Stratigraphic evolution of the Triassic\u2013Jurassic succession in the Western Southern Alps (Italy) : the record of the two-stage rifting on the distal passive margin of Adria

The Triassic-Lower Jurassic succession of the Southern Alps is characterized by rapid thickness changes, from an average of about 5000m east of Lago Maggiore to about 500m in the Western Southern Alps. The stratigraphy reflects the Triassic evolution of the Tethyan Gulf and the Early Jurassic rifting responsible for the Middle Jurassic break-up of Adria from Europe. The succession of the Western Southern Alps starts with Lower Permian volcanics directly covered by Anisian sandstones. The top of the overlying Ladinian dolostones (300m) records subaerial exposure and karstification. Locally (Gozzano), Upper Sinemurian sediments cover the Permian volcanics, documenting pre-Sinemurian erosion. New biostratigraphic data indicate a latest Pliensbachian-Toarcian age for the Jurassic synrift deposits that unconformably cover Ladinian or Sinemurian sediments. Therefore, in the Western Southern Alps, the major rifting stage that directly evolved into the opening of the Penninic Ocean began in the latest Pliensbachian-Toarcian. New data allowed us to refine the evolution of the two previously recognized Jurassic extensional events in the Southern Alps. The youngest extensional event (Western Southern Alps) occurred as tectonic activity decreased in the Lombardy Basin. During the Sinemurian the Gozzano high represents the western shoulder of a rift basin located to the east (Lombardy). This evolution documents a transition from diffuse early rifting (Late Hettangian-Sinemurian), controlled by older discontinuities, to rifting focused along a rift valley close to the Pliensbachian-Toarcian boundary. This younger rift bridges the gap between the Hettangian-Sinemurian diffuse rifting and the Callovian-Bathonian break-up. The late Pliensbachian-Toarcian rift, which eventually lead to continental break-up, is interpreted as the major extensional episode in the evolution of the passive margin of Adria. The transition from diffuse to focused extension in the Southern Alps is comparable to the evolution of the Central Austroalpine during the Early Jurassic and of the Central and Northern Atlantic margins

Non-small cell lung cancer testing on reference specimens: an italian multicenter experience

Introduction: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. Methods: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. Results: Overall, a median DNA concentration of 3.3 ng/μL (range 0.1–10.0 ng/μL) and 13.4 ng/μL (range 2.0–45.8 ng/μL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/μL (range 0.2–11.9 ng/μL) and 9.3 ng/μL (range 0.5–18.0 ng/μL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. Conclusions: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice

Is there still a role for fine-needle aspiration cytology in breast cancer screening? Experience of the Verona Mammographic Breast Cancer Screening Program with real-time integrated radiopathologic activity (1999-2004).

[No abstract available

Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors

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

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)

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