Ultrasensitive Ultrasound Microvessel Imaging for Characterizing Benign and Malignant Breast Tumors.

Tumor angiogenesis plays an important role during breast tumor growth. However, conventional Doppler has limited sensitivity to detect small blood vessels, resulting in a large overlap of Doppler features between benign and malignant tumors. An ultrasensitive ultrasound microvessel imaging (UMI) technique was recently developed. To evaluate the performance of UMI, we studied 44 patients with 51 breast masses. Tumor pathology served as the gold standard: 28 malignancies and 23 benignities. UMI provided a significant improvement in depicting smaller vessels compared with conventional Doppler. The microvessel morphologies observed on UMI were associated with tumor benign/malignant classification. The diagnostic accuracy of correct Breast Imaging Reporting and Data System (BI-RADS) classification rate (BI-RADS ≥4a: test positive; BI-RADS ≤3: test negative) as a fraction of total mass population was improved by 16% after combining conventional ultrasound with UMI compared with using conventional ultrasound alone. This improvement indicates the potential of UMI in reducing unnecessary benign biopsies and avoiding missed malignant biopsies.

Follow-up outcomes of benign vascular lesions of breast diagnosed on core needle biopsy: A study of 117 cases.

Benign vascular lesions of breast are uncommon findings on core biopsy and surgical excision has been recommended to rule out a more serious lesion. However, a recent study suggested that excision may be spared for vascular lesion without atypia. The aim of this study was to assess the follow-up outcomes in lesions yielding benign vascular lesions on core biopsy. We retrospectively reviewed 117 patients with diagnosis of hemangioma (106 patients) and atypical hemangioma (11 patients) on core biopsy at our institution over an 18-year period. Majority of benign vascular lesions were followed-up clinically and/or radiologically. Surgical excision was performed on 18 patients (16.9%) with benign hemangiomas and all 11 patients (100%) with atypical hemangiomas. Upon excision, the majority of patients (82.8%, 24/29) retained benign final pathology and five patients (17.2%) were atypical hemangioma. There was no upgrade on excision. All patients had a benign course regardless whether the lesions were excised or not. Our findings support the recent study that benign vascular lesion of breast may not require surgical excision.

Lymphatic and blood vessels in male breast cancer.

BACKGROUND: It is assumed that lymphatic vessels are responsible for breast cancer dissemination. PATIENTS AND METHODS: In 32 male breast carcinomas we evaluated the correlation between: (i) lymphatic vessel density (LVD), distribution of podoplanin-immunostained vessels (DPV), blood vessel density (BVD), infiltration of immune cells and (ii) known clinicopathological parameters. RESULTS: Lymphatic and blood vessels were found in 77.8% and 100% of breast carcinomas, respectively. Double-negative estrogen and progesterone receptor tumors (ER-/PR-) presented significantly higher LVD than ER/PR positive cases, while high-grade tumors exhibited significantly higher DPV than low-grade carcinomas. We detected significantly higher frequency of vascular invasion in high-grade and double-negative carcinomas than in low-grade and ER/PR-positive ones, respectively. CONCLUSION: The relationship between high number of lymphatic vessels and high tumor grade or steroid receptor negativity might confirm the hypothesis regarding the influence of lymphangiogenesis on the formation of a more aggressive phenotype in male breast cancer.

COX-2 expression does not correlate with microvessel density in breast cancer.

BACKGROUND: Cyclooxygenase-2 (COX-2), implicated in carcinogenesis and tumour progression in many cancers including breast cancer, is hypothesised to cause progression by promoting angiogenesis. The exact mechanism of such action is not known and the clinical evidence of such interaction is weak. We studied COX-2 expression and microvessel density (MVD) in malignant breast tissues. METHODS: COX-2 expression was analysed by immunohistochemistry in 89 breast cancer cases. MVD was assessed by CD31 immunohistochemistry using the Chalkey count method. COX-2 expression and MVD data were correlated with each other and with other prognostic factors. RESULTS: COX-2 expression, observed in 70 (79%) cases, correlated positively with tumour type (p = 0.037) and tumour grade (p = 0.045), but negatively with oestrogen receptor (p = 0.013). It did not correlate with tumour size, axillary lymph node status, progesterone receptor and HER-2 status. MVD varied from 2.09 to 40.38, correlated positively with tumour grade (p = 0.050) and tumour size (p = 0.044), but negatively with progesterone receptor (p = 0.040). MVD did not correlate with tumour type, axillary lymph node status, oestrogen receptor and HER-2. There was no correlation between COX-2 expression and MVD (p = 0.702). CONCLUSIONS: COX-2 expression does not correlate with angiogenesis in breast cancer. Angiogenesis in breast cancer may be dependent on multiple genes, rather than on COX-2 alone.

Pleomorphic hyalinizing angiectatic tumor of the male breast: a heretofore unreported occurrence.

Pleomorphic hyalinizing angiectatic tumor (PHAT) is considered an unusual mesenchymal tumor of intermediate malignant potential that is distinguished by a prominent angiectatic vasculature with clusters of thin-walled, fibrin-lined vessels surrounded by sheets of spindled and pleomorphic cells. This lesion occurs mostly in the subcutaneous soft tissues of the lower extremities. In this paper, the authors report the first case of PHAT involving the breast parenchyma of a 75-year-old man. The patient was referred to the hospital with a history of a painless left breast mass that had been growing for several years. The lesion did not recur after surgery. The tumor exhibited histopathologic and immunohistochemical features identical to those of a PHAT of other sites. The purpose of this report is to add a rare tumor to the differential diagnosis of mammary spindle cell neoplasms.

B-mode, power Doppler and contrast-enhanced power Doppler ultrasonography in the diagnosis of breast tumors.

PURPOSE: To investigate the role of B-mode and unenhanced and enhanced power Doppler ultrasonography (US) in differentiating solid breast lesions, and to find out whether morphologically different tumors differ in terms of vascularity. MATERIAL AND METHODS: Sixty-five lesions, indeterminate or suggestive of malignancy after mammography were prospectively examined with B-mode and unenhanced and enhanced power Doppler US. The lesions were classified as benign, indeterminate or malignant at B-mode, and as benign or malignant at power Doppler US. The results were compared to the histologic diagnoses. Vascularity was analyzed also quantitatively to find out whether threshold values for differential diagnostics could be set. RESULTS: The sensitivity, specificity, and overall accuracy of the morphologic evaluation were 100%, 10%, and 57%, respectively. Rounded lesions were more vascular than spiculated lesions, but vascular assessment was only helpful when it supported a benign morphology. In quantitative analysis, due to the overlap between the benign and malignant lesions, no threshold values could be set. CONCLUSION: Morphologic criteria were useful in characterizing malignant lesions, but the large proportion of indeterminate findings decreased the specificity of US. Neither unenhanced, nor enhanced power Doppler US was able to improve diagnostic accuracy.

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer.

BACKGROUND AND OBJECTIVES: p53, c-erbB-2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer. METHODS: A retrospective study of expression of p53, c-erbB-2, and tumor microvascular density was done on a group of 26 male breast cancer patients. Biotin-streptavidin immunohistochemical study with specific anti-p53, anti-c-erbB-2, and anti-CD34 antibodies was carried out on paraffin sections of breast carcinoma. The data of expression of the biomarkers were merged with clinicopathological data such as tumor grade, T class, TNM stage, estrogen receptor status, tumor recurrence, and patient survival. RESULTS: p53 and c-erbB-2 were expressed in 46% and 39% of carcinomas, respectively. No correlation was found between positive immunoreactivity of p53, and tumor grade, size, T class, TNM stage, and survival. Nor was any relation found between tumor size, T class, TNM stage, survival, and c-erbB-2 overexpression. c-erbB-2 overexpression was significantly higher in high grade carcinomas. Estrogen receptor (ER) were positive in 21 out of 26 of tumors (81%). No trends were observed between estrogen receptor status and clinicopathological parameters or survival (data not shown). There was a positive correlation between mean microvascular density (MVD), advanced T class, and survival: higher MVD counts were found in patients with advanced tumors and in those who had tumor relapses or died of metastatic disease. CONCLUSIONS: This study suggests that tumor microvascular density may serve as a potential prognostic tool in male breast carcinoma.

Double-phase Tc-99m sestamibi scintimammography to assess angiogenesis and P-glycoprotein expression in patients with untreated breast cancer.

This study evaluated the relation of Tc-99m sestamibi (MIBI) uptake and washout in untreated breast cancer with immunohistochemically determined angiogenesis and P-glycoprotein expression. Thirty-one patients with untreated breast cancer were studied prospectively. Tc-99m MIBI scintigraphy and immunohistochemical analyses of angiogenesis and P-glycoprotein expression were used to evaluate surgically removed tumor tissues. Anterior and both lateral planar images were acquired 10 and 180 minutes after intravenous injection of 740 MBq (20 mCi) Tc-99m MIBI. The tumor-to-normal breast ratio (T:N) and washout index (early T:N - late T:N divided by early T:N) were calculated. A significant correlation was found between angiogenesis and T:N at early and late images. Pearson's correlation coefficients and probability values were r = 0.54, P = 0.002 at early images and r = 0.47, P = 0.008 at late images. The T:N of both early and late images were not different among different groups of P-glycoprotein expression (P = 0.367 and P = 0.113, respectively), although the washout index was significantly different among the groups (P = 0.001). A strong correlation was found between the washout index and P-glycoprotein expression (r = 0.67, P < 0.01). Double-phase scintimammography to assess the early tumoral uptake and washout of Tc-99m MIBI can be used as a simple functional test for in vivo imaging of tumoral angiogenesis and P-glycoprotein expression in patients with untreated breast cancer.

D-galactose-based signal-enhanced color Doppler sonography of breast tumors and tumorlike lesions.

RATIONALE AND OBJECTIVES: This study sought to evaluate prospectively the diagnostic potential of unenhanced and enhanced color Doppler and power Doppler for the differentiation of tumors and tumorlike lesions of the breast. METHODS: Ninety-two patients with 110 tumors or tumorlike lesions of the breast were investigated by unenhanced and enhanced color and power Doppler ultrasound. The sonomorphologic aspects of vascularization were analyzed. In addition, maximal systolic frequency shift, resistance, and pulsatility indices were determined. RESULTS: In 15 (24%) of 63 primary carcinomas, 15 (68%) of 22 fibroadenomas, and all (100%) of 14 postoperative lesions, the sonomorphologic analysis for the differential diagnosis of breast tumors was improved after contrast enhancement in color Doppler mode. In comparing unenhanced color Doppler to power Doppler, the latter was found to be slightly superior (sensitivity, 60% vs. 67%; specificity, 39% vs. 45%, respectively); after enhancement, both modes were equivalent (sensitivity, 100% vs. 100%; specificity, 95% vs. 95%, respectively). Signal enhancement resulted in a significant improvement in sensitivity and specificity (P < 0.01). Typical signs of malignancy were irregular vessel calibers, serpiginous courses, penetration of the tumor's margin, and irregular reticular vascularization. The quantitative parameters proved not to be helpful for the differential diagnosis of breast tumors. CONCLUSIONS: By improved analysis of the vascularization pattern, d-galactose-enhanced color Doppler sonography was found to provide more reliable differential diagnostic information than unenhanced Doppler ultrasound in tumors and tumorlike lesions of the breast.

Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis.

PURPOSE: To compare qualitative and quantitative magnetic resonance (MR) mammographic features of breast lesions with histopathologic findings, especially tumor angiogenesis. MATERIALS AND METHODS: Seventy-three patients (72 women, one man; aged 30-78 years; mean age, 51.0 years) with suspicious breast lesions underwent MR imaging. Noncontrast medium-enhanced localization imaging and then gadolinium-enhanced dynamic fast spoiled gradient-recalled-echo (SPGR) imaging were performed in all patients. In selected patients, subtraction fast SPGR images were obtained. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between enhancement parameters and microvessel determinations. RESULTS: Time intensity curve type correlated with microvessel density grade (Spearman rank correlation test: r = .90, P < .001). The steepest slope of contrast medium uptake correlated with microvessel counts (Pearson correlation test; r = .83, P < .001). Peripheral enhancement in invasive carcinomas (n = 9) correlated with high peripheral and low central microvessel densities, which were associated with desmoplasia and/or necrosis. Internal septations (n = 2) were seen only in fibroadenomas. CONCLUSION: The density and distribution of microvessels may play major roles in the determination of the initial rate of contrast medium uptake and the heterogeneity of tumor enhancement.