Comparison of prone and upright, stereotactic, and tomosynthesis-guided biopsies with secondary analysis of ultrasound-occult architectural distortions.

OBJECTIVES: Compare prone and upright, stereotactic, and tomosynthesis-guided vacuum-assisted breast biopsies (prone DM-VABB, prone DBT-VABB, upright DM-VABB, and upright DBT-VABB) in a community-practice setting and review outcomes of ultrasound-occult architectural distortions (AD). METHODS: Consecutive biopsies performed at two community-based breast centers from 2016 to 2019 were retrospectively reviewed. Technical details of each procedure and patient outcomes were recorded. Separate analyses were performed for ultrasound-occult ADs. Two sample t-tests and Fisher's exact test facilitated comparisons. RESULTS: A total of 1133 patients underwent 369 prone DM-VABB, 324 prone DBT-VABB, 437 upright DM-VABB, and 123 upright DBT-VABB with 99.2%, 100%, 99.3%, and 99.2% success, respectively (p-values > 0.25). Mean lesion targeting times were greater for prone biopsy (minutes: 6.94 prone DM-VABB, 8.54 prone DBT-VABB, 5.52 upright DM-VABB, and 5.51 upright DBT-VABB; p-values < 0.001), yielding longer total prone procedure times for prone biopsy (p < 0.001). Compared to DM-VABB, DBT-VABB used fewer exposures (p < 0.001) and more commonly targeted AD, asymmetries, or masses (p < 0.001). Malignancy rates were similar between procedures: prone DM-VABB 22.4%, prone DBT-VABB 21.9%, upright DM-VABB 22.8%, and upright DBT-VABB 17.2% (p-values > 0.19). One hundred forty of the 1133 patients underwent 145 biopsies for ultrasound-occult AD (143 DBT-VABB and 2 DM-VABB). Biopsy yielded 27 malignancies and 47 high-risk lesions (74 of 145, 51%). Malignancy rate was 20.7% after surgical upgrade of one benign-discordant and two high-risk lesions. CONCLUSIONS: All biopsy procedure types were extremely successful. The 20.7% malignancy rate for ultrasound-occult AD confirms a management recommendation for tissue diagnosis. Upright biopsy was faster than prone biopsy, and DBT-VABB used fewer exposures than DM-VABB. CLINICAL RELEVANCE: Our results highlight important differences between prone DM-VABB, prone DBT-VABB, upright DM-VABB, and upright DBT-VABB. Moreover, the high likelihood of malignancy for ultrasound-occult AD will provide confidence in recommending tissue diagnosis in lieu of observation or clinical follow-up. KEY POINTS: • Upright and prone stereotactic and tomosynthesis-guided breast biopsies were safe and effective in the community-practice setting. • The malignancy rate for ultrasound-occult architectural distortion of 20.7% confirms the management recommendation for biopsy. • Upright procedures were faster than prone procedures, and tomosynthesis-guided biopsy used fewer exposures than stereotactic biopsy.

18F-FDG PET/CT for the Evaluation of Therapy Response in Hormone Receptor-Positive Bone-Dominant Metastatic Breast Cancer.

Fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT has shown promise for use in assessing treatment response in patients with bone-only or bone-dominant (BD) metastatic breast cancer (mBC). In this single-institution, prospective single-arm study of 23 women (median age, 59 years [range, 38-81 years]) with biopsy-proven estrogen receptor-positive bone-only or BD mBC about to begin new endocrine therapy between October 3, 2013, and August 3, 2018, the value of early 4-week 18F-FDG PET/CT in predicting progression-free survival (PFS) was evaluated. 18F-FDG PET/CT was performed at baseline, 4 weeks, and 12 weeks. Maximum standardized uptake value (SUVmax) and peak SUV (SUVpeak) were measured for up to five index lesions. The primary end point was PFS. Secondary end points were overall survival (OS) and time to skeletal-related events (tSREs). All end points were compared between responders (reduction of 30% or more in the sum of SUVmax for target lesions) and nonresponders at 4 weeks and 12 weeks. Percentage change from baseline in SUVmax at 4- and 12-week 18F-FDG PET/CT were highly correlated (r = 0.81). At the 4-week time point PET responders had numerically longer PFS (14.2 months vs 6.3 months; P = .53), OS (44.0 months vs 29.7 months; P = .47), and tSRE (27.4 months vs 25.2 months; P = .66) compared with nonresponders, suggesting the clinical utility of 4-week 18F-FDG PET/CT as an early predictor of treatment failure. Keywords: Breast Cancer, Metastatic Breast Cancer, Bone-Dominant Metastatic Breast Cancer, FDG PET/CT, Estrogen-Receptor Positive Metastatic Breast Cancer Supplemental material is available for this article. Clinical trial registration no. NCT04316117 © RSNA, 2022.

Perfusion-only imaging in pregnant women: A comparative reader study with implications for practice patterns.

This study seeks to understand the value of ventilation imaging in pregnant patients imaged for suspected pulmonary embolism (PE). Ventilation-perfusion (VQ) scans in this high-risk population were compared to ventilation-only scans. We hypothesize that in this relatively healthy population, the exclusion of ventilation scans will not impact the rate of scans interpreted as positive. This retrospective blinded comparative reader study on collated VQ scans performed on pregnant patients in the course of routine clinical care in a > 5 year period (03/2012 to 07/2017). Each set of VQ and perfusion only (Q) studies were reviewed by 8 readers (4 nuclear radiology fellows and 4 nuclear medicine faculty) in random order; the Q scans simply omitted the ventilation images. Readers recorded each study as PE, no PE, or non-diagnostic (prospective investigative study of acute PE diagnosis classifications). Logistic mixed effects models were used to test the association between scan type (VQ vs Q). 203 pairs of studies in 197 patients were included (6 patients had 2 scans). Subjects ranged from 14 to 45 years of age, with a median 28 years. A significant association between scan type and positive/negative classification. Q-scans received more positive classifications than VQ-scans (median of 7.6% vs 6.7%). No association was seen between scan type and positive/indeterminate classification, nor between scan type and negative/indeterminate classification. The exclusion of ventilation images in VQ-scans was associated with a higher rate of positive studies, but this difference was small (<1%). Given the overwhelmingly normal percentage of Q-exams (>90% in our study), and the benefits of omitting ventilation imaging, perfusion-only imaging should be considered a reasonable option for imaging the pregnant patient to exclude PE.

Breast MRI: False-Negative Results and Missed Opportunities.

Breast MRI is the most sensitive modality for the detection of breast cancer. However, false-negative cases may occur, in which the cancer is not visualized at MRI and is instead diagnosed with another imaging modality. The authors describe the causes of false-negative breast MRI results, which can be categorized broadly as secondary to perceptual errors or cognitive errors, or nonvisualization secondary to nonenhancement of the tumor. Tips and strategies to avoid these errors are discussed. Perceptual errors occur when an abnormality is not prospectively identified, yet the examination is technically adequate. Careful development of thorough search patterns is critical to avoid these errors. Cognitive errors occur when an abnormality is identified but misinterpreted or mischaracterized as benign. The radiologist may avoid these errors by utilizing all available prior examinations for comparison, viewing images in all planes to better assess the margins and shapes of abnormalities, and appropriately integrating all available information from the contrast-enhanced, T2-weighted, and T1-weighted images as well as the clinical history. Despite this, false-negative cases are inevitable, as certain subtypes of breast cancer, including ductal carcinoma in situ, invasive lobular carcinoma, and certain well-differentiated invasive cancers, may demonstrate little to no enhancement at MRI, owing to differences in angiogenesis and neovascularity. MRI is a valuable diagnostic tool in breast imaging. However, MRI should continue to be used as a complementary modality, with mammography and US, in the detection of breast cancer. ©RSNA, 2021.

Abbreviated Breast Magnetic Resonance Imaging for Supplemental Screening of Women With Dense Breasts and Average Risk.

PURPOSE: Although mammography is the standard of care for breast cancer screening, dense breast tissue decreases mammographic sensitivity. We report the prevalent cancer detection rate (CDR) from the first clinical implementation of abbreviated breast magnetic resonance imaging (AB-MR) as a supplemental screening test in women with dense breasts. METHODS: The study was approved by the institutional review board and is Health Insurance Portability and Accountability Act complaint. This retrospective review includes women who were imaged between January 1, 2016 and February 28, 2019. On a 1.5 Tesla magnet, the imaging protocol consisted of three sequences: Short-TI Inversion Recovery (STIR), precontrast, and postcontrast. A subtraction sequence and a maximum intensity projection were generated. We report the patient-level CDR and the positive predictive value of AB-MR examinations after negative/benign digital breast tomosynthesis (DBT). RESULTS: Out of 511 prevalent rounds of AB-MR examinations, 36 women were excluded. The remaining 475 asymptomatic women with dense breasts had negative/benign DBT examinations before the AB-MR. There were 420 of 475 (88.4%) benign/negative examinations, 13 of 475 (2.7%) follow-up recommendations, and 42 biopsy recommendations. Thirty-nine biopsies were completed, resulting in 12/39 (30.8%) malignancies in 12 women: seven invasive carcinomas and five ductal carcinoma in situ. One additional patient was diagnosed with invasive ductal carcinoma at the time of 6-month follow-up. The CDR was 27.4 per 1,000 (13 of 475; 95% CI, 16.1 to 46.3). The size of invasive carcinomas ranged from 0.6-1.0 cm (mean, 0.5 cm). Of the seven women who underwent surgical evaluation of the axilla, zero of seven patients had positive nodes. There were no interval cancers at 1-year follow-up. CONCLUSION: Preliminary results from clinical implementation of screening AB-MR resulted in a CDR of 27.4/1,000 at the patient level after DBT in women with dense breasts. Additional evaluation is warranted.

Five Consecutive Years of Screening with Digital Breast Tomosynthesis: Outcomes by Screening Year and Round.

Background Limited data exist beyond prevalence rounds of digital breast tomosynthesis (DBT) screening. Purpose To compare DBT outcomes over multiple years and rounds to outcomes of digital mammography (DM) screening. Materials and Methods Retrospective analysis included 1 year of DM and 5 years of DBT screening (September 2011 to September 2016); 67 350 examinations were performed in 29 310 women. Recall rate (RR) percentage, cancer detection rate (CDR) per 1000 women screened, false-negative rate per 1000 women screened, positive predictive value of recall (PPV1) percentage, positive predictive value of biopsies performed percentage, sensitivity, and specificity were calculated. Cancers diagnosed within 1 year of screening were captured by means of linkage to state cancer registry, and biologic characteristics were grouped by prognostic factors. Performance trends across DBT rounds were compared with those from DM rounds by using logistic regression to account for examinations in the same woman. Analyses were adjusted for age, race, breast density, baseline examination, and reader. Results There were 56 839 DBT and 10 511 DM examinations. The mean patient age (± standard deviation) was 56 years ±11 for the entire cohort, 55 years ±11 for the DBT group, and 57 years ±11 for the DM group. RRs were significantly lower for the DBT group (8.0%, 4522 of 56 839; 95% confidence interval [CI]: 7.7, 8.2) than for the DM group (10.4%, 1094 of 10 511; 95% CI: 9.8, 11.0) (P < .001). CDRs were higher with DBT (6.0 per 1000 women screened; 95% CI: 5.4, 6.7 per 1000 women screened; 340 of 56 839) than with DM (5.1 per 1000 women screened; 95% CI: 3.9, 6.6 per 1000 women screened; 54 of 10 511) (P = .25), but this difference was not statistically significant. Both RR and CDR remained improved compared with DM for 5 years of DBT at the population level. False-negative rates were slightly lower for DBT (0.6 per 1000 women screened; 95% CI: 0.4, 0.8 per 1000 women screened; 33 of 56 839) than DM (0.9 per 1000 women screened; 0.4, 1.6 per 1000 women screened; nine of 10 511) overall (P = .30), but the difference was not statistically significant. In adjusted analyses, RR, biopsy recommendation rates, and PPV1 were improved for DBT versus DM (P ≤ .001). Compared with DM, a higher proportion of DBT-detected cancers were invasive (70% [238 of 340] vs 68.5% [37 of 54]) and had poor prognoses characteristics (32.6% [76 of 233] vs 25.0% [nine of 36]). Conclusion Favorable outcomes with digital breast tomosynthesis screening were sustained over multiple years and rounds. Digital breast tomosynthesis screening was associated with detection of a higher proportion of poor-prognosis cancers than was digital mammography. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Moy and Heller in this issue.

Microglandular Adenosis: A Possible Non-Obligate Precursor to Breast Carcinoma With Potential to Either Luminal-Type or Basal-Type Differentiation.

Microglandular adenosis (MGA) of the breast is exceedingly rare, with only a few case reports and series published to date. Previous studies have elegantly demonstrated the progression of benign MGA to atypical MGA to MGA-in situ carcinoma to invasive carcinoma and therefore suggest MGA as a possible non-obligate precursor lesion to a subset of breast carcinomas. Immunohistochemically, MGA is negative for estrogen receptor (ER), progesterone receptor (PR), and HER2-neu oncoprotein expression, and carcinomas arising in the setting of MGA are often reported to be triple negative. In this article, we present a unique case of an ER+/PR+/HER2- invasive carcinoma associated with MGA and atypical MGA. Our case highlights the diagnostic pitfall of MGA and suggests that MGA is a heterogeneous group of lesions with potential for either luminal-type or basal-type differentiation during progression to breast carcinoma.

Breast Cancer Conspicuity on Simultaneously Acquired Digital Mammographic Images versus Digital Breast Tomosynthesis Images.

Background Digital breast tomosynthesis (DBT) has been shown to improve screening outcomes compared with digital mammography (DM) alone. However, little is known about differences in breast cancer conspicuity between DM and DBT or by mammographic view. Purpose To compare conspicuity of breast cancers at DM versus DBT and by mammographic view, craniocaudal (CC) versus mediolateral oblique (MLO). Materials and Methods Lesion conspicuity was graded by three readers by using a 0-5 numerical scale on both DM and DBT images from combined DM and DBT studies for 197 consecutive screening-detected cancers in women (mean age, 60.4 years ± 11.1 [standard deviation]) from October 1, 2011, through December 31, 2014. Intermodality (ie, DM vs DBT) and intramodality (ie, CC vs MLO) analyses were performed. For intramodality analyses, conspicuity was analyzed by view, CC versus MLO, within the same modality. Conspicuity grades were dichotomized into low (scores 0-3) and high (scores 4 and 5) conspicuity. This binary result was assessed by using a generalized linear mixed-effects model with logit link function, random-effect intercept for reader, and compound symmetry covariance structure for lesion. Results Cancers were more likely to be high conspicuity at DBT than at DM (odds ratio [OR], 2.4; 95% confidence interval [CI]: 1.9, 3.0; P < .01). At both DM and DBT, cancers were more likely to be high conspicuity at the CC than the MLO view (DM vs DBT OR, 1.6 [95% CI: 1.3, 1.9] vs 1.7 [95% CI: 1.3, 2.1], respectively; P < .01 for both). Cancers seen at one view only were more often detected at CC than MLO for both DM and DBT (DM vs DBT OR, 1.6 [95% CI: 1.2, 2.0] vs 3.6 [95% CI: 1.9, 7.0], respectively; P < .01.). Conclusion Cancers were more conspicuous at digital breast tomosynthesis than at digital mammography. Cancers may only be detected at one of two views, and they are more likely to be seen at the craniocaudal view. © RSNA, 2019.

Pediatric Patient With Cerebral Metastasis From Papillary Thyroid Cancer.

Brain metastasis from papillary thyroid carcinoma is uncommon. Concurrent cerebral and pulmonary metastases from papillary thyroid carcinoma is rare, especially in pediatric patients. We report a case of a brain metastasis revealed on post-therapy I scan in a 12 year old girl with thyroid cancer who also had diffuse pulmonary metastases which were partially responsive to sequential I therapy.

Strategies to Increase Cancer Detection: Review of True-Positive and False-Negative Results at Digital Breast Tomosynthesis Screening.

Digital breast tomosynthesis (DBT) represents a valuable addition to breast cancer screening by decreasing recall rates while increasing cancer detection rates. The increased accuracy achieved with DBT is due to the quasi-three-dimensional format of the reconstructed images and the ability to "scroll through" breast tissue in the reconstructed images, thereby reducing the effect of tissue superimposition found with conventional planar digital mammography. The margins of both benign and malignant lesions are more conspicuous at DBT, which allows improved lesion characterization, increased reader confidence, and improved screening outcomes. However, even with the improvements in accuracy achieved with DBT, there remain differences in breast cancer conspicuity by mammographic view. Early data suggest that breast cancers may be more conspicuous on craniocaudal (CC) views than on mediolateral oblique (MLO) views. While some very laterally located breast cancers may be visualized on only the MLO view, the increased conspicuity of cancers on the CC view compared with the MLO view suggests that DBT screening should be performed with two-view imaging. Even with the improved conspicuity of lesions at DBT, there may still be false-negative studies. Subtle lesions seen on only one view may be discounted, and dense and/or complex tissue patterns may make some cancers occult or extremely difficult to detect. Therefore, radiologists should be cognizant of both perceptual and cognitive errors to avoid potential pitfalls in lesion detection and characterization. ©RSNA, 2016 Online supplemental material is available for this article.

Parametric mapping of contrasted ovarian transvaginal sonography.

The purpose of this study was to assess the accuracy of parametric analysis of transvaginal contrast-enhanced ultrasound (TV-CEUS) for distinguishing benign versus malignant ovarian masses. A total of 48 ovarian masses (37 benign and 11 borderline/malignant) were examined with TV-CEUS (Definity; Lantheus, North Billerica, MA; Philips iU22; Philips Medical Systems, Bothell, WA). Parametric images were created offline with a quantification software (Bracco Suisse SA, Geneva, Switzerland) with map color scales adjusted such that abnormal hemodynamics were represented by the color red and the presence of any red color could be used to differentiate benign and malignant tumors. Using these map color scales, low values of the perfusion parameter were coded in blue, and intermediate values of the perfusion parameter were coded in yellow. Additionally, for each individual color (red, blue, or yellow), a darker shade of that color indicated a higher intensity value. Our study found that the parametric mapping method was considerably more sensitive than standard region of interest (ROI) analysis for the detection of malignant tumors but was also less specific than standard ROI analysis. Parametric mapping allows for stricter cutoff criteria, as hemodynamics are visualized on a finer scale than ROI analyses, and as such, parametric maps are a useful addition to TV-CEUS analysis by allowing ROIs to be limited to areas of the highest malignant potential.

Incidence, risk factors, and outcome of pneumatosis intestinalis in pediatric stem cell transplant recipients.

BACKGROUND: Pneumatosis Intestinalis (PI) is a rare complication following hematopoietic stem cell transplant (HSCT). We sought to assess the incidence, risk factors, and outcome associated with PI. PROCEDURE: We retrospectively reviewed the incidence of PI among 178 patients who underwent allogeneic HSCT between September 1999 and February 2010. RESULTS: Eighteen of 178 children (10.1%) who received allogeneic HSCT developed PI at a median of 94 days (range, 11-1169) after transplant. All patients presented with either abdominal pain or distention, and half of the patients had free air on radiographs. Patients who developed PI had a significantly higher proportion of acute (83% vs. 44%, P = 0.002) and chronic graft versus host disease (GVHD; 56% vs. 18%, P < 0.001). Only 39% of patients with PI had GVHD involving the gasterointestinal track. All patients were managed conservatively without surgery. Transplant related mortality (TRM) was significantly higher in patients who developed PI compared to those who did not (OR 4.3, 95% CI: 1.3-13.1; P = 0.007), but no deaths were attributable to PI. CONCLUSIONS: We conclude that PI is a common complication associated with treatment of GVHD after HSCT, and patients who develop PI experience higher TRM. Patients who develop PI should be managed medically.

NRF2 deficiency reduces life span of mice administered thoracic irradiation.

Subsets of cancer survivors who have been subjected to thoracic irradiation face the prospect of developing pulmonary injury. Radiation-induced pulmonary fibrosis is an insidious injury that presents 6 to 24 months after irradiation and continues to progress over a period of years. TGF-ß and reactive oxygen species contribute significantly to the pathogenesis of this injury. The transcription factor NRF2 controls antioxidant gene expression and therefore regulates the cellular oxidant burden. This work demonstrates an additional paradigm for NRF2: suppression of TGF-ß-mediated signaling, assessed by measuring expression of a surrogate TGF-ß1 target gene (PAI-1) in lung fibroblasts. Thoracic irradiation of Nfe2l2(-/-) mice resulted in rapid expression of PAI-1 and FSP-1 compared to irradiated wild-type mice. Examination of lung tissue 16 weeks after thoracic irradiation of Nfe2l2(-/-) mice revealed the presence of distended alveoli and decreased numbers of alveoli compared to wild-type mice. Suppression of NRF2 expression shortened life span in mice administered 16 Gy to the thorax. Nfe2l2(+/-) and Nfe2l2(-/-) mice exhibited a mean life span of 176 days compared to wild-type mice, which lived an average of 212 days. These novel results identify NRF2 as a susceptibility factor for the development of late tissue injury.