Naoko Mori

Radiologic-pathologic correlation of ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) accounts for 20%-25% of breast cancers detected at screening mammography. The lesions are diverse and commonly are classified on the basis of their mammographic features and histologic characteristics such as nuclear grade and presence or absence of necrosis. The most common mammographic finding in DCIS is microcalcifications, but a low-grade lesion without necrosis is less likely to manifest with calcifications than either an intermediate- or a high-grade lesion. Other mammographic findings might include a mass or architectural distortion. Magnetic resonance (MR) imaging has higher sensitivity than mammography for the detection of DCIS and greater accuracy for depicting the extent of disease. The MR imaging appearance of DCIS depends primarily on the presence and extent of abnormal periductal or stromal vascularity. Nonmasslike enhancement, the most common MR imaging finding, is often seen in association with clumped internal enhancement. The enhancement kinetics in dynamic MR studies vary, and no kinetic pattern is pathognomonic of a particular nuclear grade of DCIS. However, the kinetic pattern at delayed imaging does appear to be correlated with the mammographic findings: Mass lesions show strong washout; fine pleomorphic, fine linear, and fine linear-branching calcifications demonstrate a plateau enhancement pattern; and amorphous calcifications exhibit persistent enhancement. Multidetector computed tomography might be a useful adjunct to MR imaging for preoperative mapping.

Luminal-type breast cancer: correlation of apparent diffusion coefficients with the Ki-67 labeling index.

PURPOSE To evaluate the correlation between apparent diffusion coefficient ( ADC apparent diffusion coefficient ) values and the Ki-67 labeling index for luminal-type (estrogen receptor-positive) breast cancer not otherwise specified ( NOS not otherwise specified ) diagnosed by means of biopsy. MATERIALS AND METHODS The institutional review board approved this retrospective study, and the requirement for informed consent was waived. Between December 2009 and December 2012, 86 patients with 86 lesions with luminal-type invasive breast cancer NOS not otherwise specified underwent magnetic resonance imaging, including dynamic contrast material-enhanced imaging and diffusion-weighted imaging with b values of 0 and 1000 sec/mm(2). Conventional measurement of the minimum and mean ADC apparent diffusion coefficient s by placing regions of interest and histogram analysis of pixel-based ADC apparent diffusion coefficient data of the entire tumor were performed by two observers independently and correlated with the Ki-67 labeling index of surgical specimens. RESULTS For the interobserver reliability, interclass correlation coefficients for all parameters with the exception of the minimum ADC apparent diffusion coefficient exceeded 0.8, indicating almost perfect agreement. The minimum ADC apparent diffusion coefficient and mean ADC apparent diffusion coefficient and the 25th, 50th, and 75th percentiles of the histograms showed negative correlations with the Ki-67 labeling index (r = -0.49, -0.55, -0.54, -0.53, and -0.48, respectively). Receiver operating characteristic curve analysis for the differential diagnosis between the high-proliferation (Ki-67 ≥ 14; n = 44) and low-proliferation (Ki-67 < 14; n = 42) groups revealed that the most effective threshold for the mean ADC apparent diffusion coefficient was lower than 1097 × 10(-6) mm(2)/sec, with sensitivity and specificity of 82% and 71%, respectively. The area under the receiver operating characteristic curve (AUC) was 0.81 for the mean ADC apparent diffusion coefficient . There were no significant differences in the AUC among the parameters. CONCLUSION Considering convenience for routine practice, the authors suggest that the mean ADC apparent diffusion coefficient of the conventional method would be practical to use for estimating the Ki-67 labeling index.

Kinetic Analysis of Benign and Malignant Breast Lesions With Ultrafast Dynamic Contrast-Enhanced MRI: Comparison With Standard Kinetic Assessment

OBJECTIVE The purposes of this study were to evaluate diagnostic parameters measured with ultrafast MRI acquisition and with standard acquisition and to compare diagnostic utility for differentiating benign from malignant lesions. MATERIALS AND METHODS Ultrafast acquisition is a high-temporal-resolution (7 seconds) imaging technique for obtaining 3D whole-breast images. The dynamic contrast-enhanced 3-T MRI protocol consists of an unenhanced standard and an ultrafast acquisition that includes eight contrast-enhanced ultrafast images and four standard images. Retrospective assessment was performed for 60 patients with 33 malignant and 29 benign lesions. A computer-aided detection system was used to obtain initial enhancement rate and signal enhancement ratio (SER) by means of identification of a voxel showing the highest signal intensity in the first phase of standard imaging. From the same voxel, the enhancement rate at each time point of the ultrafast acquisition and the AUC of the kinetic curve from zero to each time point of ultrafast imaging were obtained. RESULTS There was a statistically significant difference between benign and malignant lesions in enhancement rate and kinetic AUC for ultrafast imaging and also in initial enhancement rate and SER for standard imaging. ROC analysis showed no significant differences between enhancement rate in ultrafast imaging and SER or initial enhancement rate in standard imaging. CONCLUSION Ultrafast imaging is useful for discriminating benign from malignant lesions. The differential utility of ultrafast imaging is comparable to that of standard kinetic assessment in a shorter study time.

Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment

Background:Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment.Methods:Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis.Results:Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues.Conclusion:These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens.

Multidetector row helical computed tomography for invasive ductal carcinoma of the breast: correlation between radiological findings and the corresponding biological characteristics of patients.

The aim of this study is to evaluate the correlation between multidetector row helical computed tomography (MDCT) findings and the histopathological characteristics of patients with invasive ductal carcinoma. We retrospectively reviewed MDCT findings and the corresponding histopathological features of 442 women with invasive ductal carcinoma. We received informed consent from the patients and the protocol was approved by the Ethics Committee at Tohoku University. The median age was 53 years (26–89 years). We examined the MDCT findings based on mass shape classified into well, moderate, poorly and scattered demarcated shapes, the enhancement pattern classified into homogenous, heterogeneous, rim and poor, and mass density classified into high, intermediate or low. We subsequently compared these radiological findings with the histological characteristics and clinical outcome. Poorly demarcated types were higher in ER+/HER2− (P = 0.008), while the well‐demarcated type was higher in ER−/HER2− and ER−/HER2+ (P < 0.001 and P = 0.010). Rim pattern was higher in ER−/HER2− (P < 0.001). Intermediate or low density was higher in ER−/HER2− (P < 0.001, respectively). Further analysis based on histological grade, mitotic counts and lymphovascular invasion demonstrated that the well‐demarcated shape was higher in grade 2 and 3 (P = 0.006 and P < 0.001, respectively), and rim pattern was observed in grade 3 (P < 0.001). Regarding mitotic counts, poorly and scattered demarcated shapes were observed in score 1 (P = 0.008 and P = 0.014), while well‐demarcated shape and rim enhancement were observed in score 3 (P < 0.001, respectively). Lymphovascular invasion correlated with a moderate demarcated shape (P = 0.029). Regarding recurrence rates, there were statistically significant differences between well and moderate, poorly or scattered demarcated shapes (P = 0.007, 0.028 and 0.035, respectively). These proposed MDCT diagnostic criteria based on biological characteristics contribute to more accurately predicting the biological behavior of breast cancer patients. (Cancer Sci 2012; 103: 67–72)

Value of breast MRI for patients with a biopsy showing atypical ductal hyperplasia (ADH)

To evaluate the diagnostic value of dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) for patients with atypical ductal hyperplasia (ADH) in predicting malignant upgrade.

18 F-fluorodeoxyglucose specimen-positron emission mammography delineates tumour extension in breast-conserving surgery: Preliminary results

ObjectivesWe aimed to determine whether high-resolution specimen-positron emission mammography (PEM) using fluorodeoxyglucose (18F-FDG) can reveal extension of breast cancer in breast-conserving surgery (BCS), and assess the safety of radiation exposure to medical staff.MethodsSixteen patients underwent positron emission tomography, and then BCS with intraoperative frozen section analysis on the same day. Resected specimens with remaining 18F-FDG accumulation were scanned by high-resolution PEM. At least 1 day after surgery, tumour extension was evaluated by three independent experienced readers and by binarized images from the specimen-PEM data. Intraoperative exposure of medical staff to 18F-FDG was measured.ResultsSpecimen-PEM evaluations of binarized images and the three investigators detected all (100 %, 12/12) invasive lesions and 94.4 % (17/18) of in situ lesions using both methods. The positive predictive value of the accumulated lesions was 74.4 % (29/39) for the binarized images and 82.9 % (29/35) for the three investigators. Analysis of intraoperative frozen sections detected 100 % (2/2) of the margin-positive cases, also detected by both specimen-PEM evaluation methods with no false-positive margin cases. The mean exposure of the medical staff to 18F was 18 μSv.ConclusionsSpecimen-PEM detected invasive and in situ lesions with high accuracy and allowable radiation exposure.Key points• Specimen-PEM detected invasive and in situ lesions with high accuracy.• Specimen-PEM predicted complete resection with the same accuracy as frozen section analysis.• Breast-conserving surgery after fluorodeoxyglucose injection was performed with low medical staff exposure.

The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed ankylosing arthritis

[Background] McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop arthritis in the ankle, leading finally to ankylosis. There is no published data that drug treatment has been trialed on these mice. [Objectives] This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16-1, for the treatment of ankylosis in McH-lpr/lpr-RA1 mice. [Methods] Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16-1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines. [Results] Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at every age. The kappa coefficient was 0.77. However, progression of ankylosis persisted in the MR16-1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16-1 treated groups. [Conclusions] Administration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for spondyloarthritis. IL6 signal blockade could contribute to the treatment of spondyloarthritis, and further studies should be carried out to confirm its potential in the prevention of deformity associated with ankylosis.

Assessment of the risk of low bone mineral density in premenopausal Japanese female patients with systemic lupus erythematosus

Background The aim of this study was to assess the relationships between clinical parameters and bone mineral density (BMD) in Japanese female patients with systemic lupus erythematosus (SLE). Methods A total of female 136 SLE patients without menopause were retrospectively assessed to identify associations between age, disease duration, body mass index (BMI), glucocorticoid usage and disease activity and BMD based on the treatment with or without bisphosphonate. There were 71 patients treated with bisphosphonate (bisphosphonate group) and 65 patients without (non-bisphosphonate group). We evaluated the impact of age, disease duration, BMI, serologic SLE markers, glucocorticoid use on BMD of the anterior-posterior (AP) and lateral lumbar spine, total hip and femoral neck using univariate and multivariate linear regression analyses of both bisphosphonate and non-bisphosphonate groups. Results Multivariate linear regression analyses showed that in non-bisphosphonate group disease duration was negatively associated with BMD of AP spine and femoral neck, whereas in bisphosphonate group these negative associations were not present. However, multivariate linear regression analyses showed a significant relationship between BMI and BMD of the AP spine, femoral neck and total hip, regardless of bisphosphonate treatment. Conclusions Bisphosphonate treatment eliminated the negative relationships between disease duration and the BMD of the spine and hip. AP spine and hip BMD in patients with SLE depend on BMI, regardless of bisphosphonate use. SLE serologic markers and glucocorticoid use were not negatively associated with generalized bone loss. SLE patients with low BMI have a high risk of generalized bone loss, and should be assessed and treated to prevent osteoporosis even before menopause.

Diagnostic value of electric properties tomography (EPT) for differentiating benign from malignant breast lesions: comparison with standard dynamic contrast-enhanced MRI

ObjectivesTo evaluate the diagnostic utility of electric properties tomography (EPT) in differentiating benign from malignant breast lesions in comparison with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).MethodsIn this institutional review board-approved retrospective study, 116 consecutive patients with 141 breast lesions (50 benign and 91 malignant) underwent 3-T MRI, including 3D turbo-spin echo (TSE) sequence and standard DCE-MRI scans between January 2014 and January 2017. The lesions were segmented semi-automatically using subtraction DCE-MR images, and they were registered to the phase images from 3D TSE. The mean conductivity of the lesion was obtained from phase-based reconstruction of lesions. From the DCE-MRI, initial enhancement rate (IER) and signal enhancement ratio (SER) were calculated from signal intensity (SI) as follows: IER = (SIearly - SIpre)/SIpre, SER = (SIearly - SIpre)/(SIdelayed - SIpre). The parameters from EPT and the DCE-MRI were compared between benign and malignant lesions.ResultsThere was significant difference in mean conductivity (0.14 ± 1.77 vs 1.14 ± 1.36 S/m, p < 0.0001) and SER (0.77 ± 0.28 vs 1.04 ± 0.25, p < 0.0001) between benign and malignant lesions, but not in IER (p = 0.06). Receiver operating curve (ROC) analysis revealed that the area under the curve (AUC) of the mean conductivity and SER was 0.71 and 0.80, respectively, without significant difference (p = 0.15).ConclusionsThe mean conductivity of EPT was significantly different between benign and malignant breast lesions as well as kinetic parameter or SER from DCE-MRI.Key Points• The conductivity of malignant lesions was higher than that of benign lesions.• EPT helps differentiatie benign from malignant lesions.• Diagnostic ability of EPT was not significantly different from that of DCE-MRI.