Additional Excision Biopsy in Patients With Atypical Ductal Hyperplasia at Ultrasound-guided Vacuum-assisted Breast Biopsy.

BACKGROUND/AIM: We conducted this single-center, retrospective study to identify predictors of upgrading to malignancy and to discuss the necessity of additional excision biopsy in patients who were diagnosed with atypical ductal hyperplasia (ADH) at ultrasound (US)-guided vacuum-assisted breast biopsy (VABB) based on our 18-year, single-center experience. PATIENTS AND METHODS: The current study was conducted in a total of 12,160 patients who were evaluated at our medical institution during an 18-year period between January of 2003 and December of 2020. We included the patients who were diagnosed with ADH at US-guided VABB using the Mammotome® (Devicor Medical Products, Inc., Cincinnati, OH, USA). We therefore included a total of 114 patients (n=114) with ADH in the current study. RESULTS: Of 114 eligible patients, 36 underwent additional excision biopsy and the remaining 78 did not. Of these 36 patients, 15 were found to have an upgrading to malignancy at a rate of upgrading of 41.7%. These include 7 cases (46.6%) of low-grade ductal carcinoma in situ (DCIS), 3 cases (20.0%) of intermediate grade DCIS, 1 case (6.7%) of microinvasive DCIS, 3 cases (20.0%) of multifocal lobular carcinoma in situ, and 1 case (6.7%) of mucinous carcinoma. Finally, only suspicious microcalcification on mammography was a significant predictor of upgrading to malignancy (p=0.023). CONCLUSION: An additional excision biopsy is recommended to reduce the rate of upgrading to malignancy in patients who were diagnosed with ADH through a US-guided VABB.

Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort.

BACKGROUND: BRCA1 and BRCA2 (BRCA1/2) variants classified ambiguously as variants of uncertain significance (VUS) are a major challenge for clinical genetic testing in breast cancer; their relevance to the cancer risk is unclear and the association with the response to specific BRCA1/2-targeted agents is uncertain. To minimise the proportion of VUS in BRCA1/2, we performed the multifactorial likelihood analysis and validated this method using an independent cohort of patients with breast cancer. METHODS: We used a data set of 2115 patients with breast cancer from the nationwide multicentre prospective Korean Hereditary Breast Cancer study. In total, 83 BRCA1/2 VUSs (BRCA1, n=26; BRCA2, n=57) were analysed. The multifactorial probability was estimated by combining the prior probability with the overall likelihood ratio derived from co-occurrence of each VUS with pathogenic variants, personal and family history, and tumour characteristics. The classification was compared with the interpretation according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG/AMP) guidelines. An external validation was conducted using independent data set of 810 patients. RESULTS: We were able to redefine 38 VUSs (BRCA1, n=10; BRCA2, n=28). The revised classification was highly correlated with the ACMG/AMP guideline-based interpretation (BRCA1, p for trend=0.015; BRCA2, p=0.001). Our approach reduced the proportion of VUS from 19% (154/810) to 8.9% (72/810) in the retrospective validation data set. CONCLUSION: The classification in this study would minimise the 'uncertainty' in clinical interpretation, and this validated multifactorial model can be used for the reliable annotation of BRCA1/2 VUSs.

Recurrence Rates and Characteristics of Phyllodes Tumors Diagnosed by Ultrasound-guided Vacuum-assisted Breast Biopsy (VABB).

BACKGROUND/AIM: Recently, the development of ultrasonography (US)-guided vacuum-assisted breast biopsy (VABB) has enabled the excision of benign breast tumors with normal surrounding breast tissues; thus, complete excision is possible without residual tumor tissue. We sought to identify the clinicopathological characteristics and recurrence rates of benign phyllodes tumors diagnosed by US-guided VABB. PATIENTS AND METHODS: Data from 11,221 US-guided VABBs performed at the Gangnam Cha Medical Center over 12 years were analyzed. Eighty-three lesions were diagnosed as benign phyllodes tumors; 67 with >24 months of follow-up data were investigated. All lesions were excised using an 8-gauge probe without residual tissue; patients underwent follow-up US every 3-6 months. RESULTS: Five patients (7.46%) experienced local recurrence during a mean follow-up period of 27.8 months; no distant metastases occurred. The mean tumor size was 3.0 cm in the recurrence group and 1.87 cm in the non-recurrence group (p=0.05). CONCLUSION: Benign phyllodes tumors excised and diagnosed using VABB showed a low recurrence rate during the follow-up period; thus, these tumors, particularly those <3 cm, can be safely monitored with ultrasonography instead of performing immediate re-excision.

Clinicopathological Analysis of Ultrasound-guided Vacuum-assisted Breast Biopsy for the Diagnosis and Treatment of Breast Disease.

BACKGROUND/AIM: To evaluate the usefulness and safety of vacuum-assisted breast biopsy (VABB) for breast lesion diagnosis and treatment. PATIENTS AND METHODS: Clinical and histopathological data of 8,748 patients, who underwent 11,221 VABB procedures were analyzed. RESULTS: Most patients (58.2%) were <40 years old. Most lesions (39.6%) were 0.6-1.0 cm in diameter while 3.2% were ≥3.0 cm; fibroadenomas were the most common (46.6%). Eight (14% of 57) cases of atypical ductal hyperplasia were underestimated. The positive predictive values (PPVs) of breast imaging reporting and data system (BI-RADS) ultrasound category were 0.6%, 3.4%, 34.8%, 66.2%, and 93.8% for category 3, 4a, 4b, 4c, and 5 lesions, respectively. The mean number of core specimens was 9.5±8.8; the mean procedure time was 3.4±2.7 min. No residual lesions were found in 94.4% of the 7,480 patients. CONCLUSION: VABB could replace ultrasound-guided core biopsy and surgical excisional biopsy for the diagnosis of breast disease and the treatment of benign breast lesions.

Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015.

BACKGROUND: No nationwide epidemiological study evaluating the prevalence of subclinical and overt forms of hypothyroidism and hyperthyroidism has yet been conducted in Korea. This study aimed to evaluate the reference range of serum thyroid stimulating hormone (TSH) and the national prevalence of thyroid dysfunctions in Korea. METHODS: Nation-wide cross-sectional data were analyzed from a representative sample of the civilian, non-institutionalized Korean population (n=6,564) who underwent blood testing for thyroid function and anti-thyroid peroxidase antibody (TPOAb) as part of the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). RESULTS: The reference interval of serum TSH in the Korean reference population was 0.62 to 6.68 mIU/L. Based on this reference interval, the prevalence of overt and subclinical hypothyroidism was 0.73% (males 0.40%, females 1.10%) and 3.10% (males 2.26%, females 4.04%), respectively. The prevalence of hypothyroidism increased with age until the age group between 50 to 59 years. Positive TPOAb were found in 7.30% of subjects (males 4.33%, females 10.62%). The prevalence of overt and subclinical hypothyroidism TPOAb-positive subjects was 5.16% and 10.88%, respectively. The prevalence of overt and subclinical hyperthyroidism was 0.54% (males 0.30%, females 0.81%) and 2.98% (males 2.43%, females, 3.59%), respectively. CONCLUSION: The Serum TSH reference levels in the Korean population were higher than the corresponding levels in Western countries. Differences were found in the prevalence of hypothyroidism and hyperthyroidism according to age, sex, and TPOAb positivity. This study provides important baseline information for understanding patterns of thyroid dysfunction and diseases in Korea.

Differences between the clinical and histopathological tumor stages in breast cancer diagnosed using vacuum-assisted breast biopsy.

The present study aimed to determine the difference between the clinical tumor stage (T stage) based on pre-operative ultrasound and the histopathological T stage subsequent to surgery in vacuum-assisted breast biopsy (VABB)-diagnosed breast cancer. Tumor sizes measured ultrasonography (USG) and histologically were retrospectively calculated and analyzed using paired t-tests in 209 patients diagnosed with breast cancer using VABB. The patients were classified into two groups, consisting of breast imaging reporting and data system (BI-RADS) category 4a or below, who underwent complete resection by VABB, and BI-RADS category 4b or above, who underwent incisional biopsy by VABB. The histopathological tumor size was found to be smaller compared with the USG-determined size in 92.3% of pT1a, 75.5% of pT1b, 44.2% of pT1c, 47.7% of pT2 and 0% of pT3 cases. Furthermore, the histopathological tumor size was smaller compared with the USG-determined size in 62.8% of cases classified as BI-RADS category 3-4a and in 53.7% of cases classified as BI-RADS category 4b-5. The smaller the primary tumor at the time of diagnosis by VABB, the higher the likelihood of pathological underestimation on post-operative histopathological assessment compared to pre-operative USG.

Vacuum-assisted breast biopsy for breast cancer.

Sonographic examination of the breast with state-of-the-art equipment has become an essential part of the clinical work-up of breast lesions and a valuable adjunct to mammographic screening and physical examination. Fine-needle aspiration (FNA) and core-needle biopsy (CNB) are well-established, valuable techniques that are still used in most cases, whereas vacuum-assisted breast biopsy (VABB) is a more recent technique. VABB has proven clinical value and can be used under sonographic, mammographic, and magnetic resonance imaging guidance. The main indication for the use of VABB is for biopsies of clustered microcalcifications, which are usually performed under stereotactic guidance. This method has been proven reliable and should replace surgical biopsies. The ultrasound-guided procedure is still more a matter of discussion, but it should also replace surgical biopsies for nodular lesions, and it should even replace surgery for the complete removal of benign lesions. This viewpoint is gradually gaining acceptance. Different authors have shown increased diagnostic accuracy of VABB compared to FNA and CNB. VABB particularly leads to less histological underestimation. The other indications for VABB are palpable or nonpalpable nodular lesions or American College of Radiology Breast Imaging Reporting and Data System 3 and 4A lesions. For masses that are likely benign or indeterminate, we attempt to completely remove the lesion to eliminate uncertainty on later follow-up images. VABB offers the best possible histological sampling and aids avoidance of unnecessary operations. VABB complications include bleeding or pain during the procedure, as well as postoperative pain, hemorrhaging, and hematomas. But, these hemorrhaging could be controlled by the post-procedural compression and bed resting. Overall, VABB is a reliable sampling technique with few complications, is relatively easy to use, and is well-tolerated by patients. The larger amount of extracted tissue reduces sampling error.

A multi-institutional study on the association between BRCA1/BRCA2 mutational status and triple-negative breast cancer in familial breast cancer patients.

Triple-negative breast cancer (TNBC) accounts for 12-24 % of all breast cancers. Here, we studied 221 familial breast and/or ovarian cancer patients from 37 hospitals using a comprehensive approach to identify large genomic rearrangements (LGRs) as well as sequence variants, and investigated the association between BRCA1/2 mutational status and TNBC. We performed direct sequencing or mutation scanning followed by direct sequencing. Then, 143 BRCA1/2 mutation-negative patients were screened for LGRs. In this study, the prevalence of BRCA1/2 mutations was high (36.9 %). The prevalence of BRCA1 mutations was similar to that of BRCA2 mutations: 49.4 versus 50.6 %, respectively. TNBC was diagnosed in 35.2 % of BRCA1/2 mutation carriers and 57.1 % of BRCA1 mutation carriers. Conversely, two-thirds of TNBC patients carried BRCA1/2 mutation(s), and about half were BRCA1 mutation carriers. When stratified by the mutated gene, TNBC prevalence in BRCA1 mutation carriers was significantly lower when there was a family history of ovarian cancer. Our multinomial logistic regression model demonstrated that no single factor was sufficient, and at least two factors, such as a patient with family history of both breast cancer and ovarian cancer or a patient diagnosed at a relatively young age (<40 years) with a TNBC phenotype, are necessary to indicate BRCA1/2 genetic testing in this population. Our results suggest that TNBC is a strong predictor for the presence of a BRCA1 mutation in this population, but additional risk factors should also be evaluated to ascertain a 10 % or higher prior probability of BRCA1/2 mutation testing.

Nationwide survey of use of vacuum-assisted breast biopsy in South Korea.

BACKGROUND: Image-guided vacuum-assisted breast biopsy (VABB) is used for detecting breast lesions in South Korea. However, no clear guidelines for VABB exist. MATERIALS AND METHODS: A 53-item survey was administered to members of the Korean Breast Cancer Society between July 27 and August 27, 2010. RESULTS: Among 62 respondents, 87.1% had performed VABB, with 63.0% performing both diagnosis and treatment. Around 62.5% used VABB for diagnosing Ultrasound Breast Imaging-Reporting and Data System (USG BIRAD) Category 3 lesions, 55% for Category 4A, 57.5% for microcalcifications detected by ultrasonography, and 30% for small Category 5. Furthermore, 81.3% used VABB to treat Category 3 lesions; while 67.8% diagnosed benign lesions on core needle biopsy, requiring surgical excision. About 83% used VABB for small tumors (<3 cm). Among therapeutically excised tumors, 86.4% reported fibroadenoma. CONCLUSION: VABB is performed for diagnosis and treatment in South Korea, and complies with the available guidelines. However, national and global standards and guidelines for VABB need to be established.

Long-term follow-up result of benign phyllodes tumor of the breast diagnosed and excised by ultrasound-guided vacuum-assisted breast biopsy.

PURPOSE: Percutaneous removal of benign breast tumors using ultrasound-guided vacuum-assisted breast biopsy (VABB) has been recently regarded as a feasible and safe method without serious complications. The aim of this study was to evaluate the efficacy and safety of the VABB in the treatment of benign phyllodes tumors, and to identify whether or not surgical re-excision is necessary for benign phyllodes tumors diagnosed and excised by VABB. METHODS: From January 2003 to December 2011, a total of 6,923 VABB were performed in 5,434 patients. Out of 6,923 lesions, 53 were benign phyllodes tumors. Among these, 31 lesions, with a follow-up period of longer than 24 months, were enrolled in this study. Ultrasonography follow-up was performed at 3 to 6 month intervals in order to assess recurrence. The mean follow-up period was 75.9±13.5 months (range, 24-94 months). RESULTS: The mean patient age at presentation was 31.6±9.4 years. The mean size of the lesion was 1.60±0.88 cm. The majority of lesions, 74.2% (23 cases), were palpable, and 25.8% (8 cases) were non-palpable. Twenty-two lesions (71.0%) were classified as Breast Imaging Reporting and Data System category 3, and nine lesions (29.0%) were classified as category 4a, by ultrasonography. During the follow-up period, local recurrence developed in one lesion, making the local recurrence rate 3.2%. CONCLUSION: If a benign phyllodes tumor is diagnosed, and sufficiently excised by VABB, observing the clinical course may be considered as an alternative to performing immediate wide local excision; this is the case despite the fact that it would need to be observed for a prolonged period of time.

The current role of vacuum assisted breast biopsy system in breast disease.

The gold standard for breast biopsy procedures is currently an open excision of the suspected lesion. However, an excisional biopsy inevitably makes a scar. The cost and morbidity associated with this procedure has prompted many physicians to evaluate less invasive, alternative procedures. More recently, image-guided percutaneous core-needle biopsy has become a frequently used method for diagnosing palpable and non-palpable breast lesions. Although sensitivity rates for core-needle biopsy are high, it has the disadvantage of histological underestimation, which renders the management of atypical ductal hyperplasia, papillary lesions, and fibroepithelial lesions somewhat difficult. Vacuum assisted breast biopsy (VABB) was developed to overcome some of these negative aspects of core-needle biopsy. VABB allows for a sufficient specimen to be obtained with a single insertion and can provide a more accurate diagnosis and completely remove the lesion under real-time ultrasonic guidance. The advantage of complete lesion removal with VABB is to reduce or eliminate sampling error, to decrease the likelihood of a histological underestimation, to decrease imaging-histological discordance, to decrease the re-biopsy rate, and to diminish the likelihood of subsequent growth on follow-up. In recent years, with the advancement of VABB instruments and techniques, many outcome studies have reported on the use of VABB for resecting benign breast lesions with a curative intent. VABB is highly accurate for diagnosing suspicious breast lesions and is highly successful at treating presumed benign breast lesions. Thus, in the near future, VABB will be routinely offered to all appropriately selected patients.

BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations.

We analyzed the mutation spectrum of BRCA1 and BRCA2 genes in 354 Korean breast cancer patients. Overall, 40 patients carried 25 distinct BRCA1/2 mutations including 12 novel mutations. Seven district mutations were found in multiple unrelated patients, with the BRCA2 c.7480C>T mutation detected in eight unrelated patients, accounting for 50% of the mutations detected in BRCA2. The large number (25/40, 62.5%) of recurrent mutations suggests the possibility of developing a simple screening test for these mutations. The frequency of mutations was related to the number and kinds of risk factors, varying from 10.4 to 25% in the five major risk factor groups. The frequency of BRCA mutations in patients with two or more risk factors was markedly higher than that in patients with one risk factor.

Application of the breast imaging reporting and data system final assessment system in sonography of palpable breast lesions and reconsideration of the modified triple test.

OBJECTIVE: The purpose of our study was to evaluate the utility of the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS) sonographic final assessment system and palpation-guided fine-needle aspiration (FNA) for evaluation of palpable breast lesions. METHODS: Our computerized database identified 160 palpable lesions of the breast in which follow-up palpation-guided FNA, targeted sonography, and pathologic confirmation were performed. We used BI-RADS sonographic data on all lesions. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of malignancy were calculated for sonography and palpation-guided FNA. Two-sample binomial proportion tests were used as the statistical analysis (P<.05). RESULTS: The FNA results were defined as benign, atypical cells, suspicious for malignancy, malignancy, and insufficiency. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 90.9%, 82.7%, 84.3%, 57.7%, and 97.2%, respectively, on sonography and 75.8% to 90.9%, 82.7% to 98.4%, 84.3% to 94.4%, 57.7% to 92.6%, and 93.9% to 97.2% on FNA. There was no statistically significant difference for sensitivity and negative predictive value between the two examinations. CONCLUSIONS: The diagnostic accuracy of sonography was similar to that of palpation-guided FNA for not missing the malignancy. Clinical application of FNA results can be difficult, especially when the result is insufficiency or atypical cells. Moreover, FNA is invasive and overlaps other procedures. Therefore, we conclude that sonography can replace palpation-guided FNA for diagnosis of palpable lesions of the breast when the BI-RADS sonographic final assessment system is used appropriately.

Lymphoepithelial cyst of the thyroid mimicking malignancy on sonography.

A 52-year-old man presented with a palpable left neck mass that had been present for several months. A sonogram showed a 2-cm hypoechoic mass with internal coarse macrocalcifications in the left lobe of the thyroid gland. CT revealed a well-demarcated hypodense mass within the left thyroid lobe. A left thyroidectomy was performed at the patient's request because of the possibility of malignancy based on sonographic findings. Pathologically, the mass was composed of pseudostratified ciliated columnar epithelial cells simulating respiratory epithelium surrounded by florid lymphoid hyperplasia with germinal centers, consistent with an intrathyroidal lymphoepithelial cyst.

Sonographic findings in complications of cosmetic breast augmentation with autologous fat obtained by liposuction.

A 37-year-old woman presented with breast pain after breast augmentation utilizing autologous fat obtained by liposuction. Mammography and sonography demonstrated fat necrosis in the right breast and a solid inflammatory mass in the left breast. The diagnoses were confirmed by biopsy.

Imaging findings in a case of epidermal inclusion cyst arising within the breast parenchyma.

Epidermal inclusion cysts rarely occur in the breast, but when they do, the consequences can be severe. Here, we report the case of a 23-year-old woman who presented with a palpable mass in the right breast. The mass had persisted for 4 years and had been causing pain for 1 month at the time of the patient's presentation. We examined the mass by means of mammography and sonography. Sonographic examination revealed a well-circumscribed solid, avascular mass suggestive of an epidermal inclusion cyst. Excision was performed at the patient's request. Histopathologic examination of the mass after excision confirmed the diagnosis of epidermal inclusion cyst and its localization within the breast parenchyma. To our knowledge, reports on epidermal inclusion cysts within the breast parenchyma are rare.