Low-Field NMR Relaxometry for Intraoperative Tumour Margin Assessment in Breast-Conserving Surgery.

As conserving surgery is routinely applied for the treatment of early-stage breast cancer, the need for new technology to improve intraoperative margin assessment has become increasingly important. In this study, the potential of fast field-cycling 1H-NMR relaxometry as a new diagnostic tool was evaluated. The technique allows the determination of the tissue proton relaxation rates (R1), as a function of the applied magnetic field, which are affected by the changes in the composition of the mammary gland tissue occurring during the development of neoplasia. The study involved 104 small tissue samples obtained from surgical specimens destined for histopathology. It was found that a good accuracy in margin assessment, i.e., a sensitivity of 92% and a specificity of 85%, can be achieved by using two quantifiers, namely (i) the slope of the line joining the R1 values measured at 0.02 and 1 MHz and (ii) the sum of the R1 values measured at 0.39 and 1 MHz. The method is fast, and it does not rely on the expertise of a pathologist or cytologist. The obtained results suggest that a simplified, low-cost, automated instrument might compete well with the currently available tools in margin assessment.

Lesions of uncertain malignant potential of the breast (B3) on vacuum-assisted biopsy for microcalcifications: Predictors of malignancy.

PURPOSE: To investigate clinical, radiologic and pathologic features of B3 lesions diagnosed on VABB targeting microcalcifications, for identifying predictors of malignancy. METHOD: This retrospective multi-centre study included consecutive VABBs performed over a 10-year period on suspicious microcalcifications not associated with other radiological signs diagnosed as B3 on histology from VABB, with outcomes ascertained by surgical excision. Clinical, demographic, radiological and histological (B3 subcategory) data were collected. For statistical analysis (univariate and binary logistic regression), the primary outcome variable was the upgrade rate to malignancy after surgery. Predictors of upgrade to malignancy were identified from clinical, demographic, radiological and pathological variables (including B3 subcategory). RESULTS: Amongst 447 VABBs, there were 57(12.7 %) upgrades to malignancy at surgical histology (36 DCIS and 21 invasive cancer). At univariate analysis, variables significantly associated with increased risk of upgrade to malignancy were age>55 years (p = 0.01), lesion size>10 mm (p < 0.0001), BI-RADS 4b-c and 5 (p = 0.0001), and fine pleomorphic morphology (p = 0.002) of microcalcifications. Binary logistic regression confirmed as significant independent risk factors age, lesion size and BI-RADS category (p = 0.02, 0.02 and 0.0006 respectively). Amongst subcategories of B3 lesions, lobular neoplasia was significantly(p = 0.04) associated with upgrade, confirmed as an independent risk factor [p = 0.03, OR = 2.3(1.1-4.7)]. Flat epithelial atypia was significantly(p = 0.004) associated with reduced odds of upgrade, but binary logistic regression showed only borderline association [p = 0.052, OR = 0.4(0.2-1.01)]. CONCLUSIONS: Across B3 lesions diagnosed on histology from VABB of suspicious microcalcifications, older age, size>10 mm, BI-RADS category≥ 4b on imaging, and lobular neoplasia were risk factors for upgrade to malignancy. This information can be used to discuss patients' tailored management options.

Intraoperative breast specimen assessment in breast conserving surgery: comparison between standard mammography imaging and a remote radiological system.

OBJECTIVE: To compare standard specimen mammography (SSM) with remote intraoperative specimen mammography (ISM) assessment in breast conserving-surgery (BCS) based on operative times, intraoperative additional excision (IAE) and re-intervention rates. METHODS AND MATERIALS: We retrospectively compared 129 consecutive patients (136 lesions) who had BCS with SSM at our centre between 11/2011 and 02/2013 with 138 consecutive patients (144 lesions) who underwent BCS with ISM between 08/2014 and 02/2015.SSM or ISM were performed to confirm the target lesions within the excised specimen and margin adequacy. The utility of SMM and ISM was evaluated considering pathology as gold-standard, using χ2 or Fisher's exact tests for comparison of categorical variables, and non-parametric Mann-Whitney test for continuous variables. RESULTS: The two groups did not statistically differ for age (p = 0.20), lesion size (p = 0.29) and morphology (p = 0.82) or tumor histology type (p = 0.65). Intraoperative time was significantly longer (p < 0.00001) for SSM (132 ± 43 min) than for ISM (90 ± 42 min). The proportions requiring IAE did not significantly differ between SSM group (39/136 lesions (40%)) and ISM group (52/144 lesions (57%)) (p = 0.19), overall and in stratified analysis by mammographic features. Re-intervention rates were not statistically different between the two groups [SSM:19/136 (14%), ISM:13/144 (9%); p = 0.27]. CONCLUSION: The introduction of ISM in BCS significantly reduced surgical time but did not change IAE and re-intervention rates, highlighting facilitated communication between surgeons and radiologists. ADVANCES IN KNOWLEDGE: Compared to standard mammography imaging, the use of ISM significantly reduced surgical time.

Preoperative breast cancer staging with multi-modality imaging and surgical outcomes.

PURPOSE: To compare the rates of mastectomy and re-operation after breast-conserving surgery (BCS) among patients who had different pre-operative multi-modality imaging, hence identifying significant predictors of mastectomy and re-operations within each group. METHOD: Retrospective study of consecutive patients with primary breast cancer treated January 2010 - December 2016, divided in 3 groups, undergoing pre-operative local staging respectively with conventional imaging modalities only (2D mammography, ultrasound (US)), conventional imaging and tomosynthesis (DBT) and/or MRI. The primary outcome was identification of significant predictors of surgical outcomes, within each group. Study variables examined in univariate analysis were age, lesion dimension, breast density, multifocality, tumor size, histology, and if associated with outcomes they were included in binary logistic regression analysis. RESULTS: Amongst 1547 patients, patient and tumor characteristics differed across the three groups, as did mastectomy rates which were 18 % (102/562) for 2D + US, 36 % (154/428) for 2D + DBT + US, 45 % (250/557) for 2D+/-DBT + US + MRI(p < 0.001). Variables strongly associated with mastectomy were larger lesions and multifocality (as was multi-modality group). Re-operation rate showed an opposite trend: 12.2 % (56/459) for 2D + US, 8 % (22/272) for 2D + DBT + US, 6.5 % (20/306) for 2D+/-DBT + US + MRI. Re-operation rate for 2D+/-DBT + US + MRI was lower than for 2D + US (p = 0.01) but similar to 2D + DBT + US (p = 0.58). Patients who had 2D + US and re-operations had significantly larger lesions, more underestimation, higher proportion of invasive carcinoma with in-situ component than those who did not require re-operation. CONCLUSIONS: Patients who had larger tumors and multifocal disease were more frequently staged by adding DBT and/or MRI to conventional imaging (mammography and US) which was associated with more extensive surgical treatment but lower reoperation rates.

Eccrine spiradenoma of the nipple: Case report, differential diagnosis and literature review.

Eccrine spiradenoma is a rare lesion originating from eccrine sweat glands, with only few cases reported in breast tissue: we here describe for the first time, an eccrine spiradenoma arising in the nipple. An 84 year-old woman with a lesion enlarging her right nipple, showing ulcerations and eczema-like changes of the covering skin, was admitted to our hospital. Surgical excision of the central quadrant with nipple-areola complex was performed, followed by histopathological evaluation which revealed an adenoma with predominantly basaloid epithelial cells. The lesion was composed of tightly packed small and large groups of cells, arranged in diffuse alveolar/pseudorosette formations. The small cells expressed p63 and calponin, while a positive expression of CK7 and CD117 was detected in large cells. After careful and detailed examination, excluding various similar entities, a diagnosis of eccrine spiradenoma has been rendered. Although extremely rare, eccrine spiradenoma should be taken into account in the differential diagnosis of subcutaneous primary breast tumors.

Closed Incision Negative Pressure Therapy in Oncological Breast Surgery: Comparison with Standard Care Dressings.

BACKGROUND: Negative pressure wound therapy was developed for treating wounds associated with unfavorable healing factors. The principles of the negative pressure wound therapy applied on clean and closed surgical incision originate the closed incision negative pressure therapy (ciNPT). We evaluated the use of ciNPT in the setting of oncological breast surgery. METHODS: From January 1, 2015, to June 31, 2015, we prospectively selected 37 patients undergoing oncological breast surgery with a minimum of 4 risk factors. Seventeen patients (25 surgeries) voluntary tested ciNPT (ciNPT sample), whereas the remaining 20 (22 surgeries) chose conventional postsurgery dressing (Standard Care sample). Follow-up controls to evaluate postsurgical complications were performed on days 7, 14, 30, and 90. At 12 months, the quality of life, scar, and overall aesthetic outcomes were evaluated with specific questionnaires filled in by surgeon and patient. The Standard Care sample was investigated on risk factors associated with poor healing. RESULTS: The ciNPT sample showed a significant prevalence of high risk factors, especially extensive undermining and bilateral surgeries, and a predominance of women under 65 years; only 1/25 (4%) surgical procedures was followed by complications. In the Standard Care sample, 10 of 22 surgeries (45%) were followed by complications. The difference in complication rate between the 2 samples was significant. The BIS (Body Image Scale) scores suggested that most patients were satisfied with their body image regardless of the type of dressing. All other questionnaire scores clearly vouched for a significant superiority of the ciNPT. Previous surgery ≤ 30 days emerged as the surgery-related high risk factor most frequently associated with postsurgery complications. CONCLUSION: The results of our study support the use of ciNPT in oncological breast surgery: it showed to be a well-tolerated, adaptable, and reliable dressing capable of reducing postsurgical complications and improving scar outcomes in patients presenting with high risk factors.

Digital Breast Tomosynthesis (DBT) to Characterize MRI-Detected Additional Lesions Unidentified at Targeted Ultrasound in Newly Diagnosed Breast Cancer Patients.

OBJECTIVES: Preoperative breast magnetic resonance (MR) often generates additional suspicious findings needing further investigations. Targeted breast ultrasound (US) is the standard tool to characterize MR additional lesions. The purpose of this study is to evaluate the potential role of digital breast tomosynthesis (DBT) to characterize MR detected additional findings, unidentified at targeted breast US. METHODS: This prospective study included women who a) had biopsy-proven, newly diagnosed breast cancers detected at conventional 2D mammography and/or US, referred to breast MR for tumour staging; and b) had DBT if additional MR findings were not detected at targeted ('second look') US. RESULTS: In 520 patients, MR identified 164 (in 114 women, 22%) additional enhancing lesions. Targeted US identified 114/164 (69.5%) of these, whereas 50/164 (30.5%) remained unidentified. DBT identified 32/50 of these cases, increasing the overall characterization of MR detected additional findings to 89.0% (146/164). Using DBT the identified lesions were significantly more likely to be malignant than benign MR-detected additional lesions (p = 0.04). CONCLUSIONS: DBT improves the characterization of additional MR findings not identified at targeted breast US in preoperative breast cancer staging. KEY POINTS: • Targeted US identified 114 of 164 (69.5%) additional enhancing lesions at preoperative breast MRI. • DBT identified a further 32 of the 50 lesions unidentified on targeted US. • DBT improved the characterization of additional MR findings for breast cancer staging.

Efficiency of a preoperative axillary ultrasound and fine-needle aspiration cytology to detect patients with extensive axillary lymph node involvement.

BACKGROUND: Recent studies have demonstrated that axillary lymph node dissection (ALND) does not affect patient survival, even in those with one or two positive sentinel lymph nodes (SLNs). On the other hand, patients with 3 or more metastatic lymph nodes are eligible for chemotherapy. Therefore, it is crucial to identify a priori patients at risk of having a high number of metastatic axillary lymph nodes for their surgical and/or clinical management. Ultrasound (US) guided Fine-Needle Aspiration (FNA) has been proven to be a useful and highly specific method for detecting metastatic axillary lymph nodes. However, only one recent study has evaluated the efficiency of this method in identifying patients with high metastatic nodal involvement. Our aim was to validate US-guided FNA as a reliable method to discriminate a priori patients with >3 metastatic lymph nodes. METHODS: A retrospective series of 1287 breast cancer patients who underwent a simultaneous preoperative breast and axillary US to stage their axilla was collected. A total of 365 patients, with either positive SLNs (278) or positive axillary lymph nodes detected via US-guided FNA (87), underwent ALND. In these two subgroups, we compared the number of metastatic lymph nodes in the axilla. RESULTS: The number of metastatic axillary lymph nodes in patients who underwent US-guided FNA was significantly higher (63% had >3 metastatic lymph nodes) than that in patients with SLNs positive for micro- or macrometastases (3% and 27%, respectively) (P<0.001, χ(2) = 117.897). CONCLUSIONS: Preoperative axillary US-guided FNA could act as a reliable tool in identifying breast cancer patients with extensive nodal involvement.

A new clinical cut-off of cytokeratin 19 mRNA copy number in sentinel lymph node better identifies patients eligible for axillary lymph node dissection in breast cancer.

AIMS: Cytokeratin 19 (CK19) mRNA copy number predicts the probability of tumour load in axillary lymph nodes (ALN) and can help in decision-making regarding the axillary dissection. The purpose of this study was to define a new cut-off of CK19 mRNA copy number using the one-step nucleic acid amplification (OSNA) assay on metastatic sentinel lymph nodes (SLN) in order to identify cases at risk of having one or more positive ALN. METHODS: 1296 SLN from 1080 patients were analysed with the OSNA assay. 194 patients with positive SLN underwent ALN dissection and the mean value of CK19 copy number (320 000) of their SLN was set as initial cut-off. Receiver operative characteristics curve identify a best cut-off of 7700 (sensitivity 78%, specificity 57%). A comparison between our and the traditional cut-off (5000) was performed. RESULTS: The cut-off of 7700 successfully identifies patients with positive ALN (p=0.001, false- negative cases: 17%). In the range between 5000 and 7700, one patient with positive ALN would not undergo axillary dissection, whereas eight patients with negative ALN would be correctly identified. CONCLUSIONS: We suggest that the level of CK19 mRNA copy number could be the only parameter to consider in the intraoperative management of the axilla.

Accuracy of mammography, digital breast tomosynthesis, ultrasound and MR imaging in preoperative assessment of breast cancer.

AIM: To define the accuracy of digital breast tomosynthesis (DBT) and magnetic resonance imaging (MRI) added to digital mammography (DM) and ultrasound (US) in the preoperative assessment of breast cancer. PATIENTS AND METHODS: We performed a prospective study of 200 consecutive women with histologically-proven breast cancer using the above imaging techniques. Accuracy measurements were estimated using a lesion-by-lesion analysis for unifocal, multifocal/multicentric, bilateral and all carcinomas. We also calculated sensitivity according to breast density. RESULTS: DBT had higher sensitivity than DM (90.7% vs. 85.2%). Combined DM and DBT with US yielded a 97.7% sensitivity; despite high sensitivity of MRI (98.8%), the addition of MRI to combined DM with DBT and US did not significantly improve sensitivity. Overall accuracy did not significantly differ between MRI and DM with DBT and US (92.3% vs. 93.7%). Breast density affected sensitivity of DM and DBT (statistically significant difference for DM), not MRI. CONCLUSION: There is little gain in sensitivity and no gain in overall accuracy, by performing MRI for patients who have been evaluated with DM with DBT and US.

Reliability of whole sentinel lymph node analysis by one-step nucleic acid amplification for intraoperative diagnosis of breast cancer metastases.

OBJECTIVE: To assess the reliability of using the One-Step Nucleic Acid Amplification (OSNA) assay as a single test on whole sentinel lymph nodes (SLN) as a method of intraoperative diagnosis and staging of SLNs in breast cancer. BACKGROUND: Combining histological and molecular assessment of metastasis on the same SLN may not fully reproduce the actual load of cancer cells present in the SLN and create problems in decisions regarding axillary dissection. METHODS: Selection criteria for the whole SLN OSNA test required that the primary tumor expressed CK19 in more than 80% of tumor cells. Imprint cytology analysis of SLNs was performed together with the OSNA. RESULTS: Of the 279 patients enrolled for SLN evaluation, 123 gave consent to the OSNA protocol and 156 to the standard histology. Thirteen patients were excluded from OSNA evaluation because of low CK19 gene expression in the primary tumor; only 2.3% were truly negative. The kappa of concordance between the imprint cytology and OSNA results was 0.52. The rate of macrometastases determined by OSNA was 11% versus 20% determined by histology, whereas the rate of OSNA-micrometastases (18%) was significantly higher than that determined by histology (8%). The rate of SLN-negative cases was similar between the 2 protocols. Macrometastases correlated with the presence of vascular invasion in both protocols. The rate of axillary lymph node metastases was consistent with SLN tumor load. CONCLUSIONS: Intraoperative OSNA assay performed on the whole SLN gave objective and reproducible results that were useful for directing decisions regarding axillary dissection and for accurately defining the SLN stage.

Impact of axillary nodal metastases on lymphatic mapping and sentinel lymph node identification rate in patients with early stage breast cancer.

PURPOSE: The aim of this study was to define the impact of the presence of axillary nodal metastases on lymphatic mapping and sentinel lymph node (SLN) identification rate in patients with early breast cancer. METHODS: Two hundred and forty-six lymphatic mapping procedures were performed with both labelled nanocolloid and blue dye, followed by SLN biopsy and/or complete axillary dissection. The following parameters were recorded: patient's age, tumour laterality and location, tumour size, tumour histology, tumour stage, tumour grade, lymphovascular invasion, radiotracer injection site (subdermal-peritumoural/peri-areolar), SLN visualisation at lymphoscintigraphy, SLN metastases (presence/absence, size) and other axillary metastases (presence/absence, number). Discriminant analysis was used to analyse the data. RESULTS: SLNs were identified by labelled nanocolloid alone in 94.7% of tumours, by blue dye alone in 93.5% and by the combined technique in 99.2%. Discriminant analysis showed the gamma probe SLN identification rate to be significantly limited by the presence of axillary nodal metastases. In particular, the size of SLN metastases and the number of other axillary metastases were the most important variables in reducing the gamma probe SLN identification rate (p = 0.004 and p = 0.002, respectively). On the other hand, high tumour grade was the only parameter limiting the blue dye SLN identification rate. CONCLUSION: The accuracy of lymphatic mapping with labelled nanocolloid is limited by the presence of axillary nodal metastases, and particularly by the degree of SLN tumoural invasion and the presence and number of other axillary nodal metastases. Neither of these elements seems to interfere with the blue dye identification rate. The combination of the two tracers maximises the SLN identification rate.

Sentinel lymph node detection in patients with early-stage breast cancer: comparison of periareolar and subdermal/peritumoral injection techniques.

UNLABELLED: Periareolar (PA) injection offers several potential advantages over other techniques for visualizing sentinel lymph nodes (SLNs) in patients with early breast cancer. However, few studies have been published on this procedure. This study was designed to validate PA injection technique and compare it with the subdermal/peritumoral (SD/PT) injection technique. METHODS: The study included 324 patients in whom 330 breast cancers (T) had been identified by biopsy. This population was divided in 4 groups: (A) 148 patients (150 T) in whom lymphatic mapping was performed by injecting radiotracer with the SD/PT technique; (B) 59 patients (60 T) in whom lymphatic mapping was performed with a combination of blue dye injected with the PA technique and radiotracer injected with the SD/PT technique; (C) 58 patients (60 T) in whom blue dye was injected subdermally and radiotracer was injected periareolarly; and (D) 59 patients (60 T) in whom both blue dye and radiotracer were injected periareolarly. RESULTS: Concordances in the SLN detection rate between blue dye and radiotracer in groups B, C, and D were 98.1%, 100%, and 100%, respectively. The SLN identification rates with the PA technique were 98.3% and 95%, respectively, for radiotracer and blue dye. With the SD/PT technique, these rates were 90.5% and 88.3%, respectively, for radiotracer and blue dye. At lymphoscintigraphy, SLN visualization required the acquisition of late images (3 h after the injection) in 20% of patients who received PA injections and 39.5% of patients who received SD/PT injections. CONCLUSION: These findings validate the PA injection technique and underline some of its reported advantages in comparison with the SD/PT technique.