201 | 217 | 201 | 220 | 201 | 217 | 113 | 185 | |||||
| TN | 12 | 1 | 20 | 3 | 38 | 26 | 40 | 41 | 40 | 41 | |||||
| FP | 1 | 0 | 1 | 0 | 3 | 15 | 1 | 0 | 1 | 0 | |||||
| FN | 6 | 7 | 21 | 23 | 78 | 59 | 78 | 62 | 166 | 94 | |||||
| Sensitivity | 97.1 (94.8–99.4) | 96.9 (94.6–99.2) | 0.892 | 90.5 (86.7–94.4) | 90.4 (86.7–94.1) | 0.964 | 72.0 (66.8–77.3) | 78.9 (74.1–83.6) | 0.036 | 72.0 (66.8–77.3) | 77.8 (72.9–82.7) | 0.072 | 40.5 (34.7–46.3) | 66.3 (60.8–71.9) | <0.001 |
| Specificity | 92.3 (77.8–100) | 100 (100–100) | 0.298 | 95.2 (86.1–100) | 100 (100–100) | 0.306 | 92.7 (84.7–100) | 63.4 (48.7–78.2) | <0.001 | 97.6 (92.8–100) | 100 (100–100) | 0.311 | 97.6 (92.8–100) | 100 (100–100) | 0.311 |
| Accuracy | 96.8 (94.5–99.1) | 96.9 (94.6–99.2) | 0.966 | 90.9 (87.3–94.6) | 90.5 (86.9–94.2) | 0.876 | 74.7 (69.9–79.5) | 76.9 (72.3–81.5) | 0.481 | 75.3 (70.6–80.0) | 80.6 (76.3–84.9) | 0.058 | 47.8 (42.3–53.3) | 70.6 (65.6–75.6) | <0.001 |
| PPV | 99.5 (98.5–100) | 100 (100–100) | 0.316 | 99.5 (98.5–100) | 100 (100–100) | 0.316 | 98.5 (96.9–100) | 93.6 (90.5–96.7) | 0.003 | 99.5 (98.5–100) | 100 (100–100) | 0.316 | 99.1 (97.4–100) | 100 (100–100) | 0.315 |
| NPV | 66.7 (44.9–88.4) | 12.5 (0–35.4) | <0.001 | 48.8 (33.5–64.1) | 11.5 (0–23.8) | <0.001 | 32.8 (24.2–41.3) | 30.6 (20.8–40.4) | 0.585 | 33.9 (25.4–42.4) | 39.8 (30.4–49.3) | 0.054 | 19.4 (14.0–24.8) | 30.4 (22.6–38.1) | <0.001 |
| Nodules ≥1 cm (n=177) | |||||||||||||||
| TP | 102 | 105 | 102 | 105 | 102 | 108 | 102 | 105 | 65 | 91 | |||||
| TN | 11 | 0 | 19 | 2 | 34 | 23 | 36 | 37 | 36 | 37 | |||||
| FP | 1 | 0 | 1 | 0 | 3 | 14 | 1 | 0 | 1 | 0 | |||||
| FN | 3 | 3 | 10 | 11 | 38 | 32 | 38 | 35 | 75 | 49 | |||||
| Sensitivity | 97.1 (93.9–100) | 97.2 (94.1–100) | 0.972 | 91.1 (85.8–96.4) | 90.5 (85.2–95.8) | 0.888 | 72.9 (65.5–80.2) | 77.1 (70.2–84.1) | 0.302 | 72.9 (65.5–80.2) | 75 (67.8–82.2) | 0.589 | 46.4 (38.2–54.7) | 65 (57.1-72.9) | <0.001 |
| Specificity | 91.7 (76.0–100) | NA | - | 95 (85.4–100) | 100 (100–100) | 0.305 | 91.9 (83.1–100) | 62.2 (46.5–77.8) | 0.001 | 97.3 (92.1–100) | 100 (100–100) | 0.311 | 97.3 (92.1–100) | 100 (100–100) | 0.311 |
| Accuracy | 96.6 (93.3–99.9) | 97.2 (94.1–100) | 0.783 | 91.7 (87–96.4) | 90.7 (85.4–95.9) | 0.789 | 76.8 (70.6–83.1) | 74.0 (67.6–80.5) | 0.474 | 78 (71.9–84.0) | 80.2 (74.4–86.1) | 0.479 | 57.1 (49.8–64.4) | 72.3 (65.7–78.9) | <0.001 |
| PPV | 99.0 (97.1–100) | 100 (100–100) | 0.315 | 99 (97.1–100) | 100 (100–100) | 0.315 | 97.1 (93.9–100) | 88.5 (82.9–94.2) | 0.004 | 99.0 (97.1–100) | 100 (100–100) | 0.315 | 98.5 (95.5–100) | 100 (100–100) | 0.314 |
| NPV | 78.6 (57.1–100) | 0 (0–0) | <0.001 | 65.5 (48.2–82.8) | 15.4 (-4.2–35) | <0.001 | 47.2 (35.7–58.8) | 41.8 (28.8–54.9) | 0.310 | 48.6 (37.3–60.0) | 51.4 (39.8–62.9) | 0.479 | 32.4 (23.7–41.1) | 43.0 (32.6–53.5) | <0.001 |
| Nodules ≥2 cm (n=58) | |||||||||||||||
| TP | 17 | 19 | 17 | 19 | 17 | 22 | 17 | 19 | 15 | 17 | |||||
| TN | 9 | 0 | 16 | 2 | 24 | 14 | 25 | 25 | 25 | 25 | |||||
| FP | 0 | 0 | 0 | 0 | 1 | 11 | 0 | 0 | 0 | 0 | |||||
| FN | 1 | 1 | 3 | 4 | 16 | 11 | 16 | 14 | 18 | 16 | |||||
| Sensitivity | 94.4 (83.9–100) | 95 (85.4–100) | 0.939 | 85 (69.4–100) | 82.6 (67.1–98.1) | 0.832 | 51.5 (34.5–68.6) | 66.7 (50.6–82.8) | 0.118 | 51.5 (34.5–68.6) | 57.6 (40.7–74.4) | 0.476 | 45.5 (28.5–62.4) | 51.5 (34.5–68.6) | 0.525 |
| Specificity | 100 (100–100) | NA | - | 100 (100–100) | 100 (100–100) | >0.999 | 96 (88.3–100) | 56 (36.5–75.5) | <0.001 | 100 (100–100) | 100 (100–100) | >0.999 | 100 (100–100) | 100 (100–100) | >0.999 |
| Accuracy | 96.3 (89.2–100) | 95 (85.4–100) | 0.832 | 91.7 (82.6–100) | 84 (69.6–98.4) | 0.382 | 70.7 (58.9–82.4) | 62.1 (49.6–74.6) | 0.270 | 72.4 (60.9–83.9) | 75.9 (64.8–86.9) | 0.478 | 69 (57.1–80.9) | 72.4 (60.9–83.9) | 0.526 |
| PPV | 100 (100–100) | 100 (100–100) | >0.999 | 100 (100–100) | 100 (100–100) | >0.999 | 94.4 (83.9–100) | 66.7 (50.6–82.8) | <0.001 | 100 (100–100) | 100 (100–100) | >0.999 | 100 (100–100) | 100 (100–100) | >0.999 |
| NPV | 90 (71.4–100) | 0 (0–0) | <0.001 | 84.2 (67.8–100) | 33.3 (-4.4–71.1) | 0.013 | 60 (44.8–75.2) | 56 (36.5–75.5) | 0.591 | 60.9 (46.0–75.9) | 64.1 (49.0–79.2) | 0.478 | 58.1 (43.4–72.9) | 61 (46.0–75.9) | 0.527 |
FNA, fine-needle aspiration; CNB, core-needle biopsy; TP, true-positive; TN, true-negative; FP, false-positive; FN, false-negative; PPV, positive predictive value; NPV, negative predictive value; NA, not applicable; SUSP, suspicious for malignancy; FN/SFN, follicular neoplasm or suspicious for follicular neoplasm; AUS/FLUS, atypia of undetermined significance or follicular lesion of undetermined significance.
Values are numbers or percentages (95% confidence intervals). In Criteria 1, “benign” was considered as test-negative, and “SUSP” and “malignancy” were considered as test-positive. In Criteria 2, “benign” was considered as test-negative, and “FN/SFN,” “SUSP” and “malignancy” were considered as test-positive. In Criteria 3, “nondiagnostic,” “benign,” and “AUS/FLUS” were considered as test-negative, and the remaining categories were considered as test-positive. In Criteria 4, “SUSP” and “malignancy” were considered as test-positive, and the remaining categories were considered as test-negative. In Criteria 5, “malignancy” was considered as test-positive, and the remaining categories were considered as test-negative.
When applying Criteria 1 and 2, diagnostic performance mostly did not differ between FNA and CNB in all nodules, except for NPV, which was better for FNA FNA (66.7%; 95% CI: 44.9–88.4 for Criteria 1 and 48.8%; 95% CI: 33.5–64.1 for Criteria 2) than for CNB (12.5%; 95% CI: 0–35.4 for Criteria 1 and 11.5%; 95% CI: 0–23.8 for Criteria 2) (p<0.001). When applying Criteria 3, specificity and PPV were higher for FNA (92.7%; 95% CI: 84.7–100 for specificity and 98.5%; 95% CI: 96.9–100 for PPV) than for CNB (63.4%; 95% CI: 48.7–78.2 for specificity and 93.6%; 95% CI: 90.5–96.7 for PPV) (p<0.001 and p=0.003, respectively). Accuracy and NPV were not statistically different between FNA and CNB. The sensitivity (78.9%; 95% CI: 74.1–83.6) of CNB was higher than that (72%; 95% CI: 66.8–77.3) of FNA (p=0.036). When applying Criteria 4, the diagnostic performance of FNA was similar to that of CNB. When applying Criteria 5, sensitivity, accuracy, and NPV were significantly higher for CNB than FNA.
In nodules ≥1 cm, FNA showed superior diagnostic performance over CNB in terms of NPV with Criteria 1 and 2 and specificity and PPV with Criteria 3. The other measures of diagnostic performance were not different between FNA and CNB when Criteria 1–3 were used. When Criteria 4 was applied, none of the diagnostic performance measures of FNA significantly differed from CNB. When applying Criteria 5, sensitivity, accuracy, and NPV were significantly higher for CNB than for FNA.
In nodules ≥2 cm, FNA showed superior diagnostic performance over CNB in terms of NPV with Criteria 1 and 2 and specificity and PPV with Criteria 3. The other measures of diagnostic performance were not different between FNA and CNB when Criteria 1–3 were used. When Criteria 4 and 5 were applied, the diagnostic performance of FNA did not statistically differ from that of CNB.
DISCUSSION
In this study, the diagnostic performance of FNA was mostly the same as that of CNB, regardless of nodule size, except for NPV, which was better for FNA than for CNB when applying Criteria 1 and 2. When applying Criteria 3, the specificity and PPV of FNA were superior to CNB regardless of size. When applying Criteria 4, diagnostic performance did not differ between FNA and CNB, regardless of size, unlike the results of a previous study that found CNB to have higher sensitivity and accuracy than FNA.4 After applying Criteria 5, diagnostic performance did not differ between FNA and CNB in nodules ≥2 cm (not small nodules). However, in nodules ≥1 cm and all nodules, the sensitivity, accuracy, and NPV of CNB were better than those of FNA, findings which were similar to those of a published study.8
Several investigators have suggested that CNB is superior to FNA and that it may be a potential first-line diagnostic tool.4,8,14,16 In these studies, the “nondiagnostic,” “benign,” “AUS/FLUS,” and “FN/SFN” categories were regarded as test-negative, and the “nondiagnostic,” “benign,” “AUS/FLUS,” and “FN/SFN” categories with and without the “SUSP” category were regarded as test-positive, which were the same designations used for Criteria 4 and 5, respectively, in our study.4,8,14,16 In other studies, the diagnostic performance of FNA was calculated by regarding the “benign” category with and without the “nondiagnostic” category as test-negative (Criteria 1 and 2 in our study, respectively) or by regarding the combination of the “nondiagnostic,” “benign,” and “AUS/FLUS” categories as test-negative (Criteria 3 in our study).23,24 According to BSRTC, the risk of malignancy was 15–30% and 60–75% for thyroid nodules categorized as “FN/SFN” and “SUSP,” respectively.12 Considering that “FN/SFN” and “SUSP” nodules have relatively high risks of malignancy and are recommended for surgery according to the BSRTC, a nodule with the above cytologic categories should not be considered as test-negative when calculating the diagnostic performances of FNA or CNB (Criteria 4 and 5). Based on the results of our study, we need to reconsider previous research that found CNB to be more reliable or accurate than FNA, and CNB cannot be considered as a first-line diagnostic tool for diagnosing thyroid nodules without more supportive evidence.
To obtain tissue samples without damage to the adjacent tissues, it is important to visualize the entire needle. Therefore, the core needle should be positioned parallel to the transducer. Unlike the core needle in CNB, the fine needle in FNA can be inserted in various directions with to-and-fro motions to obtain cells from different sites of the thyroid nodule for representative sampling.25 Differences in the methods of FNA and CNB may explain their different diagnostic performances.
Percutaneous CNB is a useful diagnostic tool for diagnosing soft tissue lesions, especially breast lesions, and surgical excision biopsies can be avoided with its use.26,27 CNB has also been reported as a safe tool for diagnosing thyroid nodules with low complication rates.2 However, as the core needle is thicker than the fine needle, it might cause more severe and permanent damage to the adjacent major organs than the thinner fine needle (Supplementary Figs. 1 and 2, only online).
This study has several limitations. First, patient selection bias exists because we included patients who underwent both FNA and CNB before surgery. Second, we could not evaluate the experience levels of the physicians who performed both FNA and CNB as these procedures took place at outside clinics. However, the results of this study can reflect the real clinical value of FNA and CNB. Third, the results of the first procedure may have affected the next procedure. Commonly, FNA is performed before CNB even when they are both performed during the same session/visit. Therefore, the results of CNB can be influenced by the procedures undertaken for FNA. Fourth, although our findings indicate that CNB cannot be a main diagnostic tool for thyroid nodules, it can still play a role in diagnosing thyroid lymphoma, anaplastic carcinoma, and metastasis from other organs.28,29,30 In this study, we were unable to evaluate the selective indications of CNB. Finally, we did not assess diagnostic performance for predicting neoplasm because there were only a small number of FNs in this study.
In conclusion, CNB did not show superior diagnostic performance to FNA for diagnosing thyroid nodules.
ACKNOWLEDGEMENTS
There was no funding for this research.
Footnotes
The authors have no potential conflicts of interest to disclose.
- Conceptualization: Jin Young Kwak and Ilah Shin.
- Data curation: Jin Young Kwak and Ilah Shin.
- Formal analysis: Hye Sun Lee.
- Investigation: Ilah Shin, Si Eun Lee, Eun-Kyung Kim, Hee Jung Moon, Jung Hyun Yoon, and Vivian Youngjean Park.
- Methodology: Ilah Shin and Hye Sun Lee.
- Project administration: Jin Young Kwak.
- Resources: Eun-Kyung Kim, Hee Jung Moon, Jung Hyun Yoon, Vivian Youngjean Park, and Si Eun Lee.
- Software: Ilah Shin and Hye Sun Lee.
- Supervision: Jin Young Kwak and Eun-Kyung Kim.
- Validation: Eun-Kyung Kim, Hee Jung Moon, Jung Hyun Yoon, and Vivian Youngjean Park.
- Visualization: Ilah Shin and Si Eun Lee.
- Writing—original draft: Jin Young Kwak and Ilah Shin.
- Writing—review and editing: Eun-Kyung Kim, Hee Jung Moon, Jung Hyun Yoon, Vivian Youngjean Park, and Si Eun Lee.
- Approval of final manuscript: All authors.
SUPPLEMENTARY MATERIALS
US images of a 27-year-old female with a papillary thyroid carcinoma detected at an outside clinic. (A) A 1.7-cm solid hypoechoic nodule (arrows) with microlobulated margins and microcalcifications was seen on the axial scan of US (arrowheads, esophagus). (B) The specimen notch (arrows) of the core biopsy needle is seen on the edge of the adjacent esophageal wall (arrowheads). (C) After firing, the tip of the core biopsy needle (arrows) is seen in the esophageal wall (arrowheads). US, ultrasonography.
Ultrasonography images of a 65-year-old female with a papillary thyroid carcinoma detected at an outside clinic. The tip of the core biopsy needle (arrowheads) is seen on the edge of the adjacent common carotid artery. The specimen notch (arrows) of the core biopsy needle is seen within the nodule.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
US images of a 27-year-old female with a papillary thyroid carcinoma detected at an outside clinic. (A) A 1.7-cm solid hypoechoic nodule (arrows) with microlobulated margins and microcalcifications was seen on the axial scan of US (arrowheads, esophagus). (B) The specimen notch (arrows) of the core biopsy needle is seen on the edge of the adjacent esophageal wall (arrowheads). (C) After firing, the tip of the core biopsy needle (arrows) is seen in the esophageal wall (arrowheads). US, ultrasonography.
Ultrasonography images of a 65-year-old female with a papillary thyroid carcinoma detected at an outside clinic. The tip of the core biopsy needle (arrowheads) is seen on the edge of the adjacent common carotid artery. The specimen notch (arrows) of the core biopsy needle is seen within the nodule.

