Standardization of radiological evaluation of dynamic contrast enhanced MRI: application in breast cancer diagnosis.

Dynamic contrast enhanced MRI is applied as an adjuvant tool for breast cancer detection, diagnosis, and follow-up of therapy. Despite improvements through the years in achieving higher spatial and temporal resolution, it still suffers from lack of scanning and processing standardization, and consequently, high variability in the radiological evaluation, particularly differentiating malignant from benign lesions. We describe here a hybrid method for achieving standardization of the radiological evaluation of breast dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI) protocols, based on integrating the model based three time point (3TP) method with principal component analysis (PCA). The scanning and image processing procedures consisted of three main steps: 1. 3TP standardization of the MRI acquisition parameters according to a kinetic model, 2. Applying PCA to test cases and constructing an eigenvectors' base related to the contrast-enhancement kinetics and 3. Projecting all new cases on the eigenvectors' base and evaluating the clinical outcome. Datasets of overall 96 malignant and 26 benign breast lesions were recorded on 1.5T and 3T scanners, using three different MRI acquisition parameters optimized by the 3TP method. The final radiological evaluation showed similar detection and diagnostic ability for the three different MRI acquisition parameters. The area under the curve of receiver operating characteristic analysis yielded a value of 0.88 ± 0.034 for differentiating malignant from benign lesions. This 3TP+PCA hybrid method is fast and can be readily applied as a computer aided diagnostic tool of breast cancer. The underlying principles of this method can be extended to standardize the evaluation of malignancies in other organs.

Eosinophilic cystitis in a 4-year-old boy: successful long-term treatment with cyclosporin A.

A 4-year-old Jewish boy presented with dysuria, urinary dribbling, increased urinary frequency, and new onset of diurnal enuresis. An infiltrating solid mass involving the entire bladder wall was found. Biopsy revealed "tumor-forming" eosinophilic cystitis, a rare bladder lesion of unclear cause. Antitoxocariasis treatment was unsuccessful. High-dose corticosteroids failed. The child's clinical condition and bladder sonographic findings continued to deteriorate. Treatment with cyclosporin A was given for 8 months, with a complete clinical, radiologic, and histopathologic cure and no side effects. Two years of follow-up showed a complete recovery.

Lupus-like syndrome with submassive hepatic necrosis associated with hepatitis A.

Hepatitis A is a common self-limited liver disease. However, 15% of patients may have some complications. Autoimmune hepatitis that is triggered by viral hepatitis has been reported. We hereby describe an unrecognized association of hepatitis A with a full blown lupus-like syndrome manifested by the appearance of arthralgia, exudative pleural effusion with the presence of lupus erythematosus cells and autoantibodies. All these findings disappeared after a short course of steroid treatment. The case is presented and the literature is reviewed.

Topoisomerase IIalpha expression in ductal carcinoma in situ of the breast: a preliminary study.

Ductal carcinoma in situ (DCIS) of the breast, a precursor lesion of invasive breast cancer, is a heterogeneous disease in terms of histomorphologic features and biologic behavior. Our aim was to assess the proliferative activity, expressed as topoisomerase IIalpha (Topo IIalpha) immunoreactivity and c-erbB-2 expression in relation to morphologic features and architectural pattern of DCIS. The study included 26 DCIS, which were reclassified according to the recommendations of Consensus Conference. Topo-IIalpha and c-erbB-2 immunoreactivity were detected on paraffin sections. Topo IIalpha was consistently negative in normal ductal epithelium. Topo IIalpha-labeling index (Topo IIalpha-LI) was 0.7+/-0.6% for grade I, 4.3+/-3.9% for grade II, and 13.4+/-8.9 for grade III lesions (P<.01). For mixed nuclear grade DCIS, Topo IIalpha-LI was 6.8+/-4.8. There was no difference in Topo IIalpha-LI between different architectural patterns in low- and intermediate-grade lesions. In high nuclear grade DCIS, there was a progressive increase in Topo IIalpha-LI from solid toward cribriform and comedo-type DCIS. Positive c-erbB-2 immunoreactivity was found in 46% of DCIS, being highest in DCIS with high nuclear grade (78%) and in lesions with extensive necrosis. Topo IIalpha-LI was significantly higher in c-erbB-2-positive lesions (Topo IIalpha-LI- 12.4+/-8.5) as compared with negative lesions (Topo IIalpha-LI- 3.9+/-4.5, P<. 0001). Overexpression of c-erbB-2 and Topo IIalpha is associated with poorly differentiated lesions. Proliferative activity in individual ducts of DCIS depended primarily on the nuclear grade and was independent of architectural patterns of individual ducts in architecturally heterogeneous lesions.

Telomerase activity in ductal carcinoma in situ of the breast.

Telomerase plays an important role in maintaining the stability of the chromosomes. Activity of telomerase has been detected in proliferating and immortalized cell lines and in a number of malignant tumors including invasive breast cancer. The aim of the study was to examine telomerase activity in ductal carcinoma in situ (DCIS), which is considered to be a precursor lesion of infiltrating breast carcinoma, using a PCR-based telomerase activity protocol (TRAP). We examined 35 samples obtained from histologically confirmed breast biopsies, including 13 normal breast tissues, 11 infiltrating ductal carcinoma (IDC), nine DCIS, and two DCIS with microinvasion. Telomerase activity was demonstrated in 8/9 samples of DCIS, both samples of DCIS with microinvasion, and all but one sample of IDC. Normal breast tissue had no demonstrable telomerase activity. Our results indicate that telomerase is activated frequently in early breast carcinogenesis, although its utilization as a biomarker in DCIS is questionable.