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Background Optoacoustic imaging can assess tumor hypoxia coregistered with US gray-scale images. The combination of optoacoustic imaging and US may have a role in distinguishing breast cancer molecular subtypes. Purpose To investigate whether optoacoustic US feature scores correlate with breast cancer molecular subtypes. Materials and Methods A total of 1972 women (with a total of 2055 breast masses) underwent prebiopsy optoacoustic US in a prospective multi-institutional study between December 2012 and September 2015. Seven readers blinded to pathologic diagnosis scored gray-scale US and optoacoustic US features of the known cancers. Optoacoustic US features within (internal) and outside of the tumor boundary (external) were scored. Immunohistochemistry findings were obtained from pathology reports. Multinomial logistic regression analysis was used to fit the US scores, adding optoacoustic US features to the model to investigate the incremental benefit of each feature. Kruskal-Wallis tests were used to analyze the relationship between molecular subtypes and feature scores. Results Among 653 invasive cancers identified in 629 women, a total of 532 cancers in 519 women, all of which had molecular markers available, were included in the analysis. Mean age ± standard deviation was 57.9 years ± 12.6. Mean total external optoacoustic US feature scores of luminal (A and B) breast cancers were higher (9.9 vs 8.8; P < .05) and total internal scores were lower (6.8 vs 7.7; P < .001) than those of triple-negative and human epidermal growth factor receptor 2-positive (HER2+) cancers. A multinomial logistic regression model showed that optoacoustic internal vessel (odds ratio [OR], 0.6; 95% confidence interval [CI]: 0.5, 0.8; P = .002), optoacoustic internal blush (OR, 0.7; 95% CI: 0.5, 0.9; P = .02), and optoacoustic internal hemoglobin (OR, 0.6; 95% CI: 0.5, 0.8; P = .001) were associated with classification of luminal versus triple-negative and HER2+ cancer subtypes. Conclusion Combined optoacoustic US imaging and gray-scale US features may help distinguish luminal breast cancers from triple-negative and human epidermal growth factor receptor 2-positive cancers. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Mann in this issue.

Optoacoustic ultrasound breast imaging is a fused anatomic and functional modality that shows morphologic features, as well as hemoglobin amount and relative oxygenation within and around breast masses. The purpose of this study is to investigate the positive predictive value (PPV) of optoacoustic ultrasound features in benign and malignant masses.In this study, 92 masses assessed as BI-RADS category 3, 4, or 5 in 94 subjects were imaged with optoacoustic ultrasound. Each mass was scored by seven blinded independent readers according to three internal features in the tumor interior and two external features in its boundary zone and periphery. Mean and median optoacoustic ultrasound scores were compared with histologic findings for biopsied masses and nonbiopsied BI-RADS category 3 masses, which were considered benign if they were stable at 12-month follow-up. Statistical significance was analyzed using a two-sided Wilcoxon rank sum test with a 0.05 significance level.Mean and median optoacoustic ultrasound scores for all individual internal and external features, as well as summed scores, were higher for malignant masses than for benign masses (p0.0001). High external scores, indicating increased hemoglobin and deoxygenation and abnormal vessel morphologic features in the tumor boundary zone and periphery, better distinguished benign from malignant masses than did high internal scores reflecting increased hemoglobin and deoxygenation within the tumor interior.High optoacoustic ultrasound scores, particularly those based on external features in the boundary zone and periphery of breast masses, have high PPVs for malignancy and, conversely, low optoacoustic ultrasound scores have low PPV for malignancy. The functional component of optoacoustic ultrasound may help to overcome some of the limitations of morphologic overlap in the distinction of benign and malignant masses.

False-positive findings remain challenging in breast imaging. This study investigates the incremental value of optoacoustic imaging in improving BI-RADS categorization of breast masses at ultrasound.The study device is an optoacoustic breast imaging device with a handheld duplex laser and internal gray-scale ultrasound probe, fusing functional and morphologic information (optoacoustic ultrasound). In this prospective multisite study, breast masses assessed as BI-RADS category 3, 4A, 4B, 4C, or 5 by site radiologists underwent both gray-scale ultrasound and optoacoustic imaging with the study device. Independent reader radiologists assessed internal gray-scale ultrasound and optoacoustic ultrasound features for each mass and assigned a BI-RADS category. The percentage of mass reads for which optoacoustic ultrasound resulted in a downgrade or upgrade of BI-RADS category relative to internal gray-scale ultrasound was determined.Of 94 total masses, 39 were biopsy-proven malignant, 44 were biopsy-proven benign, and 11 BI-RADS category 3 masses were stable at 12-month follow-up. The sensitivity of both optoacoustic ultrasound and internal gray-scale ultrasound was 97.1%. The specificity was 44.3% for optoacoustic ultrasound and 36.4% for internal gray-scale ultrasound. Using optoacoustic ultrasound, 41.7% of benign masses or BI-RADS category 3 masses that were stable at 12-month follow-up were downgraded to BI-RADS category 2 by independent readers; 36.6% of masses assigned BI-RADS category 4A were downgraded to BI-RADS category 3 or 2, and 10.1% assigned BI-RADS category 4B were downgraded to BI-RADS category 3 or 2. Using optoacoustic ultrasound, independent readers upgraded 75.0% of the malignant masses classified as category 4A, 4B, 4C, or 5, and 49.4% of the malignant masses were classified as category 4B, 4C, or 5.Optoacoustic ultrasound resulted in BI-RADS category downgrading of benign masses and upgrading of malignant masses compared with gray-scale ultrasound.

Background The internal mammary (IM) lymph node chain, along with the axillary nodal basin, is a first-echelon breast lymphatic draining site. A growing body of evidence supports irradiation of this region in node-positive breast cancer. This study evaluated the effectiveness of radiotherapy in treating magnetic resonance imaging (MRI)-detected abnormal IM lymph nodes in newly-diagnosed non-metastatic breast cancer. Methods A structured query was performed on an electronic institutional database to identify women with radiographic evidence of abnormal IM node(s) on breast MRI from 2005 to 2013. Manual review narrowed inclusion to patients with a primary diagnosis of non-metastatic breast cancer with abnormal IM node(s) based on pathologic size criteria and/or abnormal enhancement. Results Of the 7070 women who underwent pre-treatment MRI, 19 (0.3%) were identified on imaging to have a total of 25 abnormal pre-treatment IM lymph nodes, of which 96% were located in the first two intercostal spaces and 4% in the third space. A majority of the primary tumors were high-grade (94.7%) and hormone-receptor negative (73.7%), while 47.4% overexpressed HER-2/neu receptor. Axillary nodal disease was present in 89.5% of patients, while one patient had supraclavicular involvement. At a median follow-up of 38 months, 31.6% of patients had developed metastatic disease and 21.1% had died from their disease. Of the patients who received IM coverage, none had progressive disease within the IM lymph node chain. Conclusions Radiologic evidence of pre-treatment abnormal IM chain lymph nodes was associated with advanced stage, high grade, and negative estrogen receptor status. The majority of positive lymph nodes were located within the first two intercostal spaces, while none were below the third. Radiation of the IM chain in combination with modern systemic therapy was effective in achieving locoregional control without surgical resection in this cohort of patients.

Purpose To compare the diagnostic utility of an investigational optoacoustic imaging device that fuses laser optical imaging (OA) with grayscale ultrasonography (US) to grayscale US alone in differentiating benign and malignant breast masses. Materials and Methods This prospective, 16-site study of 2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging Reporting and Data System (BI-RADS) categories assigned by seven blinded independent readers to benign and malignant breast masses using OA/US versus US alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven histologic findings and BI-RADS 3 masses stable at 12 months were eligible. Independent readers reviewed US images obtained with the OA/US device, assigned a probability of malignancy (POM) and BI-RADS category, and locked results. The same independent readers then reviewed OA/US images, scored OA features, and assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were calculated for US and OA/US. Benign and malignant mass upgrade and downgrade rates, positive and negative predictive values, and positive and negative likelihood ratios were compared. Results Of 2105 consented subjects with 2191 masses, 100 subjects (103 masses) were analyzed separately as a training population and excluded. An additional 202 subjects (210 masses) were excluded due to technical failures or incomplete imaging, 72 subjects (78 masses) due to protocol deviations, and 41 subjects (43 masses) due to high-risk histologic results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%] malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%) for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI: 12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99% CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI-RADS 4B) to a posttest probability of 2% (BI-RADS 3). Conclusion OA/US increases the specificity of breast mass assessment compared with the device internal grayscale US alone. Online supplemental material is available for this article. © RSNA, 2017.

Intraductal papillomas (IDPs) of the breast can be associated with a variety of clinical symptoms and radiologic findings. Surgical excision is often recommended based on the possibility of an associated high-grade lesion. Although the rate of upgrades has been extensively evaluated for IDPs, many studies are hindered by broad inclusion criteria, a lack of pathologic-radiologic concordance, and no standard definition of what constitutes an upgrade. In the current study, we evaluate the risk of upgrade for a specific subset of IDPs: non-mass-associated IDPs. We identified all breast needle core biopsies with a diagnosis of IDP between 2003 and 2010. Patients with associated masses, architectural distortion, or ipsilateral breast cancer were excluded. All needle core biopsy slides and relevant imaging studies were reviewed to ensure pathologic-radiologic concordance. Excision pathology was also reviewed; an upgrade was defined as the presence of ductal carcinoma in situ or invasive carcinoma in the excision. Seventy-nine IDPs that met inclusion criteria were identified and were further divided into 3 histologic categories: micropapilloma, fragmented IDP, and atypical IDP. Micropapillomas and fragmented IDPs had no upgrades (0/37). In patients who did not undergo excision, none subsequently developed ipsilateral breast cancer (follow-up, 50-61 months). This is in contrast to atypical IDPs that had a 33% upgrade rate. One patient with an unexcised atypical IDP developed ipsilateral breast cancer within 2 years. Our data suggest that conservative follow-up is reasonable for non-mass-associated IDPs without atypia regardless of microscopic size, provided that careful pathologic-radiologic correlation is achieved.

Vascular tumors occur in approximately 10% of all infants and may be associated with significant morbidity. Available therapies for vascular tumors, such as systemic corticosteroids, vincristine, and interferon-alpha, may cause toxicity, limiting their use to complicated cases. Using a mouse hemangioendothelioma model, we investigated the efficacy and mechanism of action of imiquimod, a topically applied inducer of cytokines. Application of imiquimod cream, whether initiated at the time of cell inoculation or when tumors became visible, significantly decreased tumor growth and increased animal survival in comparison with control mice. Imiquimod-treated tumors showed decreased tumor cell proliferation, increased tumor apoptosis, and increased expression of tissue inhibitor of matrix metalloproteinase-1 with decreased activity of matrix metalloproteinase-9. The demonstration that local application of imiquimod inhibits vascular tumor enlargement in the mouse vascular tumor model suggests a novel, less toxic means of treating infantile hemangioendotheliomas and perhaps other cutaneous vascular tumors.

Purpose The purpose of this study was to identify the axillary lymph nodes on pretreatment diagnostic computed tomography (CT) of the chest to determine their position relative to the anatomic axillary borders as defined by the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Methods and Materials Pretreatment diagnostic CT chest scans available for 30 breast cancer patients with clinically involved lymph nodes were fused with simulation CT. Contouring of axillary levels I, II, and III according to the RTOG guidelines was performed. Measurements were made from the area of distal tumor to the anatomic borders in 6 dimensions for each level. Results Of the 30 patients, 100%, 93%, and 37% had clinical involvement of levels I, II, and III, respectively. The mean number of lymph nodes dissected was 13.6. The mean size of the largest lymph node was 2.4 cm. Extracapsular extension was seen in 23% of patients. In 97% of patients, an aspect of the involved lymph node lay outside of the anatomic border of a level. In 80% and 83% of patients, tumor extension was seen outside the cranial (1.78 ± 1.0 cm; range, 0.28-3.58 cm) and anterior (1.27 ± 0.92 cm; range, 0.24-3.58 cm) borders of level I, respectively. In 80% of patients, tumor extension was seen outside the caudal border of level II (1.36 ± 1.0 cm, range, 0.27-3.86 cm), and 0% to 33% of patients had tumor extension outside the remaining borders of all levels. Conclusions To cover 95% of lymph nodes at the cranial and anterior borders of level I, an additional clinical target volume margin of 3.78 cm and 3.11 cm, respectively, is necessary. The RTOG guidelines may be insufficient for coverage of axillary disease in patients with clinical nodal involvement who are undergoing neoadjuvant chemotherapy, incomplete axillary dissection, or treatment with intensity modulated radiation therapy. In patients with pretreatment diagnostic CT chest scans, fusion with simulation CT should be considered for tumor delineation.

Objectives Symptomatic groin hernias in women may be difficult to assess clinically and commonly mimic pathologic musculoskeletal and gynecologic conditions. The objective of our study was to investigate the accuracy of sonography in women with groin pain and normal physical examination findings. Methods A consecutive group of 87 women (median age, 44.6 years; range, 19-82 years) with groin pain and normal physical examination findings were included in the study. All patients had a standardized sonographic examination of the groin performed by an experienced radiologist or a sonographer. If a groin hernia was identified, it was classified as indirect, direct, or femoral. Normal examination findings and alternate pathologic groin conditions were also recorded. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the sonographic findings and compared to the findings for patients sent for surgery. Results Of the 87 women with groin pain, 37 groin hernias were diagnosed in 35 patients. Surgery was performed in 26 patients (27 groins). Sonography correctly depicted and classified groin hernias in 18 of the 21 groins that had surgical confirmation. Six women without groin hernias also had surgical exploration of the affected side. The sensitivity, specificity, positive predictive value, and negative predictive value for the patients with surgical confirmation were 95%, 75%, 95%, and 75%, respectively. Groin pain in 26 patients was attributed to other causes. The remainder of the patients had normal examination findings or were lost to follow-up. Conclusions Groin hernias in women can be occult and confound the clinical diagnosis. In a woman with groin pain and normal or indeterminate physical examination findings, we have found that sonography can accurately depict and classify groin hernias and other pathologic processes.