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Background Metastasized NSCLC with an ALK fusion are sensitive to a range of tyrosine kinase inhibitors. ALK-positive NSCLC has been identified in the pivotal phase III trial with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC+ FISH-. The aim of this study was to collect ALK IHC+ cases and compare within this group response to crizotinib treatment of ALK FISH+ cases with ALK FISH- cases. Method A prospective multicenter investigator initiated research study was started in Europe. Stage IV ALK IHC+ NSCLC cases treated with crizotinib were collected centrally. Slides were validated centrally for ALK IHC (with 5A4 ETOP and D5F3 Ventana protocol) and ALK FISH (Vysis probes). Result The study started April 1, 2014 and closed in November 2017. Fifteen centers participated. Registration of 3523 ALK IHC tests revealed prevalence of 2.6% ALK IHC+ cases. Local ALK FISH analysis resulted in 46 concordant (ALK IHC+/FISH+) and 18 discordant (ALK IHC+/FISH-) cases. Central validation revealed 37 concordant and 6 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The time to treatment failure did not differ for concordant nor discordant cases, and neither for local nor validated ALK testing (HR=0.78; 95% CI= 0.27-2.3; p=0.64) and (HR=2.2; 95% CI= 0.72-6.5; p=0.16), respectively). However, overall survival was significantly better for concordant cases than discordant cases after central validation (HR=4.5; 95% CI= 1.2-15.9; p=0.010), but not according to local testing (HR=1.7; 95% CI= 0.45-6.2; p=0.44). Conclusion ALK IHC+ FISH- NSCLC cases are an infrequent finding. We recommend such cases to be validated carefully because our data indicate that ALK IHC+ FISH- cases have a worse survival when treated by crizotinib compared to ALK IHC+ FISH+ cases. This study was funded by an independent research grant by Pfizer.

Introduction/ Background The whole slide imaging (WSI) market has developed enormously in the recent years. This evolution has made the selection and the implementation of digital pathology more complicated. Based on a validation process, we developed recommendations that need to be taken into account when implementing whole slide imaging. In addition to selecting the right hardware, one should also focus on laboratory organization, integration, training and handling. Aims The aim is to integrate WSI as efficiently as possible in a standardized process. This should lead to a user friendly workflow for pathologists and must ensure the quality of the diagnosis. Methods We organized on-site demonstrations to test several available WSI systems with a fixed set of histology slides. We evaluated scanning quality, measured the scanning time, the amount of data produced and made a simulation of a routine workflow. We developed a to-be workflow beginning with the scanning process until the final diagnosis of the pathologist. The workflow focused on the integration of the system into the laboratory information system. We standardized the technical laboratory processes to increase the quality of the slides and the efficiency of WSI. The standardization included good labeling, adequate quality, standardized location and correct number of sections on the slide. We introduced a continuous workflow to reduce batch size and to decrease the turn-around-time. The pathologists were only allowed to work with WSI after training in order to manipulate the images as efficiently as possible. Finally we validated the system according to CAP guidelines for WSI for diagnostic purpose in pathology. Results It is very important to determine what the purpose of WSI implementation in the lab is. The different systems show large variations between them and not every set up will fit in the specific workflow of each lab. The workflow simulation gave us an idea of the scanning turn-around-time and made it possible to estimate the amount of scanners that would be necessary in daily routine. Another focus point is the total integration of WSI to find a synergy between the hardware, workflow and the way the system can be integrated into the IT infrastructure of the lab. Beside the bidirectional communication with the laboratory information system, data storage organization and its influence on the lab’s productivity is also very important. Organizing the laboratory with a standardized continuous workflow will reduce the amount of data, increase speed and lower the amount of rescans. To prevent that WSI is used inefficiently, it is crucial to train the pathologists before they start using it. A lack of training will lead to a dislike of WSI due to poor knowledge of the available applications. The pathologists are indicating that it’s crucial to have the correct hardware to manipulate the image in order to ensure diagnostic speed and to lower the threshold towards WSI. We may conclude that choosing and implementing the correct WSI solution needs a systematic approach to succeed on the long term. Defining and optimizing the workflow before implementing whole slide imaging is crucial. Hardware, workflow and IT infrastructure should match to ensure productivity. Training of the pathologists is decisive in order to ensure efficient use., Diagnostic Pathology, Vol 1 No 8 (2016): 13. European Congress on Digital Pathology

Background and Objectives: The diagnostic role of endoscopic ultrasound (EUS) in children has been demonstrated only recently. Data on the technique’s therapeutic indications remain scarce. We evaluated diagnostic and interventional EUS indications, safety, and impact in children with pancreaticobiliary disorders. Patients and Methods: We retrospectively reviewed our single pediatric center experience covering a 14-year period. Results: Between January 2000 and 2014, 52 EUS procedures were performed on 48 children (mean age 12 years) with pancreaticobiliary disorders for suspected biliary obstruction (n = 20/52), acute/chronic pancreatitis (n = 20), pancreatic mass (n = 3), pancreatic blunt trauma (n = 7), and ampullary adenoma (n = 2). Positive impact of EUS was observed in 51/52 procedures (98%), precluding using endoscopic retrograde cholangiopancreatography (ERCP) (n = 9), focusing on endotherapy (n = 21), or reorienting therapy toward surgery (n = 7). EUS-guided fine needle aspiration was carried out on 12 patients. Thirteen therapeutic EUS procedures were conducted, nine of which were combined EUS-ERCP procedures (three EUS-guided pseudocyst drainage, one EUS-guided transgastric biliary drainage of a metastatic rhabdomyosarcoma). Conclusions: We report on a large pediatric EUS series for diagnostic and therapeutic pancreaticobiliary disorders, showing a significant impact of diagnostic EUS and affording insights into novel EUS and combined EUS-ERCP therapeutic applications. We suggest considering EUS as a diagnostic and therapeutic tool in the management of pediatric biliopancreatic diseases.

In medical care cervical cancer screening is important because it enables the detection of precancer and cancer at an early stage. By adequate treatment after a screening-detected lesion it helps to reduce the mortality related to cervical cancer. Worldwide, many millions of women have smears taken at a more or less regular base and of these, approximately 7% are abnormal, and follow-up is thus required. As this represents an important cost in medical health care and has serious consequences for the affected women, it is important to have uniform and clear guidelines to allow an optimal follow-up and clinical management. A system for the uniform reporting of cervical cytology has been designed by the National Cancer Institute (USA) and resulted in the Bethesda System 1991. The present paper and the terminology used are based on the Bethesda System revised in 2001. It explains the guidelines, based on the 2001 Bethesda System and the 2004 consensus guidelines for the management of women with cervical cytological abnormalities, as developed by the members of the Board of the Belgian Society of Clinical Cytology, and adapted to the Belgian situation.