ORAL PRESENTATION INSTRUCTIONS
Oral presentations will be 10 minutes long plus 5 minutes for discussion. All Oral presentations will take place between 1100 and 1230 on Monday, July 14.
A computer and full powerpoint set up will be provided. Presenters must bring their presentation file on a USB stick.
Presentations will be loaded on the onsite computer early on Monday morning. Details on the time and place to meet to load your presentation will be provided to you when you register at the conference.
Monday, July 13, 1100-1230
Oral Presentations Session 1 – Innovations in Residency Education and Assessment
O101 The Development of a Digital Slide Library for Resident Teaching: The McGill University Experience
P.O. Fiset1, B.T. Cloutier1, A. Lei1, L. Florianova1, V.H. Nguyen1, C. Bernard1. 1Department of Pathology, McGill University Health Centre, Montreal, Quebec.
The development of diagnostic expertise in Pathology depends on case exposure and mentorship. However, day-to-day clinical cases may not expose residents to all pertinent pathologies, and staff pathologists have limited time for teaching. Oftentimes, residents rely on teaching collections which are subject to fading, breakage and misplacement. Whole-slide imaging (WSI) will likely serve as a modern, practical and dependable tool for resident teaching. WSI has already become part of licensure examination, and resident familiarity with this technology is mandatory. The McGill University Digital Slide Library was created as a repository of WSI of slide collections from the McGill University Hospital Centre and affiliated sites. Its goal is to create a database that is easy to access, develop, upgrade and that is interactive for self-learning and self-examination. Over 3000 slides were obtained from collections of eight staff pathologists. Patient info was removed from the slides and WSI was performed using the Aperio ScanScope XT system. An interactive Microsoft PowerPoint presentation template was created to access pertinent clinical histories, diagnoses, WSI of the slides and anonymous pathology reports. After omitting faded or broken slides, 1600 clinical cases were entered into the database. Quality, memory size limitations, patient confidentiality, and network accessibility were some issues resolved in the process. Residents and staff pathologists appreciate the quality of the WSI and the value given by the interactivity of the database. The database is both portable and easy to distribute among residents. The McGill University Digital Slide Library continues to grow and will not only fulfill resident teaching goals but will also serve to prepare for the era of Digital Pathology.
O102 Multi-Site Video-Pathology Gross Specimen Rounds: Assessing Impact on Resident Education and Faculty/Pathologist Assistant Consultation
D.M. Ravi1, I. Alexopoulou1, S. Tomasic1, L. Turner-Smith1. 1Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5.
Aim: To implement and monitor affordable, real time, high-definition (HD) video- pathology gross specimen rounds between two teaching hospitals in Hamilton, Ontario. Background: Gross specimen examination is a critical step in assessing pathology specimens and key in postgraduate education. Residents attend local gross specimen rounds but often miss the opportunity to review remote site cases. In addition, recent Canadian practice trends have resulted in some centers having no pathologist on-site due to redistribution. This creates new challenges. A traditional telepathology solution is often prohibitive due to high cost.
Method: This pilot observational study was conducted between two hospitals over two consecutive years. The equipment included an encoder, decoder, video camera, projector screen and audio system. The specimens were viewed through live video streaming within password protected hospital intranet server on computer monitors or projected via HD liquid crystal display projector. Progress was monitored through feedback from pathologists, residents and pathology assistants (PA).
Results: This technology proved to be a successful off-site specimen viewing method and educational tool for residents. Faculty pathologists and residents at university site and the offsite PA visually assess the remote site’s specimens thus determining the optimal specimen sampling plan.
Conclusion: This pilot study confirms that this is an easy to use, low-cost option. The number of specimen recalls for onsite grossing has been reduced to zero, residents educational experience is expanded by adding offsite gross specimens to their training and the PA job satisfaction has improved. We are planning to extend the technology to include all sites and frozen section sampling. This set up has the potential to enhance resident educational experience with specimens from across the world.
O103 Evaluation and Implementation of a Mobile Digital Tool for Assessment of Resident Grossing Skills
W. Stecho1, A. Haig1, A. Osmond1, M. Weir1. 1Department of Pathology, London Health Science Centre, Schulich School of Medicine & Dentistry, London, Ontario.
Introduction: The upcoming transition to competency-based medical education (CBME) within Canadian residency programs will require an increased frequency of high-quality trainee assessment. A robust and efficient assessment tool will enable supervisors to meet these new educational demands while minimizing the increased administrative burden. In preparation for this transition, our centre evaluated and implemented mobile computing technology for the assessment of resident grossing competencies.
Methods: Pre-existing paper-based grossing skill competency assessment tools were reformatted for easy digital data entry using Microsoft Word. Documents were then converted into fillable PDF forms using Adobe Acrobat XI. An Apple iPad running the PDF Expert app was utilized to allow evaluators to complete digital forms in the grossing room during residency competency assessments. Completed assessments were immediately digitally signed by the supervisor and resident before being secured to prevent further modification. Secured digital copies were emailed to the supervisor and resident for inclusion in their learning portfolios.
Results: The use of fillable PDF forms mimicked the intuitive ease of paper forms, improved data security, and minimized data entry and administration time. Utilization of a mobile platform minimized data replication and offered increased convenience over traditional computing devices. The entire process, from form completion to email distribution, took only minutes and was performed entirely on the iPad at the gross bench upon completion of the assessment. The supervisors were able to learn to use the device and software quickly and easily.
Conclusion: Through the use of mobile computing devices and digital PDF forms, we developed an efficient system which combines the ease-of-use and convenience of our previous paper-based assessment tool, with the speed and data security of computer and web-based assessment systems. Future obstacles to implementation include initial capital costs for the digital device and software, and a shallow software learning curve.
O104 Case Load Assessment During Residency: Towards an Electronic Case Portfolio at the University of Toronto Anatomical Pathology Program
Carlo V. Hojilla1 MD PhD and Simon Raphael1 MD FRCPC. 1Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, 1 King’s College Circle, 6th Floor, Toronto, Ontario M5S 1A8.
Objectives: To our knowledge, pathology residency programs have not made use of case portfolios as an assessment tool. Our goal was to assess the nature of cases at various sites in the University of Toronto Anatomical Pathology Program.
Methods: Laboratory Information Systems were mined for cases by three residents during the 2010-2013 training period. Sites with general and subspecialty practice were included. Total numbers, consults vs. in-house, and “small” vs. “big” cases between residents were compared. For subspecialty training (gastrointestinal [GI], gynecological [Gyne], breast [Brst], genito-urinary [GU], dermatopathology [Derm], and lymphoma [Lymph]), the types of diagnoses were broadly stratified between neoplastic vs. non-neoplastic as well as benign, premalignant and malignant diagnoses.
Results: General sign-out sites showed that >65% of total cases were GI and Gyne cases. Most cases (>99%) seen were in-house cases, with equivalent “small” and “big” cases among trainees. In subspecialty rotations, there was great variation between total number of cases among trainees in GI, Gyne, Brst and Derm. Residents generally saw comparable percentage of neoplastic and non-neoplastic cases. There was considerable disparity between benign, premalignant, and malignant neoplastic diagnoses, with some residents having 0% malignant cases in a GI rotation to seeing as much as 88% malignant cases during a Lymph rotation.
Conclusions: Our study shows substantial differences in case numbers and types seen among residents. As residency training moves towards a competency-based model, our study provides a benchmark measure of resident case loads. The next step is to transform the data to an electronic case portfolio that is in line with competency-based metrics as well as to serve as a complement to residency evaluation.
O105 Developing A Wiki-Based Case Simulator For Anatomical Pathology
M. Bonert, Y. Gao, S. Mortuza, F. X. Torres, S. S. Raab. Eastern Health and the Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador.
Background: Simulated environments are used routinely outside of pathology, and allow individuals to master routine and uncommon situations. Wikis are websites with a relatively easy-to-learn user interface to generate, revise and navigate content. Onlinepathology.org is a free nonprofit wiki-based website, based on the software MediaWiki (mediawiki.org).
Objectives: Develop a set of templates to easily create virtual cases on Onlinepathology.org, using the MediaWiki mark-up language and templates derived from Wikipedia. Reproduce important decision-making steps in anatomical pathology, in a virtual environment, including choosing to (1) examine the tissue at high magnification, (2) seek additional clinical information, (3) order ancillary tests (e.g. special stains, immunostains, molecular tests) and (4) solicit the opinion of a colleague.
Results: Seventy-five virtual cases (www.onlinepathology.org/wiki/index.php/virtualcases) were rapidly created and categorized by subspeciality, and subcategorized by difficulty into three levels (junior resident, senior resident and fellow/expert).
Conclusions: The internal links to the content of the wiki allows for rapid case development, and hierarchically organizes the wealth of information in the wiki that is peripheral to the case. The revision tracking in MediaWiki facilitated case review and discussion. The wiki environment could facilitate long distance case discussions and integrate virtual slides. The simulated environment shows promise as a teaching tool. The simulated cases could be used for self-assessment of diagnostic skills and decision making skills, and for continuing medical education.
O106 A Fully Digital Anatomical Pathology Royal College Of Physicians and Surgeons (RCPS(C)) Certification Examination in Canada: A Pilot Study
Lorna Mirham1, Christopher Naugler2, Malcom Hayes3, Annie Belisle4, Nadia Ismiil1, Sachar Sade1 ,Catherine Streutker1, Christina MacMillan1, Golnar Rasty1, Snezana Popovic5, Beverley Carter6, Mariamma Joseph7, Manal Gabril7, Richard Hegele1, Penny Barnes8, George M Yousef1. 12Departments of Laboratory Medicine 1University of Toronto, 2University of Calgary, 3University of British Columbia, 4University of Montreal, 5McMaster University, 6Memorial University, 7Western University, 7Dalhousie University.
Objectives: The organizing committees for the RCPS(C) Examinations in Canada are currently contemplating digitizing the Pathology certification examinations. To test the feasibility of a fully digital examination, we performed a pilot test followed by an online survey geared towards senior residents across Canada.
Methods: We compared resident performance using glass slides (2 minutes/slide) vs. digital slides (2 vs. 3 minutes / slide). 50% of residents from each program performed the glass slide portion and the remaining 50% performed the digital version of the identical set.
Results: In both groups, the mean score was 4% higher when glass slides were used. This was not statistically significant (p= 0.312). There was no apparent advantage in allowing additional time with the digital slides (3 minutes vs. 2 minutes). The survey showed that majority of residents express concerns especially with the current level of exposure to digital whole scan slides during training.
Discussion: Digital examination has a number of advantages over glass slides, including the ability to use a wider case variety and elimination of the need to carry a microscope to the exam. However, common issues faced by residents that underwent the digital portion were slowly functioning software, image blurring, poor detail of images, particularly nuclear features.
Conclusion: Additional training is necessary before the idea could be implemented. A gradual transition into a digital theme might be considered.
Oral Presentations Session 2 – New Techniques, New Observations, New Perspectives
O201 Identification of Factors Affecting the Success of Next-Generation Sequencing Testing in Solid Tumour Tissue: Evaluation of 614 Clinical Cases
Rashmi S. Goswami, Keyur P. Patel, Hyvan D. Dang, Rajesh R. Singh, Bedia A. Barkoh, Mark J. Routbort, Kenneth D. Aldape, Stanley R. Hamilton, Russell R. Broaddus, Rajyalakshmi Luthra, Hui Chen; Departments of Hematopathology and Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054.
Background and objective of the study: Next-generation sequencing (NGS) is being increasingly used to detect targetable mutations in solid tumour specimens, which is made more challenging due to the limited nature of the specimen. Currently, there are few established guidelines for tissue sample quality to generate successful results on NGS platforms. The objective of our study was to examine various specimens from solid tumours including FFPE and cytology specimens to establish minimum tissue quality parameters for successful NGS analysis.
Methods: We examined 614 consecutive clinical cases tested using a 50 gene hotspot mutation panel (Ion Torrent PGM platform). We determined the minimum qualification criteria for various factors that can affect successful NGS analysis including procedure type, tumour percentage, tumour site, histology, block age, treatment effect and presence of decalcification.
Data and results obtained: Overall, 544/614 (89%) samples were successfully analyzed and reported. Resection specimens and large biopsies were associated with a high success rate.
Factors associated with failure of NGS analysis were procedure type, with cytological specimens and core biopsies showing lower success rates, as well as the use of decalcification procedures.
Conclusions: A high success rate of NGS-based mutation profiling can be achieved by appropriate pre-selection of solid tumour tissue. Identification of factors that negatively affect NGS analysis allows optimization of processes involved in procurement of solid tumour tissue for mutation analysis.
O202 Cancerization of Lymphatic Endothelium in Thyroid Carcinoma
C.G. Ball, S.W. Hakim, E.C. Marginean, B.M. Purgina, C.K. Lai, B. Olberg, K.T. Mai. Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, Ontario.
Introduction: We hypothesize that the cystic structures in metastatic papillary thyroid carcinoma (PTC) develop along the framework of lymphatic channels in lymph nodes. In addition, lymphatic vessel invasion of PTC in the thyroid parenchyma is difficult to identify despite the high potential of lymph node metastasis.
Methods: Ten cases from each different category of PTC with or without solid or cystic lymph node metastasis were immunostained for D2-40 and TTF-1.
Results: TTF-1 was reactive in the endothelial lining of lymphatic channels in lymph nodes as suggested by collapsed cystic or branching, cleft-like spaces in lymph nodes with metastatic PTC. D2-40 displayed focal reactivity in TTF-1-reactive follicular thyroid cells lining the cysts and lymphatic-like channels. In addition, in solid and cystic primary and metastatic PTC, TTF-1-reactive cells were identified lining focally and occasionally in extensive areas of the lymphatic endothelium. These cells may appear as benign or atrophic thyroid follicular cells. We were able to identify the above changes in 10/10, 8/10, 4/10, and 0/10 PTC associated with cystic metastasis, solid metastasis, classic PTC without metastasis, and encapsulated follicular variant of PTC, respectively. For metastatic PTC with or without cystic architecture, the above changes were seen in 8/10 and 6/10 cases, respectively.
Conclusion: Evidence of endothelial cancerization is supported by TTF-1-reactive thyroid follicular cells lining cleft-like spaces, reminiscent of lymphatic channels in cystic lymphangioma as well as expression of both TTF-1 and D2-40 by these cells. The recognition of these changes is helpful in the identification of hidden lymphatic invasion that often masquerade as apparent benign or malignant follicles.
O203 Nuclear OCT4 Expression in Diffuse Large B Cell Lymphoma – A Potential Pitfall in Diagnosis of Poorly Differentiated Malignancies
Williams AS1, Shawwa AA2, Merrimen J1, Dakin Haché K1. Divisions of 1Anatomical Pathology & 2Hematopathology, QEII Health Sciences Centre & Dalhousie University, Halifax, Nova Scotia.
OCT4 (POU5F1) is a transcription factor expressed in embryonic stem cells and germ cells involved in the maintenance of pleuripotency. It is down-regulated in all differentiated tissues. Nuclear expression of OCT4 revealed through immunohistochemistry is widely cited as a sensitive and specific marker of some primary and metastatic germ cell tumors (gonadoblastoma, seminoma/(dys)germinoma, embryonal carcinoma). At our institution, strong nuclear expression of OCT4 was observed during the work-up of a case of diffuse large B cell lymphoma (DLBCL). At that time, there were no reports of nuclear OCT4 expression in DLBCL and personal communication with experts in immunohistochemistry and genitourinary pathology confirmed that it was not a known phenomenon. This observation prompted a quality assurance review of nuclear OCT4 expression in cases of DLBCL at our institution. In addition to our index case, we have identified nuclear OCT4 expression in 2 of 32 additional cases (6%) of extra-testicular DLBCL. Interestingly, we observed co-expression of nuclear OCT4 and CD5 in 2 of the 3 cases. CD5 expression is only observed in about 10% of DLBCL cases and may be an indicator of poor prognosis. Since initiating our review in 2012, there has been a single report of nuclear OCT4 expression in 1 of 45 cases (2%) of testicular DLBCL. Our ongoing quality assurance review is the first to document nuclear OCT4 expression in extra-testicular DLBCL and highlights that antigens widely accepted as evidence for specific differentiation can be unexpectedly expressed in poorly differentiated malignancies.
O204 Breast Cancer Proliferative Markers Correlate Variably Based On Time Decorrelation Between Cell Cycle Phases
Lee LH1, Yang H1, Bigras G2. 1Department of Pathology, University of Calgary, Calgary Alberta; 2Department of Pathology, University of Alberta, Edmonton, Alberta.
Objective: Cell proliferation is used to measure tumor growth and as a prognostic/predictive marker in pathology. Various markers highlight different cell cycle stage, but little is known about how this affects their counts. This study assesses correlations between mitotic count, PhH3, and MIB-1 in breast cancers and attempts to determine the relationship between them.
Methods: 49 consecutive cases of resected invasive breast carcinoma with Ki67 index requests were identified prospectively. A breast pathologist reviewed the cases and selected the block with the highest mitotic activity. Two slides were made: one stained for Ki67 (MIB-1) and one for PhH3. ImageJ software with tailored algorithms was used for PhH3 and MIB-1 counts. Mitotic count was performed manually on H&E. Average nuclear integrated optical density (IOD) of hemotoxylin nuclear stain for each tumor was digitally measured on H&E to assess DNA content. The exact same areas of each tumor were assessed for each variable.
Results: PhH3 strongly correlated with mitosis (r = 0.94). Weaker correlations were found between MIB-1 vs PhH3 (r = 0.79) and mitotic count (r = 0.83). IOD correlated best with MIB-1 (r = 0.37) compared to mitotic count (r = 0.23) and PhH3 (r = 0.34). Assessing the linear regression between MIB-1 and PhH3, significantly more grade 3 tumors lie above the best fit line compared to low grade tumors (p = 0.017).
Conclusion: The weaker correlation for MIB-1 vs PhH3 and MIB-1 vs mitosis, as compared to PhH3 vs mitosis, is due to time decorrelation between cell cycle phases with high grade tumors spending more time in S phase relative to M phase. This is demonstrated by two findings. High grade tumors display higher than expected MIB-1 counts. Also, high grade tumors have increased IOD, which correlates better with cell cycle duration than with mitotic duration. Thus, while PhH3 and mitotic count measure proliferation, MIB-1 is more a marker of cell cycle abnormality.
O205 miRNA-Mediated Anti-Oncogenic Pathways in Breast Cancer Induced by KLK5
K.G. Sidiropoulos1, N M.A. White1,2, Anna Bui1, Peter Boulos1, Georgios Pampalakis3, Qiang Ding1, Heba Khella1, Joseph N. Samuel1, Georgia Sotiropoulou3,and George M. Yousef1,2. 1The Keenan Research Center in the Li Ka Shing Knowledge Institute and Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, Canada, M5B 1W8; 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, M5S 1A8; 3Department of Pharmacy, University of Patras, 26500, Rion-Patras, Greece.
We examined the effect of miRNA networks and their mRNA targets influenced by differential expression of the serine protease KLK5 in the molecular subtypes of breast cancer. KLK5 reconstitution in MDA-MB-231 cell lines significantly altered expression of a subset of miRNAs in an array of over 900. Target prediction, pathway analyses, large scale mRNA microarrays, and further experimental evidence identified extracellular matrix (ECM) molecules as miRNA-mediated regulatory targets through which KLK5 may affect breast tumor phenotypes. We validated our findings by analyzing the data of over 500 breast cancer patients from The Cancer Genome Atlas (TCGA). Long-term patient survival (OS and RFS) correlated with dysregulation of KLK5 and interacting ECM genes. Our data suggests the biological differences between breast cancer molecular subtypes (including basal-like, Her2, Luminal A, and Luminal B), patient survival, and their propensity for invasion and metastasis can be explained in part by miRNA networks induced by KLK5.
O206 Tumour Regression in Mammary High Grade Ductal Carcinoma in situ is Associated with Hormone Status but not Invasion
Jason K Wasserman and Carlos Parra-Herran. Department of Pathology and Laboratory Medicine – University of Ottawa, The Ottawa Hospital and Eastern Ontario Regional Laboratory Association. Ottawa, ON K1H 8L6.
Objective: Regression changes in high grade ductal carcinoma in situ (HG-DCIS) are associated with increased risk of concomitant or subsequent invasive carcinoma. Its prevalence and relationship with other relevant morphologic and molecular features has not been fully explored.
Methods: We reviewed breast biopsy cases with diagnosis of HG-DCIS followed by excision in a two – year period. We assessed features such as periductal inflammation, fibrosis and epithelial changes ranging from flattening to complete obliteration of the lesion. Degree of regression was documented in terms of intensity and distribution. Hormone receptor status and presence of invasive carcinoma on excision were recorded.
Results: 52 patients were included. Regression changes were frequently observed, including periductal fibrosis (49 cases, 94%), flattening of the intraductal neoplastic population (39 cases, 75%) and complete obliteration (20 cases, 38%). Invasive cancer was diagnosed on subsequent excision in 17 cases (32.6%). Regression in HG-DCIS was not associated with invasive outcome. Hormone receptor status was available in 48 patients: 28 and 22 patients were positive for estrogen and progesterone receptors, respectively; 20 patients were negative for both receptors. Hormone negative tumours were positively associated with regressive changes, specifically flattening of the intraductal neoplastic population (p = 0.007) and complete ductal obliteration (p = 0.031).
Conclusions: Regression changes are common in HG-DCIS. Regression appears to be related to distinct molecular subtypes of intraductal neoplasia, and may represent a targeted immunological response. Based on our results, regression does not portend an increased risk of invasive cancer on subsequent resection.