False negative breast cancers on imaging and associated risk factors: a single institution six-year analysis.

PURPOSE: Mitigating false negative imaging studies remains an important issue given its association with worse morbidity and mortality in patients with breast cancer. We aimed to identify risk factors that predispose to false negative breast imaging exams. METHODS: In an IRB-approved, HIPAA compliant retrospective study, we identified all patients who were diagnosed with breast cancer within 365 days of a negative imaging study assessed as BI-RADS 1-3 between January 1, 2014 and January 31, 2020. A matched cohort based on mammographic breast density was created from randomly selected studies with BI-RADS 4-5 designation that yielded breast cancer at pathology within the same time frame. Patient and cancer characteristics, prior personal history of breast cancer and gene mutation status were collected from patient charts. Pearson chi-squared and Student's t-test on two independent groups with significance at < 0.05 was used for statistical analysis. RESULTS: We identified 155 false negative studies of 129 missed cancers and 128 breast density matched true positive cancers. False negative studies were screening mammograms in 57.42% (89/155), diagnostic mammograms in 29.68% (46/155), ultrasounds in 6.45% (10/155) and MRIs in 6.45% (10/155). Rates of personal (41.09% vs. 18.75%, p < 0.001) and family history of breast cancer (68.22% vs. 49.21%, p = 0.002) were higher in the false negative cohort and remained significant when asymptomatic MRI-detected cancers were removed. CONCLUSION: Our findings suggest that supplemental screening may be useful in breast cancer survivors.

Breast Cancer Disparity and Outcomes in Underserved Women.

Women in the United States who continue to face obstacles accessing health care are frequently termed an underserved population. Safety-net health care systems play a crucial role in mitigating health disparities and reducing burdens of disease, such as breast cancer, for underserved women. Disparities in health care are driven by various factors, including race and ethnicity, as well as socioeconomic factors that affect education, employment, housing, insurance status, and access to health care. Underserved women are more likely to be uninsured or underinsured throughout their lifetimes. Hence they have greater difficulty gaining access to breast cancer screening and are less likely to undergo supplemental imaging when needed. Therefore, underserved women often experience significant delays in the diagnosis and treatment of breast cancer, leading to higher mortality rates. Addressing disparities requires a multifaceted approach, with formal care coordination to help at-risk women navigate through screening, diagnosis, and treatment. Mobile mammography units and community outreach programs can be leveraged to increase community access and engagement, as well as improve health literacy with educational initiatives. Radiology-community partnerships, comprised of imaging practices partnered with local businesses, faith-based organizations, homeless shelters, and public service departments, are essential to establish culturally competent breast imaging care, with the goal of equitable access to early diagnosis and contemporary treatment. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the Online Learning Center. See the invited commentary by Leung in this issue.

Imaging and Management of Fibroepithelial Lesions of the Breast: Radiologic-Pathologic Correlation.

Fibroepithelial lesions (FELs) are among the most common breast masses encountered by breast radiologists and pathologists. They encompass a spectrum of benign and malignant lesions, including fibroadenomas (FAs) and phyllodes tumors (PTs). FAs are typically seen in young premenopausal women, with a peak incidence at 20-30 years of age, and have imaging features of oval circumscribed hypoechoic masses. Although some FA variants are especially sensitive to hormonal influences and can exhibit rapid growth (eg, juvenile FA and lactational adenomas), most simple FAs are slow growing and involute after menopause. PTs can be benign, borderline, or malignant and are more common in older women aged 40-50 years. PTs usually manifest as enlarging palpable masses and are associated with a larger size and sometimes with an irregular shape at imaging compared with FAs. Although FA and FA variants are typically managed conservatively unless large and symptomatic, PTs are surgically excised because of the risk of undersampling at percutaneous biopsy and the malignant potential of borderline and malignant PTs. As a result of the overlap in imaging and histologic appearances, FELs can present a diagnostic challenge for the radiologist and pathologist. Radiologists can facilitate accurate diagnosis by supplying adequate tissue sampling and including critical information for the pathologist at the time of biopsy. Understanding the spectrum of FELs can facilitate and guide appropriate radiologic-pathologic correlation and timely diagnosis and management of PTs. Published under a CC BY 4.0 license. Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Imaging Challenges in Diagnosing Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) refers to a heterogeneous group of carcinomas that have more aggressive biologic features, faster growth, and a propensity for early distant metastasis and recurrence compared with other breast cancer subtypes. Due to the aggressiveness and rapid growth of TNBCs, there are specific imaging challenges associated with their timely and accurate diagnosis. TNBCs commonly manifest initially as circumscribed masses and therefore lack the typical features of a primary breast malignancy, such as irregular shape, spiculated margins, and desmoplastic reaction. Given the potential for misinterpretation, review of the multimodality imaging appearances of TNBCs is important for guiding the radiologist in distinguishing TNBCs from benign conditions. Rather than manifesting as a screening-detected cancer, TNBC typically appears clinically as a palpable area of concern that most commonly corresponds to a discrete mass at mammography, US, and MRI. The combination of circumscribed margins and hypoechoic to anechoic echogenicity may lead to TNBC being misinterpreted as a benign fibroadenoma or cyst. Therefore, careful mammographic and sonographic evaluation with US image optimization can help avoid misinterpretation. Radiologists should recognize the characteristics of TNBCs that can mimic benign entities, as well as the subtle features of TNBCs that should raise concern for malignancy and aid in timely and accurate diagnosis. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Outcome of Imaging and Biopsy of BI-RADS Category 3 Lesions: Follow-Up Compliance, Biopsy, and Malignancy Rates in a Large Patient Cohort.

OBJECTIVES: To identify biopsy rates and indications for BI-RADS 3 lesions in a large cohort of patients and compare with follow-up compliance and malignancy outcomes. METHODS: We retrospectively reviewed all BI-RADS category-3 lesions seen on mammography and/or ultrasound between 2013 and 2015. Patient age, lesion size, follow-up rates at 6-, 12-, and 24-months were collected. Biopsy timing, indication, and outcomes (malignant vs benign) were recorded using at least 2-year follow-up or biopsy pathology as endpoint. RESULTS: Of 2319 BI-RADS 3 lesions in 2075 women analyzed, biopsy was performed in 173 (7.5%). Most biopsies were performed upfront (99, 57.2%), followed by at 6 (44, 25.4%), 12 (21, 12.1%), and 24-month follow-up (9, 5.2%; P < .001). Palpable (P < .001) and larger (median 1.4 vs 1.0 cm, P < .001) lesions in women <40 years (15.2% vs 4.8%, P < .001) were more likely to undergo biopsy. Most biopsies were prompted by patient/physician desire (64.5%, P < .001). Of 783 lesions with available endpoint, 5 (0.6%) were cancer. All cancers were identified either at presentation (in 0-5 months, n = 1) or 6-month follow-up (in 5-9 months, n = 4) with biopsy prompted by either morphology change (n = 3) or lesion growth (n = 2). Of the 1855 lesions which were expected for follow up, only 310 (16.7%) underwent all follow-ups, while 482 (26.1%) had two, 489 (26.5%) one, and 565 (30.6%) had no follow-up. CONCLUSIONS: In our cohort, BI-RADS category 3 lesions had significantly higher biopsy rates compared with the small malignancy rate, all of which were identified at baseline or first follow-up. Overall patient follow-up compliance low. Imaging follow-up, especially at first 6-month time point, should be encouraged in BI-RADS 3 lesions, instead of upfront biopsies.

Axillary Lymphadenopathy in the COVID-19 Era: What the Radiologist Needs to Know.

Axillary lymphadenopathy caused by the high immunogenicity of messenger RNA (mRNA) COVID-19 vaccines presents radiologists with new diagnostic dilemmas in differentiating vaccine-related benign reactive lymphadenopathy from that due to malignant causes. Understanding axillary anatomy and lymphatic drainage is key to radiologic evaluation of the axilla. US plays a critical role in evaluation and classification of axillary lymph nodes on the basis of their cortical and hilar morphology, which allows prediction of metastatic disease. Guidelines for evaluation and management of axillary lymphadenopathy continue to evolve as radiologists gain more experience with axillary lymphadenopathy related to COVID-19 vaccines. General guidelines recommend documenting vaccination dates and laterality and administering all vaccine doses contralateral to the site of primary malignancy whenever applicable. Guidelines also recommend against postponing imaging for urgent clinical indications or for treatment planning in patients with newly diagnosed breast cancer. Although conservative management approaches to axillary lymphadenopathy initially recommended universal short-interval imaging follow-up, updates to those approaches as well as risk-stratified approaches recommend interpreting lymphadenopathy in the context of both vaccination timing and the patient's overall risk of metastatic disease. Patients with active breast cancer in the pretreatment or peritreatment phase should be evaluated with standard imaging protocols regardless of vaccination status. Tissue sampling and multidisciplinary discussion remain useful in management of complex cases, including increasing lymphadenopathy at follow-up imaging, MRI evaluation of extent of disease, response to neoadjuvant treatment, and potentially confounding cases. An invited commentary by Weinstein is available online. ©RSNA, 2022.

ACR BI-RADS Category 3 Lesions in Women Younger Than 30: Follow-up Outcomes and Factors Associated With Biopsy.

OBJECTIVE: Investigate imaging follow-up patterns and assessment of malignancy rate of BI-RADS 3 lesions in women younger than 30 years. METHODS: We retrospectively reviewed consecutive studies between January 1, 2013 and January 1, 2015 with BI-RADS 3 assessment in women <30 years. Lesion size, follow-up rate, and biopsy rate were recorded. Completion of 24-month imaging follow-up or biopsy determined the endpoint. Statistical analysis of follow-up rates and biopsy timing was performed. RESULTS: Of 2525 BI-RADS 3 lesions, 278 were identified in 215 women <30 years. Fifty-two (24%) women underwent a biopsy which was more frequently done at patient request than for lesion growth [33 (63.4%) versus 19 (36.5%), P <.01]. The odds of having biopsy upfront was significantly higher in lesions >2 cm in diameter (OR: 4.4 [95% CI 2.1-9.4], P <.01). The malignancy rate in our cohort was 0% (95% CI 0-1.7%). Of the 188 women expected for follow-up imaging, 58 (30%) were lost to follow-up, while 103 (55%) had 6-month follow-up, 74 (39%) 12-month follow-up, and 56 (30%) 24-month follow-up. CONCLUSIONS: BI-RADS 3 lesions identified in our cohort had high biopsy rates and low compliance with no cancers. Our findings suggest that probable fibroadenomas in young women may only warrant abbreviated short-term follow-up at 6-months.

Multimodality Imaging-based Evaluation of Single-Lumen Silicone Breast Implants for Rupture.

Breast implants are frequently encountered on breast imaging studies, and it is essential for any radiologist interpreting these studies to be able to correctly assess implant integrity. Ruptures of silicone gel-filled implants often occur without becoming clinically obvious and are incidentally detected at imaging. Early diagnosis of implant rupture is important because surgical removal of extracapsular silicone in the breast parenchyma and lymphatics is difficult. Conversely, misdiagnosis of rupture may prompt a patient to undergo unnecessary additional surgery to remove the implant. Mammography is the most common breast imaging examination performed and can readily depict extracapsular free silicone, although it is insensitive for detection of intracapsular implant rupture. Ultrasonography (US) can be used to assess the internal structure of the implant and may provide an economical method for initial implant assessment. Common US signs of intracapsular rupture include the "keyhole" or "noose" sign, subcapsular line sign, and "stepladder" sign; extracapsular silicone has a distinctive "snowstorm" or echogenic noise appearance. Magnetic resonance (MR) imaging is the most accurate and reliable means for assessment of implant rupture and is highly sensitive for detection of both intracapsular and extracapsular rupture. MR imaging findings of intracapsular rupture include the keyhole or noose sign, subcapsular line sign, and "linguine" sign, and silicone-selective MR imaging sequences are highly sensitive to small amounts of extracapsular silicone. ©RSNA, 2017.

Radiologic-Pathologic Correlation of Fibroepithelial Lesions: A Pictorial Review.

Fibroepithelial lesions (FEL) of the breast encompass a spectrum of masses ranging from benign to malignant. Although these lesions are on the same biologic spectrum, differences in their clinical behaviors necessitate different management approaches. While imaging features are nonspecific, small size (less than 3 cm), oval shape, circumscribed margins, growth in diameter less than 20% in six months, and homogeneous echotexture on US favor fibroadenoma (FA). Conversely, larger size (3 cm or larger), rapid growth, irregular shape, noncircumscribed margins, and heterogeneous echotexture suggest possible phyllodes tumor (PT). Histopathologically, increased stromal cellularity, stromal atypia, and mitotic activity characterize PT, while FA typically lack these features. In this review, we summarize the imaging and pathology characteristics of nonmalignant FEL, including simple, juvenile, and complex FA, and benign and borderline PT and highlight the collaborative role of radiologists and pathologists in informing diagnosis and clinical management.

Pilot Clinical Study Investigating the Thermal Physiology of Breast Cancer via High-Resolution Infrared Imaging.

This descriptive study investigates breast thermal characteristics in females histologically diagnosed with unilateral breast cancer and in their contralateral normal breasts. The multi-institutional clinical pilot study was reviewed and approved by the Institutional Review Boards (IRBs) at participating institutions. Eleven female subjects with radiologic breast abnormalities were enrolled in the study between June 2019 and September 2019 after informed consent was obtained. Static infrared images were recorded for each subject. The Wilcoxon signed rank test was used to conduct paired comparisons in temperature data between breasts among the eight histologically diagnosed breast cancer subjects (n = 8). Localized temperatures of cancerous breast lesions were significantly warmer than corresponding regions in contralateral breasts (34.0 ± 0.9 °C vs. 33.2 ± 0.5 °C, p = 0.0142, 95% CI 0.25-1.5 °C). Generalized temperatures over cancerous breasts, in contrast, were not significantly warmer than corresponding regions in contralateral breasts (33.9 ± 0.8 °C vs. 33.4 ± 0.4 °C, p = 0.0625, 95% CI -0.05-1.45 °C). Among the breast cancers enrolled, breast cancers elevated temperatures locally at the site of the lesion (localized hyperthermia), but not over the entire breast (generalized hyperthermia).

Neurofibroma in the Breast: Diagnosis and Management Considerations.

Neurofibroma (NF) of the breast is an uncommon benign entity that occurs sporadically or in association with neurofibromatosis type 1 (NF1). Sporadic NF of the breast is very rare and can present at any age. Neurofibroma of the breast associated with NF1 is more common. Neurofibroma commonly presents as oval, circumscribed masses that overlap with many benign entities. The histopathologic diagnosis of NF of the breast can present a management dilemma for the breast radiologist. An NF that is not associated with NF1 has good post-resection prognosis if superficial, sporadic, and solitary. However, NF of the breast diagnosed in an otherwise healthy patient should prompt evaluation for NF1 and formal genetic risk assessment. Patients diagnosed with NF1 have a higher lifetime risk for developing breast cancer and therefore may benefit from both initiating screening mammography at a younger age and supplemental screening MRI.

Determining the thermal characteristics of breast cancer based on high-resolution infrared imaging, 3D breast scans, and magnetic resonance imaging.

For over the three decades, various researchers have aimed to construct a thermal (or bioheat) model of breast cancer, but these models have mostly lacked clinical data. The present study developed a computational thermal model of breast cancer based on high-resolution infrared (IR) images, real three-dimensional (3D) breast surface geometries, and internal tumor definition of a female subject histologically diagnosed with breast cancer. A state-of-the-art IR camera recorded IR images of the subject's breasts, a 3D scanner recorded surface geometries, and standard diagnostic imaging procedures provided tumor sizes and spatial locations within the breast. The study estimated the thermal characteristics of the subject's triple negative breast cancer by calibrating the model to the subject's clinical data. Constrained by empirical blood perfusion rates, metabolic heat generation rates reached as high as 2.0E04 W/m3 for normal breast tissue and ranged between 1.0E05-1.2E06 W/m3 for cancerous breast tissue. Results were specific to the subject's unique breast cancer molecular subtype, stage, and lesion size and may be applicable to similar aggressive cases. Prior modeling efforts are briefly surveyed, clinical data collected are presented, and finally thermal modeling results are presented and discussed.

Breast Lesions in Women Aged Younger than 30 Years: Clinical Presentation, Diagnosis, and Management.

Women aged younger than 30 years frequently present with palpable breast lesions, breast pain, and nipple discharge. Diagnostic work-up often results in benign findings, including a variety of benign solid masses, infectious or inflammatory conditions, pregnancy- or lactation-related abnormalities, and normal variants. While rare, breast cancer can occur within this demographic, and it is often more advanced and aggressive than in older women. Other rare tumors can present within this patient demographic, including primary sarcoma of the breast and granular cell tumors. A knowledge of the clinical presentation, diagnostic approach, and management of this spectrum of pathologic entities is crucial to ensure optimal and cost-effective care within this patient demographic.

Lymphangitic spread of invasive lobular carcinoma to the contralateral breast.

Breast cancer typically spreads primarily to regional lymph nodes and subsequently to distant sites via hematogenous routes. Occasionally metastasis can occur through lymphangitic spread, usually to the lungs, resulting in lymphangitic carcinomatosis. Lymphangitic spread of several malignancies have been reported at other sites in the body with varying degrees of clinical significance. In this case report, we describe a rare case of lymphangitic spread of invasive lobular carcinoma to the contralateral breast identified on imaging as significant background enhancement without a discrete suspicious mass.

Magnetic resonance imaging characteristics of granulomatous mastitis.

Granulomatous mastitis (GM) is a benign chronic inflammatory condition of the breast. This study was performed to determine the utility of magnetic resonance imaging (MRI) in differentiating GM from malignancy. MRI findings in 12 women with clinical or histopathologically-proven GM were retrospectively reviewed. Non-mass enhancement on MRI was present in all 12 patients with clustered ring enhancement being the most common pattern (n=7, 58%). Architectural distortion (n=10, 83%), skin thickening (n=10, 83%) and focal skin enhancement (n=10, 83%) were also very common. MRI features of GM are often identical to features considered suspicious for malignancy on MRI.