Breast calcifications on mammography from systemic amyloidosis: A case report.

Calcifications on mammography from systemic disease at times meet diagnostic criteria for histologic sampling to exclude malignancy. We present a case of bilateral groups of new calcifications on mammography that yielded amyloidosis on core biopsy. Awareness of our patient's known diagnosis of systemic light chain amyloidosis (AL) prompted use of Congo red staining to confirm the histologic diagnosis. Knowledge of systemic diseases with possible manifestations on mammography can facilitate cogent and clinically relevant radiology-pathology correlation.

Patient Utilization of Weekend and Evening Appointments for Screening Mammography: An 8-Year Observational Cohort Study.

OBJECTIVE: To characterize the patient population using weekend and evening appointments for screening mammography versus standard appointment times across four outpatient facilities in our academic health system. METHODS: In this institutional review board-approved retrospective cohort study, there were 203,101 screening mammograms from 67,323 patients who had a screening mammogram performed at outpatient centers at a multisite academic institution from January 1, 2015, to December 31, 2022. Screening appointments were defined as "standard appointment time" (between 8 am and 5 pm on Monday through Friday) or "weekend or evening appointment time" (scheduled after 5 pm on Monday through Friday or at any time on a Saturday or Sunday). Associations between appointment group and patient characteristics were analyzed using univariate and multivariate logistic regression. RESULTS: Most screening mammograms (n = 185,436, 91.3%) were performed at standard times. The remainder (n = 17,665, 8.7%) were performed during weekends or evenings. As we created additional weekend and evening appointments after the coronavirus disease 2019 pandemic, the annual percentage of all screening mammograms performed on evenings and weekends increased. On multivariate analysis, when compared with standard appointment times, we found that patients who were younger than age 50 (P < .001), a race other than non-Hispanic White (P < .001), non-English speakers (P < .001), and from less advantaged zip codes (P < .03) were more likely to use weekend and evening appointment times compared with those aged 70 and above, non-Hispanic White patients, English speakers, and those from the most advantaged zip codes. CONCLUSIONS: Weekend and evening appointment availability for screening mammograms might improve screening access for all patients, particularly for those younger than age 50, those of races other than non-Hispanic White, and those from less advantaged zip codes.

Metaplastic carcinoma with osteosarcomatous differentiation in the breast: Case report.

Metaplastic breast carcinoma is rare and may present as a highly aggressive subtype of breast cancer. In this case report of metastatic metaplastic breast carcinoma with osteosarcomatous differentiation in a female patient previously treated for invasive ductal carcinoma, we describe the new presentation of a palpable mass with associated calcifications on imaging near the site of prior partial mastectomy. This article will detail the clinical presentation, imaging findings, histopathology, and clinical course following treatment of our case. Knowledge of the clinical and imaging presentation of this rare subtype, which can present with benign features on mammography and ultrasound, can facilitate timely diagnosis as treatment paradigms evolve.

Can breast MRI predict pathologic response following neoadjuvant chemotherapy for breast cancer? A retrospective cohort study.

PURPOSE: For patients treated with neoadjuvant chemotherapy (NAC) for breast cancer, it is standard of care to perform pre- and post-NAC imaging to evaluate response to therapy prior to surgery. In this study we assess outcome metrics of magnetic resonance imaging (MRI) following NAC. METHODS: We conducted a retrospective analysis of patients with invasive breast cancer who underwent a breast MRI before and after NAC between 2016 and 2021 at a single, multisite academic institution. All breast MRI studies were characterized as either radiologic complete response (rCR) or non-rCR. Corresponding surgical pathology reports were reviewed and categorized as pathologic complete response (pCR) or non-pCR. We defined a positive test as having residual enhancement on MRI (non-rCR) and a positive outcome as having residual disease on final surgical pathology (non-pCR). RESULTS: There were 225 patients included in the study (mean age 52 ± 12 years). Breast cancer receptor distribution was HR+/HER2- (n = 71, 32%), HR+/HER2+ (n = 51, 23%), HR-/HER2- (n = 72, 32%), and HR-/HER2+ (n = 31, 14%). In total, 78 (35%) had rCR and 77 (34%) had pCR; 43 (19%) had both rCR and pCR. The overall accuracy rate was 69% (156/225), sensitivity 76% (113/148), specificity 56% (43/77), positive predictive value 77% (113/147), and negative predictive value 55% (43/78). The PPV was significantly associated with receptor status (p = 0.004). No patient or imaging characteristics were associated with sensitivity. CONCLUSION: Breast MRI only moderately predicts pathologic response for invasive breast cancer treated with NAC (overall accuracy 69%). PPV is significantly associated with receptor status.

High-risk lesions in the breast diagnosed by MRI-guided core biopsy: upgrade rates and features associated with malignancy.

PURPOSE: This study assessed the upgrade rates of high-risk lesions (HRLs) in the breast diagnosed by MRI-guided core biopsy and evaluated imaging and clinical features associated with upgrade to malignancy. METHODS: This IRB-approved, retrospective study included MRI-guided breast biopsy exams yielding HRLs from August 1, 2011, to August 31, 2020. HRLs included atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), radial scar, and papilloma. Only lesions that underwent excision or at least 2 years of MRI imaging follow-up were included. For each HRL, patient history, imaging features, and outcomes were recorded. RESULTS: Seventy-two lesions in 65 patients were included in the study, with 8/72 (11.1%) of the lesions upgraded to malignancy. Upgrade rates were 16.7% (2/12) for ADH, 100% (1/1) for pleomorphic LCIS, 40% (2/5) for other LCIS, 0% (0/19) for ALH, 0% (0/18) for papilloma, and 0% (0/7) for radial scar/complex sclerosing lesion. Additionally, two cases of marked ADH bordering on DCIS and one case of marked ALH bordering on LCIS, were upgraded. Lesions were more likely to be upgraded if they presented as T2 hypointense (versus isotense, OR 6.46, 95% CI 1.27-32.92) or as linear or segmental non-mass enhancement (NME, versus focal or regional, p = 0.008). CONCLUSION: Our data support the recommendation that ADH and LCIS on MRI-guided biopsy warrant surgical excision due to high upgrade rates. HRLs that present as T2 hypointense, or as linear or segmental NME, should be viewed with suspicion as these were associated with higher upgrade rates to malignancy.

BI-RADS 3 Assessment on MRI: A Lesion-Based Review for Breast Radiologists.

Unlike mammography and US, limited data exist to establish well-defined criteria for MRI findings that have a ≤2% likelihood of malignancy. Therefore, determining which findings are appropriate for a BI-RADS 3 assessment on MRI remains challenging and variable among breast radiologists. Emerging data suggest that BI-RADS 3 should be limited to baseline MRI examinations (or examinations with less than two years of prior comparisons) performed for high-risk screening and only used for masses with all of the typical morphological and kinetic features suggestive of a fibroadenoma or dominant enhancing T2 hypointense foci that is distinct from background parenchymal enhancement and without suspicious kinetics. This article presents an updated discussion of BI-RADS 3 assessment (probably benign) for breast MRI using current evidence.

Differential response of endothelial cells to simvastatin when conditioned with steady, non-reversing pulsatile or oscillating shear stress.

Few studies have investigated whether fluid mechanics can impair or enhance endothelial cell response to pharmacological agents such as statin drugs. We evaluated and compared Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) expression in human abdominal aortic endothelial cells (HAAEC) treated with increasing simvastatin concentrations (0.1, 1 or 10 µM) under static culture and shear stress (steady, non-reversing pulsatile, and oscillating). Simvastatin, steady flow, and non-reversing pulsatile flow each separately upregulated KLF2, eNOS, and TM mRNA. At lower simvastatin concentrations (0.1 and 1 µM), the combination of statin and unidirectional steady or pulsatile flow produced an overall additive increase in mRNA levels. At higher simvastatin concentration (10 µM), a synergistic increase in eNOS and TM mRNA expression was observed. In contrast, oscillating flow impaired KLF2 and TM, but not eNOS expression by simvastatin at 1 µM. A higher simvastatin concentration of 10 µM overcame the inhibitory effect of oscillating flow. Our findings suggest that oscillating shear stress renders the endothelial cells less responsive to simvastatin than cells exposed to unidirectional steady or pulsatile flow. Consequently, the pleiotropic effects of statins in vivo may be less effective in endothelial cells exposed to atheroprone hemodynamics.

Laminar shear stress prevents simvastatin-induced adhesion molecule expression in cytokine activated endothelial cells.

In addition to lowering cholesterol, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been shown to modulate gene expression in endothelial cells. The effect of statins on cell adhesion molecule expression is unclear and largely unexplored in endothelial cells exposed to shear stress, an important regulator of endothelial cell function. In this study, the effect of simvastatin on vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression was evaluated in human abdominal aortic endothelial cells (HAAEC) conditioned with various levels of laminar wall shear stress with or without tumor necrosis factor alpha (TNFα). As expected, TNFα alone greatly enhanced both VCAM-1 and ICAM-1 mRNA and protein. In static culture, simvastatin potentiated the TNFα-induced increase in VCAM-1 and ICAM-1 mRNA but not total protein at 24 h. Mevalonate, a precursor to cholesterol biosynthesis, eliminated the effect of simvastatin. Exposure of endothelial cells to elevated levels of laminar shear stress during simvastatin treatment prevented the potentiating effect of simvastatin on cell adhesion molecule mRNA. A shear stress of 12.5 dyn/cm² eliminated the increase in VCAM-1 by simvastatin, while 25 dyn/cm² was needed for ICAM-1. We conclude that simvastatin enhances VCAM-1 and ICAM-1 gene expression in TNFα-activated endothelial cells through inhibition of HMG-CoA reductase. High levels of laminar shear stress prevented the upregulation of VCAM-1 and ICAM-1 by simvastatin suggesting that an induction of cell adhesion molecules by statins may not occur in endothelial cells exposed to shear stress from blood flow.

The response of human aortic endothelial cells in a stenotic hemodynamic environment: effect of duration, magnitude, and spatial gradients in wall shear stress.

Inflammation plays a key role in the development and stability of coronary plaques. Endothelial cells alter their expression in response to wall shear stress (WSS). Straight/tubular and asymmetric stenosis models were designed to study the localized expression of atheroprone molecules and inflammatory markers due to the presence of the spatial wall shear stress gradients created by an eccentric plaque. The effects of steady wall shear stress duration (0-24 h) and magnitude (4.5-18 dynes/cm(2)) were analyzed in human abdominal aortic endothelial cells through quantitative real-time polymerase chain reaction (PCR) and immunofluorescence analysis in straight/tubular models. Regional expression was assessed by immunofluorescence and confocal microscopy in stenosis models. Under steady fully developed flow, endothelial cells exhibited a sustained increase in levels of atheroprotective genes with WSS duration and magnitude. The local response in the stenosis model showed that expression of endothelial nitric oxide synthase and Kruppel-like factor 2 is magnitude rather than gradient dependent. A WSS magnitude dependent transient increase in translocation of transcription factor nuclear factor kappaB was observed. Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin exhibited a sustained increase in protein expression with time. The mRNA levels of these molecules were transiently upregulated and this was followed by a decrease in expression to levels lower than static controls. Regionally, increased inflammatory marker expression was observed in regions of WSS gradients both proximal and distal to the stenosis when compared with the uniform flow regions, whereas the atheroprotective markers were expressed to a greater extent in regions of elevated WSS magnitudes. The results from the straight/tubular model cannot explain the regional variation seen in the stenosis models. This may help explain the localization of inflammatory cells at the shoulders of plaques in vivo.

Effect of simvastatin on Kruppel-like factor2, endothelial nitric oxide synthase and thrombomodulin expression in endothelial cells under shear stress.

AIMS: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) and fluid wall shear stress have been reported to modulate the expression of genes related to inflammation, blood coagulation, thrombosis, and vascular constriction in cultured endothelial cells. In this study, we investigated the combined effect of laminar shear stress (LSS) and statins on endothelial cell gene expression. MAIN METHODS: Kruppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) mRNA and protein expression were evaluated in human abdominal aortic endothelial cells (HAAEC) treated with simvastatin (0.1, 1 or 10 microM) at various levels of LSS (0, 1.25, 12.5 or 25 dynes/cm(2)). KEY FINDINGS: As expected, simvastatin and LSS separately enhanced KLF2, eNOS, and TM mRNA expressions. The combination of simvastatin and LSS resulted in significantly higher mRNA levels of all three genes compared to cells treated with LSS only. The highest KLF2, eNOS, and TM mRNA levels were detected at 10 microM simvastatin and 25 dynes/cm(2). Under these conditions, eNOS and TM protein levels were also elevated. Combining LSS and simvastatin produced an overall additive increase in KLF2, eNOS, and TM mRNA. Treatment of the endothelial cells with 10 microM simvastatin and 200 microM mevalonate completely eliminated the effect of simvastatin. SIGNIFICANCE: Our results suggest an additive increase in KLF2, eNOS, and TM expressions when simvastatin and LSS are combined. These results may help to explain the proposed non-lipid lowering benefits of statins observed in the clinic.

Concentration and time effects of dextran exposure on endothelial cell viability, attachment, and inflammatory marker expression in vitro.

Dextran is commonly used to alter growth medium rheological properties for in vitro flow experiments in order to match physiological parameters. Despite its acceptance in literature, few studies have examined dextran effects on cells. In this study, we investigated changes in endothelial cell function due to dextran, under static and flow conditions, in a concentration and time-dependent manner. Dextran increased endothelial cell viability, decreased their ability to attach to culture plates and decreased leukocyte adhesion to endothelial cells. Under static conditions, dextran increased protein and mRNA expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in a concentration and time-dependent manner and caused the nuclear translocation of NF-kappaB. Steady laminar wall shear stress modulated the effects of dextran on ICAM-1, VCAM-1, and NF-kappaB expression in straight/tubular in vitro models. When the expression was normalized to their respective time matched static dextran control, it did not affect the ability to detect changes caused by shear on the mRNA expression of ICAM-1 and VCAM-1. This study demonstrates that dextran can alter endothelial cell function and therefore, caution is advised and time matched dextran controls are necessary when using dextran for dynamic cell studies.

Long-circulating poly(ethylene glycol)-coated emulsions to target solid tumors.

The purpose of this study was to develop oil-in-water emulsions (100-120 nm in diameter) and to correlate the surface properties of the emulsions with blood residence time and accumulation into neoplastic tissues by passive targeting. We investigated the effect of phospholipid and sphingolipid emulsifiers, hydrogenated soybean phosphatidylcholine (HSPC) and egg sphingomyelin (ESM), in combination with polysorbate 80 (PS-80) and 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE)-PEG lipids of various PEG chain lengths and structures in prolonging circulation time and enhancing accumulation into B16 melanoma or C26 colon adenocarcinoma. The relationship between amphiphile molecular packing at the air/water interface on emulsion stability upon dilution in albumin and circulation longevity in vivo was also explored for non-PEGylated emulsions. PEGylation of the droplet surface with 10-15 mol% of DSPE-PEG 2000 or 5000 enhanced the circulation time of the emulsions, however, accumulation was only observed in the C26 tumor model. The tighter molecular packing observed with ESM/PS-80 monolayers at the air/water interface compared to HSPC/PS-80 correlated with improved emulsion stability in vitro, however, enhanced circulation time in vivo was not observed. A better understanding of the relationships between composition and performance will result in improved emulsion-based drug delivery vehicles for cancer therapy.