Demystifying Breast Disease Markers.

Breast imaging radiologists regularly perform image-guided biopsies of suspicious breast lesions based on features that are associated with a likelihood of malignancy ranging from 2% to greater than 95% (Breast Imaging Reporting and Data System categories 4 and 5). As diagnostic partners, pathologists perform histopathologic assessment of these tissue samples to confirm a diagnosis. Correlating the imaging findings with the histopathologic results is an integral aspect of multidisciplinary breast care. Assessment of radiologic-pathologic concordance is vital in guiding appropriate management, as it enables identification of discordant results, minimizing the chance of misdiagnosis. Undersampling can lead to false-negative results, with the frequencies of false-negative diagnoses varying on the basis of multiple factors, including biopsy type (eg, core needle, vacuum-assisted needle), needle gauge, and type of lesion sampled at biopsy (ie, mass, calcifications, asymmetry, architectural distortion). Improving a radiologist's knowledge of macroscopic and microscopic breast anatomy and more common breast diseases and their expected imaging findings ensures more accurate radiologic-pathologic correlation and management recommendations. The histopathologic and molecular characteristics of biopsy-sampled breast lesions aid in making an accurate diagnosis. Hematoxylin-eosin staining provides critical morphologic details, whereas immunohistochemical staining enables molecular characterization of many benign and malignant lesions, which is critical for tailored treatment. The authors review commonly encountered benign and malignant breast diseases, their corresponding histopathologic phenotypes, and the histopathologic markers that are essential to clinching the diagnosis of these entities. As part of a multidisciplinary team that provides optimal patient care, radiologists should be knowledgeable of the foundations of histopathologic diagnosis and the implications for patient management to ensure appropriate radiologic-pathologic concordance. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Social determinants of health and the prediction of missed breast imaging appointments.

BACKGROUND: Predictive models utilizing social determinants of health (SDH), demographic data, and local weather data were trained to predict missed imaging appointments (MIA) among breast imaging patients at the Boston Medical Center (BMC). Patients were characterized by many different variables, including social needs, demographics, imaging utilization, appointment features, and weather conditions on the date of the appointment. METHODS: This HIPAA compliant retrospective cohort study was IRB approved. Informed consent was waived. After data preprocessing steps, the dataset contained 9,970 patients and 36,606 appointments from 1/1/2015 to 12/31/2019. We identified 57 potentially impactful variables used in the initial prediction model and assessed each patient for MIA. We then developed a parsimonious model via recursive feature elimination, which identified the 25 most predictive variables. We utilized linear and non-linear models including support vector machines (SVM), logistic regression (LR), and random forest (RF) to predict MIA and compared their performance. RESULTS: The highest-performing full model is the nonlinear RF, achieving the highest Area Under the ROC Curve (AUC) of 76% and average F1 score of 85%. Models limited to the most predictive variables were able to attain AUC and F1 scores comparable to models with all variables included. The variables most predictive of missed appointments included timing, prior appointment history, referral department of origin, and socioeconomic factors such as household income and access to caregiving services. CONCLUSIONS: Prediction of MIA with the data available is inherently limited by the complex, multifactorial nature of MIA. However, the algorithms presented achieved acceptable performance and demonstrated that socioeconomic factors were useful predictors of MIA. In contrast with non-modifiable demographic factors, we can address SDH to decrease the incidence of MIA.

MRI Changes in Breast Skin Following Preoperative Therapy for Patients with Inflammatory Breast Cancer.

RATIONALE AND OBJECTIVES: Preoperative systemic therapy (PST) followed by mastectomy and radiation improves survival for patients with inflammatory breast cancer (IBC). Residual disease within the skin post-PST adversely impacts surgical outcome and risk of local-regional recurrence (LRR). We aimed to assess magnetic resonance imaging (MRI) breast skin changes post-PST with pathologic response and its impact on surgical resectability. MATERIALS AND METHODS: We retrospectively reviewed 152 baseline and post-PST breast MRIs of 76 patients with IBC. Using the ACR-BIRADS MRI lexicon, we correlated skin thickness, qualitative enhancement, and kinetic analysis with pathologic response in the skin at mastectomy. RESULTS: Baseline MRI showed skin thickening in all 76 patients, 75/76 (99%) showed skin enhancement, 54/75 (72%) had medium/fast initial kinetics, usually with persistent delayed kinetics in 49/54 (91%). Following PST, 66/76 (87%) had residual skin thickening with 64/76 (84%) showing a decrease; 33/76 (43%) had persistent enhancement. The median thickness post-PST was 4.7 mm with residual tumor in the skin, and 3.0 mm without residual tumor (p = 0.008). Regardless of pathologic response, the majority of patients had persistent skin thickening on MRI following PST (100% [14/14] with residual tumor and 84% [52/62] without residual tumor). There was no association between post-PST skin thickness on breast MRI and rate of LRR. CONCLUSION: Patients with IBC have skin thickening and enhancement on baseline breast MRI, with a statistically significant reduction in skin thickness following successful PST. Despite persistent skin changes on MRI, patients achieving a partial or complete parenchymal response to PST may proceed to mastectomy with low LRR rates.

Calcified Axillary Lesions on Mammography: Review and Management.

When interpreting mammography, breast radiologists may identify radiopaque densities in the axilla on the mediolateral oblique or lateral projections. When such densities are encountered, true calcifications must be differentiated from pseudocalcifications (artifact). Using imaging, breast radiologists should be able to localize the finding as being dermal, within the soft tissues, within a lymph node, or intramuscular. By combining the anatomic location with the clinical presentation and any other imaging findings, breast radiologists will be able to determine the most appropriate management.

Systemic diseases affecting the breast: Imaging, diagnosis, and management.

Various systemic diseases of benign or malignant etiologies can clinically manifest in the breast. Some imaging findings of breast lesions can be pathognomonic for a given condition, while others are non-specific, mimicking primary breast carcinoma and requiring tissue biopsy for definitive diagnosis. In addition to obtaining a detailed clinical history, radiologists should be familiar with the diverse clinical and imaging characteristics of these conditions to help exclude primary breast cancer and avoid unnecessary interventions. This review aims to discuss the clinical presentations, imaging features, pathologic findings, and management of systemic conditions that may affect the breast.

Male Breast Disease: What the Radiologist Needs to Know.

The male breast is susceptible to a variety of benign and malignant processes, many of which clinically present as a palpable finding, focal pain, or breast enlargement. Gynecomastia is the most common abnormality in the male breast and must be distinguished from malignancy. Imaging of the symptomatic male breast begins with a diagnostic mammogram in a patient ≥25 years and targeted ultrasound in a patient <25 years. If the breast finding is incompletely imaged or occult at mammography, targeted ultrasound must be performed. Similarly, if the breast finding is suspicious at targeted ultrasound in a younger patient, mammography must be performed. After a complete diagnostic evaluation, suspicious findings require biopsy because of overlap in clinical and imaging features of benign and malignant pathologies. Although no breast cancer screening program exists for men due to the <1% incidence of breast cancer, transgender male to female patients >50 years and treated with exogenous hormone therapy for >5 years should undergo breast cancer screening. This paper will review the anatomy of the male breast, appropriate imaging of the symptomatic male breast, gynecomastia and other benign conditions, and male breast cancer and other malignant conditions. Finally, we will discuss imaging of the transgender patient.

Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing.

During animal development, Wnt/Wingless (Wg) signaling is required for the patterning of multiple tissues. While insufficient signal transduction is detrimental to normal development, ectopic activation of the pathway can be just as devastating. Thus, numerous controls exist to precisely regulate Wg signaling levels. Endocytic trafficking of pathway components has recently been proposed as one such control mechanism. Here, we characterize the vesicular trafficking of Wg and its receptors, Arrow and DFrizzled-2 (DFz2), and investigate whether trafficking is important to regulate Wg signaling during dorsoventral patterning of the larval wing. We demonstrate a role for Arrow and DFz2 in Wg internalization. Subsequently, Wg, Arrow and DFz2 are trafficked through the endocytic pathway to the lysosome, where they are degraded in a hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-dependent manner. Surprisingly, we find that Wg signaling is not attenuated by lysosomal targeting in the wing disc. Rather, we suggest that signaling is dampened intracellularly at an earlier trafficking step. This is in contrast to patterning of the embryonic epidermis, where lysosomal targeting is required to restrict the range of Wg signaling. Thus, signal modulation by endocytic routing will depend on the tissue to be patterned and the goals during that patterning event.

Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity.

Activation of the Wnt signaling cascade provides key signals during development and in disease. Here we provide evidence, by designing a Wnt receptor with ligand-independent signaling activity, that physical proximity of Arrow (LRP) to the Wnt receptor Frizzled-2 triggers the intracellular signaling cascade. We have uncovered a branch of the Wnt pathway in which Armadillo activity is regulated concomitantly with the levels of Axin protein. The intracellular pathway bypasses Gsk3beta/Zw3, the kinase normally required for controlling beta-catenin/Armadillo levels, suggesting that modulated degradation of Armadillo is not required for Wnt signaling. We propose that Arrow (LRP) recruits Axin to the membrane, and that this interaction leads to Axin degradation. As a consequence, Armadillo is no longer bound by Axin, resulting in nuclear signaling by Armadillo.