In this paper we evaluate tissue elasticity as a longstanding but qualitative biomarker for prostate cancer and sonoelastography as an emerging imaging tool for providing qualitative and quantitative measurements of prostate tissue stiffness. A Kelvin-Voigt Fractional Derivative (KVFD) viscoelastic model was used to characterize mechanical stress relaxation data measured from human prostate tissue samples. Mechanical testing results revealed that the viscosity parameter for cancerous prostate tissue is greater than that derived from normal tissue by a factor of approximately 2.4. It was also determined that a significant difference exists between normal and cancerous prostate tissue stiffness (p < 0.01) yielding an average elastic contrast that increases from 2.1 at 0.1 Hz to 2.5 at 150 Hz. Qualitative sonoelastographic results show promise for cancer detection in prostate and may prove to be an effective adjunct imaging technique for biopsy guidance. Elasticity images obtained with quantitative sonoelastography agree with mechanical testing and histological results. Overall, results indicate tissue elasticity is a promising biomarker for prostate cancer.

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Biomechanical properties of soft tissues are important for a wide range of medical applications, such as surgical simulation and planning and detection of lesions by elasticity imaging modalities. Currently, the data in the literature is limited and conflicting. Furthermore, to assess the biomechanical properties of living tissue in vivo, reliable imaging-based estimators must be developed and verified. For these reasons we developed and compared two independent quantitative methods -crawling wave estimator (CRE) and mechanical measurement (MM) for soft tissue characterization. The CRE method images shear wave interference patterns from which the shear wave velocity can be determined and hence the Young's modulus can be obtained. The MM method provides the complex Young's modulus of the soft tissue from which both elastic and viscous behavior can be extracted. This article presents the systematic comparison between these two techniques on the measurement of gelatin phantom, veal liver, thermal-treated veal liver, and human prostate. It was observed that the Young's moduli of liver and prostate tissues slightly increase with frequency. The experimental results of the two methods are highly congruent, suggesting CRE and MM methods can be reliably used to investigate viscoelastic properties of other soft tissues, with CRE having the advantages of operating in nearly real time and in situ.

The plasmacytoid variant of urothelial carcinoma is rare, of which less than 40 cases have been reported in the English language literature. Herein we report the largest series to date of 17 cases of urothelial carcinoma with plasmacytoid features and report the associated clinicopathologic findings. The architectural pattern of the tumor varied from cells arranged in cords and single cells (35%), small nests (17%), solid sheetlike growth (29%), and diffuse discohesive patternless architecture (23%). The plasmacytoid component varied from 15% to 100% of the specimen analyzed; in 12 cases the plasmacytoid component composed greater than 50% of the tumor. The individual tumor cells had striking morphologic overlap with plasma cells with an eccentrically placed nucleus and abundant amphophilic to eosinophilic cytoplasm. The nuclei were of low to intermediate nuclear grade with minimal nuclear pleomorphism. Thirteen of 17 cases (76%) were associated with conventional high-grade invasive urothelial carcinoma and 9 cases showed very focal intracytoplasmic vacuoles mimicking signet ring cells. One case also showed sarcomatoid dedifferentiation. The tumor cells were positive for cytokeratin 7 (94%) and cytokeratin 20 (31%); CD138 was positive in 94% of cases. All cases were invasive -- 7 into at least the lamina propria, 7 into at least the muscularis propria, and 3 into perivesical fat. Follow-up information was available in 16 cases (range: 2 wk to 43 mo; mean 10 mo; median 5.5 mo). Eleven patients died of disease and 5 patients were alive with disease. Plasmacytoid variant of urothelial carcinoma is an aggressive subtype associated with poor prognosis. In limited samples, it may be misdiagnosed as chronic cystitis or plasmacytoma, a pitfall further compounded by CD138 expression. Distinction from metastatic carcinoma from other primary sites such as stomach and breast is critical due to differing therapeutic implications.

PURPOSE: To prospectively evaluate the accuracy of 3D sonoelastography for detection of prostate cancer relative to gray scale sonography in vitro.METHODS: Using an Institutional Review Board-approved, HIPAA compliant protocol with informal consent, 19 prostatectomy specimens from patients 46 to 70 years of age with biopsy proven prostate cancer were scanned in 3D using conventional B-scan and sonoelastography using vibrations above 100Hz.Step-sectioned whole-mount histology was utilized to create a 3D volume of the prostate and tumors within it. B-scan ultrasound images and regions of low vibration in the sonoelastography images (hard regions) were formatted in 3D. The lesions in the nineteen cases were analyzed as two groups: G1) pathology-confirmed tumors of 1.0 cc or greater; and G2) pathology-confirmed tumor size less than 1.0 cc. G1 cases were evaluated for B-scan ultrasound and sonoelastography vs. histology as a reference standard and were scored as either a True Positive, a False Positive, a True Negative, or a False Negative. G2 cases were evaluated for sonoelastography only. True positives required 3D lesion correlation between pathology and imaging data. Conventional definitions of accuracy and sensitivity were employed to calculate these statistics. RESULTS: G1 (7 lesions with tumor volume 1.0 cc or greater): Sonoelastography: accuracy of 55%, sensitivity of 71%. B-scan: accuracy of 17%, sensitivity of 29%. Mean tumor size is 3.1cc +/-2.1cc. G2 (22 lesions with tumor volume less than 1.0 cc). Mean tumor size is 0.32 cc +/-0.21 cc. Sonoelastography: accuracy of 34%, sensitivity of 41%, false positives: 6.CONCLUSIONS: Sonoelastography performed considerably better than gray scale sonography in the detection of prostate cancer tumors over 1 cc.