Lobular Neoplasia Research Articles

High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: imaging characteristics, outcome of surgical excision or imaging follow-up.

To evaluate imaging characteristics, outcome of surgical excision or imaging follow-up on high-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy (MRI-VABB). We retrospectively reviewed 598 lesions undergoing 9-gauge MRI-VABB from January 2015 to April 2018 to identify high risk breast lesions.We collected patient demographics, breast MRI BI-RADS descriptors, histopathological diagnosisat MRI-VABB and surgical excision, frequency of upgrade to malignancy and imaging follow-up of high-risk lesions. The x2 test and Fisher exact tests were performed for univariate analysis. 114 patients with 124/598 findings (20.7%) had high-risk lesions at MRI-VABB, includingatypical ductal hyperplasia (ADH) (21/124, 16.9%), lobular neoplasia (40/124, 32.3%), radial scar/complex sclerosing lesion (RS/CSL) (13/124, 10.5%), papillary lesions (49/124, 39.5%), and flat epithelial atypia (FEA) (1/124, 0.8%).84/124 (67.7%) high-risk lesions wereexcised.19/84 (22.6%) were upgraded to malignancy (7 invasive cancer, 12 DCIS).The upgrade rate for ADH and lobular neoplasia was7/18 (38.9%) and 9/31 (29.0%), respectively. The upgrade rate for RS/CSL was 1/10 (10%). Of the 25 papillary lesions excised, 2 (8%) demonstrated pathologic atypia and were upgraded to DCIS. The other 23 papillary lesions had no upgrade or atypia. Excised high-risk lesions showing upgrade varied from 0.4 to 6cm in length (mean 1.6cm). There was a non-significant trend (p = 0.054) between larger lesion and upgrade to malignancy;however, there were no other specific imaging features to predict malignancy upgrade. There were no specific MRI imaging characteristics of high-risk lesions to predict malignancy upgrade. Therefore, surgical excision is recommended for high-risk lesions, especially ADH or lobular neoplasia.

Atypical Ductal Hyperplasia and Lobular Neoplasia: Update and Easing of Guidelines.

OBJECTIVE. Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) are among high-risk lesions that have been previously recommended for surgical excision when diagnosed on core needle biopsy. Recent studies have examined whether imaging surveillance is a reasonable alternative to surgical management for these lesions. This article synthesizes the evidence regarding management of atypical hyperplasia and LCIS diagnosed on core needle biopsy and clinical implications of these diagnoses on future breast cancer risk as well as highlights areas of further research needed to improve practice guidelines for these high-risk lesions. CONCLUSION. Although surgical excision is still recommended after diagnosis of ADH on core needle biopsy, in specific circumstances ALH and LCIS can safely be managed by imaging surveillance.

Outcomes of classic lobular neoplasia diagnosed on breast core needle biopsy: a retrospective multi-center study.

Management of classic lobular neoplasia (cLN) diagnosed on core needle biopsy (CNB) is controversial. Our aim in this study was to review cases of cLN diagnosed on CNB to determine the rate and risk factors of an upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma on excision. All breast CNBs with a diagnosis of atypical lobular hyperplasia (ALH) or classic lobular carcinoma in situ (cLCIS) from three different institutions within a single health care system between 2013 and 2018 were retrieved. Cases with any additional high-risk lesions in the same CNB or discordant radiological-pathological correlation were excluded. Information about age, personal history of prior or concurrent breast cancer (P/CBC), and radiological and histological findings were recorded. A total of 287 cLN cases underwent surgical excision. Analysis of these 287 cLN cases showed 11 (3.8%) upgrade lesions on excision. Among the 172 ALH cases, there were 3 (1.7%) upgrades, which were all invasive lobular carcinomas (ILCs). On the other hand, 8 of 115 (7%) cLCIS cases revealed upgrade on excision (2 ILC, 5 DCIS. and 1 ILC + DCIS). Statistical analysis revealed that cLN cases with P/CBC, radiological asymmetry, or architectural distortion had a statistically significant higher upgrade rate on excision. Our findings revealed a low upgrade rate (3.8%) on the excision of classic lobular neoplasia diagnosed on breast core needle biopsy. Clinicoradiological surveillance can be appropriate when lobular neoplasia is identified on core biopsy with pathological radiological concordance in patients without a history of breast cancer, with the caveat that radiological asymmetry and architectural distortion are associated with a significant increase in an upgrade on excision.

Flat Epithelial Atypia in Breast Core Needle Biopsies With Radiologic-Pathologic Concordance: Is Excision Necessary?

Flat epithelial atypia (FEA) is an alteration of terminal duct lobular units by a proliferation of ductal epithelium with low-grade atypia. No consensus exists on whether the diagnosis of FEA in core needle biopsy (CNB) requires excision (EXC). We retrospectively identified all in-house CNBs obtained between January 2012 and July 2018 with FEA. We reviewed all CNB slides and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma (IC) and/or ductal carcinoma in situ in the EXC. The EXC slides of all upgraded cases were rereviewed. Out of ∼15,700 consecutive CNBs in the study period, 106 CNBs from 106 patients yielded FEA alone or with classic lobular neoplasia (LN). We excluded 52 CNBs (40 patients with prior/concurrent carcinoma and 12 without EXC). After rereview, we reclassified 14 cases (2 marked nuclear atypia, 10 focal atypical ductal hyperplasia, 2 benign). The final FEA study cohort consisted of 40 CNBs from 40 women. The CNB targeted mammographic calcifications in 36 (90%) cases, magnetic resonance imaging nonmass enhancement in 3 (8%), and 1 (2%) sonographic mass. All CNBs were deemed radiologic-pathologic concordant. FEA was present alone in 34 CNBs and with LN in 6. EXC yielded 2 low-grade IC, each spanning <2 mm, identified in tissue sections without biopsy site changes. The remaining 38 cases had no upgrade. Classic LN did not affect the upgrade. The upgrade rate of FEA was 5%; both minute, low-grade "incidental" IC. We conclude that nonsurgical management may be considered in patients without prior/concurrent carcinoma and radiologic-pathologic concordant CNB diagnosis of FEA.

Heterogeneous risk profiles among B3 breast lesions of uncertain malignant potential.

Most cases of breast lesions of uncertain malignant potential (B3) undergo surgical intervention. We aimed to analyze the outcome of B3 lesion subtypes in a large series of screen-detected cases. We screened 2,986 core needle biopsies to classify B3 lesions. Positive predictive values (PPVs) for malignancy were calculated for a comprehensive risk characterization according to clinicopathologic and morphologic variables. B3 lesions comprised 35% atypical ductal hyperplasia (PPV = 20%), 16.7% flat epithelial atypia (PPV = 12%), 22.7% lobular neoplasia (PPV = 16.2%), 9% papillary lesion (PPV = 18.5%), 8.6% phyllodes tumor (PPV = 3.8%), and 8% radial scars (PPV = 4.1%) based on histopathologic diagnosis. Upgrade rates were 15.9% for calcifications, 13.7% for mass lesions, and 16.7% for architectural deformities, with 8.3% of malignant lesions classified as ductal carcinoma in situ and 6.7% as invasive cancers (PPV = 15%). B3 lesions entail a heterogeneous risk of malignancy, and careful radiologic-pathologic correlation is required for optimal treatment.

Lobular neoplasia and invasive lobular breast cancer: Inter-observer agreement for histological grading and subclassification

Lobular neoplasia (LN), invasive lobular breast cancer (ILBC) and related pleomorphic variants represent a distinct group of neoplastic mammary gland lesions. This study assessed the inter-observer agreement of histological grading in a series of ILBC and LN.54 cases (36x ILBC, 18x LN) were evaluated by 17 observers. 3978 classification calls on various histological features, including nuclear grade, proliferative activity (Ki67 immunohistochemistry, categorical scoring), histological grade and pleomorphism were obtained. Pairwise Cohen’s kappa values were calculated and compared between various features and different observer subsets with variable histomorphological experience.In ILBC, pairwise inter-observer agreement for histological grade ranged from poor to almost perfect concordance and was higher in advanced and experienced histopathologists compared with beginners (P < 0.001). Agreement for proliferation (Ki67) ranged from slight to almost perfect concordance and was also higher in advanced and experienced histopathologists (P < 0.001). Considering different features, agreement for proliferation (Ki67) was superior to agreement for histological grade and nuclear grade, even among advanced and experienced histopathologists (P < 0.001). In LN, agreement for B-classification ranged from poor to almost perfect concordance and was higher in advanced and experienced histopathologists (P < 0.001). Considering different features, agreement for proliferation (Ki67 in LN) was superior to subclassification agreement based on conventional features, such as acinar distention and nuclear grade (P < 0.001).In summary, pairwise inter-observer concordance of histological grading of ILBC and LN is dependent on histomorphological experience. Assessment of proliferation by Ki67 immunohistochemistry is associated with favorable inter-observer agreement and can improve histological grading of ILBC as well as LN.

Outcome of radial scar/complex sclerosing lesion associated with epithelial proliferations with atypia diagnosed on breast core biopsy: results from a multicentric UK-based study

AimsThe clinical significance of radial scar (RS)/complex sclerosing lesion (CSL) with high-risk lesions (epithelial atypia) diagnosed on needle core biopsy is not well defined. We aimed at assessing the upgrade...

Our Radiological Experience on B3 Lesions: Correlation Between Mammographic and MRI Findings With Histologic Definitive Result

IntroductionThe purpose of this study was to evaluate mammographic and magnetic resonance imaging (MRI) features in B3 lesions. Patients and MethodsFrom 2011 to 2018, 139 patients with histologically proven B3 lesions who underwent mammography or/and MRI, were retrospectively reviewed. B3 lesions were classified in: atypical ductal hyperplasia (ADH), lobular neoplasia (LN), papillary lesion (PL), radial scar (RS), flat epithelial atypia (FEA), phyllodes tumor (PT), or mesenchymal lesion. Imaging features evaluated were: the presence of microcalcifications, mass and architectural distortions on mammograms and type of margins (circumscribed, irregular, spiculate), enhancement (mass-like, non-mass-like), size (≤ 15 mm, > 15 mm), and kinetics curves (I, II, III) on MRI. The definitive histologic results confirmed benign lesion or were upgraded to malignancy, and the positive predictive value was calculated. ResultsHistologic classification of B3 lesions counted 45 (32.37%) ADH, 12 (8.63%) LN, 25 (17.99%) PL, 5 (3.61%) RS, 31 (22.31%) FEA, 20 (14.39%) PT, and 1 (0.70%) mesenchymal lesion. One hundred seven patients had mammography, and 38 had MRI. In 90 (65%) cases, the histologic diagnosis confirmed B3, in 15 (11%) cases, benign lesion, and in 34 (24%) cases, malignancies were found, with best positive predictive value for mesenchymal tumor (1), ADH (0.36), and FEA (0.4). Significant correlations comparing core needle biopsy groups and microcalcifications (P = .016) and presence of mass (P = .002) and comparing definitive histology with the presence of mass (P = .023), were found. Regarding MRI, the morphology correlated with core needle biopsy groups (P = .038); morphology (P = .024), dimension (P = .040), and kinetic curve (P = .005) correlated with malignancy. ConclusionsThe B3 category includes different entities, with various risk of malignancy; their heterogeneity is associated with specific mammographic and MRI features, although further confirmations are needed.

An audit of mammographic screen detected lesions of uncertain malignant potential (B3) diagnosed on initial image guided needle biopsy: how has our practice changed over 10 years?

To review all cases of B3 lesion diagnosed at initial image-guided needle biopsy over two 5-year cohorts to identify upgrade rates to malignancy and the effect of changing guidance on the management of such lesions. Data was collected retrospectively. Mammographic features, biopsy type and management were recorded for each lesion. Upgrade rates for each B3 histological category were quantified. Statistical analysis was performed using SPSS. There were 224 cases in 2005-2010 and 240 cases in 2010-2015. Mammographically 211 lesions were microcalcifications, 182 masses, 65 distortions and six asymmetric densities with no difference in the mammographic features in the two cohorts. Two hundred and eight 14 G core biopsies and 256 initial vacuum-assisted biopsies were performed. There was a statistically significant reduction in benign surgical biopsies and an increase in second-line vacuum biopsy/excision in the latter cohort, with no significant change in the upgrade rate. There was an overall 6% upgrade to invasive malignancy and 13% upgrade to ductal carcinoma in situ (DCIS). The upgrade rates for the following histological categories were atypical intraductal epithelial proliferation (AIDEP) 33.2% (21/63); classical (not pleomorphic) in situ lobular neoplasia (ISLN) 18.2% (6/33); flat epithelial hyperplasia (FEA) 21.7% (20/92); papilloma with atypia 53.8% (7/13), without atypia 12.1% (8/66); and radial scar/complex sclerosing lesion with atypia 16.7% (2/12), and without atypia 7.9% (6/76). Upgrade rates remain high for some histological categories even with first-line use of vacuum biopsy. Management of borderline lesions should be considered carefully in a multidisciplinary meeting. In many cases, the need for diagnostic surgical excision has been replaced by image-guided vacuum sampling.

Screening breast MRI in patients with history of atypia or lobular neoplasia.

Our goal was to determine outcomes of screening breast MRI in patients with prior history of atypia or lobular neoplasia (LN). Review of the MRI data base revealed 264/7482 (3.5%) screening MRIs in 145 patients with history of atypia or LN. Overall, 39/264 (14.7%) received an abnormal interpretation, with 7.2% BI-RADS 4 and 5 (19/264) and 7.6% BI-RADS 3 (20/264). PPV1 was 38.4% (six cancers in 39 BI-RADS 3, 4, 5); PPV3 was 28.5% (six cancers in 21 biopsies). Screening breast MRI use in this population is low (3.5%), although PPVs are comparable to other high-risk groups for which breast MRI is recommended.

Abstract P5-02-06: High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: Imaging characteristics, outcome of surgical excision or imaging follow-up

Abstract PURPOSE To evaluate imaging characteristics, outcome of surgical excision or imaging follow-up on high-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy (MRI-VAB). MATERIALS AND METHODS We retrospectively reviewed 581 lesions, to include benign, high-risk and malignant lesions, undergoing 9-gauge MRI-VAB from January 2015 to April 2018. We collected patient demographics, risk factors and indications, breast MRI BI-RADS descriptors, histopathological diagnosis at MRI-VAB and surgical excision, frequency of upgrade to malignancy and imaging follow-up of high-risk lesions found in this period. RESULTS 101 patients with 107/581 (18.4% of all lesions) had high risk lesions at MRI-VAB, including atypical ductal hyperplasia (ADH)(n=19/107, 17.8%), lobular neoplasia (n=35/107, 32.7) including atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), ALH plus LCIS, papillary lesions (n=44/107, 41.1%), radial scar/complex sclerosing lesion (RS/CSL)(n=8/107, 7.5%) and flat epithelial atypia (FEA)(n=1/107, 1%). 71/107 (66.4%) high risk lesions were excised. 16/71 (22.5%) were upgraded to malignancy (4 invasive cancer, 12 DCIS). The upgrade rate for ADH and lobular neoplasia was 5 /16 (31.3%) and 8/26 (30.8%) respectively. The upgrade rate for RS/CSL was 1/6 (16.7%). Of the 22 papillary lesions excised, 2 (9.1%) demonstrated pathologic atypia and were upgraded to DCIS. The other 20 papillary lesions had no upgrade or atypia. Excised high risk lesions showing upgrade varied from 0.4 to 6 cm in length (average 2.1 cm). Increasing size correlated with tendency towards increased upgrade to malignancy, but there were no other specific imaging features to predict malignancy upgrade. CONCLUSION There were no specific MRI imaging characteristics of high-risk lesions to predict malignancy upgrade. Therefore, surgical excision is recommended for high risk lesions especially ADH or lobular neoplasia. Additionally, non-atypical papillomas did not demonstrate malignancy upgrade in our small study. And further larger studies may demonstrate that these lesions may not need to be surgically excised. Citation Format: Okamoto S, Covelli JD, DeMartini WB, Daniel BL, Ikeda DM. High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: Imaging characteristics, outcome of surgical excision or imaging follow-up [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-02-06.

Breast Benign Findings and Disease

Patients often seek the opinion of physicians for benign breast conditions, because of substantial concern about cancer. It is important that general surgeons are armed with the necessary information to thoroughly evaluate and treat benign breast conditions. In this chapter, the more common benign breast complaints and benign breast pathology are reviewed and appropriate management is discussed. The workup and management of masses, cysts, breast pain, nipple discharge, fibrocystic changes, various fibroepithelial lesions (including fibroadenoma) will be reviewed. Borderline lesions including atypical hyperplasias radial scars, and lobular neoplasia will also be discussed with special attention directed to the comparative risks of upgrade to malignancy and the need for surgical excision. Gynecomastia will also be reviewed, along with the various causes, treatments and distinctions from malignancy. Lastly, we will review the management of breast infections and inflammatory conditions, as well as more uncommon breast lesions. This review contains 11 figures, 6 tables, and 38 references. Key Words: Breast masses, Breast pain/Mastalgia, Nipple Discharge, Fibrocystic Changes, LCIS, Radial Scar, Atypical Hyperplasia, Lobular neoplasia, Papillomas, gynecomastia

Isolated Flat Epithelial Atypia on Core Biopsy Specimens Is Associated With a Low Risk of Upgrade at Excision.

We present a retrospective review of 111 breast core biopsy specimens with flat epithelial atypia (FEA) and corresponding excision to better understand rates of upgrade following this diagnosis. In total, 252 breast core biopsy specimens were identified. Cases were excluded if biopsy slides or excision results were unavailable, for ipsilateral carcinoma or other findings warranting excision, or biopsy performed for indications other than mammographically detected calcifications. Coincident atypical lobular hyperplasia was not excluded. Diagnoses were confirmed by breast pathologists, and mammographic images were reviewed. Ultimately, 111 biopsy specimens with FEA were included. In subsequent excisions, one (1%) of 111 showed invasive carcinoma, 20 (18%) atypical ductal hyperplasia, 20 (18%) lobular neoplasia, 31 (28%) FEA, and 39 (35%) no atypical findings. FEA on core biopsy specimens is associated with a low rate of upgrade to invasive carcinoma. Close follow-up may be a reasonable alternative to excision for isolated FEA on core needle biopsy specimens.

Supplemental ultrasound screening in patients with a history of lobular neoplasia.

To investigate the role of ultrasound (US) screening as an adjunct to annual mammography (M) in breast cancer detection in women with a history of lobular neoplasia (LN) diagnosed following core needle or excisional biopsy. A retrospective review of our database was performed between 11/2006 and 11/2011 to identify patients diagnosed with LN, and underwent annual screening. Patients with a lifetime risk >20% per risk modeling were excluded. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and cancer detection rate (CDR) of each screening test were identified. Cancer type and detection modality were recorded. A total of 100 patients who had M and/or US screening were included. Mean patient age was 54.7years (range 33-83). All 100 patients underwent a mean of 3.9 rounds of screening M and 93 (93%) received US screening (mean 3.3 rounds). Of 93 patients who received both M and US screening, 12 (13%) were diagnosed with breast cancer. Mammographic CDR was 4%. Incremental US CDR was 6.5%. The sensitivity, specificity, and NPV for M screening alone was 33% (10%, 65%), 77% (67%, 85%), and 89% (80%, 95%), respectively. US and mammography screening had a combined sensitivity: 83% (52%, 98%), Specificity: 72% (62%, 81%), NPV: 97% (89%, 100%). Supplemental US screening resulted in a significant increase in sensitivity, yielding 6.5% incremental CDR in this high-risk patient subgroup that does not fulfill ACS high-risk MRI screening criteria.

Role of one-pass breast lesion excision system in complete excision of high-risk breast lesions with atypia expressed as clusters of microcalcifications.

To assess the role of the breast lesion excision system (BLES) in complete removal of clusters of microcalcifications found on mammogram proved histologically to be high-risk lesions with cell atypia. Three hundred ninety-four consecutive women (mean age 58.5years, range 39-78years) with 400 clusters of suspicious microcalcifications underwent stereotactic biopsy using the intact BLES device between January 2014 and January 2016. All cases proved histologically to be high-risk lesions were subsequently assessed for complete removal. The underestimation rate was also assessed. Thirty-eight out of 400 (9.5%) lesions were high-risk lesions with atypia with mean size 7.63mm (st. dev. = 4.03mm) which was within the size that the BLES needle can excise (20mm). Four (10.5%) papillomas with atypia, 14 (36.8%) cases with flat epithelial atypia (FEA), 10 (26.3%) cases with lobular intraepithelial neoplasia (LIN-LIN 1, LIN 2), 8 (21.2%) with atypical ductal hyperplasia (ADH) and 2 (5.3%) cases with mucocele-like lesions (MLL) with atypia were found. Twenty-nine out of 38 lesions had subsequent surgery. Complete excision was achieved in 23/29 lesions (79.3%). No underestimation was found. Two-year mammographic stability was found in all lesions. Non-parametric statistical analysis showed no other significant predictive factor for complete excision apart from the distance of the lesions from the specimen margins (p = 0.031 Mann-Whitney test). One-pass BLES intact biopsy technique is a safe method of complete removal of high-risk atypical lesions with high accuracy rates for certain histologies and could be potentially used as an alternative excision method to diagnostic surgery in selected cases. • Breast lesion excision system (BLES) is an image-guided biopsy technique that uses radiofrequency to remove an intact piece of tissue including the target breast neoplasm. • Breast lesion excision system (BLES) under stereotactic guidance is able to accurately biopsy high-risk breast lesions expressed mammographically as clusters of suspicious microcalcifications. • BLES under stereotactic guidance is an accurate technique for en bloc excision of selected cases of small clusters of suspicious microcalcifications proved to be high-risk lesions with histopathologically disease-free margins of excision.

Triaging Atypical Lobular Hyperplasia and Lobular Carcinoma In Situ on Percutaneous Core Biopsy to Surgery or Observation: Assiduous Radiologic-Pathologic Correlation Works, Quantitating Extent of Disease Does Not.

The management of lobular neoplasia (LN) found on core biopsy is controversial and ranges from obligatory surgical excision to clinical/imaging observation. To determine if in cases of core needle biopsy yielding LN, quantification of normal and diseased terminal ductal lobular units (TDLUs) can predict which cases require surgical excision and which can be safely followed. A secondary goal is to assess whether the concordance or discordance of core biopsy results, determined by rigorous radiologic-pathologic correlation, can predict for upgrade to malignancy at excision. In this retrospective study, 79 specimens from 78 women who underwent image-guided core needle biopsies between 2005 and 2012 yielding LN were evaluated for total number of TDLUs and total number and percentage of TDLUs involved by LN. Additionally, radiologic-pathologic correlation was performed to assess concordance or discordance. All were correlated with the results of surgical excisional biopsy or imaging/clinical follow-up. There were 5 upgrades to malignancy. There was no association between upgrade to malignancy and any of the 3 TDLU variables evaluated, including total TDLUs in the specimen (P = .42), total abnormal TDLUs (P = .56), and percent of TDLUs that are abnormal (P = .07). Kendall rank correlation demonstrated a correlation between discordance and upgrade to cancer at surgery that was statistically significant (τb = -0.394, P < .001). Quantifying total TDLU and those involved by LN on core biopsy will not aid in triaging patients to surgery or observation. Assiduous radiologic-pathologic correlation to determine lesion concordance/discordance can predict those patients who would benefit from surgical excision.

Role of columnar cell lesions in breast carcinogenesis: analysis of chromosome 16 copy number changes by multiplex ligation-dependent probe amplification

Columnar cell lesions have been proposed as precursor lesions of low-grade breast cancer. The molecular characteristic of low-grade breast neoplasia is whole-arm loss of chromosome 16q. Copy number changes of 6 genes on 16p and 20 genes on 16q were analysed by multiplex ligation-dependent probe amplification in 165 lesions of 103 patients. Twenty-three columnar cell lesions and 19 atypical ducal hyperplasia lesions arising in columnar cell lesions were included, as well as cases of usual ductal hyperplasia, blunt duct adenosis, ductal carcinoma in situ, lobular neoplasia and invasive carcinoma. Usual ductal hyperplasia and blunt duct adenosis lacked whole-arm losses of 16q. In contrast, columnar cell lesions without atypia, columnar cell lesions with atypia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ and low-grade invasive carcinomas increasingly harboured whole-arm losses of 16q (17%, 27%, 47% and 57%, respectively). However, no recurrent losses in specific genes could be identified. In several patients, columnar cell lesions and atypical ductal hyperplasia harboured similar losses as related ductal carcinoma in situ or invasive carcinomas within the same breast. There were indications for 16q breakpoints near the centromere. Whole-arm gains on 16p were relatively scarce and there was no relation between whole-arm gains of 16p and progression of lesions of the low-grade breast neoplasia family. In conclusion, columnar cell lesions (with and without atypia) often harbour whole-arm losses of 16q, which underlines their role as precursors in low-grade breast carcinogenesis, in contrast with usual ductal hyperplasia and blunt duct adenosis. However, no recurrent losses in specific genes could be identified, pointing to minor events in multiple tumour suppressor genes rather than major events in a single 16q gene contributing to low-grade breast carcinogenesis.

A new risk stratification score for the management of ultrasound-detected B3 breast lesions.

To develop a predictive scoring system for ultrasound-detected B3 lesions at ultrasound-guided core needle biopsy (US-CNB). A total of 2724 consecutive US-CNBs performed in our Institution (January 2011 to December 2014) were retrospectively reviewed. Inclusion criteria were as follows: (a) histopathological examination of the entire lesion or (b) availability of radiologic follow-up (FUP) ≥24months. Patient- and lesion-related variables-patients' age, lesion consistency, lesion size, vascularization, BI-RADS category, and US-CNB result-were analyzed. Positive predictive values (PPVs) for malignancy were calculated correlating US-CNB results with excision histology or FUP. A scoring system for underlying malignancy was developed using risk factors weighting. A total of 102 B3 lesions were included: 27 atypical ductal hyperplasia (26.5%), 5 lobular intraepithelial neoplasia (4.9%), 32 radial scar (31.4%), 37 papillary lesions (36.3%), and 1 fibroepithelial lesion (0.9%). Surgery was performed on 71/102 (69.6%) lesions, and 22/71 were malignant; the remaining 31/102 lesions (30.4%) were unchanged at FUP. The overall PPV for malignancy was 21.6%. Patients' age (odds ratio [OR]=3.63, P=0.008), lesion consistency (OR=5.96, P=0.001), BI-RADS category (OR=17.52, P<0.001), and CNB result (OR=3.6, P=0.008) were associated with a higher risk of malignancy underestimation and selected as risk factors in the score definition. Two risk groups were identified: low (0-2 points) and high risk (3-5 points), with significantly different risk of malignancy underestimation (8.0% vs 59.3%, P<0.001). The proposed score helps to predict the risk of malignancy underestimation and choose the management of B3 lesions at US-CNB.

Malignancy rates of B3-lesions in breast magnetic resonance imaging \u2013 do all lesions have to be excised?

BackgroundApproximately 10% of all MRI-guided vacuum-assisted breast biopsies (MR-VAB) are histologically classified as B3 lesions. In most of these cases surgical excision is recommended. The aim of our study was to evaluate the malignancy rates of different B3 lesions which are visible on MRI to allow a lesion-adapted recommendation of further procedure.MethodsRetrospective analysis of 572 consecutive MR-VAB was performed. Inclusion criteria were a representative (=successful) MR-VAB, histologic diagnosis of a B3 lesion and either the existence of a definite histology after surgical excision or proof of stability or regression of the lesion on follow-up MRI. Malignancy rates were evaluated for different histologies of B3 lesions. Lesion size and lesion morphology (mass/non-mass enhancement) on MRI were correlated with malignancy.ResultsOf all MR-VAB 43 lesions fulfilled the inclusion criteria. The malignancy rate of those B3 lesions was 23.3% (10/43). The highest malignancy rate was found in atypical ductal hyperplasia (ADH) lesions (50.0%; 4/8), 33.3% (2/6) in flat epithelial atypia (FEA), 28.6% (2/7) in lobular intraepithelial neoplasia (LIN) and 12.5% (2/16) in papillary lesions (PL). All 6 complex sclerosing lesions were benign. Mass findings were significantly more frequently malignant (31.3%, 10/32; p < 0.05) than non-mass findings (0/11). Small lesions measuring 5–10 mm were most often malignant (35.0%; 7/20). All large lesions (> 20 mm) were not malignant (0/10). Intermediate sized lesions (11–20 mm) turned out to be malignant in 23.1% (3/13).ConclusionsThe malignancy rate of B3 lesions which were diagnosed after MR-VAB was 23.3%. ADH, FEA and LIN showed considerable malignancy rates (50%, 33% and 29%) and should therefore undergo surgical excision. None of the cases, which were diagnosed as radial scars, non-mass enhancement or larger lesions (> 20 mm) were malignant. Here, a follow-up MRI seems to be advisable to avoid unnecessary operations.Trial registrationRetrospective study design, waived by the IRB.

Lesions of \u201cuncertain malignant potential\u201d in the breast (B3) identified with mammography screening

BackgroundCore needle biopsy (CNB) is a standard diagnostic procedure in the setting of breast cancer screening. However, CNB may result in the borderline diagnoses of lesion of uncertain malignant potential (B3). The aim of this study was to access the outcome of lesions diagnosed as B3 category in a large series of screen-detected cases to evaluate the rates of malignancy for the different histological subtypes.MethodsWe identified all CNBs over a six-year period (2009-2015) in a breast cancer screening unit in Germany. A total of 8.388 CNB’s were performed for screen detected breast lesions. B3 diagnosis comprised 4.5% (376/8.388). Of the 376 patients who were diagnosed as B3, 299 underwent subsequent excision biopsy with final excision histology.ResultsOut of 376 patients diagnosed with B3 lesions, the prevalence of different histopathology showed 161 (42.8%) patients with atypical ductal hyperplasia (ADH), 98 (26.1%) with flat epithelial atypia (FEA), 50 women (13.3%) showed lobular neoplasia (LN), in 40 (10.6%) patients papillary findings and in 27 patients (7.2%) a radial scar complex. Final excision histology was benign in 74% (221/299) and malignant in 26% (78/299) of the patients. Lesion specific positive predictive values (PPV) for a subsequent diagnosis of in situ or invasive carcinoma were as follows: ADH 40%, FEA 20.5%, papillary lesion 13.5%, radial scar 16.6%, LN 0%.ConclusionOur results show that approximately one-third of core needle biopsies of screen detected breast lesions classified as B3 are premalignant or malignant on excision.Lesions of uncertain malignant potential of the breast (B3) are heterogeneous in respect to risk of malignancy.