Breast Pseudoaneurysm in a Woman after Core Biopsy: Intravascular Glue Embolization.

Core needle biopsy of breast masses is a common procedure for tissue diagnosis of breast lesions. The incidence of complications is low, with pseudoaneurysm (PA) after core biopsy has been described in the literature, and the subsequent need for surgical management. Ultrasonography is the most common modality used for not only diagnosis but also treatment of a PA. Color Doppler images show a heterogeneous echoic lesion with whirling flow inside of the lesion. We describe a patient whose breast PA that developed after core needle biopsy was successfully treated with sonographically-guided intravascular glue embolization.

Comparison of Diagnostic Performance and Confidence between Contrast-Enhanced Computed Tomography Scan and Non-Contrast-Enhanced Computed Tomography Plus Abdomen Ultrasound for Hepatic Metastasis in Patients with Breast Cancer.

Background: The purpose of this study was to compare the performance between noncontrast-enhanced computed tomography (NECT) plus abdominal ultrasound (US) (NECT + US) with contrast-enhanced computed tomography (CECT) for the detection of hepatic metastasis in breast cancer patient with postsurgical follow-up. Methods: A total of 1470 patients without already diagnosed hepatic metastasis were included. All patients underwent US and multiphase CECT including the NECT. Independent reviewers analyzed images obtained in four settings, namely, abdominal US, NECT, NECT + US, and CECT and recorded liver metastases using a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance), and area under the receiver operating characteristic curve (AUC, diagnostic confidence) were calculated. Interoperator agreement was calculated using the kappa test. Results: Reference standards revealed no metastases in 1108/1470 patients, and metastasis was detected in 362/1470 patients. Abdominal US (P < 0.01) and NECT (P = 0.01) significantly differed from CECT, but NECT + US did not significantly differ from CECT in terms of sensitivity (P = 0.09), specificity (P = 0.5), and AUC (P = 0.43). After an additional review of abdominal US, readers changed the diagnostic confidence scores of 106 metastatic lesions diagnosed using NECT. Interobserver agreements were good or very good in all four settings. Additional review of abdominal US with NECT allowed a change in the therapeutic plan of 108 patients. Conclusion: Abdominal US + NECT showed better diagnostic performance for the detection of hepatic metastases than did NECT alone; its diagnostic performance and confidence were similar to those of CECT.

The Emerging Crisis of Stakeholders in Implant-based Augmentation Mammaplasty in Korea.

BACKGROUND: Korea is no longer safe from the risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL); the first reported case was a Korean woman in her 40s who had a 7-year-history of receiving an implant-based augmentation mammaplasty using a textured implant. We conducted this study to discuss the emerging crisis of stakeholders in implant-based augmentation mammaplasty and to propose a multi-disciplinary approach to early detection of its complications. METHODS: We analyzed medical examination data that was collected from patients who visited us between August 12 and September 27, 2019. We evaluated a total of 114 women (n = 114) in the current study. They were evaluated for whether they were in healthy condition. Moreover, their baseline characteristics were also examined; these included age, gender, height (cm), weight (kg), duration since surgery (years), possession of a breast implant card, the site of surgical incision, side of symptoms and reasons for outpatient visit. Furthermore, the patients were also evaluated for their subjective awareness of the manufacturer, surface and shape of the breast implant. Potential complications include malrotation, folding, seroma, capsule thickening, upside-down rotation, rupture, capsule mass and breast mass. RESULTS: A majority of the patients had a past history of receiving textured implants. The corresponding percentage was 78.95% (90/114) and 85.09% (97/114) based on their subjective awareness of a breast implant and sonographic findings, respectively. That is, it was slightly increased with the use of a breast ultrasound. CONCLUSION: Here, we propose the following approaches. First, patient data should be prospectively collected. By tracking outcomes and complications of an implant-based augmentation mammaplasty, both high-quality care and patient safety can be ensured. Second, stakeholders in implant-based augmentation mammaplasty should collaborate with customers and regulatory authorities. Third, surgeons should consider applying imaging modalities for early detection of postoperative complications.

Safety and Efficacy of Radiofrequency Ablation for Nonfunctioning Benign Thyroid Nodules in Children and Adolescents in 14 Patients over a 10-Year Period.

PURPOSE: To evaluate the efficacy and safety of radiofrequency (RF) ablation for nonfunctioning benign thyroid nodules in children and adolescents. MATERIALS AND METHODS: Fourteen pediatric patients (10 female, 4 male; mean age 15.7 ± 2.3 years, range 12-19 years) with nonfunctioning benign thyroid nodules (mean longest diameter 3.7 ± 1.1 cm, range 2.0-5.6 cm) treated with the use of RF ablation from 2005 to 2015 were evaluated. The inclusion criteria for RF ablation therapy were (i) age <20 years, (ii) benign cytological confirmation by ≥2 separate fine-needle aspiration or core needle biopsies, (iii) pressure symptoms or cosmetic problems caused by thyroid nodules, (iv) absence of any suspicious feature as determined with the use of ultrasound (US), (v) normal serum levels of thyroid hormone and thyrotropin, and (vi) follow-up of >6 months. RF ablation was performed with the use of an RF generator and an 18-gauge internally cooled electrode. RF ablation was performed under local anesthesia without conscious sedation or general anesthesia. Changes in nodules on follow-up US, changes in symptomatic and cosmetic scores, and complications arising during or after RF ablation were evaluated. RESULTS: Mean follow-up period was 36.9 ± 21.7 months (range 6-69 months). At last follow-up visits, mean longest nodule diameter and volume had decreased significantly (3.7 ± 1.1 cm vs 1.4 ± 0.9 cm and 14.6 ± 13.3 mL vs 1.7 ± 4.4 mL; P < 0.001). Both cosmetic and compressive symptoms significantly improved (3.8 ± 0.6 vs 1.4 ± 0.6 and 3.4 ± 1.0 vs 0.1 ± 0.4; P < 0.001). The mean number of ablation sessions was 2.1 ± 1.2 (range 1-5 sessions) and no major complication was encountered during or after RF ablation. CONCLUSIONS: RF ablation might be a safe and effective treatment modality for nonfunctioning benign thyroid nodules in children and adolescents.

Agreement between MRI and pathologic analyses for determination of tumor size and correlation with immunohistochemical factors of invasive breast carcinoma.

Background There may be discordance between tumor size determined by magnetic resonance imaging (MRI) and that observed during pathologic analyses. Purpose To evaluate MRI-pathology concordance of tumor size in patients with invasive breast carcinoma. Material and Methods Data from 307 invasive breast carcinomas were analyzed retrospectively. Preoperative breast MRI was reviewed for size, lesion type, morphology, and dynamic contrast-enhanced tumor kinetics. MRI tumor size was compared with tumor size measurements from the pathologic analysis. Concordance was defined as a difference in diameter of ≤ 0.5 cm. MRI-pathology concordance was compared according to clinical and histopathologic features. Results The mean tumor size on MRI was 2.48 ± 1.41 cm. Tumor measurements determined by MRI were not significantly different from those recorded in the pathologic reports (2.56 ± 1.61 cm, P = 0.199). MRI-pathology concordance was found in 229/307 (74.6%) cases; the size was overestimated in 36 (11.7%) tumors and underestimated in 42 (13.7%). On univariate analysis, MRI-pathology discordance was associated with larger tumor size ( P < 0.001), estrogen receptor (ER) negativity ( P = 0.006), and lymphovascular invasion ( P = 0.003). Human epidermal growth factor receptor 2 positive molecular subtype showed worse correlation between the tumor size measured by MRI and pathology compared with luminal A and luminal B subtypes ( P = 0.008 and 0.007). On multivariate analysis, tumor size and ER status significantly influenced MRI-pathology concordance ( P < 0.05). Conclusion ER negativity and larger tumor size were strongly associated with MRI-pathology discordance in invasive breast carcinomas. Awareness of these factors might improve surgical planning.

Ultrasonographic hyperechoic lesions of the breast: are they always benign?

BACKGROUND: Most of the breast lesions show hypoechogenicity relative to fat on ultrasonography. The frequency and malignancy rate of hyperechoic lesions are not investigated in a large series. PURPOSE: To evaluate the frequency and malignancy rate of hyperechoic lesions on breast sonography and to investigate sonographic characteristics that may predict malignancy in hyperechoic breast lesions. MATERIAL AND METHODS: Radiologic reports of 16,416 patients who underwent breast sonography between 2007 and 2008 were searched using "hyperechoic", "echogenic" or "heterogeneous echoic" to describe lesions. Sonographic findings were evaluated according to the Breast Imaging Reporting and Data System lexicon. Clinical records including follow-up and pathologic findings were also reviewed. We calculated the frequency of hyperechoic lesions and their malignancy rate. Differences in sonographic appearances between benign and malignant lesions were also investigated. RESULTS: Among the 16,416 patients, 103 (0.6%) hyperechoic lesions were identified (mean size, 1.79 cm). Of these 103 lesions, 27 (26.2%) were pathologically evaluated and five (4.9%, 4 invasive ductal carcinoma and 1 mucinous carcinoma) were confirmed as malignant. Among the 819 malignant lesions diagnosed using sonography-guided core needle biopsy, five (0.6%) were hyperechoic. In benign lesions, fat necrosis and fibroadenoma were common pathologic diagnoses. Malignant lesions were more likely to have irregular shape (P = 0.003), non-parallel orientation (P = 0.002), non-circumscribed margin (P = 0.007), and a hypoechoic area (P = 0.027) than benign lesions. All hyperechoic carcinomas were seen as suspicious masses on mammograms. CONCLUSION: Hyperechoic masses are very rare and mostly benign. As an adjunct to mammography, the imaging findings reported here could help to avoid misdiagnosis for malignant hyperechoic lesion.

Analysis of the effect of breast magnetic resonance imaging on the outcome in women undergoing breast conservation surgery with radiation therapy.

BACKGROUND: It remains uncertain whether MRI identification of additional foci of disease leads to improved outcome. We undertook a study to evaluate the influence of breast MRI on early and long-term outcome. METHODS: Among 1,271 patients undergone breast cancer surgery between January 2005 and December 2006, 785 patients were attempted for BCS. Operative approach and radiologic findings were compared according to MRI use. We reselected 615 patients with unilateral early-stage breast cancer treated with BCS including RT. We compared the histopathologic characteristics and outcomes according to MRI use. RESULTS: In patients attempted for BCS (n = 785), re-excision rates were not significantly different according to MRI use (P = 1.000). Conversion to mastectomy or bilateral cancer surgery were higher in MRI group (P = 0.002). The IBTR rate was higher in the non-MRI group (P = 0.020). Difference in contralateral cancer rate and total recurrence rates failed to reach statistical significance (P = 0.168, 0.383, respectively). Multivariate study after adjustment showed no difference in recurrence rates and IBTR rates between the two groups (hazard ratios 1.34, 6.37 Ps = 0.385, 0.076). CONCLUSION: Use of MRI in patients with early-stage breast cancer did not result in improvement of a patient's outcome.

Measurement of Perfusion Heterogeneity within Tumor Habitats on Magnetic Resonance Imaging and Its Association with Prognosis in Breast Cancer Patients.

The purpose of this study was to identify perfusional subregions sharing similar kinetic characteristics from dynamic contrast-enhanced magnetic resonance imaging (MRI) using data-driven clustering, and to evaluate the effect of perfusional heterogeneity based on those subregions on patients' survival outcomes in various risk models. From two hospitals, 308 and 147 women with invasive breast cancer who underwent preoperative MRI between October 2011 and July 2012 were retrospectively enrolled as development and validation cohorts, respectively. Using the Cox-least absolute shrinkage and selection operator model, a habitat risk score (HRS) was constructed from the radiomics features from the derived habitat map. An HRS-only, clinical, combined habitat, and two conventional radiomics risk models to predict patients' disease-free survival (DFS) were built. Patients were classified into low-risk or high-risk groups using the median cutoff values of each risk score. Five habitats with distinct perfusion patterns were identified. An HRS was an independent risk factor for predicting worse DFS outcomes in the HRS-only risk model (hazard ratio = 3.274 [95% CI = 1.378-7.782]; p = 0.014) and combined habitat risk model (hazard ratio = 4.128 [95% CI = 1.744-9.769]; p = 0.003) in the validation cohort. In the validation cohort, the combined habitat risk model (hazard ratio = 4.128, p = 0.003, C-index = 0.760) showed the best performance among five different risk models. The quantification of perfusion heterogeneity is a potential approach for predicting prognosis and may facilitate personalized, tailored treatment strategies for breast cancer.

A critical review of abdominopelvic computed tomography for the detection of asymptomatic metastasis in new and recurrent breast cancers.

AIM: Abdominopelvic computed tomography (APCT) is a commonly used staging investigation to detect asymptomatic metastasis in breast cancer including early breast cancer (EBC). This study aimed to assess the usefulness of APCT in breast cancers at each clinical stage. METHODS: Patients with new or recurrent invasive breast cancer between January 2009 and December 2014 were included in the study. All staging APCT results were reviewed to evaluate its yield and false positive rate (FPR) and how many investigations are needed to confirm indeterminate results. Odds ratios (ORs) for positive APCT results were calculated for possible risk factors for asymptomatic metastasis. RESULTS: Sixty-five asymptomatic metastases were detected from 1002 APCTs, giving an overall yield of 6.5%. The overall false-positive rate was 14.9 % due to 149 indeterminate findings that were found not to be metastases after further investigations or observation. Whereas the APCTs have a low yield of 3.1% in EBC, but advanced breast cancer and recurrent breast cancer have a high incidence of asymptomatic metastases (13.8% and 16.3%, respectively). The most common cause of indeterminate findings was small liver nodules, including liver cysts and liver hemangiomas. Human epidermal growth factor receptor2 (HER2) status and tumor stage are most significant predictors for positive results of staging APCT scans with high ORs (3.9 and 3.7, respectively). CONCLUSION: Staging APCT is associated with a high incidence of FPRs and low yield, especially among EBCs. It is desirable to choose this investigation more selectively according to HER2 status and tumor stage.

A case of nontuberculous mycobacteria-associated thyroiditis mimicking subacute thyroiditis.

We describe a case of nontuberculous mycobacteria infection in the thyroid gland in a 54-year-old woman who had painful thyroid enlargement. Ultrasonography showed ill-defined hypoechoic lesions without increased vascularity in both upper lobes of the thyroid gland. Fine needle aspiration biopsy was performed, and pathology showed granulomatous inflammation with necrotic debris that the pathologist suspected was subacute granulomatous thyroiditis or tuberculosis of the thyroid gland. Nontuberculous mycobacteria infection was confirmed after right hemithyroidectomy. Antimycobacterial therapy was initiated as the treatment of choice. Nontuberculous mycobacteria in the thyroid gland appear to be rare. In clinical practice, however, it should be considered as a differential diagnosis of a painful thyroid mass. For accurate diagnosis, clinical and radiological features plus histological examination are required.

Diagnostic accuracy of non-contrast abdominopelvic computed tomography scans in follow-up of breast cancer patients.

OBJECTIVES: To evaluate the effectiveness of follow-up with non-enhanced CT (NECT) in patients with breast cancer. METHODS: The present retrospective study included 1396 patients with breast cancer. Group A included patients with no metastasis to evaluate the diagnostic performance of NECT in detecting newly developed metastasis. Group B included patients with known hepatic metastasis to evaluate the accuracy of NECT for the assessment of hepatic metastasis. RESULTS: Group A included 895 patients (mean age 52.8 years). Among them, 145 patients had 160 metastases. The per-patient sensitivities for diagnosing newly developed metastasis were 68.3 and 53.8% according to the two reviewers, while the per-lesion sensitivities were 89.4 and 85.0%. Sensitivities for bone metastasis were 98.9 and 95.9%, while sensitivities for hepatic metastasis were 73.7 and 68.4%. In group B, the accuracy of hepatic metastasis response evaluation according to the RECIST criteria was 70.8% for reviewer 1 and 63.8% for reviewer 2. CONCLUSIONS: NECT showed inadequate diagnostic performance in detecting newly developed metastasis and in evaluating the response of hepatic metastasis. However, NECT can be utilized as a follow-up modality in patients with decreased renal function or hypersensitivity to iodinated contrast media. ADVANCES IN KNOWLEDGE: The risk of side effects of contrast media should be considered as important when NECT can be utilized as a follow-up modality in decreased renal function patients.

Percutaneous radiofrequency ablation for hepatic tumors abutting the diaphragm: clinical assessment of the heat-sink effect of artificial ascites.

OBJECTIVE: This study was designed to assess whether artificial ascites has a heat-sink effect on the ablation zone for percutaneous radiofrequency ablation (RFA) of hepatic tumors abutting the diaphragm. MATERIALS AND METHODS: We retrospectively assessed 28 patients who underwent percutaneous RFA for the treatment of a single nodular hepatic tumor that abutted the diaphragm from July 2000 to December 2006. All patients underwent ultrasound-guided RFA using internally cooled electrodes. A single ablation for 12 minutes was applied using 3-cm active-tip electrodes. We divided patients into two groups on the basis of whether artificial ascites was introduced before RFA: Group A consisted of patients who received artificial ascites with a mean of 760 mL of a 5% dextrose in water solution (n = 15) and group B consisted of patients who did not receive artificial ascites (n = 13). The volume of the ablation zone was measured on CT images obtained immediately after the ablation procedure, and imaging findings were compared for both groups using the Student's t test. We also compared the local tumor progression rate between both groups using the chi-square test (mean follow-up, 37.4 months). RESULTS: There was no significant difference between the two patient groups with regard to age, sex, Child-Pugh class, or tumor location (p > 0.05). The tumors were significantly smaller in group A patients (mean +/- SD, 1.6 +/- 0.5 cm) than in group B patients (2.1 +/- 0.7 cm) (p = 0.019). The mean volume of the RFA zone was 31.6 +/- 11.9 cm(3) in group A patients and 30.9 +/- 11.0 cm(3) in group B patients. There was no significant difference between the groups in the ablation volume (p = 0.871). Local tumor progression was noted in four patients (26.7%) in group A and in three patients (23.1%) in group B. There was no significant difference in the local tumor progression rate between the two groups (p = 0.83). CONCLUSION: Artificial ascites did not show a heat-sink effect on the volume of the ablation zone after percutaneous RFA for the treatment of a hepatic tumor abutting the diaphragm.

Preoperative dynamic breast magnetic resonance imaging kinetic features using computer-aided diagnosis: Association with survival outcome and tumor aggressiveness in patients with invasive breast cancer.

OBJECTIVES: To evaluate whether preoperative breast dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging kinetic features, assessed using computer-aided diagnosis (CAD), can predict survival outcome and tumor aggressiveness in patients with invasive breast cancer. MATERIALS AND METHODS: Between March and December 2011, 301 women who underwent preoperative DCE MR imaging for invasive breast cancer, with CAD data, were identified. All MR images were retrospectively evaluated using a commercially available CAD system. The following kinetic parameters were prospectively recorded for each lesion: initial peak enhancement, the proportion of early phase medium and rapid enhancement, and the proportion of delayed phase persistent, plateau, and washout enhancement. The Cox proportional hazards model was used to determine the association between the kinetic features assessed by CAD and disease-free survival (DFS). The peak signal intensity and kinetic enhancement profiles were compared with the clinical-pathological variables. RESULTS: There were 32 recurrences during a mean follow-up time of 55.2 months (range, 5-72 months). Multivariate analysis revealed that a higher peak enhancement (DFS hazard ratio, 1.004 [95% confidence interval (CI): 1.001, 1.006]; P = .013) on DCE MR imaging and a triple-negative subtype (DFS hazard ratio, 21.060 [95% CI: 2.675, 165.780]; P = .004) were associated with a poorer DFS. Higher peak enhancement was significantly associated with a higher tumor stage, clinical stage, and histologic grade. CONCLUSIONS: Patients with breast cancer who showed higher CAD-derived peak enhancement on breast MR imaging had worse DFS. Peak enhancement and volumetric analysis of kinetic patterns were useful for predicting tumor aggressiveness.

Breast Imaging Reporting and Data System Category 3 Lesions Detected on Whole-Breast Screening Ultrasound.

PURPOSE: This study assessed the incidence and cancer rate of probably benign lesions detected on bilateral whole-breast screening ultrasound (US), which corresponded to US Breast Imaging Reporting and Data System (BI-RADS) category 3, and evaluated the proper management of those lesions. METHODS: This study was approved by the Institutional Review Board in our institution, which waived informed patient consent. We retrospectively reviewed US images of 1,666 patients who underwent bilateral whole-breast screening US as a supplemental screening test to negative screening mammography or screening US only. The incidence, clinical course, and cancer rate of screening US-detected probably benign lesions corresponding to US BI-RADS category 3 were investigated, and the size and multiplicity of screening US-detected category 3 lesions were evaluated. RESULTS: Probably benign lesions corresponding to US BI-RADS category 3 were detected in 689 of 1,666 patients (41.4%) who underwent screening US. Among them, 653 had follow-up US images for at least 24 months, and among these 653, 190 (29.1%) had multiple bilateral category 3 lesions. Moreover, 539 of 1,666 patients (32.4%) had lesions ≤1 cm in size and 114 of 1,666 (6.8%) had lesions >1 cm (median, 0.82 cm; range, 0.3-4.2 cm). Four of the 653 patients (0.6%) showed suspicious interval changes and were categorized into BI-RADS category 4. Biopsy analysis confirmed only one lesion as invasive ductal carcinoma at the 6-month follow-up; another lesion was an intraductal papilloma and the remaining two were fibroadenomas. Overall cancer rate of the screening US-detected BI-RADS category 3 lesions was 0.2%. CONCLUSION: The incidence of category 3 lesions detected on screening US only was very high, but the cancer rate was very low. Therefore, in an average-risk population, routine screening US is preferable over short-term follow-up for BI-RADS category 3 lesions detected on whole-breast screening US.

A comparison of lymphocytic thyroiditis with papillary thyroid carcinoma showing suspicious ultrasonographic findings in a background of heterogeneous parenchyma.

PURPOSE: The aim of this study was to compare ultrasonographic features in patients with lymphocytic thyroiditis (LT) and papillary thyroid carcinoma (PTC) having suspicious thyroid nodule(s) in a background of heterogeneous parenchyma and to determine the clinical and radiological predictors of malignancy. METHODS: We reviewed the cases of 100 patients who underwent ultrasonography between April 2011 and October 2012, and showed suspicious thyroid nodule(s) in a background of heterogeneous parenchyma. Eight patients who did not undergo ultrasonography-guided fineneedle aspiration cytology (FNAC) and 34 cases of follow-up ultrasonography after initial FNAC were excluded. We compared the benign and malignant nodules in terms of their clinical and radiological factors. RESULTS: For the 58 nodules including 31 LTs (53.4%) and 27 PTCs (46.6%), the mean tumor sizes of the two groups were 0.96 cm for LT and 0.97 cm for PTC. A univariate analysis revealed that PTCs were more frequent in patients younger than 45 years and having microcalcifications than was LT. An independent predictor of PTC after adjustment was an age of <45 years. CONCLUSION: LT mimics malignancy in a background of heterogeneous parenchyma on ultrasonography. A young age of <45 years is the most important predictor of malignancy in this condition.

Preoperative ultrasonographic features of papillary thyroid carcinoma predict biological behavior.

BACKGROUND: Although ultrasound (US) features of papillary thyroid carcinoma (PTC) are well established, little is known regarding biological behavior according US features. We investigated whether there was a difference in biological behavior between PTCs that did and did not meet malignant US criteria. PATIENTS AND METHODS: We retrospectively reviewed clinical records and histological and US findings of the index tumors in 488 patients who underwent surgery for PTC. Benign-looking PTC (B-PTC) was defined as showing none of the accepted US criteria for malignancy. Malignant-looking PTCs (M-PTCs) and B-PTCs were compared in terms of patients' age, sex, tumor size, histological subtype, multifocality, lymph node (LN) metastasis, extrathyroidal extension, stage, recurrence, and distant metastasis. RESULTS: B-PTCs accounted for 74 (15%) of all 488 PTCs. Mean tumor size was not significantly different between the groups, with 1.10 cm for M-PTC and 1.11 cm for B-PTC (P = .947). Univariate and multivariate analysis indicated that M-PTC more frequently had LN metastasis, extrathyroidal extension, and a higher stage than B-PTC (all P < .05). The results were significant in tumors ≥1.0 cm, whereas there were no significant differences in tumors <1 cm. As the number of malignant US features increased, multifocality, extrathyroidal extension, LN metastasis, and a higher stage were more likely. CONCLUSION: PTCs that did not meet malignant US criteria had better prognostic indicators than PTCs that met US criteria. Therefore, US features at the time of diagnosis can serve as a useful tool for predicting biological behavior in PTC.

BRAF V600E mutation analysis of thyroid nodules needle aspirates in relation to their ultrasongraphic classification: a potential guide for selection of samples for molecular analysis.

BACKGROUND: Proper candidates to improve the effectiveness of molecular testing for thyroid nodules detected on ultrasonography (US) in a clinical setting are not well known. We aimed at evaluating the effective indication and method of BRAF(V600E) mutation analysis of aspiration specimens according to the US features of thyroid nodules in a BRAF(V600E) mutation-prevalent area. METHODS: A total of 244 patients with 244 thyroid nodules were prospectively classified as malignant and nonmalignant based on US. Thyroid nodules with any malignant US features including spiculated margin, the presence of microcalcifications or macrocalcifications, marked hypoechogenicity, or a taller-than-wide shape were defined as US-positives and those without these features were defined as US-negatives. All patients underwent US-guided fine-needle aspiration (FNA). The presence of the BRAF(V600E) mutation in FNA specimens was determined by allele-specific polymerase chain reaction (AS-PCR) and direct DNA sequencing. The mutation results were correlated with cytology and either surgical pathology or follow-up. RESULTS: Of 244 nodules, 66 were US-positive and 178 were US-negative. The malignancy rate was 92% (61/66) for US-positives and 14% (25/178) for US-negatives. The BRAF(V600E) mutation was identified in 67% (44/66) of US-positives and in 10% (17/178) of US-negatives. The BRAF(V600E) mutation for nodules with indeterminate or nondiagnostic cytology was present in 45% (5/11) of US-positives and in 8% (2/26) of US-negatives (p = 0.0168). A false negative cytology with the mutation was found in only one case of the US-negatives. All nodules with the mutation were surgically confirmed as papillary carcinomas. Adding the genetic analysis to the FNA as compared with the FNA alone improved the sensitivity and accuracy for US-positives, whereas there was no significant improvement for US-negatives. With regard to sensitivity and accuracy, the use of the AS-PCR was better than the use of the direct DNA sequencing for US-positives as compared with US-negatives. CONCLUSION: The application of BRAF(V600E) mutation analysis in FNA specimens is more effective for thyroid nodules with malignant US features as compared with nodules without malignant US features. The use of the AS-PCR is more valuable as compared with the direct DNA sequencing to refine the diagnosis in a clinical setting.