Strategies for modeling aging and age-related diseases.

The ability to reprogram patient-derived-somatic cells to IPSCs (Induced Pluripotent Stem Cells) has led to a better understanding of aging and age-related diseases like Parkinson's, and Alzheimer's. The established patient-derived disease models mimic disease pathology and can be used to design drugs for aging and age-related diseases. However, the age and genetic mutations of the donor cells, the employed reprogramming, and the differentiation protocol might often pose challenges in establishing an appropriate disease model. In this review, we will focus on the various strategies for the successful reprogramming and differentiation of patient-derived cells to disease models for aging and age-related diseases, emphasizing the accuracy in the recapitulation of disease pathology and ways to overcome the limitations of its potential application in cell replacement therapy and drug development.

Added value of the EUSOBI diffusion levels in breast MRI.

OBJECTIVES: To investigate whether using the diffusion levels (DLs) proposed by the European Society of Breast Imaging (EUSOBI) improves the diagnostic accuracy of breast MRI. MATERIALS AND METHODS: This retrospective study included 145 women who, between September 2019 and June 2020, underwent breast 1.5-T MRI with DWI. Reader 1 and reader 2 (R1-R2) independently assessed breast lesions using the BI-RADS on dynamic contrast-enhanced imaging and T2-weighted imaging. DWI was subsequently disclosed, allowing readers able to measure lesions ADC and subjectively express the overall risk of malignancy on a 1-5 Likert scale. ADCs were interpreted as a range of values corresponding to the EUSOBI DLs. The analysis evaluated the inter-reader agreement in measuring ADC and DLs, the per-DL malignancy rate, and accuracy for malignancy using ROC analysis against histological examination or a 3-year follow-up. RESULTS: Lesions were malignant and showed non-mass enhancement in 67.7% and 76.1% of cases, respectively. ADC was measurable in 63.2%/66.7% of lesions (R1/R2), with a minimal discrepancy on Bland-Altman analysis and 0.948 (95%CI 0.925-0.965)/0.989 (95%CI 0.988-0.991) intraclass correlation coefficient in measuring ADC/DLs. The malignancy rate (R1/R2) increased from 0.5/0.5% ("very high" DL) to 96.0/96.8% ("very low" DL), as expected. Likert categorization showed larger areas under the curve than the BI-RADS for both R1 (0.91 versus 0.87; p = 0.0208) and R2 (0.91 versus 0.89; p = 0.1171), with improved specificity (81.5% versus 78.5% for R1 and 84.4% versus 81.2% for R2). CONCLUSION: Though ADC was not measurable in about one-third of lesions, DLs were categorized with excellent inter-reader agreement, improving the specificity for malignancy. CLINICAL RELEVANCE STATEMENT: DLs proposed by the EUSOBI are a reproducible tool to interpret the ADC of breast lesions and, in turn, to improve the specificity of breast MRI and reduce unnecessary breast biopsies. KEY POINTS: • The European Society of Breast Imaging proposed diffusion levels for the interpretation of the apparent diffusion coefficient in diffusion-weighted imaging of the breast. • Adding diffusion levels to the interpretation of magnetic resonance imaging improved the diagnostic accuracy for breast cancer, especially in terms of specificity. • Diffusion levels can favor a more widespread and standardized use of diffusion-weighted imaging of the breast.

Pathological outcome of sonographically occult architectural distortions (AD) visible only on digital breast tomosynthesis, and comparison with AD visible also on 2D mammography.

PURPOSE: To evaluate the rates of malignant and of high-risk lesions among sonographically occult architectural distortions (AD) visible only on digital breast tomosynthesis (DBT) and compare them with AD visible on 2D mammography (2D) and DBT. METHOD: The records of 1104 DBT-vacuum assisted biopsies (DBT-VAB) were retrospectively reviewed and 218 cases of AD were identified. Complete radiologic examinations and pathologic results were available for 113 sonographically occult AD (1 clinically-detected, 112 clinically-occult). 2D and DBT images were reviewed and AD were divided into a "DBT-detected" group (visible on only DBT) and a "2D-detected" group (visible both in 2D and DBT). The rates of malignant and of high-risk lesions in the "DBT-detected" AD group were calculated and compared to those of the "2D-detected" AD group. RESULTS: Thirty-five (31%) of 113 AD were assessed as "DBT-detected", while 78 (69%) as "2D-detected". DBT-VAB results were benign lesions in 63 (56%) AD, high-risk lesions in 32 (28%) AD and malignant lesions in 18 (16%) AD. Four (12.5%) high-risk lesions were upgraded to malignancy at surgery. Based on final pathology, the malignancy rate was significantly higher in the "DBT-detected" group than the "2D-detected" group (34% [12/35 cases] vs 13% [10/78]; p < 0.05). The high-risk lesion rates were 32% (11/35 cases) in the "DBT-detected" group and 22% (17/78 cases) in the "2D-detected" group (p > 0.05). CONCLUSIONS: AD visible on only DBT proved to be malignant in about one third of cases, which exceeded the malignancy rate of AD visible on also 2D. A similar proportion of DBT-only AD was represented by high-risk lesions.

Multireader comparison of contrast-enhanced mammography versus the combination of digital mammography and digital breast tomosynthesis in the preoperative assessment of breast cancer.

PURPOSE: To compare preoperative contrast-enhanced spectral mammography (CEM) versus digital mammography plus digital breast tomosynthesis (DM + DBT) in detecting breast cancer (BC) and assessing its size. MATERIAL AND METHODS: We retrospectively included 78 patients with histological diagnosis of BC who underwent preoperative DM, DBT, and CEM over one year. Four readers, blinded to pathology and clinical information, independently evaluated DM + DBT versus CEM to detect BC and measure its size. Readers' experience ranged 3-10 years. We calculated the per-lesion cancer detection rate (CDR) and the complement of positive predictive value (1-PPV) of both methods, stratifying analysis on the total of lesions, index lesions, and additional lesions. The agreement in assessing cancer size versus pathology was assessed with Bland-Altman analysis. RESULTS: 100 invasive BCs (78 index lesions and 22 additional lesions) were analyzed. Compared to DM + DBT, CEM showed higher overall CDR in less experienced readers (range 0.85-0.90 vs. 0.95-0.96), and higher CDR for additional lesions, regardless of the reader (range 0.54-0.68 vs. 0.77-0.86). CEM increased the detection of additional disease in dense breasts in all readers and non-dense breasts in less experienced readers only. The 1-PPV of CEM (range 0.10-0.18) was comparable to that of DM + DBT (range 0.09-0.19). At Bland-Altman analysis, DM + DBT and CEM showed comparable mean differences and limits of agreement in respect of pathologic cancer size. CONCLUSION: Preoperative CEM improved the detection of additional cancer lesions compared to DM + DBT, particularly in dense breasts. CEM and DM + DBT achieved comparable performance in cancer size assessment.

Impact of HDAC Inhibitors on Protein Quality Control Systems: Consequences for Precision Medicine in Malignant Disease.

Lysine acetylation is one of the major posttranslational modifications (PTM) in human cells and thus needs to be tightly regulated by the writers of this process, the histone acetyl transferases (HAT), and the erasers, the histone deacetylases (HDAC). Acetylation plays a crucial role in cell signaling, cell cycle control and in epigenetic regulation of gene expression. Bromodomain (BRD)-containing proteins are readers of the acetylation mark, enabling them to transduce the modification signal. HDAC inhibitors (HDACi) have been proven to be efficient in hematologic malignancies with four of them being approved by the FDA. However, the mechanisms by which HDACi exert their cytotoxicity are only partly resolved. It is likely that HDACi alter the acetylation pattern of cytoplasmic proteins, contributing to their anti-cancer potential. Recently, it has been demonstrated that various protein quality control (PQC) systems are involved in recognizing the altered acetylation pattern upon HDACi treatment. In particular, molecular chaperones, the ubiquitin proteasome system (UPS) and autophagy are able to sense the structurally changed proteins, providing additional targets. Recent clinical studies of novel HDACi have proven that proteins of the UPS may serve as biomarkers for stratifying patient groups under HDACi regimes. In addition, members of the PQC systems have been shown to modify the epigenetic readout of HDACi treated cells and alter proteostasis in the nucleus, thus contributing to changing gene expression profiles. Bromodomain (BRD)-containing proteins seem to play a potent role in transducing the signaling process initiating apoptosis, and many clinical trials are under way to test BRD inhibitors. Finally, it has been demonstrated that HDACi treatment leads to protein misfolding and aggregation, which may explain the effect of panobinostat, the latest FDA approved HDACi, in combination with the proteasome inhibitor bortezomib in multiple myeloma. Therefore, proteins of these PQC systems provide valuable targets for precision medicine in cancer. In this review, we give an overview of the impact of HDACi treatment on PQC systems and their implications for malignant disease. We exemplify the development of novel HDACi and how affected proteins belonging to PQC can be used to determine molecular signatures and utilized in precision medicine.

Preoperative assessment of breast cancer: Multireader comparison of contrast-enhanced MRI versus the combination of unenhanced MRI and digital breast tomosynthesis.

PURPOSE: To compare the sensitivity for breast cancer (BC) and BC size estimation of preoperative contrast-enhanced magnetic resonance imaging (CEMRI) versus combined unenhanced magnetic resonance imaging (UMRI) and digital breast tomosynthesis (DBT). PATIENTS AND METHODS: We retrospectively included 56 women who underwent DBT and preoperative 1.5 T CEMRI between January 2016-February 2017. Three readers with 2-10 years of experience in CEMRI and DBT, blinded to pathology, independently reviewed CEMRI (diffusion-weighted imaging [DWI], T2-weighted imaging, pre- and post-contrast T1-weighted imaging) and a combination of UMRI (DWI and pre-contrast T1-weighted imaging) and DBT. We calculated per-lesion sensitivity of CEMRI and UMRI + DBT, and the agreement between CEMRI, UMRI and DBT versus pathology in assessing cancer size (Bland-Altman analysis). Logistic regression was performed to assess features predictive of cancer missing. RESULTS: We included 70 lesions (64% invasive BC, 36% ductal carcinoma in situ or invasive BC with in situ component). UMRI + DBT showed lower sensitivity (86-89%) than CEMRI (94-100%), with a significant difference for the most experienced reader only (p = 0.008). False-positives were fewer with UMRI + DBT (4-5) than with CEMRI (18-25), regardless of the reader (p = 0.001-0.005). For lesion size, UMRI showed closer limits of agreement with pathology than CEMRI or DBT. Cancer size ≤1 cm was the only independent predictor for cancer missing for both imaging strategies (Odds ratio 8.62 for CEMRI and 19.16 for UMRI + DBT). CONCLUSIONS: UMRI + DBT showed comparable sensitivity and less false-positives than CEMRI in the preoperative assessment of BC. UMRI was the most accurate tool to assess cancer size.

Do clinical and radiologic features help predict malignancy of B3 breast lesions without epithelial atypia (B3a)?

OBJECTIVES: To evaluate excision histology outcome of B3a lesions diagnosed at imaging-guided core biopsy and assess whether clinical and radiologic features may predict upgrade to malignancy. METHODS: A total of 153 B3a lesions (74 papillomas, 51 radial scars and 28 fibro-epithelial lesions) that underwent surgical excision were assessed. PPV for malignancy in all B3a lesions and specific for each sub-category was evaluated. Multivariate analysis was conducted to identify association between clinical (age, family or personal history of breast cancer, symptoms), diagnostic findings (imaging modality, lesion size, final BI-RADS category) and final excision outcome. RESULTS: Eleven (7%) of 153 B3a lesions were upgraded to malignancy. All carcinomas diagnosed on excision were non-high grade DCIS. Following features were significantly associated with malignancy: lesions identified only on mammography (3/21; 14%), both mammography and ultrasound (7/44; 16%), lesion size > 10 mm (10/74; 13.5%) and BI-RADS category 4-5 (8/29; 27.6%). The absence of residual microcalcification after biopsy was associated with decreased risk for malignancy (15/16[93.7%]; p = 0.0297). Lesion size > 10 mm (OR = 9.3832; 95%; p = 0.0398) and BI-RADS category 4-5 (OR = 12.6004; 95%; p = 0.0006) were found to be independent predictors of upgrade to malignancy. CONCLUSIONS: B3a lesions are associated with low risk of malignancy at excision. Lesion size > 10 mm and BI-RADS 4-5 category may represent useful predictors of upgrade to malignancy.

Automated breast ultrasound: basic principles and emerging clinical applications.

Automated breast ultrasound (ABUS) is a recently introduced ultrasonography technique, developed with the purpose to standardize breast ultrasonography and overcome some limitations of handheld ultrasound (HHUS), such as operator dependence and the considerable amount of medical time necessary to perform and interpret HHUS. This new ultrasonography technique separates the moment of image acquisition (that may be performed also by a technician) from that of its interpretation, increasing reproducibility, reducing operator-dependence and physician time. Moreover, multiplanar reconstructions, especially the coronal view, introduce new diagnostic information. ABUS, with those advantages, has the potential to be used as an adjunctive tool to screening mammography, especially in the dense breast, where mammography has a relatively low sensitivity. Women's awareness of risks related to breast density is a hot topic, especially in the USA where legislative breast density notification laws increase the demand for supplemental ultrasound screening. Therefore, ABUS might have the potential to respond to this need. The purpose of this article is to present a summary of current state-of-the-art of ABUS technology and applications, with an emphasis on breast cancer screening. This article discusses also how to overcome some ABUS limitations, in order to be familiar with the new technique.

Automated breast volume scanner (ABVS) in assessing breast cancer size: A comparison with conventional ultrasound and magnetic resonance imaging.

OBJECTIVES: To compare automated breast volume scanner (ABVS), ultrasound (US) and MRI in measuring breast cancer size, and evaluate the agreement between ABVS and US in assessing lesion location and sonographic features. METHODS: We retrospectively included 98 women with 100 index cancers who had undergone US and ABVS followed by 1.5T MRI. Images were interpreted by a pool of readers reporting lesion size, location and breast imaging reporting and data system (BI-RADS) features. Bland-Altman analysis (with logarithmic data transformation), intraclass correlation coefficient (ICC) and Cohen's kappa statistic were used for statistical analysis. RESULTS: MRI showed the best absolute agreement with histology in measuring cancer size (ICC 0.93), with LOA comparable to those of ABVS (0.63-1.99 vs. 0.52-1.73, respectively). Though ABVS and US had highly concordant measurements (ICC 0.95), ABVS showed better agreement with histology (LOA 0.52-1.73 vs. 0.45-1.86, respectively), corresponding to a higher ICC (0.85 vs. 0.75, respectively). Except for posterior features (k=0.39), the agreement between US and ABVS in attributing site and BI-RADS features ranged from substantial to almost perfect (k=0.68-0.85). CONCLUSIONS: ABVS performs better than US and approaches MRI in predicting breast cancer size. ABVS performs comparably to US in sonographic assessment of lesions. KEY POINTS: • ABVS approaches MRI in predicting breast cancer size. • ABVS is equivalent to US in localising and characterising breast cancer. • ABVS is more accurate than US in assessing breast cancer size. • ABVS has the potential to replace US in breast cancer staging.

MR mammography using diffusion-weighted imaging in evaluating breast cancer: a correlation with proliferation index.

PURPOSE: To evaluate whether the variation of the apparent diffusion coefficient (ADC) values obtained with DWI can predict elevated levels of Ki67 proliferation index and aggressive subtypes in patients with breast cancer. MATERIALS AND METHODS: Breast MRI studies of 115 patients (mean age 57.3 years, range 36-81 years) with a biopsy-proven breast cancers were evaluated in this retrospective IRB-approved study. Examinations were performed on a 1.5 T magnet and included a Single-Shot Echoplanar DWI sequence with b values of 0 and 1000 s/mm(2). For each target lesion, ADC was measured. ADC values were compared considering Ki67 status (≥20 % or <20 %), histology, grade (G1, G2 or G3) and clinical-pathological classification (Luminal A, Luminal B HER2-positive, Luminal B HER-2 negative, HER-2 enriched and Triple Negative). Mann-Whitney U test and Kruskal-Wallis test were used for comparisons and receiver operating characteristic (ROC) curves were obtained. Inter- and intra-reader variability was evaluated in a subset of 40 patients, using interclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS: Of 115 lesions, 53 (46.1 %) were assessed as Ki67 positive and 62 (53.9 %) as Ki67 negative. ADC values were significantly (p < 0.0001) lower in Ki67-positive patients (median 0.86 × 10(-3) mm(2)/s; interquartile range 0.75-0.92) compared to Ki67-negative (median 1.03 × 10(-3) mm(2)/s; interquartile range 0.92-1.13). Median ADC was also lower in G2 and G3 cancer and in the Luminal B Her2-negative subtype (p = 0.0015). No differences were found when evaluating histology. ROC curve showed a sensitivity and specificity of 83.0 and 66.1 %, respectively, when using a cutoff of 0.95 s/mm(2) to differentiate Ki67-positive from Ki67-negative cancers. Inter- and intra-reader variability was moderate (ICC = 0.623; ICC = 0.548, respectively). No systematic differences were identified with Bland-Altman plots. CONCLUSIONS: Lower ADC values are associated with elevated Ki67 proliferation index and more aggressive pathologic features. Moderate agreement in ADC measurement could be a limitation.

Role of magnetic resonance imaging in probably benign (BI-RADS category 3) microcalcifications of the breast.

PURPOSE: This study was undertaken to evaluate whether magnetic resonance (MR) imaging is able to rule out malignancy in the case of BI-RADS 3 microcalcifications, providing a sufficient negative predictive value (NPV) for early work-up, and to reduce unnecessary stereotactically guided vacuum-assisted biopsy (SVAB) procedures. MATERIALS AND METHODS: We prospectively enrolled consecutive women with BI-RADS 3 microcalcifications, who subsequently underwent MR imaging and SVAB. The MR studies were reviewed according to the MR-BI-RADS classification system; lesions assessed as MR-BI-RADS 1 and 2 were considered negative for malignancy, categories MR-BI-RADS 3, 4 and 5 indicated malignant lesions. The presence of additional findings was recorded. Histologic analysis and follow-up were the reference standard. MR sensitivity, specificity, positive predictive value (PPV) and NPV were calculated. RESULTS: The final population consisted of 71 lesions. Histologic analysis showed malignancy in six cases (malignancy rate 8%). At MR analysis, 60 (85%) lesions were considered negative for malignancy and 11 (15%) malignant. Additional MR imaging findings were identified in 19 (27%) patients, all corresponding to nonmalignant lesions. MR sensitivity was 33%, specificity 86%, PPV 18% and NPV 93%. CONCLUSIONS: Because of its relatively low NPV, MR imaging is not able to safely exclude malignancy in the case of BI-RADS 3 microcalcifications. The relatively high malignancy rate found in this study might support SVAB in the case of BI-RADS 3 microcalcifications.

High-risk breast lesions at imaging-guided needle biopsy: usefulness of MRI for treatment decision.

OBJECTIVE: The purpose of this study is to evaluate the role of MRI for characterization of high-risk breast lesions diagnosed at imaging-guided needle biopsy. MATERIALS AND METHODS: In this retrospective analysis of 220 patients, 227 high-risk lesions (94 papillomas, 64 radial sclerosing lesions, 46 lobular neoplasias, and 23 atypical ductal hyperplasias) found at 11-gauge vacuum-assisted or 14-gauge needle biopsy were studied with dynamic MRI (time resolution, 84 or 88 seconds; gadopentetate dimeglumine or gadobenate dimeglumine, 0.1 mmol/kg). When lesions showed contrast enhancement on subtracted images, they were considered suspicious for malignancy. The reference standard was histopathologic examination after surgical excision in 190 of 227 (84%) lesions and negative follow-up (≥ 24 months) in 37 of 227 (16%) lesions. Predictive values and likelihood ratios were calculated. RESULTS: Of 227 lesions, 155 (68%) were contrast enhancing and 72 (32%) were not. Of 155 contrast-enhancing lesions, 28 (18%) were upgraded to malignancy after surgical excision (nine papillomas, one radial sclerosing lesion, 11 lobular neoplasias, and seven atypical ductal hyperplasias); there were 11 invasive carcinomas and 17 ductal carcinomas in situ, four of the latter being G3. Of 72 non-contrast-enhancing lesions, two (3%) were upgraded to malignancy after surgical excision (one radial sclerosing lesion and one lobular neoplasia), both of which were G1 ductal carcinoma in situ. Cancer probability was significantly higher for contrast-enhancing (18%) than for non-contrast-enhancing (3%) lesions (p = 0.001) and for nonmasslike (43%) than for masslike (14%) lesions (p = 0.005). The positive predictive value was 18% (28/155; 95% CI, 13-24%), the negative predictive value was 97% (70/72; 95% CI, 94-99%), the positive likelihood ratio was 1.448 (95% CI, 1.172-1.788), and the negative likelihood ratio was 0.188 (95% CI, 0.152-0.232). CONCLUSION: The absence of enhancement at dynamic MRI allowed reliable exclusion of invasive cancers among high-risk lesions diagnosed at needle biopsy.

Magnetic resonance imaging of radial sclerosing lesions (radial scars) of the breast.

PURPOSE: To identify magnetic resonance (MR) imaging (MRI) features of radial sclerosing lesions (RSLs) of the breast. METHODS AND MATERIALS: The radiologic and pathologic records for 4629 consecutive patients undergoing MR examinations of the breast were retrospectively reviewed. Patients who received a pathologic diagnosis of RSL without atypia or carcinoma at surgical excision were identified. The MR images were evaluated according to the BI-RADS-MRI lexicon by two experienced breast radiologists. The frequency of morphologic and kinetic patterns and of BI-RADS-MRI assessment categories was calculated. RESULTS: Twenty-nine patients with 29 surgically excised RSL were identified. Nine (31%) RSL were MR-occult; the remaining 20 (69%) RSL presented as masses (10/20, 50%), architectural distortions (5/20, 25%), non-mass lesions (4/20, 20%), and focus (1/20, 5%). Kinetic analysis was performed in 18 RSL: enhancement features were benign in 9 (50%) cases, suspicious in 7 (39%) cases and indeterminate in 2 (11%) cases. Twelve (41%) MR examinations were assessed as suspicious (BI-RADS-MRI 4 and 5), and 17 (59%) as negative (BI-RADS-MRI 1) or benign (BI-RADS-MRI 2 and 3). CONCLUSION: RSLs are often visualized on MR imaging. Just as in mammography and sonography, RSL can have variable morphologic and kinetic features, and not infrequently they can mimic invasive carcinoma of the breast.

Nonsurgical management of high-risk lesions diagnosed at core needle biopsy: can malignancy be ruled out safely with breast MRI?

OBJECTIVE: The purpose of this study was to investigate whether breast MRI can be used to rule out malignancy in patients with high-risk lesions diagnosed at imaging-guided core needle biopsy. SUBJECTS AND METHODS: The subjects were women consecutively registered between October 2004 and April 2010 who had high-risk lesions diagnosed at mammographically or sonographically guided core needle biopsy and subsequently underwent MRI and surgical excision. MR images were reviewed by two experienced breast radiologists. Lesions assessed as BI-RADS category 1-3 were considered negative for malignancy, and BI-RADS 4 and 5 lesions were considered malignant. Histologic findings at surgical excision were the reference standard. The sensitivity, specificity, and positive and negative predictive values of MRI in the detection of associated malignancy were calculated for the entire set of lesions and for each histologic subtype. RESULTS: The final sample consisted of 169 high-risk lesions in 166 patients. At MRI analysis, 116 (68.6%) lesions were considered negative for malignancy, and the other 53 (31.4%) malignant. At surgical excision, 22 malignant lesions were found. The overall sensitivity, specificity, and positive and negative predictive values of MRI were 72.7% (16/22), 74.8% (110/147), 30.2% (16/53), and 94.8% (110/116). The negative predictive values for papilloma, radial scar, lobular neoplasia, and atypical ductal hyperplasia were 97.4% (38/39), 97.6% (41/42), 88.0% (22/25), and 90.0% (9/10). CONCLUSION: Patients with high-risk lesions associated with the lowest likelihood of malignancy (papilloma and radial scar) and without suspicious MRI findings can safely undergo follow-up instead of surgery. Because of the low negative predictive value, however, MRI is not helpful in cases of lobular neoplasia and atypical ductal hyperplasia, and all these lesions should be excised.

Hyperechoic lesions of the breast: not always benign.

OBJECTIVE: The purposes of our study were, first, to evaluate the frequency, clinical presentation, and associated imaging findings of malignant breast lesions presenting as hyperechoic nodules in a large series of consecutive sonographically guided core needle biopsies (CNBs) and, second, to investigate sonographic features that are able to predict malignancy in hyperechoic breast lesions. MATERIALS AND METHODS: The radiologic and pathologic records for 4511 consecutive sonographically guided CNBs were retrospectively reviewed. Hyperechoic lesions were identified, and clinical notes and related mammography or MRI reports were reviewed. The sonographic images were evaluated according to the BI-RADS lexicon by two experienced breast radiologists. Surgical pathology results and follow-up served as the reference standard for lesions diagnosed as malignant or high-risk and benign at CNB, respectively. The frequency of hyperechoic carcinomas among all carcinomas was calculated. Differences in sonographic appearance between hyperechoic benign and malignant lesions were evaluated using the chi-square test or the Fisher exact test. RESULTS: Of all biopsied lesions, 25 (0.6%) were hyperechoic. Among the 1849 malignant lesions, nine (0.4%) were hyperechoic. The remaining 16 were benign. None of the hyperechoic malignancies was a "purely" sonographic lesion, because all were palpable, mammographically visible, or detectable on breast MRI. Malignant lesions were more likely than benign lesions to have noncircumscribed margins (9/9 vs 7/16; p = 0.008) and nonparallel orientation (6/9 vs 1/16; p = 0.003). CONCLUSION: When encountering a hyperechoic nodule, malignant nature cannot be excluded. Suspicious sonographic signs and correlation with other imaging techniques may help avoid misdiagnosis.

Borderline breast lesions: comparison of malignancy underestimation rates with 14-gauge core needle biopsy versus 11-gauge vacuum-assisted device.

OBJECTIVE: To compare malignancy underestimation rates in the case of percutaneous diagnosis of borderline breast lesions(B3) at 14-g core-needle-biopsy (CNB) and at 11-g vacuum-assisted-biopsy (VAB). METHODS: The histological results of 4764 image-guided breast biopsies were retrospectively reviewed. 300 B3, 151 benign papillomas, 88 radial sclerosing lesions, 46 lobular neoplasia, 15 atypical ductal hyperplasia diagnosed at ultrasound-guided 14-g CNB (76%) or stereotactically-guided 11-g VAB (24%) were identified. On average, 5 cores were obtained with CNB and 12 with VAB. Biopsy variables were reviewed and correlated with surgical excision or follow-up (>24 months). Lesion- and device-specific underestimation rates of malignancy were calculated. RESULTS: Surgical excision was performed on 237 lesions: 178 were benign, 21 atypical, 38 cancers. The remaining 63 lesions were unchanged at follow-up. Overall malignancy underestimation rate was 12.7% at 14-g CNB and 12.5% at 11-g VAB. Based on excision histology or follow-up, lesion-specific underestimation rates were: benign papillomas: 14-g CNB 11%, 11-g VAB 0%; RSL: 14-g CNB 6%, 11-g VAB 4%; LN: 14-g CNB 40%, 11-g VAB 23%; ADH: 14-g CNB 33%; 11-g VAB 22%. CONCLUSION: In the case of percutaneous diagnosis of B3 lesions, underestimation of malignancy occurs regardless of the biopsy method.

Radiation injury of the lung after stereotactic body radiation therapy (SBRT) for lung cancer: a timeline and pattern of CT changes.

Stereotactic body radiation therapy (SBRT) is a new radiotherapy treatment method that has been applied to the treatment of Stage I lung cancers in medically inoperable patients, with excellent clinical results. SBRT allows the delivery of a very high radiation dose to the target volume, while minimizing the dose to the adjacent normal tissues. As a consequence, CT findings after SBRT have different appearance, geographic extent and progression timeline compared to those following conventional radiation therapy for lung cancer. In particular, SBRT-induced changes are limited to the "shell" of normal tissue outside the tumor and have a complex shape. When SBRT-induced CT changes have a consolidation/mass-like appearance, the differentiation from tumor recurrence can be very difficult. An understanding of SBRT technique as it relates to the development of SBRT-induced lung injury and familiarity with the full spectrum of CT manifestations are important to facilitate diagnosis and management of lung cancer patients treated with this newly emerging radiotherapy method.

Magnetic resonance imaging in patients with nipple discharge: should we recommend it?

OBJECTIVES: Comparing the sensitivity of Contrast-Enhanced Magnetic Resonance Imaging (CEMRI), mammography and ultrasonography in patients with nipple discharge (ND). METHODS: We retrospectively evaluated 38 women with ND who underwent mammography, ultrasound and 1.5 T CEMRI between March 2007 and July 2009. Imaging findings, pathological diagnosis and follow-up data (mean follow-up: 20 months) were compared. Sensitivity and specificity values were reckoned. Statistical differences in sensitivity were assessed. RESULTS: 5/38 malignancies (13.2%; 3 invasive, 2 intraductal; 4 ipsilateral, 1 contralateral to ND), and 14/38 High-Risk Lesion (HRL--36.8%; 11 intraductal papillomas, 1 papilloma with LCIS, 1 sclerosing papilloma and 1 atypical intraductal hyperplasia, all ipsilateral) were found. CEMRI identified 5/5 cancers and 13/14 HRL (Overall Sensitivity-OSS = 94.7%; Overall Specificity-OSP = 78.9%). 3/5 cancers (1 invasive, 1 in-situ; 1 invasive contralateral) and 2/14 HRL were detected by CEMRI only. Mammography found 2/5 cancer and 3/14 HRL (OSS = 26.3%; OSP = 94.7%). Ultrasound identified 1/5 cancer and 11/14 HRL (OSS = 63.2%; OSP = 84.2). 1/14 HRL was detected by ultrasound only. Compared with mammography and ultrasound, CEMRI showed statistically significantly higher OSS values (p < 0.0001, p = 0.042 respectively). CONCLUSION: In women with ND, CEMRI should be recommended when conventional imaging is negative. Unexplained ND could be considered an indication for CEMRI.