Grade Ductal Carcinoma Research Articles

Management of papillary lesions without atypia of the breast diagnosed on needle biopsy.

Current surgical practice often leads to excision of all papillary lesions of the breast diagnosed on percutaneous biopsy. This study aims to identify a subset of patients with papillary lesions who may be able to avoid surgery. Between January 2000 and December 2015, 157 cases of papillary lesions with complete surgical excision pathology results were reviewed retrospectively to compare the clinical, imaging and pathology features. Of these, 50 patients with benign papillary lesions without atypia and 19 patients with benign papillary lesions with atypia on needle biopsy were analysed to determine the rate of upgrade to malignancy after surgery. Of the 50 patients with benign papillary lesions without atypia on biopsy, two (4%) were upgraded to low grade ductal carcinoma in situ after surgical excision. Both these patients had suspicious features on imaging. Of the 19 patients with papillary lesions with atypia diagnosed on needle biopsy, eight (42%) were upgraded to malignancy after surgery. The differences between benign, atypical and malignant papillary lesions were further compared. Malignant lesions were more suspicious radiologically (P = 0.001), more likely to have architectural distortion (P = 0.001), more peripherally located (P = 0.001) and were larger in size (P = 0.01). Patients diagnosed with malignant lesions were also older (P = 0.001). Younger patients diagnosed with small central benign papillary lesions without atypia on needle biopsy, and without suspicious imaging, may be managed conservatively with surveillance.

13P - Upgrade of low grade ductal carcinoma in situ (DCIS): Multimodality approach in a 10-year single institution study

13P - Upgrade of low grade ductal carcinoma in situ (DCIS): Multimodality approach in a 10-year single institution study

Active Monitoring Versus Immediate Treatment of Women With Localised, Low-Risk Ductal Carcinoma In Situ: Does It Make Economic Sense?

Background: Controversy persists about the overdiagnosis of low risk breast cancers identified by breast cancer screening programs. Low risk ductal carcinoma in situ (DCIS) is a noninvasive breast condition with an uncertain risk of invasive progression. Standard management consists of immediate surgical treatment, with or without radiotherapy and adjuvant therapy. Active monitoring of low risk DCIS via annual mammography is proposed as an alternative strategy to immediate surgery to reduce the harm of overdiagnosis, whereby the disease is only treated upon disease progression. However, the costs and benefits of active monitoring are not well researched in the breast cancer setting. Aim: To assess the cost-effectiveness of active monitoring versus immediate surgical management in women diagnosed with low grade ductal carcinoma in situ (DCIS). Methods: A Markov state transition model was constructed for a theoretical cohort of women aged 50 years and over with low risk DCIS over a lifetime horizon. A cost-utility analysis was performed to compare a strategy of observation (active monitoring) versus immediate surgical treatment using an annual time cycle. Transition probabilities, costs and utilities were obtained from national mortality and cost data, published meta-analyses, primary data collection of utilities and expert opinion. A healthcare perspective was adopted to present the results. Primary outcomes were assessed in terms of cost per quality-adjusted-life-year (cost per QALY). Multiple sensitivity analyses were undertaken to determine effect of parameter uncertainty on results. Results: The cumulative costs and QALYs for each age cohort are presented. Active monitoring is a cost-effective strategy for the management of low risk breast cancer in older women with comorbid conditions. Sensitivity analyses revealed the ICERs for all women to be affected by baseline probability of disease progression, age, cost of surgery and utility. Conclusion: Conservative management of ductal carcinoma in situ via active monitoring may be cost-effective compared with immediate surgical treatment in a selected cohort of older women with low risk disease.

Diagnostic value of Breast Specific Gamma Imaging with semiquantitative index (T/N) in Breast Cancer Diagnosis

Objective: The study in this part was to evaluate the diagnostic value of Breast Specific Gamma Imaging (BSGI) by semi-quantitative method for detection of breast cancer.
 Methods: 400 patients with indeterminate breast tumors that underwent BSGI were enrolled in this study. All included lesions were confirmed by postoperative pathology. BSGI evaluation was based on the visual interpretation and semi-quantitative parameters of the higher tumor to non-lesion (T/N) value of CC and MLO. Compared with pathological results, the optimal visual analysis and the value of T/N were calculated through ROC curve analysis. Independent t-test and Pearson linear correlation were applied for statistical analysis.
 Results: Tumor to non-lesion (T/N) ratio was available for 279 out of 400 patients. This population comprised 203 patients with malignant and 74 patients with benign lesion. ROC analysis showed critical value of T/N= 1.91, AUC is 0.83 (standard error=0.014, 95% confidence interval); BSGI sensitivity is 83.71% and specificity is 76%. T/N ratio for invasive and non-invasive cancers are 2.70± 0.88, and 2.09±0.44 respectively; the difference between two have statistical significance (t=3.32, P=0.001). Infiltrating ductal carcinoma (IDC) grade I, grade II, and grade III have T/N ratio of 2.33±0.94, 2.38±0.80, 2.89±0.89 respectively. The T/N differences between grade I and grade II have no statistical significance (t=0.12, P=0.89). The T/N differences between grade I and grade III have no statistical significance (t=1.56, P=0.12). The T/N differences between grade II and grade III have statistical significance (t=3.69, P<0.001). T/N value for tumor size <1cm and >1cm were 1.97±0.79 and 2.46±0.88 respectively; the difference between two have statistical significance (t=3.27, P=0.001).
 Conclusion: The semi-quantitative index of T/N correlates with clinico-pathological characteristics of tumor like: size, grade, and invasiveness of breast cancer, and at certain level can be helpful to determine patient’s prognosis.

Breast cancer–related deaths according to grade in ductal carcinoma in situ: A Dutch population–based study on patients diagnosed between 1999 and 2012

BackgroundThe incidence of ductal carcinoma in situ (DCIS) has drastically increased over the past decades. Because DCIS is resected after diagnosis similar to invasive breast cancer, the natural cause and behaviour of DCIS is not well known. We aimed to determine breast cancer–specific survival (BCSS) and overall survival (OS) according to grade in DCIS patients after surgical treatment in the Netherlands. Patients and methodsAll DCIS patients diagnosed between 1999 and 2012 were selected from the Netherlands Cancer Registry. The cause of death was obtained from ‘Statistics Netherlands’. BCSS and OS were estimated using multivariable Cox regression in the entire cohort and stratified for grades. ResultsIn total, 12,256 patients were included, of whom 1509 (12.3%) presented with grade I, 3675 (30.0%) with grade II, 6064 (49.5%) with grade III and 1008 (8.2%) with an unknown grade. During a median follow-up of 7.8 years, 1138 (9.3%) deaths were observed, and 179 (1.5%) were breast cancer–related. Of these, 10 patients had grade I; 46 grade II; 95 grade III and 28 an unknown grade. After adjustment for confounding, grade II and III were related to worse BCSS than grade I with hazard ratios of 1.92 (95% confidence interval [CI]: 0.97–3.81) and 2.14 (95% CI: 1.11–4.12), respectively. No association between grades and OS was observed. ConclusionBCSS and OS in DCIS patients were excellent. Because superior rates were observed for low-grade DCIS, it seems justified to investigate whether active surveillance may be a balanced alternative for conventional surgical treatment.

Intraepidermal malignancy in breast skin: A tale of two tumours

Mammary Paget's disease most commonly affects the nipple areolar complex and is frequently associated with an underlying in-situ or invasive breast carcinoma. Pagetoid Bowen's disease of the breast is extremely rare and contains cells which morphologically resemble those of Paget's disease and may also express CK7 on immunohistochemistry. Here, we report two unusual cases of a 42-year-old Chinese woman with a recurrence of high grade ductal carcinoma in-situ presenting as mammary Paget's disease away from the nipple areolar complex, and a 65-year-old Chinese woman with pagetoid Bowen's disease of the breast skin. To our knowledge, there are only two case reports that are similar to the former and one to the latter.

Impact of MRI on high grade Ductal Carcinoma In situ (HG DCIS) management: Are we using the full scope of MRI?

Introduction: Preoperative assessment of pure Ductal Carcinoma In situ (DCIS) is essential in the surgical planning. The role of Magnetic resonance imaging (MRI) has long been debated. The impact of MRI on management of High Grade (HG) DCIS was assessed in comparison to conventional imaging.

Active surveillance of women diagnosed with atypical ductal hyperplasia on core needle biopsy may spare many women potentially unnecessary surgery, but at the risk of undertreatment for a minority: 10-year surgical outcomes of 114 consecutive cases from a single center

A needle core biopsy diagnosis of atypical ductal hyperplasia is an indication for open biopsy. The launch of randomized clinical trials of active surveillance for low-risk ductal carcinoma in situ leads to the paradoxical situation of women with low-grade ductal carcinoma in situ being observed, whereas those with atypical ductal hyperplasia have surgery. If the malignancies diagnosed after surgery for atypical ductal hyperplasia are dominated by low-risk ductal carcinoma in situ, women with atypical ductal hyperplasia may also be considered for surveillance. This 10-year prospective observational study includes women diagnosed with atypical ductal hyperplasia on core biopsy after screening mammography. We retrieved their clinical, imaging and histologic data and carried out a blind review of core biopsy histology, sub-classifying the atypical ductal hyperplasia along a spectrum from hyperplasia to ductal carcinoma in situ. Using the final surgical pathology data, we calculated: (1) The proportion and grades of ductal carcinoma in situ and invasive cancers diagnosed at open biopsy. (2) The histologic extent of the malignancy at surgery. (3) The biomarker profile and nodal status of any invasive cancers. (4) Ascertained any independent predictors of (i) any malignancy, (ii) high-risk malignancy, defined in this study as invasive cancer, or high-grade ductal carcinoma in situ, or intermediate grade ductal carcinoma in situ with any necrosis. (5) Extrapolated the above to simulate active surveillance for women with screen-detected atypical ductal hyperplasia. Between January 2005 and December 2014, 114 women, mean age 59 years (range 40–79 years) were included. Surgical pathology, available in 110 (97%), confirmed malignancy in 46 (40%). All 46 malignant cases had ductal carcinoma in situ, accompanied by invasive carcinoma in 9 (8%) women. Together, 21 (19%) women had either invasive cancer (9%), high-grade ductal carcinoma in situ (6%), or necrotizing, intermediate grade ductal carcinoma in situ (6%). Only one of nine invasive breast cancers was grade 1, 3 were multifocal, all were ≤8 mm, node negative, and ER positive but two were HER2 amplified. The mean extent of the ductal carcinoma in situ in any one specimen was 19.8 mm, median 13 mm, range 2–110 mm. Overall 32 women, 29% of the whole cohort and 70% of those 46 with malignancy, required further surgery, including mastectomy in 12 (11%). A multivariable model for predicting the likelihood of any malignancy showed a statistically significant association only with the post review subtype of atypical ductal hyperplasia, adjusting for lesion size. Independent predictors of high-risk malignancy (invasive cancer or non-low-grade ductal carcinoma in situ) were not identified. If active surveillance is adopted for screen-detected atypical ductal hyperplasia diagnosed on core biopsy, 60% of women will avoid unnecessary surgery and a further 24% would meet eligibility criteria for ductal carcinoma in situ surveillance trials. However, 18% of women will have undiagnosed invasive breast cancer or non-low-risk ductal carcinoma in situ. These women with high-risk lesions are not reliably identified pre-operatively.

Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas.

Microcalcifications (MCs) are routinely used to detect breast cancer in mammography. Little is known, however, about their materials properties and associated organic matrix, or their correlation to breast cancer prognosis. We combine histopathology, Raman microscopy, and electron microscopy to image MCs within snap-frozen human breast tissue and generate micron-scale resolution correlative maps of crystalline phase, trace metals, particle morphology, and organic matrix chemical signatures within high grade ductal carcinoma in situ (DCIS) and invasive cancer. We reveal the heterogeneity of mineral-matrix pairings, including punctate apatitic particles (<2 µm) with associated trace elements (e.g., F, Na, and unexpectedly Al) distributed within the necrotic cores of DCIS, and both apatite and spheroidal whitlockite particles in invasive cancer within a matrix containing spectroscopic signatures of collagen, non-collagen proteins, cholesterol, carotenoids, and DNA. Among the three DCIS samples, we identify key similarities in MC morphology and distribution, supporting a dystrophic mineralization pathway. This multimodal methodology lays the groundwork for establishing MC heterogeneity in the context of breast cancer biology, and could dramatically improve current prognostic models.

Breast MRI as a Problem-solving Study in the Evaluation of BI-RADS Categories 3 and 4 Microcalcifications: Is it Worth Performing?

We aimed to investigate the utility of problem-solving breast magnetic resonance imaging (MRI) for mammographic Breast Imaging Reporting and Data System (BI-RADS) categories 3 and 4 microcalcifications. Between January 1, 2010 and December 31, 2011, 138 women with 146 areas of categories 3 and 4 microcalcifications without sonographic correlates underwent breast MRI and had a stereotactic core biopsy using an 11-gauge needle or follow-up at least for 24 months. Positive predictive value (PPV), negative predictive value, sensitivity, and specificity were calculated on the basis of BI-RADS category, with categories 1-3 being considered benign and categories 4 and 5 being considered malignant. Twenty-four cases (16.4%) were malignant (18 ductal carcinoma in situ, 6 invasive). MRI increased PPV and specificity from 43% to 68% and from 80% to 93% (P = .054 and .005) compared to mammography. Within 102 category 3 microcalcifications, 5 carcinomas were assessed correctly as category 4 by MRI. Within 44 category 4 microcalcifications, a correct diagnosis was made by MRI in 77% (34 of 44) as opposed to 43% (19 of 44) by mammography, and 80% (20 of 25) of unnecessary biopsies could have been avoided. Within the 24 carcinomas, 5 were negative at MRI. MRI-negative carcinomas have a significantly higher possibility of being low grade (ductal carcinoma in situ or invasive) (P = .0362). Breast MRI has the potential to improve the diagnosis of category 3 or 4 microcalcifications and could alter indications for biopsy. Breast MRI could help predict the presence or absence of higher-grade carcinoma for category 3 or 4 microcalcifications.

Breast carcinoma with osteoclast-like giant cells: A cytological-pathological correlation with a literature review.

Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare disease characterized by the infiltration of OGCs in the tumor; however, cytological aspects of this tumor type remain elusive. We examined the cytological features in fine needle aspiration (FNA) biopsy smears obtained from 5 patients who were histologically diagnosed with breast carcinoma with OGCs. We compared FNA and clinicopathological findings with results from the published literature. Histological assessment of the resected samples showed that all tumors exhibited a histological grade 1 phenotype with a predominant cribriform architecture. Four patients were estrogen receptor positive, and 1 patient showed a triple negative phenotype. All patients survived without tumor recurrence. In the FNA smears, tumor cells were arranged in loosely cohesive clusters, characterized by varying degrees of OGCs infiltration and rare formation of solid tumor nests. Occasionally, 2- or 3-dimensional clusters of tumor cells were found, accompanied by OGCs at the peripheral regions. In all patients, tumor cells were small without severe nuclear atypia. None of the patients showed significant background necrosis. In summary, cytological features of breast carcinoma with OGCs are characterized by loose aggregates of low grade tumor cells, the presence of OGCs, and the absence of necrosis, all of which were consistent with features reported previously. This peculiar form of breast tumors should be included in the differential diagnosis, when physicians encounter FNA findings including low grade ductal carcinoma with the admixture of multinucleated giant cells or OGCs.

Down regulation of KLK7 expression in breast tissues and identification of a novel spliced KLK7 mRNA

BackgroundAlternative splicing commonly occurs in cancer cells and many cancer specific splice variants have been reported as potential candidate biomarkers of the disease. We have studied human tissue Kallikrein 7 (KLK7) mRNA expression profile in breast cancer patients of our region. KLK7 is member of a multi-gene family consisting of 15 members (KLK1-KLK15).MethodsWe optimized touch down nested PCR method for the amplification of KLK7 isoforms/variants. Various bioinformatics tools were used for sequence analysis, identification of splicing pattern and prediction of encoded proteins.ResultsWe observed an unusual splicing event consisting of exon 3 (E3) truncation at 3′ end (by 124 nucleotides), exon 4 (E4) exclusion and exon 5 (E5) truncation at 5′ end (by 33 nucleotide) in 2 normal breast tissues, one obtained from invasive ductal carcinoma grade II patient and other collected from mammary dysplasia patient. Moreover, 3 other KLK7 mRNAs (KF963190, KF963191, and KF963193) expressed in breast cancer were noticed to exhibit single nucleotide polymorphism (SNPs). Bioinformatic analysis revealed that the alternatively spliced mRNA (KF963192) will potentially encode a truncated and non-functional protein. Similarly although encoded proteins have considerable homology with normal hK7 protein, SNPs seem to cause great variations in pIs, structures and molecular weights of encoded proteins.ConclusionsThere is need to further explore the impact of the unique splicing event, SNPs and characterize these population specific mutations and their possible role in the pathogenesis of breast cancer.Graphical abstract

Atypical ductal hyperplasia: Our experience in the management and long term clinical follow-up in 71 patients

IntroductionAtypical ductal hyperplasia (ADH) is a high-risk benign lesion found in approximately 1–10% of breast biopsies and associated with a variable incidence of carcinoma after surgical excision.The main goal of our study is to present our experience in the management and long-term follow-up of 71 patients with ADH diagnosed on breast biopsy. Materials and methodsResults of 3808 breast biopsy specimens from 1 January 2000 to 31 December 2005 were analyzed to identify all biopsies which resulted in a diagnosis of ADH.The histopathological results of the 45 patients who underwent surgery were analyzed. Long-term follow-up for the remaining patients was carried out. Results45 of 71 (63.4%) patients with histological diagnosis of ADH on breast biopsy underwent surgery. Definitive histological results revealed invasive carcinoma in 7 cases (15.6%), high grade Ductal Carcinoma in situ (DCIS) in 10 (22.2%) patients, Lobular Carcinoma in situ (LCIS) in 4 cases (8.9%) and benign findings in 24 cases (53.3%). 12 of 71 (16.9%) patients underwent only long term follow-up; one (8,3%) of these developed invasive breast carcinoma after 6 years. ConclusionAtypical ductal hyperplasia diagnosed on breast biopsy is associated with a relatively high incidence of invasive carcinoma and high grade ductal carcinoma in situ at the time of surgical excision. Certain radiological and cytological criteria can be used to help determine which patients should forgo surgery and be followed up with good results.Long term follow-up is always crucial for patients who have not undergone surgery.

BRCA2 carriers with male breast cancer show elevated tumour methylation

BackgroundMale breast cancer (MBC) represents a poorly characterised group of tumours, the management of which is largely based on practices established for female breast cancer. However, recent studies demonstrate biological and molecular differences likely to impact on tumour behaviour and therefore patient outcome. The aim of this study was to investigate methylation of a panel of commonly methylated breast cancer genes in familial MBCs.Methods60 tumours from 3 BRCA1 and 25 BRCA2 male mutation carriers and 32 males from BRCAX families were assessed for promoter methylation by methylation-sensitive high resolution melting in a panel of 10 genes (RASSF1A, TWIST1, APC, WIF1, MAL, RARβ, CDH1, RUNX3, FOXC1 and GSTP1). An average methylation index (AMI) was calculated for each case comprising the average of the methylation of the 10 genes tested as an indicator of overall tumour promoter region methylation. Promoter hypermethylation and AMI were correlated with BRCA carrier mutation status and clinicopathological parameters including tumour stage, grade, histological subtype and disease specific survival.ResultsTumours arising in BRCA2 mutation carriers showed significantly higher methylation of candidate genes, than those arising in non-BRCA2 familial MBCs (average AMI 23.6 vs 16.6, p = 0.01, 45% of genes hypermethylated vs 34%, p < 0.01). RARβ methylation and AMI-high status were significantly associated with tumour size (p = 0.01 and p = 0.02 respectively), RUNX3 methylation with invasive carcinoma of no special type (94% vs 69%, p = 0.046) and RASSF1A methylation with coexistence of high grade ductal carcinoma in situ (33% vs 6%, p = 0.02). Cluster analysis showed MBCs arising in BRCA2 mutation carriers were characterised by RASSF1A, WIF1, RARβ and GTSP1 methylation (p = 0.02) whereas methylation in BRCAX tumours showed no clear clustering to particular genes. TWIST1 methylation (p = 0.001) and AMI (p = 0.01) were prognostic for disease specific survival.ConclusionsIncreased methylation defines a subset of familial MBC and with AMI may be a useful prognostic marker. Methylation might be predictive of response to novel therapeutics that are currently under investigation in other cancer types.

Impact of MRI on high grade Ductal Carcinoma Insitu (HG DCIS) management, are we using the full scope of MRI?

IntroductionPreoperative assessment of pure Ductal Carcinoma Insitu (DCIS) is essential in the surgical planning. The role of Magnetic resonance imaging (MRI) has long been debated. The impact of MRI on the management of High Grade (HG) DCIS was assessed, whether it accurately captures the true size of this entity in comparison to conventional imaging, and, if MRI use would reduce the number of re-excision surgery. MethodNinety-one consecutive patients with HG DCIS, who were identified from a prospectively collected data at Kettering General Hospital between April 2011 and December 2015. All patients had preoperative MRI scan in addition to the standard breast imaging. This was compared to a control group of consecutive patients (n=52) which was obtained from a period just before 2011. Impact on surgical planning and number of surgeries for each patient was compared. The size of HG DCIS estimated by MRI was compared to the final histological size. Secondary outcomes included change of initial surgical plan and detection of occult contralateral breast cancer. ResultsMRI group had 91 patients with median age of 63. Seventy percent of which presented through the screening program. The overall sensitivity of MRI to detect HG DCIS was 77% (70/91) with a false negative rate FNR of 23% (21/91). Therefore, 70 patients only were included in the data analysis. The control group included 52 screening patients with comparable baseline characteristics.Re-excision (or completion mastectomy) rates were higher in the control group 26% compared to 8% in the MRI group (P-value 0.012).MRI use correctly converted the initial plan of breast conservation to mastectomy in 9 patients (13%). Five patients had additional ipsilateral malignant features (7%).Occult contra lateral disease, was diagnosed in 2 patients (3%). ConclusionThis study suggests that MRI could be an important tool in reducing the re-excision rates in the surgical management of HG DCIS. Although still controversial, selective MRI imaging can be useful in the preoperative diagnosis and evaluation of HG DCIS. Case by case discussion at MDT is crucial. Wider adaptation of MRI when indicated in the assessment of breast lesions with proper correlation to histology postoperatively is a key in improving our MRI interpretation skills, helping us to exploit the full scope of this useful tool.

Trends in incidence and tumour grade in screen-detected ductal carcinoma in situ and invasive breast cancer.

In a biennial screening mammography programme, we analysed the trends in incidence of screen-detected DCIS and invasive breast cancers in the era of screen-film mammography (SFM) screening, the period of the transition to full-field digital mammography (FFDM) screening and the period of FFDM screening. We also investigated a possible association between the incidence and grading of screen-detected DCIS and invasive breast cancer. In the southern part of the Netherlands, FFDM screening gradually replaced SFM screening between May 2009 and April 2010. We included a consecutive series of 484, 422 screens obtained between July 2005 and July 2015 and divided these screens into three groups; SFM-only cohort, transition cohort and FFDM-only cohort. A total of 3059 referred women were diagnosed with DCIS (n=623) or invasive breast cancer (n=2436). The majority of DCIS were high-grade (48.2%), whereas the majority of the invasive breast cancers were low-grade (45.4%) or intermediate-grade (41.6%). The cancer detection rate (CDR) per 1000 screened women showed the same distribution by grade in both groups. The transition to FFDM was characterised by an increased overall detection rate of invasive cancers. Screening mammography detects mostly high-grade DCIS and low- or intermediate-grade invasive cancers. The grade distribution as well as the CDR in the years after the introduction of FFDM remained stable compared to the era of SFM screening. By diagnosing and treating high-grade DCIS, which otherwise may develop into high-grade invasive carcinoma, our findings provide new evidence for the beneficial value of screening mammography programmes.

Quantitative diagnosis of breast tumors by morphometric classification of microenvironmental myoepithelial cells using a machine learning approach

Machine learning systems have recently received increased attention for their broad applications in several fields. In this study, we show for the first time that histological types of breast tumors can be classified using subtle morphological differences of microenvironmental myoepithelial cell nuclei without any direct information about neoplastic tumor cells. We quantitatively measured 11661 nuclei on the four histological types: normal cases, usual ductal hyperplasia and low/high grade ductal carcinoma in situ (DCIS). Using a machine learning system, we succeeded in classifying the four histological types with 90.9% accuracy. Electron microscopy observations suggested that the activity of typical myoepithelial cells in DCIS was lowered. Through these observations as well as meta-analytic database analyses, we developed a paracrine cross-talk-based biological mechanism of DCIS progressing to invasive cancer. Our observations support novel approaches in clinical computational diagnostics as well as in therapy development against progression.

The Coexistence of Carcinoma and Tuberculosis in One Breast: A Case Report and Literature Review

IntroductionAlthough tuberculosis has been a very common disease in endemic areas, isolated involvement of the breast was uncommon. The coexistences of breast carcinoma and tuberculosis mastitis was very rare but could create a dilemma in the diagnosis and treatment, as there were usually no pathognomonic features to differentiate malignancy from breast tuberculosis.Case PresentationWe have reported the case of a 40-year-old woman referred with a painful lump in her left breast and nipple retraction. Mammography has shown an irregular mass and pleomorphic micro calcifications. Breast ultrasound has revealed a hypo echoic irregular mass. The first diagnosis was breast carcinoma. Histological study confirms high grade ductal carcinoma in situ. There was also evidence of tuberculosis mastitis at histological examination of the breast specimen.ConclusionBreast tuberculosis has known as a rare disease even in endemic countries. Coexistence of breast carcinoma and tuberculosis mastitis is very rare but it could lead to many problems regarding diagnosis and treatment.

Computer-aided heterogeneity analysis in breast MR imaging assessment of ductal carcinoma in situ: Correlating histologic grade and receptor status.

To identify breast MR imaging biomarkers to predict histologic grade and receptor status of ductal carcinoma in situ (DCIS). Informed consent was waived in this Health Insurance Portability and Accountability Act-compliant Institutional Review Board-approved study. Case inclusion was conducted from 7332 consecutive breast MR studies from January 1, 2009, to December 31, 2012. Excluding studies with benign diagnoses, studies without visible abnormal enhancement, and pathology containing invasive disease yielded 55 MR-imaged pathology-proven DCIS seen on 54 studies. Twenty-eight studies (52%) were performed at 1.5 Tesla (T); 26 (48%) at 3T. Regions-of-interest representing DCIS were segmented for precontrast, first and fourth postcontrast, and subtracted first and fourth postcontrast images on the open-source three-dimensional (3D) Slicer software. Fifty-seven metrics of each DCIS were obtained, including distribution statistics, shape, morphology, Renyi dimensions, geometrical measure, and texture, using the 3D Slicer HeterogeneityCAD module. Statistical correlation of heterogeneity metrics with DCIS grade and receptor status was performed using univariate Mann-Whitney test. Twenty-four of the 55 DCIS (44%) were high nuclear grade (HNG); 44 (80%) were estrogen receptor (ER) positive. Human epidermal growth factor receptor-2 (HER2) was amplified in 10/55 (18%), nonamplified in 34/55 (62%), unknown/equivocal in 8/55 (15%). Surface area-to-volume ratio showed significant difference (P < 0.05) between HNG and non-HNG DCIS. No metric differentiated ER status (0.113 < p ≤ 1.000). Seventeen metrics showed significant differences between HER2-positive and HER2-negative DCIS (0.016 < P < 0.050). Quantitative heterogeneity analysis of DCIS suggests the presence of MR imaging biomarkers in classifying DCIS grade and HER2 status. Validation with larger samples and prospective studies is needed to translate these results into clinical applications. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1748-1759.

The outcome of papillary lesions of the breast diagnosed by standard core needle biopsy within a BreastScreen Australia service

Papillary lesions of the breast are most commonly diagnosed via mammographic screening. The standard practice has been to excise these lesions, since a subset of papillary lesions are neoplastic. However, this approach leads to a high proportion of negative excisions. In order to identify papillary lesions which could be managed by surveillance alone, we assessed the outcome of 103 papillary lesions diagnosed on core needle biopsy in a public screening program. Subsequent excision biopsy led to an upgrade to malignancy in 30% of cases. Segregation via presence or absence of atypia stratified the outcome into 72% upgrade, compared with 7% upgrade, respectively. Further, in the latter group (i.e., no atypia on core needle biopsy with 7% upgrade to malignancy), the neoplasia found in the targeted excision area was low to intermediate grade ductal carcinoma in situ only, with no invasive neoplasia (4 cases). Of the lesions identified due to microcalcification, the microcalcification was present within an adjacent benign lesion in 35% of cases and hence the papillary lesion was detected incidentally. Overall therefore, we have identified a cohort of papillary lesions in which conservative management, rather than excision, could be considered, i.e., those without atypia, including those without atypia in which the papillary lesion was found incidental to microcalcification in an adjacent benign lesion.