Stromal lymphocytes are associated with upgrade of B3 breast lesions.

Various histopathological, clinical and imaging parameters have been evaluated to identify a subset of women diagnosed with lesions with uncertain malignant potential (B3 or BIRADS 3/4A lesions) who could safely be observed rather than being treated with surgical excision, with little impact on clinical practice. The primary reason for surgery is to rule out an upgrade to either ductal carcinoma in situ or invasive breast cancer, which occurs in up to 30% of patients. We hypothesised that the stromal immune microenvironment could indicate the presence of carcinoma associated with a ductal B3 lesion and that this could be detected in biopsies by counting lymphocytes as a predictive biomarker for upgrade. A higher number of lymphocytes in the surrounding specialised stroma was observed in upgraded ductal and papillary B3 lesions than non-upgraded (p < 0.01, negative binomial model, n = 307). We developed a model using lymphocytes combined with age and the type of lesion, which was predictive of upgrade with an area under the curve of 0.82 [95% confidence interval 0.77-0.87]. The model can identify some patients at risk of upgrade with high sensitivity, but with limited specificity. Assessing the tumour microenvironment including stromal lymphocytes may contribute to reducing unnecessary surgeries in the clinic, but additional predictive features are needed.

B3 Breast Lesions: Positive Predictive Value and Follow-Up on a Large Single-Institution Series.

INTRODUCTION: Lesions of uncertain malignant potential (B3) represent 10% of core needle biopsies (CNBs) or vacuum-assisted breast biopsies (VABBs). Traditionally, B3 lesions are operated on. This study investigated the association between B3 subtypes and malignancy to determine the best management. METHODS: Pre- and postoperative histological reports from 226 patients, who had undergone excisional surgery for B3 lesions, following CNB or VABB, were retrospectively analyzed. The correlation between the CNB/VABB diagnosis and the final pathology was investigated, along with the correlation between malignancy upgrade and the type of mammographic lesion. The positive predictive value (PPV) of malignancy of B3 lesions was calculated by simple logistic regression. Patients without cancer diagnosis underwent a 7-y follow-up. RESULTS: Pathology showed 171 (75.6%) benign and 55 (24.3%) malignant lesions. The PPV was 24.3% (P = 0.043), including 31 (13.7%) ductal carcinomas in situ and 24 (10.6%) invasive carcinomas. The most frequently upgraded lesions were atypical ductal hyperplasia, 34.2% (P = 0.004), followed by lobular intraepithelial neoplasia, 27.5% (P = 0.025). The median diameter of mammographic lesions was 1.5 [0.9-2.5] cm, while for surgical specimens, it was 5 [4-7] cm (P < 0.0001). Mammographic findings and histology showed a significant correlation (P = 0.038). After a 7-y follow-up, 15 (8.9%) patients developed carcinoma, and 7 patients (4%) developed a new B3 lesion. CONCLUSIONS: We can conclude that atypical ductal hyperplasia and lobular intraepithelial neoplasia still require surgery for a significant PPV. Other types that lacked significance or confidence intervals were too wide to draw any conclusion.

Análisis del manejo de lesiones B3 de la mama en nuestro centro: comparativa con consensos y oportunidades de mejora / Analysis of the management of B3 breast lesions in our center: Comparison with consenses and opportunities for improvement

Introducción: las lesiones B3 comprenden un grupo heterogéneo de lesiones proliferativas epiteliales de mama que suponen un riesgo variable de aparición subsiguiente de carcinoma. Nuestro objetivo es analizar el manejo de las lesiones B3 en nuestro centro entre 2017 y 2021 y compararlo con las recomendaciones de los consensos internacionales. Material y métodos: análisis descriptivo retrospectivo. Se incluyeron en el estudio todos los pacientes con diagnóstico histológico (por BAG o BAV) de lesión de mama B3, intervenidos o no, en el periodo indicado. Resultados: se identificaron 79 casos. Se realizó BAG en el 83,54% de los casos y BAV en el 16,45%. El 80,3% de las BAG realizadas fueron diagnósticas de LP, en 6 casos HDA y en 5 casos TF. Se realizó BAV en 11 casos. Se indicó intervención quirúrgica en el 97,46% de los casos. El análisis anatomopatológico de la pieza quirúrgica mostró en el 63,63% de los casos LP sin atipia. Cinco casos (6,49%) fueron diagnosticados de CLIS, 5 casos de CDIS, 4 casos de TF benigno y 4 casos de HDA. Dos casos fueron diagnosticados de CR y de HD usual. Discusión: el manejo de las lesiones B3 llevado a cabo en nuestro centro está marcado por el sobretratamiento respecto a las recomendaciones de los consensos. Una adaptación más estricta a las recomendaciones vigentes, la discusión de los casos en el CMD, que incluya la correlación radio-patológica y la evaluación de la lesión residual, y el uso más frecuente de BAV podría disminuir esta tendencia. (AU)

Introduction: B3 lesions comprise a heterogeneous group of proliferative epithelial lesions of the breast that pose a variable risk of subsequent development of carcinoma. Our objective is to analyze the management of B3 lesions in our center between 2017 and 2021 and compare it with the recommendations of the international consensus. Material and methods: Retrospective descriptive analysis. All patients with a histological diagnóstico (by BAG or AVB) of a B3 breast lesion, operated on or not, in the indicated period, were included in the study. Results: 79 cases were identified. BAG was performed in 83.54% of the cases and BAV in 16.45%. 80.3% of the BAG performed were diagnostic of LP, HDA in 6 cases and TF in 5 cases. BAV was performed in 11 cases. Surgical intervention was indicated in 97.46% of the cases. The anatomopathological analysis of the surgical specimen showed LP without atypia in 63.63% of the cases. Five cases (6.49%) were diagnosed with LCIS, five cases with DCIS, four cases with benign TF, and four cases with HDA. Two cases were diagnosed with CR and usual HD. Discussion: The management of B3 lesions carried out in our center is marked by overtreatment with respect to the consensus recommendations. A stricter adaptation to the current recommendations, the discussion of the cases in the CMD, which includes the radiopathological correlation and the evaluation of the residual lesion, and the more frequent use of AVB could reduce this tendency. (AU)

Ultrasound-guided 8-Gauge vacuum-assisted excision for selected B3 breast lesions: a preliminary experience.

PURPOSE: Nowadays, surgical excision is no longer justified for all B3 lesions and a minimally-invasive therapeutic treatment has been encouraged. The aim of this study was to evaluate the feasibility and the therapeutic efficacy of ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of selected breast lesions of uncertain malignant potential (B3). MATERIAL AND METHODS: From July 2018 to December 2019, 11/48 breast lesions classified as B3 after ultrasound-guided core needle biopsy were treated with US-VAE in our Institution. Inclusion criteria were: B3 nodules ultrasonographically detectable for which VAE is recommended by international guidelines2, size ranging between 5 and 25 mm, circumscribed margins, and lesion position at least 5 mm from the skin and the nipple. A radiological follow-up to evaluate the completeness of excision, the presence of post-procedural hematoma or of residual disease/recurrence was performed after 10 and 30 days and 6 and 12 months. 12-month ultrasound was considered the gold standard. All patients were asked to complete a satisfaction survey and a full assessment of the costs of US-VAE was performed. RESULTS: Complete excision was achieved in 81.8% of US-VAE. No lesions were upgraded to carcinoma and no patients had to undergo surgery. No complications occurred during or after US-VAE. All patients were satisfied with the procedure and the cosmetic result (100%). US-VAE cost approximately 422 Euros per procedure. CONCLUSION: US-VAE has proven to be an optimal tool for the therapeutic excision of selected B3 lesions, with high success rate, good patient compliance and considerable money savings compared to surgery. This technique has the potential to reduce unnecessary surgery and healthcare costs.

Lesiones de potencial maligno incierto (B3): nuestra experiencia en el Instituto Alexander Fleming / Lesions of uncertain malignant potential (B3): Our experience at the Alexander Fleming Institute

Objetivo: Revisar la correlación radiopatológica de las lesiones de potencial maligno incierto (B3) de nuestra institución, evaluar la conducta y establecer el porcentaje de subestimación en relación a las lesiones tratadas quirúrgicamente. Material y método: Estudio retrospectivo de la base de datos de procedimientos intervencionistas efectuados en el servicio de diagnóstico por imágenes del Instituto Alexander Fleming entre mayo de 2016 y diciembre de 2019 inclusive. Se incluyeron las pacientes con resultado histológico en la biopsia percutánea de uno o más de los siguientes diagnósticos: atipia epitelial plana (AEP), cicatriz radiada/lesión esclerosante compleja (CR), hiperplasia ductal atípica (HDA), neoplasia lobular clásica (NL), lesión papilar (LP) o tumor phyllodes (TP). Resultados: De 67 pacientes analizadas, el 43.3% se manifestaron en los estudios por imágenes con nódulos y en un 37.3% con microcalcificaciones agrupadas. La LP fue la lesión B3 más frecuente en un 44.8% seguido por la AEP en un 16.4%. El 98.5% de las pacientes presentó adecuada concordancia radiopatológica. Fueron sometidas a cirugía 48 pacientes, las 19 pacientes restantes continuaron con seguimiento clínico radiológico. La anatomía patológica de la pieza quirúrgica reflejó que en un 33.3% hubo subestimación en relación a la biopsia; en más de la mitad de los casos correspondieron a CDIS. Conclusiones: El porcentaje de subestimación con resultado final de CDIS o CDI de bajo grado se encontró dentro de los parámetros hallados en la literatura. Si bien logramos reducir la tasa de cirugías al 71% de pacientes con lesiones B3, una adecuada selección para efectuar exéresis con aguja por sistema de vacío podría reducir aún más el número de cirugías innecesarias y probablemente la tasa de subestimación.

Objective: To review the radiopathological correlation of lesions of uncertain malignant potential (B3) diagnosed in our institution, as well as to evaluate the therapeutic conduct and to establish the percentage of underestimation of the excised lesions. Material and method: This work consists of a retrospective study of the database which in- cludes the interventional procedures performed in the Imaging Department of the Alexander Fleming Institute between May 2016 and December 2019. Patients with a histological outcome in the percutaneous biopsy of one or more of the following diagnosis were included: flat epithelial atypia (FEA), radial scar (RS) /complex sclerosing lesion (CSL), atypical ductal hyperplasia (ADH), classic lobular neo- plasia (LN), papillary lesión (PL) or phyllodes tumor (PT). Results: Out of the 67 analyzed patients, 43.3% were perceived as nodules at imaging examinations and 37.3% as grouped microcalcifications. Papillary lesion was the most frequently diagnosed B3 lesion (44.8%), followed by flat epithelial atypia (16.4%). 98.5% of patients presented an accurate imaging-pathology concordance. 48 patients underwent surgery and the remaining 19 patients continued with clinical and radiological follow-up. The histopathology of the surgical specimen reflected that in 33.3% of the cases there was an underestimation in relation to the percutaneous biopsy; in over half of these cases they corresponded with DCIS. Conclusions: The percentage of underestimation with final diagnosis of DCIS or low grade IDC coincided with the parameters found in current literature. Even though we were able to reduce the surgical rate to 71% of patients with B3 lesions, a proper selection of cases which could be candidates for vacuum assisted excisional biopsy could further reduce the number of unnecessary surgeries and probably the un- derestimation rate as well.

A risk stratification algorithm for lesions of uncertain malignant potential diagnosed by vacuum-assisted breast biopsy (VABB) of mammographic microcalcifications.

PURPOSE: To investigate a risk stratification strategy for lesions of uncertain malignant potential (B3) diagnosed by vacuum-assisted breast biopsy (VABB) of mammographic microcalcifications. METHODS: Patients who underwent VABB for microcalcification-only lesions with a diagnosis of B3 and subsequent surgery were included in this retrospective, IRB-approved study. Seventy-six B3-lesions (final histology: 66 benign, 10 malignant) were included (Tr). Data on B3 lesion type and presence of atypia, microcalcification characteristics (BI-RADS), removal at biopsy and concomitant lesions were collected. After univariate analysis (Chi-square test), data were combined into a risk stratification algorithm by using a ten-fold, cross-validated Classification and Regression Tree analysis (CRT). The algorithm was tested on a testing dataset (Te) of 23 B3-lesions (six malignant, 17 benign). RESULTS: Malignancy was more frequent in women with a concomitant cancer (P < 0.001) and highly suspicious microcalcifications (P < 0.001). The CRT algorithm retained three characteristics: morphology; presence of atypia; presence of concomitant cancer. The algorithm identified 25/76 (32.9 %,Tr) and 6/23 (26.1 %,Te) lesions at low risk of malignancy. No malignant cases were identified at surgery (0/31). There were 3/76 (3.9 %,Tr) and 1/23 (4.3 %,Te) lesions assigned as high-risk by the algorithm and confirmed at surgery (4/4). In the remaining lesions (48/76, 63.1 %,Tr; 16/23, 69.6 %,Te), malignancy rates varied between 9% and 88.4 %; thus, surgery could not have been avoided. CONCLUSION: We constructed and tested a risk stratification algorithm for B3 microcalcifications, including clinical, imaging, and pathological features, to assign probabilities of malignancy, which has the potential to reduce unnecessary surgeries.

Evaluation of Ultrasound-guided 8-Gauge Vacuum-assisted Excision System for the Removal of US-detectable Breast Lesions.

AIM: To assess the ability of ultrasound (US)-guided vacuum-assisted breast excision (VAE) to remove Breast Imaging Reporting and Data System (BI-RADS) ≥3 breast lesions in order to analyze US features most frequently associated with complete excision. MATERIALS AND METHODS: A total of 266 BI-RADS ≥3 lesions without microcalcifications underwent US-VAE. US-VAE and gold standard pathological results were compared. US features of lesions were analyzed. RESULTS: The complete excision rate was 93.61%; the VAE agreement rate was 99.62%. Circumscribed margins, regular shape, parallel orientation, and the absence of posterior features were favorable US features associated with complete excision. Lesions completely excised were: BI-RADS 3 ≤21.10 mm and BI-RADS 4 ≤18.70 mm with one unfavorable US characteristic, and BI-RADS 4 lesions ≤13.5 mm with two unfavorable US features hindered complete removal. Two atypical ductal hyperplasias (<10 mm, one unfavorable feature) and eight ductal carcinomas in situ (≤8.7 mm, one/two unfavorable features) were completely removed. CONCLUSION: US-VAE is highly accurate for diagnostic purpose and, in some cases, highly successful for complete lesion excision. This success also depends on the US characteristics and size of the lesion.

High risk (B3) breast lesions: What is the incidence of malignancy for individual lesion subtypes? A systematic review and meta-analysis.

INTRODUCTION: Provide evidence to support evolving management strategies for high-risk (B3) breast lesions by assessing risk of carcinoma in subgroups of B3 lesions using systematic review and meta-analysis. METHODS: Databases identified observational studies between 1980 and 2015 that reported on underestimation of malignancy following B3 lesion diagnosis at core needle biopsy. Critical appraisal, quality assessment, data extraction and meta-analysis was undertaken to calculate rate of malignancy of the whole B3 group and individual lesions. Study heterogeneity and association between variables and underestimation rate was investigated using random effects logistic modelling. RESULTS: Meta-analysis, using data from 129 studies, assessed 11 423 lesions of which 2160 were upgraded to malignancy after surgical excision biopsy (17% malignancy rate, 95% CI 15-19%). Malignancy rates varied from 6% in radial scars with no atypia (95% CI 2-13%, I2 72.8%), to 32% in papillomas with atypia (95% CI 23-41%, I2 57.4%). Differences in upgrade rates between atypical and non-atypical lesions were statistically significant (p < 0.05). Study heterogeneity could not be explained by differences in core biopsy size or year of publication. CONCLUSIONS: This comprehensive, inclusive assessment of all published literature, provides an accurate estimate of malignancy risk in subgroups of B3 lesions, to guide tailored management strategies. Some lesions have a high risk of malignancy, while others have a much lower risk, and could be safely managed with surveillance strategies rather than surgery.

Breast lesions of uncertain malignant nature and limited metastatic potential: proposals to improve their recognition and clinical management.

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over- or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision-making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed.