Lothar Ponhold

US-guided 14-gauge Core-Needle Breast Biopsy: Results of a Validation Study in 1352 Cases

PURPOSE To retrospectively determine the false-negative rate and the underestimation rate of ultrasonography (US)-guided 14-gauge core-needle breast biopsy (CNB) in nonpalpable lesions, with validation at surgical excision histologic examination and with stability during clinical and imaging follow-up. MATERIALS AND METHODS Informed consent was waived by the institutional review board for this retrospective review of 1352 cases. In 1061 cases, patients underwent surgical excision of lesions visible at US subsequent to US-guided 14-gauge CNB. Follow-up of another 291 benign lesions at US-guided 14-gauge CNB histologic examination showed stability during clinical and imaging follow-up for at least 2 years. US and histologic findings were reviewed and compared for agreement. A false-negative finding was defined as pathologically proved cancer for which biopsy results were benign. The false-negative rate was defined as the proportion of all breast cancers with a diagnosis of benign disease at US-guided 14-gauge CNB. The underestimation rate was defined as an upgrade of a high-risk lesion at US-guided 14-gauge CNB to malignancy at surgery. RESULTS US 14-gauge CNB yielded 671 (63.2%) malignant, 86 (8.1%) high-risk, and 304 (28.7%) benign lesions. Each of the 291 benign lesions without surgery remained stable during follow-up. The agreement of US-guided 14-gauge CNB results, surgical excision findings, and follow-up results was 95.8% (kappa = 0.93). False-negative findings were encountered in 11 (0.8%) of 1352 cases, and the false-negative rate was 1.6% (11 of 671 malignancies). All false-negative findings were prospectively identified owing to discordance between imaging results and US-guided 14-gauge CNB histologic findings. The underestimation rate was 31.4%. CONCLUSION US-guided 14-gauge CNB is an alternative to surgical excision for assessing nonpalpable breast lesions.

Magnetic resonance imaging of the breast improves detection of invasive cancer, preinvasive cancer, and premalignant lesions during surveillance of women at high risk for breast cancer.

Purpose: To assess the diagnostic accuracy of mammography, ultrasound, and magnetic resonance imaging (MRI) of the breast in the surveillance of women at high risk for breast cancer. Experimental Design: In this prospective comparison study, women at high risk for breast cancer were offered annual surveillance examinations, consisting of mammography, ultrasound, and MRI, at a single tertiary care breast center. The sensitivity and specificity of each modality was based on the histopathologic evaluation of suspicious findings from all modalities plus the detected interval cancers. Results: Three hundred and twenty-seven women underwent 672 complete imaging rounds. Of a total of 28 detected cancers, 14 were detected by mammography, 12 by ultrasound, and 24 by MRI, which resulted in sensitivities of 50%, 42.9%, and 85.7%, respectively (P < 0.01). MRI detected not only significantly more invasive but also significantly more preinvasive cancers (ductal carcinoma in situ). Mammography, ultrasound, and MRI led to 25, 26, and 101 false-positive findings, which resulted in specificities of 98%, 98%, and 92%, respectively (P < 0.05). Thirty-five (35%) of these false-positive findings were atypical ductal hyperplasias, lesions considered to be of premalignant character. Nine (26%) of those were detected by mammography, 2 (6%) with ultrasound, and 32 (91%) with MRI (P < 0.01). Conclusion: Our results show that MRI of the breast improves the detection of invasive cancers, preinvasive cancers, and premalignant lesions in a high-risk population and should therefore become an integral part of breast cancer surveillance in these patients.

Utility and limitations of 3-Tesla diffusion-weighted magnetic resonance imaging for differentiation of renal tumors

OBJECTIVE To investigate utility and limitations of 3-Tesla diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiation of benign versus malignant renal lesions and renal cell carcinoma (RCC) subtypes. MATERIALS AND METHODS Sixty patients with 71 renal lesions underwent 3 Tesla DW-MRI of the kidney before diagnostic tissue confirmation. The images were retrospectively evaluated blinded to histology. Single-shot echo-planar imaging was used as the DW imaging technique. Apparent diffusion coefficient (ADC) values were measured and compared with histopathological characteristics. RESULTS There were 54 malignant and 17 benign lesions, 46 lesions being small renal masses ≤ 4 cm. Papillary RCC lesions had lower ADC values (p=0.029) than other RCC subtypes (clear cell or chromophobe). Diagnostic accuracy of DW-MRI for differentiation of papillary from non-papillary RCC was 70.3% resulting in a sensitivity and specificity of 64.3% (95% CI, 35.1-87.2) and 77.1 (95% CI, 59.9-89.6%). Accuracy increased to 83.7% in small renal masses (≤ 4 cm diameter) and sensitivity and specificity were 75.0% and 88.5%, respectively. The ADC values did not differ significantly between benign and malignant renal lesions (p=0.45). CONCLUSIONS DW-MRI seems to distinguish between papillary and other subtypes of RCCs especially in small renal masses but could not differentiate between benign and malignant renal lesions. Therefore, the use of DW-MRI for preoperative differentiation of renal lesions is limited.

Prospective evaluation of diffusion-weighted MRI of the bladder as a biomarker for prediction of bladder cancer aggressiveness.

OBJECTIVES To prospectively test the utility of diffusion-weighted magnetic resonance imaging (DW-MRI) for bladder cancer (BCA) staging and grading. METHODS AND MATERIALS We prospectively enrolled 51 consecutive patients (median age = 64 y, range: 30-90y) with suspected BCA with or without gross hematuria who received 3-T DW-MRI before transurethral resection of the bladder. Parametric apparent diffusion coefficient (ADC) maps were automatically calculated from DW-MRI. ADC values (given in × 10(-3)mm(2)/s) of bladder lesions were independently measured by 2 radiologists blinded to histopathology. Comparisons of ADC values with histopathologic features were performed using unpaired t tests. Diagnostic performance was calculated by means of receiver operating characteristics (ROC) statistics. RESULTS We excluded 8 patients: 1 presenting with metastatic melanoma to the bladder, 1 who had an incomplete examination, and 6 without BCA. In the 43 remaining patients (median age = 68 y, range: 41-85 y), the ADC values were lower in high-grade (n = 19, ADC = 0.787) compared with low-grade (n = 24, ADC = 1.233) tumors (P<0.0001) and in muscle-invasive tumors (n = 10, ADC = 0.759) compared with non-muscle-invasive tumors (n = 33, ADC = 1.120, P = 0.0004). The area under the ROC curve was 0.884 for prediction of muscle invasion and 0.906 for prediction of high grade by using ADC values. Rule-in ADC criteria for high-grade lesions and rule-out ADC criteria for muscle invasion were identified by ROC analysis. CONCLUSIONS ADC measurements obtained by DW-MRI are a promising imaging biomarker for prediction of BCA stage and grade providing high sensitivity and specificity. Further studies are necessary to establish the value of this test in guiding decision making in clinical practice.

Quantitative apparent diffusion coefficient measurements obtained by 3-Tesla MRI are correlated with biomarkers of bladder cancer proliferative activity.

Purpose To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer. Materials and Methods Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied. Results Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018). Conclusion ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.

Inter-observer variation and diagnostic efficacy of apparent diffusion coefficient (ADC) measurements obtained by diffusion-weighted imaging (DWI) in small renal masses

Background Diffusion-weighted imaging (DWI) is increasingly used to diagnose renal lesion subtypes. Especially in small renal masses, identification of less aggressive tumor types is of clinical interest, as active surveillance strategies can be applied. Purpose To evaluate the inter-observer variation and diagnostic efficacy of apparent diffusion coefficient (ADC) measurements obtained by DWI in small renal masses ≤4 cm (SRM). Material and Methods This retrospective IRB-approved study included 39 patients (46 SRM: 12 benign, 34 malignant). All underwent a 3 T DWI of SRM prior to surgery. Two radiologists independently analyzed all imaging data by three measurements. Limits of agreement, intraclass correlation coefficients (ICC), group comparisons by t-tests, and ROC analysis were performed. Results Reliability of ADC measurements was very high with an ICC of >0.9 for both observers. Inter-rater reliability was high with an ICC of 0.82. Limits of agreement for average ADC values between both observers were −23.5% to 38.3% with a mean difference of 7.5% between both observers. No significant differences were found between benign and malignant lesions (P value Observer 1: 0.362, Observer 2: 0.622). Papillary carcinoma showed lower ADC values compared to non-papillary carcinoma (P value Observer 1: 0.008, Observer 2: 0.012). Consequently, ROC analysis revealed a significant (P < 0.001, respectively) area under the ROC curve of 0.853 (Observer 1) and 0.837 (Observer 2) without significant differences between both readers (P = 0.772). Conclusion ADC measurements of SRM at 3 T show a high reproducibility and differentiate papillary from non-papillary carcinoma subtypes. However, measurement variability may limit the application of fixed ADC thresholds for lesion diagnosis.