Prospective Study of Supplemental Screening With Contrast-Enhanced Mammography in Women With Elevated Risk of Breast Cancer: Results of the Prevalence Round.

PURPOSE: Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients. MATERIALS AND METHODS: A prospective, single-institution, institutional review board-approved observational study was conducted in asymptomatic elevated risk women age 35 years or older who had a negative conventional two-dimensional digital breast tomosynthesis screening mammography (MG) and no additional supplemental screening within the prior 12 months. RESULTS: Four hundred sixty women were enrolled from February 2019 to April 2021. The median age was 56.8 (range, 35.0-79.2) years; 408 of 460 (88.7%) were mammographically dense. Biopsy revealed benign changes in 22 women (22/37, 59%), high-risk lesions in four women (4/37, 11%), and breast cancer in 11 women (11/37, 30%). Fourteen cancers (10 invasive, tumor size range 4-15 mm, median 9 mm) were diagnosed in 11 women. The overall supplemental cancer detection rate was 23.9 per 1,000 patients, 95% CI (12.0 to 42.4). All cancers were grade 1 or 2, ER+ ERBB2-, and node negative. CEM imaging screening offered high specificity (0.875 [95% CI, 0.844 to 0.906]), high NPV (0.998 [95% CI, 0.993 to 1.000), moderate PPV1 (0.164 [95% CI, 0.076 to 0.253), moderate PPV3 (0.275 [95% CI, 0.137 to 0.413]), and high sensitivity (0.917 [95% CI, 0.760 to 1.000]). At least 1 year of imaging follow-up was available on all patients, and one interval cancer was detected on breast MRI 4 months after negative screening CEM. CONCLUSION: A pilot trial demonstrates a supplemental cancer detection rate of 23.9 per 1,000 in women at an elevated risk for breast cancer. Larger, multi-institutional, multiyear CEM trials in patients at elevated risk are needed for validation.

Biliary Disorders, Anomalies, and Malignancies in Children.

Biliary abnormalities in children are uncommon, and the spectrum of biliary disorders is broader than in adult patients. Unlike in adults, biliary disorders in children are rarely neoplastic and are more commonly rhabdomyosarcoma rather than cholangiocarcinoma. Pediatric biliary disorders may be embryologic or congenital, such as anatomic gallbladder anomalies, anomalous pancreaticobiliary tracts, various cholestatic processes, congenital cystic lesions, or genetic conditions. They may also be benign, such as biliary filling anomalies, biliary motility disorders, and biliary inflammatory and infectious disorders. Distinguishing these entities with a single imaging modality is challenging. US is the primary imaging modality for initial evaluation of biliary abnormalities in children, due to its wide availability, lack of ionizing radiation, and low cost and because it requires no sedation. Other examinations such as MRI, CT, and nuclear medicine examinations may provide anatomic and functional information to narrow the diagnosis further. Hepatobiliary-specific contrast material with MRI can provide better assessment of biliary anatomy on delayed images than can traditional MRI contrast material. MR cholangiopancreatography (MRCP) allows visualization of the intra- and extrahepatic biliary ducts, which may not be possible with endoscopic retrograde cholangiopancreatography (ERCP). Suspected biliary atresia requires multiple modalities for diagnosis and timely treatment. Determining the type of choledochal cyst calls for a combination of initial US and MRCP. Many benign and malignant biliary masses require biopsy for definitive diagnosis. Knowledge of the imaging appearances of different pediatric biliary abnormalities is necessary for appropriate imaging workup, providing a diagnosis or differential diagnosis, and guiding appropriate management. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Imaging Characteristics of and Multidisciplinary Management Considerations for Atypical Ductal Hyperplasia and Flat Epithelial Atypia: Review of Current Literature.

High-risk lesions of the breast are frequently encountered in percutaneous biopsy specimens. While benign, these lesions have historically undergone surgical excision due to their potential to be upgraded to malignancy. However, there is emerging evidence that a tailored management approach should be considered to reduce overtreatment of these lesions. Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are two of the most commonly encountered high-risk lesions. FEA has been shown to have a relatively low rate of progression to malignancy, and some guidelines are now recommending observation over routine excision in select cases. Selective observation may be reasonable in cases where the target lesion is small and completely removed at biopsy and when there are no underlying risk factors, such as a history of breast cancer or genetic mutation or concurrent ADH. ADH has the highest potential upgrade rate to malignancy of all the high-risk lesions. Most society guidelines continue to recommend surgical excision of this lesion. More recently, some literature suggests that ADH lesions that appear completely removed at biopsy, involve limited foci (less than two or three) with no necrosis or significant atypia, manifest as a small group of mammographic calcifications, or demonstrate no enhancement at MRI may be reasonable for observation. Ultimately, management of all high-risk lesions must be based on a multidisciplinary approach that considers all patient, radiologic, clinical, and histopathologic factors. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

MRI phenotypes associated with breast cancer predisposing genetic variants, a multisite review.

PURPOSE: Examine MRI phenotypes of breast cancers arising in patients with various pathogenic variants, to assess for imaging trends and associations. METHOD: Multisite retrospective review evaluated 410 patients from 2001 to 2020 with breast cancer and a predisposing pathogenic variant who underwent breast MRI at time of cancer diagnosis. Dominant malignant lesion features were reported, including lesion type (mass versus non-mass enhancement), size, shape, margin, internal enhancement pattern, plus other features. Kruskal-Wallis test, Fisher's exact test, and pairwise comparisons performed comparing imaging manifestations for the most frequent genetic results. RESULTS: BRCA1 (29.5 %) and BRCA2 (25.9 %) variants were most common, followed by CHEK2 (16.6 %), ATM (8.0 %), and PALB2 (6.3 %), with significant associated differences in race/ethnicity (p = 0.040), age at cancer diagnosis (p = 0.005), tumor shapes (p = 0.001), margins (p < 0.001), grade (p < 0.001), internal enhancement pattern (rim enhancement) (p < 0.001), kinetics (washout) (p < 0.001), and presence of necrosis (p < 0.001). CHEK2 and ATM tumors were often lower grade with spiculated margins (CHEK2: 47.1 %, ATM: 45.5 %), rarely exhibiting washout or tumor necrosis (p < 0.001), and were mostly comprised of luminal molecular subtypes (CHEK2: 88.2 %, ATM: 90.9 %). BRCA1 tumors had the highest proportions with round shape (31.4 %), circumscribed margins (24.0 %), rim enhancement (24.0 %), washout (58.7 %), and necrosis (19.8 %), with 47.9 % comprised of triple negative subtype. Bilateral mastectomy was performed in higher proportions of patients with BRCA1 (84.3 %) and BRCA2 (75.5 %) variants compared to others. CONCLUSIONS: Genetic and molecular profiles of breast cancers demonstrate reproducible MRI phenotypes.

Pictorial Review of Common and Uncommon Pediatric Breast Lesions.

Breast masses in children and adolescents are uncommon, and the spectrum of pediatric breast masses is predominantly benign and different from that in adults. Knowledge of the clinical presentation and imaging features of the various stages of normal development and mass-forming lesions in the pediatric breast can guide a tailored imaging approach and help the radiologist make a definitive diagnosis. Breast development begins during fetal gestation along the embryologic milk lines and continues through puberty as the breast matures through the Tanner stages of development. Normal and developmental variants and benign neoplastic and nonneoplastic lesions in the pediatric breast are common causes of concern. Malignant breast masses in children are rare and are more often due to metastasis than primary breast cancer. When clinically warranted, US is the mainstay for imaging the pediatric breast and requires careful correlation of sonographic findings with patient age and history. Breast MRI can be used to further characterize lesions and evaluate the extent of disease. Biopsy should be considered only for suspicious findings and must be weighed against the risk of iatrogenic injury to the developing breast. Given that the majority of mass-forming lesions in the pediatric breast are benign, the diagnostic and management approach should emphasize "first do no harm." Knowledge of the imaging appearance of normal breast development and the spectrum of benign and malignant pediatric breast masses is necessary to make the correct diagnosis. © RSNA, 2022.

How to Recognize and Correct Artifacts on Contrast-Enhanced Mammography.

Contrast-enhanced mammography (CEM) has emerged as an important new technology in breast imaging. It can demonstrate a number of imaging artifacts that have the potential to limit interpretation by either obscuring or potentially mimicking disease. Commonly encountered artifacts on CEM include patient motion artifacts (ripple and misregistration), pectoral highlighting artifact, breast implant artifact, halo artifact, corrugation artifact, cloudy fat artifact, contrast artifacts (retention and contamination), skin artifacts (skin line enhancement and skin overexposure), and skin lesions. Skin lesions may demonstrate a variety of imaging appearances and have both benign and malignant etiologies. It is important that the technologist, radiologist, and physicist be aware of potential artifacts and skin enhancement on CEM that may affect interpretation and understand their causes and potential solutions.

Bargain Hunting for Buffered Lidocaine: A Collaborative Discovery of Cost-saving Strategies That Can Improve Patient Care.

Buffered lidocaine is a local anesthetic option during percutaneous needle-directed procedures in the breast. At our institution, sodium bicarbonate (the buffer) is dispensed in volumes that frequently lead to medical waste and shortages. In this study, we describe how moving the buffering of lidocaine from the procedure room to our clinical hospital pharmacy results in a reduction in costs and improves satisfaction across the breast radiology department. While cost savings are difficult to tease out in practices that opt for bundled payments, we were able to access pricing and supply data and coordinate with our pharmacy to change our practice. Making these changes saves our practice $26 000 a year and allows us to continue to offer buffered lidocaine even during sodium bicarbonate shortages. This manuscript describes how these changes came about and their economic impact.

Immune defenses against Batrachochytrium dendrobatidis, a fungus linked to global amphibian declines, in the South African clawed frog, Xenopus laevis.

Batrachochytrium dendrobatidis is a chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians. It is regarded as an emerging infectious disease affecting diverse amphibian populations in many parts of the world. Because there are few model amphibian species for immunological studies, little is known about immune defenses against B. dendrobatidis. We show here that the South African clawed frog, Xenopus laevis, is a suitable model for investigating immunity to this pathogen. After an experimental exposure, a mild infection developed over 20 to 30 days and declined by 45 days postexposure. Either purified antimicrobial peptides or mixtures of peptides in the skin mucus inhibited B. dendrobatidis growth in vitro. Skin peptide secretion was maximally induced by injection of norepinephrine, and this treatment resulted in sustained skin peptide depletion and increased susceptibility to infection. Sublethal X-irradiation of frogs decreased leukocyte numbers in the spleen and resulted in greater susceptibility to infection. Immunization against B. dendrobatidis induced elevated pathogen-specific IgM and IgY serum antibodies. Mucus secretions from X. laevis previously exposed to B. dendrobatidis contained significant amounts of IgM, IgY, and IgX antibodies that bind to B. dendrobatidis. These data strongly suggest that both innate and adaptive immune defenses are involved in the resistance of X. laevis to lethal B. dendrobatidis infections.

Mirtazapine treatment after conditioning with methamphetamine alters subsequent expression of place preference.

Methamphetamine (MP) is a widely abused psychostimulant. There are currently no FDA approved pharmacotherapies for the MP addict. The antidepressant, mirtazapine (Mirt) is a high affinity antagonist at several monoaminergic receptors that are affected by MP. This study evaluated the potential of Mirt as a therapeutic agent for MP addiction and described associated changes in neuronal signaling. A single pairing conditioned place preference (CPP) paradigm was utilized as a behavioral measure of MP-induced effects. Rats learned to associate unique environmental cues with the effects of 1.0 mg/kg (i.p.) MP (day 1) or saline (day 2). Mirt (5.0 mg/kg i.p.) was given in the home cage on day 3 and CPP was assessed on day 4. To evaluate signaling events that correlate with this behavior, brain tissue of these rats were dissected for immunoblot assays of extracellular signal-regulated kinase (ERK) and a transcriptional regulator, cAMP response element-binding protein (CREB) after the CPP test. During the CPP test, rats conditioned with MP spent more time in the environment associated with MP. Importantly, rats given Mirt did not express CPP. MP-induced CPP was associated with a decrease in phosphorylated CREB (pCREB) in the ventral tegmental area, and decreased phosphorylated ERK and pCREB in the nucleus accumbens and treatment with Mirt did not reverse these changes. No changes in signaling proteins were obtained from rats similarly treated with MP and Mirt, without exposure to cues of the conditioning paradigm. Overall, a post-conditioning treatment with Mirt can nullify MP-induced associative learning. However, additional studies are needed to ascertain the molecular events underlying this effect of Mirt.