39 research outputs found

    Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors

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    CONTEXT: Lymphangioleiomyomatosis (LAM) is a cystic lung disease that can be included in the wide group of proliferative lesions named PEComas (perivascular epithelioid cell tumors). These proliferative tumors are characterized by the coexpression of myogenic and melanogenesis-related markers. In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway. These data have opened a new era in the comprehension of the pathogenesis of LAM and have also suggested new therapeutic strategies for this potentially lethal disease. OBJECTIVE: To present and discuss the pathologic and molecular features of LAM within the spectrum of PEComas, providing a rational approach to their diagnosis. DATA SOURCES: The published literature and personal experience. CONCLUSIONS: The inclusion of LAM within the PEComa category is supported by a variety of biologic data and can significantly help in providing a comprehensive view of this interesting and clinically relevant group of lesions. The demonstration of molecular alterations of the mTOR pathway in LAM and other PEComas represents a rational basis for innovative therapeutic approaches with inhibitors of mTOR signalin

    HHV-8 and EBV are not commonly found in idiopathic pulmonary fibrosis

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    BACKGROUND AND AIM OF THE WORK: Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia (IPF/UIP) is a diffuse and progressive lung disease whose pathogenesis is incompletely understood. Recently, the presence of Herpesvirus-specific DNA was detected in the large majority of cases of a series of IPF/UIP and other lung interstitial diseases. We have therefore tested our own IPF/UIP series for the presence of HHV-8 and EBV proteins. METHODS: We used a variety of sensitive technologies including immunohistochemistry with NCL-HHV8-LNA and EBV-LMP1 antibodies, as well as of EBV RNA (EBER) by in-situ hybridisation; the presence of HHV-8 and EBV DNA was also investigated by means of PCR and subsequent analysis using a microfluidic apparatus. RESULTS: Despite the good sample quality, immunohistochemical, in-situ hybridisation and PCR results were negative for both EBV and HHV-8. CONCLUSIONS: We conclude that EBV and HHV-8 are not involved in the pathogenesis of IPF/UIP

    Benign breast lesions at risk of developing cancer. A challenging problem in breast cancer screening programs. Five years\u2019 experience of the breast cancer screening programin Verona (1999-2004)

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    BACKGROUND: Cytology and core-needle biopsies are not always sufficient to exclude malignancy in benign breast lesions (BBL) that are at risk of developing cancer, and open biopsy often is mandatory. In screening programs, open biopsies performed for lesions that are at risk of developing malignancy are considered benign. The authors of this report evaluated the impact of the screen-detected BBL at risk of developing cancer that were counted in the quota of benign breast open biopsies in the Breast Cancer Screening Program of Verona. METHODS: Benign open biopsies were subdivided into 4 groups according to their risk of developing cancer: Histo1, normal histology; Histo2, 'pure' BBL (fibroadenoma, fibrocystic disease, mastitis, adenosis); Histo3, BBL with a low risk of developing cancer (radial scar, papilloma, papillomatosis, phyllodes tumor, mucocele-like lesion); and Histo4, BBL with a high risk of developing cancer (atypical columnar cell hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia). RESULTS: Of 510 open biopsies, 83 biopsies were benign, and the ratio of benign to malignant biopsies was 1:5. Histo1 was observed in 4.8% of all benign open biopsies, Histo2 was observed in 37.4%, Histo3 was observed in 31.3%, and Histo4 was observed 26.5%. CONCLUSIONS: BBL at risk of developing cancer may be numerous in screening programs. It is inappropriate to include BBL at risk of developing cancer in the overall benign open biopsy rate. The authors propose separating pure BBL from lesions at higher risk of developing cancer. To date, there is no evidence to support the premise that detecting high-risk proliferative lesions leads to benefits in terms of reduced mortality; however, these lesions need to be counted separately for future evaluations. \ua9 2008 American Cancer Society
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