Management of screening-detected lobular neoplasia in the era of digital breast tomosynthesis: A preliminary study.

PURPOSE: The purpose of this study is to determine upgrade rates of lobular neoplasia detected by screening digital breast tomosynthesis (DBT) and to determine imaging and clinicopathological features that may influence risk of upgrade. METHODS: Medical records were reviewed of consecutive women who presented with screening DBT-detected atypical lobular hyperplasia (ALH) and/or lobular carcinoma in situ (LCIS) from January 1, 2013, to June 30, 2020. Included patients underwent needle biopsy and had surgery or at least two-year imaging follow-up. Imaging and clinicopathological features were compared between upgraded and nonupgraded cases of lobular neoplasia using the Pearson's chi-squared test and the Wilcoxon signed-rank test. RESULTS: During the study period, 107 women (mean age 55 years, range 40-88 years) with 110 cases of ALH and/or LCIS underwent surgery (80.9%, n = 89) or at least two-year imaging follow-up (19.1%, n = 21). The overall upgrade rate to cancer was 5.5% (6/110), and the upgrade rate to invasive cancer was 3.6% (4/110). The upgrade rate of ALH to cancer was 4.1% (3/74), whereas the upgrade rate of LCIS to cancer was 9.4% (3/32) (p = .28). The upgrade rate of cases presenting as calcifications was 4.2% (3/71), whereas the upgrade rates of cases presenting as noncalcified findings was 7.7% (3/39) (p = .44). CONCLUSIONS: The upgrade rate of screening DBT-detected lobular neoplasia is less than 6%. Surveillance rather than surgery can be considered for lobular neoplasia, particularly in patients with ALH and in those with screening-detected calcifications leading to the diagnosis.

Management of Lobular Neoplasia Diagnosed by Core Biopsy.

Lobular neoplasia (LN) involves proliferative changes within the breast lobules. LN is divided into lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LCIS can be further subdivided into three subtypes: classic LCIS, pleomorphic LCIS, and LCIS with necrosis (florid type). Because classic LCIS is now considered as a benign etiology, current guidelines recommend close follow-up with imaging versus surgical excision. The goal of our study was to determine if the diagnosis of classic LN on core needle biopsy (CNB) merits surgical excision. This is a retrospective, observational study conducted at Mount Auburn Hospital, Cambridge, MA, from May 17, 2017, through June 30, 2020. We reviewed the data of breast biopsies conducted at our hospital over this period and included patients who were diagnosed with classic LN (LCIS and/or ALH) and excluded patients having any other atypical lesions on CNB. All known cancer patients were excluded. Of the 2707 CNBs performed during the study period, we identified 68 women who were diagnosed with ALH or LCIS on CNB. CNB was performed for an abnormal mammogram in the majority of patients (60; 88%) while 7(10.3%) had an abnormal breast magnetic resonance imaging study (MRI), and 1 had an abnormal ultrasound (US). A total of 58 patients (85%) underwent excisional biopsy, of which 3 (5.2%) showed malignancy, including 2 cases of DCIS and 1 invasive carcinoma. In addition, there was 1 case (1.7%) with pleomorphic LCIS and 11 cases with ADH (15.5%). The management of LN found on core biopsy is evolving, with some advocating surgical excision and others recommending observation. Our data show a change in diagnosis with excisional biopsy in 13 (22.4%) of patients with 2 cases of DCIS, 1 invasive carcinoma, 1 pleomorphic LCIS, and 9 cases of ADH, diagnosed on excisional biopsy. While ALH and classic LCIS are considered benign, the choice of ongoing surveillance versus excisional biopsy should be made with shared decision making with the patient, with consideration of personal and family history, as well as patient preferences.

Upgrade Rates of Pure, Radiology-Pathology Concordant Lobular Neoplasia Diagnosed on Breast Core Needle Biopsy: Is Surgical Excision Warranted?

OBJECTIVE: To determine upgrade rates of lobular neoplasia (LN) to malignancy and evaluate factors that may predict upgrade. METHODS: From 5/1/2003 to 12/30/2015, breast lesions diagnosed as LN (atypical lobular hyperplasia [ALH] or classic lobular carcinoma in-situ [LCIS]) on core biopsy that underwent surgical excision or at least 2 years imaging follow-up were identified. A subspecialty trained breast radiologist and pathologist reviewed imaging and pathology slides to confirm diagnosis and to determine if LN represented the target lesion, part of the target lesion, or an incidental finding. Imaging features, original BI-RADS final assessment category, biopsy method, biopsy device and final pathologic diagnosis were documented. Cases with both ALH and LCIS were classified as LCIS for analysis. Reason for biopsy of BI-RADS 2-3 was patient or referring physician preference. Upgrade rates to malignancy were determined for all cases. RESULTS: In this study 73.7% (115/156) lesions were ALH and 26.3% (41/156) were LCIS+/-ALH. Surgical excision and imaging follow-up were performed in 71.2% (111/156) and 28.8% (45/156), respectively. Upgrade rates for ALH and LCIS were 0.0% (0/115) and 7.3% (3/41), respectively. Cancer developed at a site separate from core biopsy in 1.7% (2/115) ALH and 7.3% (3/41) LCIS cases. We found no association of upgrade rate with biopsy type, BI-RADS or target/part of target lesion versus incidental. CONCLUSION: Our study supports consideration of excision for LCIS, given 7.3% upgrade rate. Conversely, imaging surveillance might be appropriate following diagnosis of ALH alone.

Comparison of Outcomes for Classic-Type Lobular Carcinoma In Situ Managed with Surgical Excision After Core Biopsy Versus Observation.

BACKGROUND: Studies report low upgrade rates following excision for classic-type lobular carcinoma in situ (LCIS) with radiologic-pathologic concordance. Thus, in the absence of other high-risk lesions, observation has become standard. We report long-term outcomes of excision versus observation following a core biopsy diagnosis of classic-type LCIS. METHODS: Women with LCIS treated from 2013-2020 and managed with excision or observation were identified from a prospective database. Women with cancer upgrade at excision or history of cancer were excluded. We compared rates and characteristics of subsequent breast cancers by clinical management strategy. RESULTS: Of 312 women, 170 (54%) underwent excision and 142 (46%) were managed with observation. Among the excision group, 36 of 170 (21%) had radiologic-pathologic concordant LCIS without other high-risk lesions, mass, or symptoms (concordant LCIS excision group). Overall, at 3.1 years median follow-up, 11 (6.5%) women managed with excision and 11 (7.7%) women managed with observation developed cancer. Cancer development was not associated with management choice (overall excision cohort vs. observation group [p = 0.8]) and did not differ between the concordant LCIS excision and observation groups (p > 0.9). The 5-year cancer development rate was 8.9% (95% confidence interval [CI]: 2.3-31.6%) in the concordant LCIS excision group and 10.3% (95% CI 5.5-18.6%) in the observation group. CONCLUSIONS: No difference in breast cancer rates existed among women with a core-biopsy diagnosis of classic-type LCIS managed with excision or observation. These data support management of LCIS as a risk factor, with consideration of chemoprophylaxis, rather than as an indication for surgical excision.

Evidence-Based Pragmatic Approach to the Management of Borderline or High-Risk Breast Lesions.

The management of borderline or high-risk breast lesions (HRLs) remains controversial. We propose a pragmatic evidence-based approach based on lesion type. For lobular carcinoma in situ with pleomorphism, papilloma with atypia, atypical ductal hyperplasia, and fibroepithelial lesions, surgical consultation and excision are recommended. Patients with other borderline or HRLs are referred for surgical consultation to discuss excision versus surveillance. Our recommendations align with American Society of Breast Surgeons guidelines, which aim to reduce unnecessary surgery and ensure appropriate follow-up.

Atypical Lobular Hyperplasia and Classic Lobular Carcinoma In Situ Can Be Safely Managed Without Surgical Excision.

BACKGROUND: Based on modern series demonstrating low upgrade rates for pure lobular neoplasia (LN) diagnosed on core needle biopsy (CNB), our institution no longer recommends routine excision, provided imaging is concordant. This study describes outcomes in patients managed without surgical excision. METHODS: From an institutional database, we identified all patients with a diagnosis of pure atypical lobular hyperplasia and/or classic lobular carcinoma in situ on CNB managed without surgical excision (i.e., conservative management) from 2015 to 2019. The primary outcome of interest was failure of conservative management, defined as development of ipsilateral same-quadrant ductal carcinoma in situ or invasive breast cancer within 2 years of CNB, or need for ipsilateral same-quadrant excisional biopsy. We also evaluated rates of ipsilateral same-quadrant CNB during follow-up. RESULTS: Among 96 pure LN lesions on CNB since 2015, 80 (83%) were managed without surgical excision. Median follow-up was 27 months (IQR: 16-28), with only 2 (2%) patients lost to follow-up. No patients developed an ipsilateral, same-quadrant breast cancer. The 3-year risk of conservative management failure was 6.2% (95% CI 2.3-15.7%). All failures were a result of need for excisional biopsy due to progressive imaging abnormalities at the initial CNB site, with benign final pathology. The 3-year risk of ipsilateral same-quadrant CNB was 9.2% (95% CI 3.8-21.5%). CONCLUSION: Non-surgical management of pure LN is safe, and the likelihood of requiring subsequent surgical excision or repeat CNB during follow-up is low. These data provide reassurance that routine excision of pure LN in the setting of radiologic-pathologic concordance is not required.

High-Risk Lesions Detected by MRI-Guided Core Biopsy: Upgrade Rates at Surgical Excision and Implications for Management.

OBJECTIVE. The purpose of our study was to evaluate the upgrade rates of high-risk lesions (HRLs) diagnosed by MRI-guided core biopsy and to assess which clinical and imaging characteristics are predictive of upgrade to malignancy. MATERIALS AND METHODS. A retrospective review was performed of all women who presented to an academic breast radiology center for MRI-guided biopsy between January 1, 2015, and November 30, 2018. Histopathologic results from each biopsy were extracted. HRLs-that is, atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), radial scar, papilloma, flat epithelial atypia (FEA), benign vascular lesion (BVL), and mucocelelike lesion-were included for analysis. Clinical history, imaging characteristics, surgical outcome, and follow-up data were recorded. Radiologic-pathologic correlation was performed. RESULTS. Of 810 MRI-guided biopsies, 189 cases (23.3%) met the inclusion criteria for HRLs. Of the 189 HRLs, 30 cases were excluded for the following reasons: 15 cases were lost to follow-up, six cases were in patients who received neoadjuvant chemotherapy after biopsy, two lesions that were not excised had less than 2 years of imaging follow-up, and seven lesions had radiologic-pathologic discordance at retrospective review. Of the 159 HRLs in our study cohort, 13 (8.2%) were upgraded to carcinoma. Surgical upgrade rates were high for ADH (22.5%, 9/40) and FEA (33.3%, 1/3); moderate for LCIS (6.3%, 3/48); and low for ALH (0.0%, 0/11), radial scar (0.0%, 0/28), papilloma (0.0%, 0/26), and BVL (0.0%, 0/3). Of the upgraded lesions, 69.2% (9/13) were upgraded to ductal carcinoma in situ (DCIS) or well-differentiated carcinoma. ADH lesions were significantly more likely to be upgraded than non-ADH lesions (p = .005). CONCLUSION. ADH diagnosed by MRI-guided core biopsy warrants surgical excision. The other HRLs, however, may be candidates for imaging follow-up rather than excision, especially after meticulous radiologic-pathologic correlation.

Visualization of lymphatic vascular invasion in breast cancer by multiphoton microscopy.

Lymphatic vascular invasion (LVI) is regarded as one of the independent factors which affect the prognosis of breast cancer. Once LVI is formed, it indicates the tumor has metastasized or has the possibility of metastasis. In this work, multiphoton microscopy (MPM), which relies on the two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), was applied to identify the typical morphology of LVI and also visualize the histological features of LVI. Furthermore, the pixel density of collagen fibers was extracted as a quantitative parameter to differentiate LVI from the ductal carcinoma in situ (DCIS). By comparing with the corresponding H&E-stained images, it was confirmed that MPM can be used as an auxiliary tool for pathologists to diagnose LVI, and has a possibility for the application in clinical examination.

The correlation of 18F-FDG PET/CT metabolic parameters, clinicopathological factors, and prognosis in breast cancer.

PURPOSE: To study the imaging parameters of 18F-fluorodeoxy glucose (18F-FDG) in breast cancer on positron emission tomography/computed tomography (PET/CT)-the correlation of clinical pathological factors and prognosis among the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of lesions for patients. METHODS: From January 2012 to December 2014, a total of 125 female patients were treated in our hospital for the first time and were diagnosed as breast cancer by histopathology. They were selected as the research subjects. All of them had complete 18F-FDG PET/CT examination data before surgery, the postoperative clinicopathological information, and follow-up data. They were divided into the event group (38 cases) and the event-free group (87 cases) according to whether local recurrence or distant metastasis occurred after the follow-up, with the follow-up time 4-60 months. The correlation on 18F-FDG PET/CT metabolic parameters of breast cancer with clinicopathological factors and prognosis was retrospectively evaluated. RESULTS: The primary lesions of 125 cases with breast cancers all had higher 18F-FDG uptake, and the SUVmax, MTV, and TLG of the primary tumors in the event group were significantly higher than those in the event-free group (t = 2.645, 2.782, 15.263, p = 0.011, 0.008, 0.000), p < 0.05; SUVmax, MTV, and TLG of primary breast cancer have no correlation with age and tumor site of patient (p > 0.05); there were statistically significant differences in the SUVmax, MTV, and TLG of primary tumor in the comparison of different tumor size, T stage, N stage, and histological grades (p < 0.05); all of SUVmax, MTV, and TLG in the estrogen receptor (ER) and/or progesterone receptor (PR) positive groups were lower than those in the negative group, with statistically significant difference (p < 0.05); the SUVmax, MTV, and TLG of human epidermal growth factor receptor 2 (HER2) positive group, proliferating cell nuclear antigen (Ki-67) high expression group were higher than those in the negative group and low expression group, with statistically significant difference (p < 0.05). There were 38 recurrence and metastasis cases within 125 cases with breast cancer in 5 years after operation, with the total recurrence and metastasis rate as 30.40% (38/125). The event-free survival rate in the SUVmax ≥ 8.64 group was significantly lower than that in the SUVmax < 8.64 group (p < 0.01). CONCLUSIONS: The metabolic parameters of 18F-FDG PET/CT in breast cancer can reflect the biological behavior of the tumor indirectly; therefore, it was studied on the related correlation to provide the guidance of clinical individualized comprehensive treatment and prognostic judgment.

Lobular intraepithelial neoplasia: Outcomes and optimal management.

INTRODUCTION: Lobular neoplasia is a term encompassing both atypical lobular hyperplasia and lobular carcinoma in situ. These pathological findings are of uncertain malignant potential and predispose to a higher lifetime risk of breast cancer. Debate surrounds the management of such lesions, with the rationale for diagnostic excision based on the possibility of upgrading to malignancy. In this study, we report the upgrade rate of these lesions and risk of subsequent development of breast cancer. METHODS: This is a retrospective review of a prospectively maintained data base of all biopsies of breast screening-detected abnormalities in a single Irish breast-screening unit. We included all patients with lobular neoplasia on core needle biopsy who underwent diagnostic excision from 2005 to 2012. We excluded those who had concurrent high-risk lesions on biopsy. End points included upgrade rate and subsequent diagnosis of malignancy on follow-up. RESULTS: During the study period, 66 patients met criteria for inclusion, with a mean age of 53.74 years. Upgrade rate following excision was 13.64% (n = 9/66). Of those not upgraded, 7.02% (n = 4/57) were subsequently diagnosed with malignancy. Median time to diagnosis was 59.61 months (range = 10.5-124.4). CONCLUSION: There is a significant rate of upgrade following diagnostic excision of lobular neoplasia, supporting the practice of diagnostic excision. There is an increased lifetime risk of breast cancer for women with a diagnosis of lobular neoplasia, with many of these cancers occurring outside the standard five-year monitoring period, suggesting a potential benefit in extending surveillance.

A Case Series of Malign Hyperechoic Breast Lesions.

BACKGROUND: Hyperechoic breast lesions are a rare group of breast masses in routine practice. Most of these lesions are benign. However, they rarely may be malignant. Hyperechoic lesions can be evaluated using the same criteria for malignant lesions. Clinical history, mammographic appearance, and certain sonographic features (non-circumscribed margins, irregular shape, presence of hypoechoic areas, nonparallel orientation, and association with microcalcifications can be suggestive of malignancy). In this article, hyperechoic breast lesions with malignant pathology have been presented. METHODS: Seven cases during breast ultrasound examination were detected. RESULTS: Four patients had invasive ductal carcinoma, 1 patient had invasive lobular carcinoma, 1 patient had high-grade ductal carcinoma in situ (DCIS), and 1 patient had lymphoma. Ultrasonography of the breast showed a heterogeneous appearance in all the patients, microcalcification in two patients, and an ambiguous contour in one patient. CONCLUSION: Hyperechoic breast lesions should be evaluated using specific sonographic criteria to prevent misdiagnosis and identify patients who require biopsy and further examination.

Non-invasive lobular neoplasia of the breast: Morphologic features, clinical presentation, and management dilemmas.

The designation of noninvasive lobular neoplasia applies to atypical epithelial proliferations composed of noncohesive cells secondary to loss or functional alteration of E-cadherin-mediated cell adhesion. The morphologic spectrum of noninvasive lobular neoplasia encompasses atypical lobular hyperplasia (ALH) and classic lobular carcinoma in situ (classic LCIS) and two LCIS variants, namely florid LCIS (F-LCIS) and pleomorphic LCIS (P-LCIS), as defined in the World Health Organization (WHO) Classification of Tumors of the Breast 5th ed. Herein, we review the morphologic, immunohistochemical, and molecular features of noninvasive lobular neoplasia, with special emphasis on F-LCIS and P-LCIS. We also review imaging features, management at core needle biopsy, upgrade rates at surgical excision, and clinical management dilemmas.

Evaluating the preoperative breast cancer characteristics affecting the accuracy of axillary ultrasound staging.

We evaluate the preoperative breast cancer (BC) characteristics that affect the diagnostic accuracy of axillary ultrasound (US) and determine the reliability of US in the different subgroups of BC patients. Axillary US assessments in women with invasive BC diagnosed between 2009 and 2016 in a single institution were retrospectively reviewed. The diagnostic accuracy of axillary US was obtained using surgical nodal histology as the gold standard. Preoperative breast tumor sonographic and histological factors affecting axillary US diagnostic accuracy were examined. Of the 605 newly diagnosed invasive BC cases reviewed, 251 (41.5%) had nodal metastases. Axillary US sensitivity was 75.7%, specificity 92.9%, positive predictive value 88.4%, negative predictive value 84.4%, and false-negative rate 24.3%. Lower US sensitivity was seen with invasive lobular cancer (ILC) (P = .043), grade I/II, (P = .021), unifocal (P = .039), and smaller tumors (P < .001). US specificity was lower in grade III (P < .001), estrogen receptor (ER)-negative (P < .001), progesterone receptor (PR)-negative (P = .004), HER2-positive (P = .015), triple-negative (P = .001), and larger breast tumors (P < .001). US has moderate sensitivity and good specificity in detecting metastatic axillary lymph nodes. Based on preoperative cancer characteristics, US was less sensitive for nodal metastases from ILC, unifocal, lower grade, and smaller breast tumors. It was also less specific in grade III, ER-negative, PR-negative, HER2-positive, triple-negative, and larger breast tumors. Caution is suggested in interpreting the US axillary findings of patients with these preoperative tumor features.

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.

Optimal b-values for diffusion kurtosis imaging in invasive ductal carcinoma versus ductal carcinoma in situ breast lesions.

Diffusion kurtosis imaging (DKI) is a diffusion-weighted MRI technique that probes the non-Gaussian diffusion of water molecules within biological tissues. The purpose of this study was to investigate the DKI model optimal b-values combinations in invasive ductal carcinoma (IDC) versus ductal carcinoma in situ (DCIS) breast lesions. The study included 114 malignant breast lesions (64 IDC and 50 DCIS). Patients underwent a breast MRI examination which included a diffusion-weighted sequence (b = 0-3000 s/mm2). For each lesion, the b-values were combined among each other (109 combinations) and each mean kurtosis (MK) parameter was obtained. Differences between the lesion groups and b-values combinations were assessed. Also, the diagnostic performance of the combinations was determined through receiver operating characteristic (ROC) curve analysis, and compared. Root mean square error (RMSE) was also obtained. All the b-values combinations showed significant differences between the lesion groups (p < 0.05). The combination 0, 50, 200, 750, 1000, 2000 s/mm2 showed the best performance (AUC = 0.930, sensitivity = 95.3%, specificity = 82.0%, accuracy = 89.5%), with a RMSE of 17.65. The b-values combinations with the worst performance were composed of only high or ultra-high b-values, or with b = 1000 s/mm2 as the maximum b-value. Better results were obtained when zero b-value was included in the DKI model fitting with at least one b-value below 1000 s/mm2 and one b-value above 1000 s/mm2 (conserving b = 1000 s/mm2). Six was the optimal number of b-values, nonetheless other combinations with less b-values may be considered, but with a consequent diagnostic performance loss.

Evaluation of the overdiagnosis in breast screening programmes using a Monte Carlo simulation tool: a study of the influence of the parameters defining the programme configuration.

OBJECTIVES: To build up and test a Monte Carlo simulation procedure for the investigation of overdiagnosis in breast screening programmes (BSPs). DESIGN: A Monte Carlo tool previously developed has been adapted for obtaining the quantities of interest in order to determine the overdiagnosis: the annual and cumulative number of cancers detected by screening, plus interval cancers, for a population following the BSP, and detected clinically for the same population in the absence of screening. Overdiagnosis is obtained by comparing these results in a direct way. RESULTS: Overdiagnosis between 7% and 20%, depending on the specific configuration of the programme, have been found. These range of values is in agreement with some of the results available for actual BSPs. In the cases analysed, a reduction of 11% at most has been found in the number of invasive tumours detected by screening in comparison to those clinically detected in the control population. It has been possible to establish that overdiagnosis is almost entirely linked to ductal carcinoma in situ tumours. CONCLUSIONS: The use of Monte Carlo tools may facilitate the analysis of overdiagnosis in actual BSPs, permitting to address the role played by various quantities of relevance for them.

Increasing trends in in situ breast cancer incidence in a region with no population-based mammographic screening program: results from Zurich, Switzerland 2003-2014.

PURPOSE: Increase in in situ breast cancer (BCIS) incidence has been reported across Europe and the USA. However, little is known about the trends in BCIS incidence in regions without population-based mammographic screening programs. We set out to investigate these trends in Zurich, Switzerland, where only opportunistic mammographic screening exists. METHODS: Data from 989 women diagnosed with a primary BCIS between 2003 and 2014 were used in our analyses. Age-standardized incidence rates per 100,000 person-years (ASR) were computed per year. Additional analyses by BCIS subtype, by age group at diagnosis and by incidence period were conducted. Incidence trends over time were assessed using joinpoint regression analysis. RESULTS: The overall BCIS ASR was 10.7 cases per 100,000 person-years with an increasing trend over the study period. A similar trend was observed for the ductal carcinoma in situ (DCIS) ASR, while the lobular carcinoma in situ (LCIS) ASR decreased. Age-specific analyses revealed that the 50-59 year age group had the highest BCIS ASR. The highest increase in BCIS ASR, even though not statistically significant, was observed for the < 40 year age group. CONCLUSIONS: BCIS ASR increased linearly over a 12-year period. The increase was reflected by an increase in DCIS ASR, whereas LCIS ASR decreased over time. The highest increase in BCIS ASR over the study period was observed for the < 40 year age group, even though not statistically significant. Patient and tumor characteristics of this group that may be associated with BCIS development warrant further investigation.

Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide.

CONTEXT.­: Resection of breast carcinoma with adequate margins reduces the risk of local recurrence and reoperation. Tozuleristide (BLZ-100) is an investigational peptide-fluorophore agent that may aid in intraoperative tumor detection and margin assessment. In this study, fluorescence imaging was conducted ex vivo on gross breast pathology specimens. OBJECTIVES.­: To determine the potential of tozuleristide to detect breast carcinoma in fresh pathology specimens and the feasibility of fluorescence-guided intraoperative pathology assessment of surgical margins. DESIGN.­: Twenty-three patients received an intravenous bolus dose of 6 or 12 mg of tozuleristide at least 1 hour before surgery. Fifteen lumpectomy and 12 mastectomy specimens were evaluated for fluorescence by the site's clinical pathology staff using the SIRIS, an investigational near-infrared imaging device. The breast tissue was then processed per usual procedures. Fluorescent patterns were correlated with the corresponding hematoxylin-eosin-stained sections. Clinical pathology reports were used to correlate fluorescent signal to grade, histotype, prognostic marker status, and margin measurements. RESULTS.­: Tozuleristide fluorescence was readily observed in invasive and in situ breast carcinoma specimens. Most invasive carcinomas were bright and focal, whereas in situ lesions demonstrated a less intense, more diffuse pattern. Tozuleristide was detected in ductal and lobular carcinomas with a similar fluorescent pattern. Fluorescence was detected in high- and low-grade lesions, and molecular marker/hormone receptor status did not affect signal. Fluorescence could be used to identify the relationship of carcinoma to margins intraoperatively. CONCLUSIONS.­: Tumor targeting with tozuleristide allowed visual real-time distinction between pathologically confirmed breast carcinoma and normal tissue.

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.

CONTEXT.­: The management of lobular neoplasia (LN) found on core biopsy is controversial and ranges from obligatory surgical excision to clinical/imaging observation. OBJECTIVE.­: 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. DESIGN.­: 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. RESULTS.­: 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). CONCLUSIONS.­: 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.