Benign and malignant breast lesions: efficacy of real time contrast-enhanced ultrasound vs. magnetic resonance imaging.

PURPOSE: To assess the efficacy of low mechanical index (MI) real time grey scale contrast-enhanced US (CEUS) in the differentiation of breast lesions in comparison to Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: 50 lesions previously detected at mammography or conventional US were evaluated by means of CEUS and MRI. Contrast-enhanced examinations were performed with a dedicated equipment (Esatune, Esaote, Genoa, Italy), before and after injection of 4.8 ml of Sonovue (Bracco, Milan, Italy). MRI was conducted with a 1.5 T equipment (Siemens Vision Plus, Erlangen, Germany) with bilateral dedicated superficial coil, on T2w STIR and 3D Flash T1w before and 1, 2, 3, 4, 5 minutes after the administration of contrast agent (Gd-DTPA, 1.5 ml/kg). Wash-in and wash-out curves were assessed for both procedures. A specific sonographic quantification software (Qontrast, Bracco, Milan, Italy), based on pixel by pixel signal intensity over time, was used to obtain contrast-enhanced sonographic perfusion maps for each lesion. Mc Nemar test was then calculated. RESULTS: 24 invasive ductal carcinomas, 18 fibroadenomas, 4 fibro-cystic dysplasias, 1 mucinous carcinoma, 1 invasive ducto-lobular carcinoma, 1 intraductal florid papillomatosis and 1 phylloides tumour were diagnosed. Contrast-enhanced sonographic patterns correlated well with those provided by MRI. Sensitivity, specificity, and accuracy of US were: 69.2 %, 66.7 %, and 68 %, respectively. According to the different contrast enhancement patterns and the resulting perfusion maps, all the malignant lesions and 9 out of 12 benign lesions were correctly diagnosed, thus resulting in 87.5 % of specificity and 100 % of sensitivity. Regarding the specificity, there is no difference between US and CEUS with McNemar (p = 0.18). Regarding sensitivity, the difference between contrast-enhanced US and US is significant as calculated with McNemar test (p = 0.013). The three lesions which were incorrectly classified as malignant were two hypervascularised fibroadenomas in young women and a phylloides tumour. CONCLUSION: CEUS seems to be a reliable method to differentiate breast lesions, since it provides typical enhancement patterns. Contrast sonographic perfusion curves correlate well with MRI wash in--wash out curves.

Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells.

Autocrine and paracrine mechanisms modulate the synthesis and secretion of extracellular matrix (ECM); moreover, each component of the ECM is capable of modulating the synthesis and release of other ECM molecules. Therefore, the synthesis of ECM glycoprotein fibronectin and laminin was studied in the human breast cancer cell lines MCF7 and MDA MB 23, plated on different ECM. Our results showed that the cells plated on a fibronectin substrate increased laminin synthesis: this event correlated with an increase in alpha2 and alpha3 integrin subunits. Staurosporine-induced apoptosis was then analyzed in the cell lines plated on different ECM. Staurosporine treatment determined the apoptosis of 35 and 33% respectively of MDA MB 231 and MCF7; these values increased to 60 and 64% in cells plated on laminin, to 48 and 63% in cells plated on fibronectin and to 64 and 69% in cells plated on matrigel. Moreover, staurosporine treatment decreased bcl-2 expression in the cells plated on fibronectin and laminin. Yet, staurosporine treatment determined PARP cleavage and PARP partial disappearance when the cells were plated on matrigel. Finally, a partial loss of function mutant Ras protein that activated only Raf pathway, was expressed in MCF7, in order to identify whether the increase of apoptosis induced by extracellular matrix involved the Raf/MAP kinase pathway. The increase of apoptosis of the cells plated on matrigel suggested that the activation of the Raf pathway is probably involved in the decrease of survival on matrigel. These data demonstrate that the modification of ECM modulates the apoptotic process of breast cancer cells and suggest that it is worthwhile to dissect the role of ECM in the control of apoptotic process.

[The breast phyllodes tumor: surgical therapy following histological transformation. Case report]. / II tumore filloide della mammella: terapia chirurgica in presenza di viraggio istologico. Caso clinico.

The Authors report a clinical case of mammary phyllodes tumor recurrence; characterized by the histological transformation of the recurrence respect to primary tumor. PT are 0.3-1% of all mammary neoplasia. They are classified with Tavassoli's criteria (1999). The surgical treatment of PT is the wide excision (WE). Local recurrences are detected in about 20% of patients undergone to surgery. Surgical therapy of recurrences depends on the histological grade of primary lesion. Authors believe it is necessary to perform simple mastectomy when high grade PT recurrences are detected and when histological transformation of the lesion changes from low grade to high grade.

[Changes in the organization of the extracellular matrix at the skin level during diabetes]. / Alterazione dell'organizzazione della matrice extracellulare a livello cutaneo in corso di diabete.

The ultrastructural study of cutaneous biopsies in diabetic patients highlighted in different phases of disease a progressive alteration of extracellular matrix (E.M.). In the initial phase of disease the morphologic aspect showed an increased accumulation of proteoglycan biglycan, laminin, fibronectin and type IV collagen. These components are responsible for the lamina lucida expansion and are induced by TGF-beta. In the last phase of the disease, an accumulation and a defective organization of E.M. component arises. Type V collagen, normally not present in the skin, is observed. In patients with over ten years of diabetic history, the morphological aspect is defined by a progressive disorganization of E.M. The formation of a vicious circle is responsible for the progressive remodeling of E.M. This process may be linked to the not enzymatic glycosylation of E.M., due to several episodes of hyperglycemia, and to autoinductive mechanisms of TGF-beta. These mechanisms are responsible for the cytokine synthesis and for the E.M. inhibition of degradation.

[The intracystic concentration of MCA in the fluid from large breast cysts]. / Concentrazione intracistica dell'MCA nel fluido di grosse cisti della mammella.

75 patients with breast gross cystic disease and no cancer have been included in the study. For each patients serous and intracystic concentrations of MCA have been measured. The aim of the study is to assess whether if a relation between intracystic concentration of the marker and resistance and capability of cellular reproduction exists (confirmed by the release of the cyst). The analysis of intracystic values shows that synthesis of MCA is an intrinsic peculiarity of cytologic kind. It is apparently independent from inflammatory or hemorrhagic contemporary processes.

99m Tc MIBI prone scintimammography in breast Paget's disease: a case report.

A 99m Tc MIBI prone scintimammography (PSM) was performed in a case of underlying Paget's disease of the breast. 99m Tc MIBI PSM showed a diffuse scintigraphic image like a spread of uptake from the deeply located zones of the breast toward epidermis. In vivo, 99m Tc MIBI PSM represents the spread of neoplastic Paget's cells probably attracted by chemotactic factors released by keratinocytes. This spread in Paget's disease is correlated to neu oncogene overexpression which increases the metastatic activity as a consequence of motility enhancement and growth stimulation effect. These scintigraphic images suggest that 99m Tc MIBI PSM could be relevant in management of Paget's disease of the breast.

99mTc MIBI prone scintimammography in patients with suspicious breast cancer: relationship with mammography and tumor size.

99mTc MIBI prone scintimammography (PSM) is reported to be a specific examination in order to assess the nature of breast lesions. Fifty-three patients whose mammography was stratified according to the breast imaging reporting and data system (BI-RADS), the five category classification of mammography approved by the American college of radiology, were studied with prone scintimammography, with the aim of assessing the accuracy of this exam and its usefulness in clinical practice. Thirty-five out of forty-one patients with BI-RADS category V (high probability of cancer) showed cancer at histology. Thirty-one of them had positive PSM. Three out of the six patients with mammo-graphic features of category IV indicated malignancy. PSM was positive in all of them and negative in the three benign lesions. One of the five patients with category III mammography showed cancer and positive PSM. The PSM was negative in 12/13 patients with benign patology (specificity 92.3%). When the cancers were stratified for T-category significant differences were found between the sensitivity for tumors larger or smaller than 1 cm. The sensitivity was 50% for the cancers smaller than 1 cm and 96.9% for those larger than 1 cm. PSM is a very specific method to determine the nature of breast lesions. Its sensitivity is also high but has to be improved when tumors smaller than 1 cm have to be detected. From a clinical point of view PSM can at the moment be considered as an accurate method for the study of borderline lesions of IV and also of III BI-RADS category. In this case a positive PSM indicates an impact in clinical decision making.

[Level of immunosuppressive acidic protein in the fluid of breast cysts]. / Dosaggio della proteina acida immunosoppressiva nel liquido di cisti mammarie.

IAP marker was detected by radio-immunodiffusion in breast gross cyst fluid and in serum. No correlation was found between this antigen and cyst' cytological type, serum concentrations and acute phlogosis. In most cysts IAP was not valuable; on the other hand, high levels of glycoprotein were found only in the subgroup on relapsed class of apocrine cysts.