Platform Abstracts

Oral Presentations Session A

 

1000-1015

O101 Resident and supervisor evaluation outcomes of a CBME pathology curriculum

Emily A. Goebel, MD, Matthew J. Cecchini, MD, PhD, and Michele M. Weir, MD, FRCPC

Department of Pathology & Laboratory Medicine, Western University, London, ON, Canada

Objective: Given the shift to competency based medical education (CBME) in residency programs, integration of the new curriculum will require ongoing iterative evaluations to recognize successes andareas of improvement.Outcomes of these curricular evaluations have not been well described in the Canadian literature. The purpose of this study was to examine the content of resident and supervisor iterative evaluations of a newly implemented CBME pathology curriculum for a subspecialty rotation.

Methods: Kern’s clinical based curricular model was used to develop and implement a gynecological pathology curriculum with a CBME format. Over 30 months, residents and supervisors completed periodic anonymous evaluations of the curriculum.Following each cycle of feedback, curricular adjustments were made.

Results: Benefits identified by residents and supervisors were: 1) unified, clear expectations; 2) iterative and immediate feedback; and 3) increased interaction between learner and supervisor.Resident specific benefits were: 1) assessments aided with exam preparation; 2) non-Medical Expert competency assessments were increased; and 3) peer learning activities were available. Challenges identified were: 1) increased requirement for administrative time for logbook and assessments; 2) need for a private location for assessment; and 3) increased use of paper-based documents.

Conclusions: Iterative evaluations of our CBME pathology curriculum recognized benefits for residents and supervisors, as well as challenges regarding time, space and resources. These evaluation outcomes will help inform CBME implementation for residency programs implementing CBME curricula.

Keywords: competency based medical education; anatomical pathology curriculum; evaluation of CBME in pathology

 

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1015-1030

O102 “Pathology is relevant, but we don’t want to do it.” Medical student attitudes to pathology teaching and understanding of pathologists.

Joanna C. Walsha, Jessica Padgettb, Michele M. Weira, Saad Chahinec.

aDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry,

bDepartment of Psychology,

cCentre for Education Research and Innovation (CERI), Schulich School of Medicine & Dentistry, Western University, London, ON, Canada

Objective: Inadequate pathologist staffing in Canadian hospitals is cited as a contributory factor to pathology errors. Pathologists play a key role in patient care, yet few students choose pathology as a career. This paper presents comparative findings between students and pathologists on pre-conceived notions of pathologists’working environment and lifestyle.

Methods: Second year medical students at Western University and Canadian pathologists completed an on-line survey. Descriptive and mean comparisons were used to compare perceptions.

Results: Response rates were 85% (students) and 19% (pathologists). The majority of students selected medical school as their main source of pathology knowledge; 75% believe that pathology teaching is as relevant as other specialties. While 67% thought pathology was an interesting subject, < 1% intended to pursue a career in pathology. The majority (54%) did not have a good understanding of pathologist duties. Students thought the entertainment industry’s portrayal of pathology was more accurate than pathologists (t(295)=-4.679, p < .001, d=.55). Pathologists were less satisfied with their careers than students perceived (t(192.05)=-4.885, p < .001, d=.56).

Conclusions: Lack of knowledge about pathology is a potential factor contributing to poor recruitment. After 2 years of pathology teaching at Western, the majority of students do not have a good understanding of what a pathologist does. It is imperative to understand why this lack of understanding is present, and to address students’ perceptions and attitudes towards pathology to inform how training can enhance interest in the field. Strategies to increase recruitment may include increased pathologist visibility throughout training and input into career counseling.

Keywords: Pathology; education; recruitment; perception

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1030-1045

O103 Death certification in northern Alberta: educational intervention

Kimberly A. Wooda, Seth H. Weinbergb, Mitchell L. Weinbergc.

aLaboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, AB

bDepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA

cAlberta Office of the Chief Medical Examiner, Edmonton, AB

Background: A variety of educational interventions1-6 have shown to improve death certificate (DC) error rate, with greatest improvements from interactive case-based sessions2,7. A needs assessment performed by this group8 demonstrated that family physicians complete the majority (73%) of DCs with the most common errors being use of abbreviations (Abbr, 26%), mechanism used as underlying cause of death (McUCoD, 23%) and no underlying cause of death recorded (NoUCoD, 22%).

Aim: To evaluate the effectiveness of a didactic/case-based seminar targeting the most common and important errors in DCs.

Methods: A 60 minute didactic/case-based seminar delivered to family medicine residents and staff physicians at Grand Rounds with administration of pre-, immediate post, and 2-month post surveys.

Results: Pre-survey (n=72) demonstrated an overall error occurrence (EO) rate of 71.5% (64% without formatting errors), with no statistical significance between staff (n=9) and residents (n=63) frequency of DC competition. A lower EO rate (P<0.05, without formatting errors) was observed for persons with formal DC education (54%) or electives in pathology (56%) and palliative care (60%) compared to those with informal DC education (67%) or no electives (71%) in pathology/palliative care, respectively. Immediate post (n=75) and 2 month post (n=24) surveys demonstrated a lower overall EO rate (without formatting errors) of 34% (12%) and 24% (15%), compared to the pre-survey (P<0.05). The majority of participants found the seminar to be useful or very useful (n=61), were more confident in completing DCs (n=61), and recommended repetition (n=71).

Conclusion: A 60-minute didactic/case-based seminar on DC can significantly reduce EO rate with long-term effects.

References:

1Weeramanthri, T. et al. 1993. Aust Clin Rev 13:185.

2Lakkireddy, D.R. et al. 2007. SGIM 22:544.

3Pain, C.H. et al. 1996. Med Educ 30: 434.

4Myers, K.A., Farquhar, D.R.E. 1998. Can Med Assoc J 158: 1317.

5Villar, J., Perex-Mendez, L. 2007. BMC Health Serv Res 7:183.

6Walker, S. et al. 2012. Health Inf Manag 41:4.

7Aung, E. et al. 2010. Postgrad Med J 86:143.

8Wood, K.A., Weinberg, S., Weinberg, M. 2017. Unpublished data.

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1045-1100

O104 Pathology job openings in Canada and USA: a longitudinal observational study

Shi, T.a.

aDepartment of Pathology and Laboratory Medicine, The University of Western Ontario, London, ON.

The state of the pathology job market is of endless curiosity, where anecdotes abound, but comprehensive data is lacking. This longitudinal observational study aims to furnish such data using available online resources. Major Canadian and American pathology Websites were monitored for new postings of permanent pathology jobs over the period of July 1 2016 to present. Parameters noted include incidence of new posting, location, certification/subspecialty preference, job type, experience and reference required, as well as information regarding compensation and benefits. The data show a stable number of new month-to-month new postings, with the majority of jobs in Eastern USA. There were about 10 times the jobs in USA compared to Canada. AP+CP was the most commonly required primary certification while hematopathology was the most thought after subspecialty in both USA and Canada. While it was difficult to discern the type of job at times, there appear to be more private than academic jobs, with the most commonly required number of references been 3. Data on compensation and benefits were scant. Overall, hematopathology unequivocally has the most optimistic job prospect at the present. The limitations of this study include the sampling method used and its generalizability to the broader market. Future studies should correlate this data with data from graduating residents and medical board registrations.

Keywords: job market, Canada, USA, resident, fellow

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1100-1115

O105 The Canadian Pathology Workforce Planning Needs a Comprehensive Strategy

Linton David R. Sellena, Gabor Fischerb.

aAnatomical Pathology Resident, University of Manitoba, Winnipeg, MB.

bDepartment of Pathology, University of Manitoba, Winnipeg, MB.

Background: The daily routine of the future anatomical pathologists is unpredictable and possibly very different from today’s practice. New technologies, increasing workloads, and growing clinical demands for detailed pathologic information bring constant change to an environment where recruitment to the specialty remains challenging.

Materials and Methods: A comprehensive literature search was conducted to evaluate the projected changes in anatomical pathology affecting workforce related issues and the strategies to respond in different countries.

Results: A tremendous amount of change takes place in an environment where our specialty is still affected by a suboptimal image, negative stereotypes and low success rate in attracting medical students. Digital pathology has been changing the diagnostic and consulting practices worldwide. Software analysis of digital images has the potential to contribute to diagnostic interpretations.Training programs are being considered or have been developed in several countries to prepare non-medical graduates to sign-out low complexity / low risk cases. The nature of knowledge for pathologists has expanded from morphologic data to include molecular signature. The significance of certain subspecialties seems to be decreasing worldwide (cytology) while others have been gaining more recognition (molecular pathology). The more successful responses to these challenges have been broad (often national) and proactive rather that local and reactive.

Conclusions: A national pathology workforce strategy should be developed to move from reactive actions of answering immediate needs to proactive workforce planning. A careful detailed analysis is necessary to synchronize the future efforts in recruitment and training with the projected needs of our dynamically changing specialty.

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1115-1130

O106 Tracking laboratory testing selectivity of Calgary-area physicians using the Mean Abnormal Result Rate.

Andrew P. Bracka,c,d, Maggie Guoc, Irene Maa,c, Christopher T. Nauglera-d.

aDepartment of Pathology and Laboratory Medicine,

bDepartment of Family Medicine, Cumming School of Medicine, University of Calgary;

cCalgary Laboratory Services;

dAlberta Health Services; Calgary, AB.

Objectives: The Mean Abnormal Result Rate (MARR), calculated from the quotient of abnormal test results divided by total tests ordered, offers an opportunity to assess testing selectivity in a broad range of analytes using only data already present in a laboratory information system (LIS). We hypothesized that increasing physician awareness of the importance of high-yield laboratory testing would manifest as increasing MARRs during the period 2010-2015.

Methods: We accessed the LIS for Calgary Laboratory Services to find aggregate MARRs for family physician-requisitioned tests on community out-patients. We considered only a patient’s first requisition in a given year. We counted only analytes with reference limits derived from a Gaussian distribution, i.e. non-disease-specific reference limits, and meeting other inclusion criteria.

Data and Results: Thirty-nine analytes met our inclusion criteria, resulting in assessment of 20.4 million tests and 1.75 million abnormal results. The annual aggregate MARR increased every year from 8.1% in 2010 to 9.0% in 2015 (p<0.0005 by Pearson X2 and p<0.0005 by the XMH 2 test for linear trend). The annual number of tests performed and the number of tests performed per requisition increased from 2010 to 2014 before decreasing in 2015.

Conclusions: The increasing MARR for tests on out-patients in Calgary and surrounding area suggests a broad-based shift in family physician test ordering towards higher-yield testing, distinct from any single analyte-specific intervention. Further data from other jurisdictions is needed before inferring more widespread trends in family physician test ordering selectivity.

Keywords: Laboratory Utilization Management, Pathology Informatics, Mean Abnormal Result Rate, Clinical Chemistry.

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1130-1145

O107 Evaluation of the Real-world Impact of the Process Mining Methodology on a Quality Assurance Process for Auditing Red Blood Cell

Calvino Cheng, Andrew Kumar-Misir, Stephanie Watson, Joan Macleod, Irene Sadek

Background: The conventional understanding and auditing of transfusion product inventories relies on the use of key performance indicators (KPIs) such as wastage rates (%) and inventory size (#). Conventional auditing is difficult when a process is complex or if significant human resources are required. A process-based approach using process mining has been recently adapted for use in transfusion inventory analysis by Quinn et al. (Transfusion, 2017, in press) and Cheng (Transfusion, 2017, in press). We illustrate the use of a process mining methodology within a quality assurance/process improvement context to audit two areas too complex for conventional auditing: Hemosafe ™ fridge usage and red cell wastage root causes. Our study reports the insights and perspectives gained using the process mining methodology.

Methods: Process mining was performed on red cell inventory transaction data extracted from the laboratory information system. Subject matter experts from transfusion services (BTS) provided comments on their own processes while real-time process map generation was performed and moderated by a process mining and transfusion subject matter expert. Comments were thematically coded using Atlas Ti and qualitatively analysed.

Results: Participants ranged from 4-41 years of experience in BTS in all ranks. Wastage analysis: There were 163 comments with the four most grounded codes (248/344, 72.1%) relating to insight (25/344, 7.3%), process confirmation (34/344, 9.9%), clarification (74/344, 21.5%), and future application (115/344, 33.4%). Hemosafe ™ analysis: There were 141 separate comments with most comments on process confirmation and insight (54.6%, 143/262), insight (38.2%, 100/262), and confirmation of the process. Process-based comments were 7.8 fold and 4.7 greater vs. value-based comments respectively.

Conclusions: We demonstrate the real-world potential of inserting the process mining methodology into an already-established quality assurance process to increase blood transfusion subject matter awareness of red cell inventory processes in the transfusion laboratory, in the context of guidance by a process mining subject matter expert. This technique allowed for increased process insight and clarification to occur in two areas of the inventory which were explored.

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1145-1200

O108 Next generation quality: An automated assessment of 11,364 large bowel polyp specimens for adenomas with and without a villous component stratified by the endoscopist and pathologist

Jennifer M Dmetrichuka, Michael Bonerta, MarkCrowthera, David Morganb, Asghar Naqvia.

aPathology and Molecular Medicine, McMaster University, Hamilton, ON;

bGastroenterology, McMaster University, Hamilton, ON

Objective: Large bowel polyp specimens (LBPS) are common and their pathologic classification drives management decisions. In order to assess quality, automated analyses may be amenable to monitoring endoscopists’ “catch” and pathologists’ “call” for common diagnoses, such as tubular adenoma (TA) and traditional adenoma with a significant villous component (TVA+VA).

Method: All surgical pathology reports for a 3-year period in a large academic center were data-mined using a custom computer program that extracted LBPS and relevant information (endoscopist, pathologist, diagnosis, anatomic location). Computerized categorizations were compared to human reads to assess accuracy.

Results: A total of 11,457 LBPS were extracted from 54,631 surgical pathology reports. At least 200 LBPS were seen by 14 pathologists (range 1359-231) and 15 endoscopists (range 2199-231). Computer classifications were correct in >98% of randomly selected LBPS (N=300). The pathologists’ and endoscopists’ TA rates average and standard deviation (SD) were: 51.4% (SD=3.8) and 52.0% (SD=2.3) respectively. The pathologists’ and endoscopists’ TVA+VA rates by comparison were: 4.5% (SD=2.4) and 4.7% (SD=1.7) respectively. The pathologists with the seven highest and seven lowest TA rate had significantly different mean TVA+VA rates (3.1% vs 6.0%); two-tailed T-test, p<0.05.

Conclusions: The SD is higher among pathologists for TA and TVA+VA versus endoscopists, and high TA pathologists have low TVA+VA rates implying that (1) the variation may be due to interpretation and (2) the discordance is likely at the TA-TVA interface. These findings suggest standardized histological criteria for villous adenomas may be needed to improve patient risk stratification.

Keywords: quality, computerized categorization, tubular-villous adenoma, villous adenoma, tubular adenoma

 

 

Oral Presentations Session B

 

O201 Papillary renal cell carcinoma histological, immunophenotypical and molecular characterization; new classification system with associated clinical implications

Rola Saleeba,b, Fadi Brimoc, Alexis R-Brodeurc, Fabio Rotondoa, Mina Faraga, Pamela Planta, George M Yousefa,b.

aDepartment of Pathology and Laboratory Medicine, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON;

bDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON;

cDepartment of Pathology, McGill University Health Center, Montreal, QC.

Objective: Papillary Renal Cell Carcinoma (PRCC) has two histological subtypes. About 50% of the cases fail to meet all morphological criteria for either type, hence are best characterized as PRCC NOS. There are yet no reliable markers to resolve the PRCC NOS. That in turn reflects the dilemma of how to manage these patients.

Methods: PRCC cohort of 115 cases was selected. Cases were subtyped histologically into PRCC types 1, 2 and NOS. Markers ABCC2, CA9, GATA3, SAll4, and BCL2 selected from our previous genomic analysis, were assessed by immunohistochemistry (IHC). A total of 31 cases were further selected for molecular analysis (miRNA, mRNA and CNV). Univariate and multivariate survival analysis were performed.

Data and Results: ABCC2, CA9 and GATA3 exhibited distinct staining patterns between the two classic PRCC subtypes; and successfully classified the PRCC NOS cases. Moreover, immunomarkers revealed a third subtype of PRCC (35% of the PRCC cohort). Molecular analysis confirmed the presence of three distinct molecular signatures corresponding to the 3 subtypes. On univariate analysis DFS was significantly enhanced in the type1 versus 2& 3 (p value 0.047), which retained significance on multivariate analysis (p value 0.025, HR:6, 95% CI 1.25 to 32.2).

Conclusions: We propose a new classification system of PRCC integrating morphological, immunophenotypical, and molecular analysis. Our classification reveals a 3rd PRCC subtype. Molecularly PRCC3 has a distinct signature and clinically it behaves similar to PRCC type 2. The new classification stratifies PRCC patients into clinically relevant subgroups with significant implications to clinical management.

Keywords: Papillary renal cell carcinoma, Papillary renal cell carcinoma NOS, ABCC2

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1015-1030

O202 Optimization of multiple assays protocol of droplet digital PCR for urine exosome miRNA detection

Cong Wanga,b, Qiang (Colleen) Dinga, Zsuzsanna Lichnera, Rola Saleeba,c, Ashley Di Meoa,c, Mina Faraga, George Yousefa,c.

aKeenan Biomedical Research Centre, Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, ON, Canada

bDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Shandong, China

cDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

Objective: Droplet digital PCR (ddPCR) was developed to provide high-precision, absolute quantification of nucleic acid target sequences for both research and clinical diagnostic applications. In order to optimize the use of urine exosome miRNAs as prostate cancer biomarkers, 45 candidate miRNAs were evaluated to optimize the protocol for multiple assays.

Methods: We set a range of annealing temperatures, extension time, PCR cycles and RT assays pooling groups to optimize the separation between positive and negative droplets. Besides, we analyzed the impact of pipette types, assay volumes and types, as well as inter-Technician variable.

Results: Via comparing the fluorescence amplification separation, we found that the optimal annealing temperature is 60°C, extension time is 90s and PCR cycles is 45. Although as much as 45 assays could be pooled for RT running, 16 assays had the best yields comparing to single assay. The more assays pooled, the less ddPCR specificity was generated. The amount of accepted droplets could be raised by replacing a manual single-channel pipette by an automatic pipette, though the differences were not significant. Importantly, PCR assay volume of 1ul, 0.5ul and 0.3ul generated no significant impacts on fluorescence amplification. The fluorescence amplification ranges of positive droplets with FAM assays were more sharpened than VIC assays. The cut-off values varied between technicians while no significant impact on results were found.

Conclusions: The most efficient way to optimize ddPCR is to run across a gradient to identity the optimal annealing temperature, extension time and PCR cycles.

Keywords: ddPCR; optimization; exosome; miRNA

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1030-1045

O203 Linking histological phenotype to molecular changes in sunitinib-treated clear cell renal cell carcinoma.

Zsuzsanna Lichner1,2, Rola Saleeb1,2, Henriett Butz1, Mina Farag1, Roy Nofech-Mozes1, Sara Riad1, Andras Kapus1, George M Yousef1,2.

1St Michael’s Hospital, Toronto, ON, Canada

2University of Toronto, Department of Laboratory Medicine and Pathobiology

Objective: About 80% of advanced clear cell renal cell carcinoma (ccRCC) patients develop resistance for the first-line-of-treatment, sunitinib. Our objective was to discover histological and molecular changes that occur early under sunitinib treatment, and to investigate their contribution to drug resistance.

Methods: ACHN, 786-O and Renca cell lines and xenografts were treated with sunitinib. mRNA and miRNA expression was screened with Illumina HT-12 bead chip array and Nanostring nCounter assay. R, Reactome and miRPath software were used for data analysis.

Data and Results: In vitro and in vivo sunitinib treatment led to several early changes. Tumor xenografts showed the emergence of live tumor areas within the necrotic spaces that were membranous positive for E-cadherin, and β-catenin. The in vitro model recapitulated these findings, as treated cultures developed E-cadherin and β-catenin positive cancer spheroids. ccRCC spheroids were highly tumorigenic and metastatic, and expressed established cancer stem cell markers. Transcriptome analysis revealed a shift from tyrosin receptor-induced PI3K activation to G-protein-induced activation and enhanced cell-cell interactions. Time-lapse microscopy, proliferation and apoptosis assay confirmed that sunitinib treatment favors the survival and proliferation of ccRCC spheroids, compared to non-sphere cells. Blocking E-cadherin mediated cell-cell contact sensitized ccRCC cell lines for sunitinib treatment.

Conclusions: Sunitinib treatment causes early phenotypic changes of the tumor in vivo and in vitro. We provide preliminary evidence that the in vitro sunitinib-induced cancer spheres and the tumor areas surviving within the necrotic patches of treated animals, are related.

Keywords: renal cell carcinoma, sunitinib, resistance, cancer spheroid, PI3K

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1045-1100

O204 Gene Expression Profiling of Appendiceal Goblet Cell Carcinoid Tumors Reveals Upregulation of Olfactory Receptor Genes in Well-Differentiated as Compared to Poorly-Differentiated Tumors.

Chelsea Maedlera, Daniel Gastona, Nourah M Obaida, Thomas Arnasona, Karen Bedarda, Weei-Yuarn Huanga.

aDepartment of Pathology and Laboratory Medicine and Pathology, Dalhousie University, Halifax, NS

Introduction: Appendiceal goblet cell carcinoid (GCC) tumors exhibit a wide spectrum of tumor differentiation ranging from well-differentiated to poorly differentiated adenocarcinoma ex-GCC. Prognostic stratification of GCCs remains a source of debate. Identifying novel molecular signatures of well-differentiated and poorly-differentiated GCCs may help in prognostication of disease outcomes. Olfactory genes have been previously described as being upregulated in well-differentiated small bowel neuroendocrine tumors.

Design: A total of 10 GCCs were selected, including 2 well-differentiated (group A, as per Tang et al.), 4 signet-ring carcinoma ex-GCC (group B) and 4 poorly differentiated adenocarcinoma ex-GCC (group C). Total RNA, extracted from formalin-fixed paraffin embedded blocks, underwent RNA-sequencing analysis using Illumina HiSeq 2500. RNA-seq data was analyzed using a combination of HiSat2 for alignment, featureCounts for gene level count estimation, and DESeq2 for differential expression analysis and quality control. Differential expression was estimated for all pairwise comparisons. Genes were differentially expressed if they had a >2-fold change in either direction and a Benjami-Hochberg adjusted p-value < 0.05. Lists of differentially expressed genes were then used for enrichment analysis using the DAVID platform (version 6.8).

Results: Several olfactory receptor genes were among the most strongly upregulated genes in the ‘A’ compared to the ‘C’ group. These included OR51E2, OR8H3, OR1J2, OR1F1, OR7A10, OR2A5.

Conclusion: Interestingly, there is differential olfactory gene expression between well-differentiated GCC and adenocarcinoma ex-GCC. This finding draws parallels with previously described findings in other gastrointestinal tumors. These findings may represent a novel molecular signature of well-differentiated GCCs which may help to distinguish them from more poorly-differentiated GCCs.

Keywords: Goblet cell carcinoid, appendix, neuroendocrine, gastrointestinal

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1100-1115

O205 The Utility of CDX2 Loss as a Prognostic Marker in Stage II Colon Cancer

Matthew J. Cecchini1, Joanna C. Walsh1, Jeremy Parfitt1, Subrata Chakrabarti1, Rohann Correa2, Mary J. MacKenzie3, David K. Driman1.

1Department of Pathology and Laboratory Medicine, London Health Science Centre

2Division of Radiation Oncology, London Regional Cancer Program

3Division of Medical Oncology, London Regional Cancer Program

Introduction: Colorectal cancer (CRC) is the second most common cause of cancer-related death in Canadians. In patients with stage II cancer, there is no clear benefit for chemotherapy but it is still commonly used for those perceived to be at high risk. A recent landmark paper identified that cancers with loss of CDX2 expression had a significantly worse prognosis and that this marker could be utilized to identify patients who would benefit from chemotherapy.

Methods: To validate these studies we obtained 122 archival cases of stage II colon cancer that did not receive adjuvant chemotherapy. All cases were reviewed and three blocks were selected for CDX2 immunohistochemistry.

Results: CDX2 expression was diffusely lost in 11% and focally lost in 30% of cases. Furthermore, we identified significant variation in CDX2 expression in a given tissue section in more than half of the cases. This study did not identify a difference in survival based on CDX2 expression. We also assessed CDX2 in cases with metastatic disease and found that CDX2 was maintained in the majority of cases.

Discussion: Our results with whole slide immunohistochemistry are distinct from previous studies. This may be due to the fact that these studies were largely based upon tissue microarrays in which only small parts of the tumor were assessed for CDX2 expression. This raises doubt about the use of CDX2 as a prognostic marker in clinical practice. We are currently working to identify other markers that may be more reliable predictors of survival in CRC.

Keywords: Colon cancer, CDX2, chemotherapy

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1115-1130

O206 Validation of p16 Immunocytochemistry on Cytology Cell Blocks for Oropharyngeal Squamous Cell Carcinoma

Hemlata Shirsat1, Kelly Dakin1, Robert Hart2, Matthew Rigby2, Mark Taylor2, Jonathan Trites2, Martin Bullock1.

1Dept. of Pathology, Dalhousie University, Halifax, Canada;

2Dept. of Otolaryngology, Dalhousie University, Halifax, Canada

Background: P16 IHC is a reliable surrogate marker for HPV causation in Oropharyngeal Squamous Cell Carcinoma (OPSCC) and is requested on neck FNA. However, p16 IHC is not validated on cytology cell blocks with no established interpretation guidelines.

Aim: The current study compared p16 IHC in cytology and surgical specimens, to devise criteria for accurate p16 evaluation in cytology cell blocks to ensure close to 100% specificity of a positive result.

Design: p16 IHC was examined in 27 matched FNA and surgical cases of OPSCC over a 2-year period. Fifty viable basaloid tumor cells in clusters were considered adequate. Both cytoplasmic and nuclear staining was evaluated. Extent of nuclear p16 staining was scored as < 25%, 25-50%, 50-75% or >75%; intensity scored as mild, moderate or intense.

Results: 3/27 were p16 negative on both the cytology and surgical specimens and served as negative controls. Remaining 24 cases were p16 positive on the surgical specimens. 8 were excluded due to low cellularity or presence of only desquamated individual keratinized tumor cells. 6/27 showed > 75% cells with weak-intense nuclear staining. 3/27 showed 50-75% cells with weak-intense nuclear staining. 1/27 had weak nuclear staining in <25% cells. 3/27 showed only weak cytoplasmic staining. 3/27 had no nuclear or cytoplasmic staining.

Conclusion: At least 50 viable basaloid cells in small groups should be assessed. Cells with any cytoplasmic staining should be evaluated for nuclear staining. A threshold of 25% nuclear staining results in a specificity of 100%.

Keywords: Oropharyngeal Squamous cell carcinoma, p16, cytology, cell block

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1130-1145

O207 Comprehensive analysis of CD10 and IFITM1 in the distinction of endometrial stromal neoplasms from their gynecologic tract mimickers

Anjelica Hodgson1, Bojana Djordjevic1, Tao Wang1, Nadia Ismiil1, and Carlos Parra-Herran1.

1Department of Anatomic Pathology, Sunnybrook Health Sciences Centre – University of Toronto. Toronto ON, Canada

Objective: Distinction between endometrial stromal tumors (EST) and uterine smooth muscle tumors (SMT) can be challenging, particularly in high grade lesions. We aimed to compare the expression of endometrial stromal markers CD10 and IFITM1 in the distinction between EST, SMT and sex cord stromal tumors (SCST).

Design: CD10 and IFITM1 immunohistochemistry was performed on 182 tumors: 24 EST, 119 SMT, and 39 SCST. Intensity and distribution staining was scored semi-quantitatively from 0-3.A combined score of ≥5 was considered positive.

Results: Table 1 shows expression rates (%). In the distinction of EST vs SMT, CD10 had greater sensitivity, specificity, PPV and NPV for EST compared to IFITM1. Positivity for both markers increased specificity but decreased sensitivity. When only high grade EST and non-benign SMT were considered, positivity for both CD10 and IFITM1 conferred 80% sensitivity, 80% specificity, 20% PPV and 99% NPV. CD10 was negative in all SCST while IFITM1 was frequently positive in this group.

Conclusions: CD10 is a useful marker of endometrial stromal neoplasia and showed superior diagnostic performance compared to IFITM1. Adding IFITM1 to CD10 as part of a panel may have value sincestrong/diffuse expression for both markers is specific for EST (especially high grade).

Table 1

CD10+

IFITM1+

CD10+ AND IFITM1+

Low grade ESS

79

47

42

High grade ESS

100

100

100

Undifferentiated uterine sarcoma

66

100

66

ALL EST

79

58

50

Leiomyoma

11

11

0

Leiomyoma with bizarre nuclei

11

22

6

Epitheloid SMT

40

40

20

Myxoid SMT

30

70

20

Smooth muscle tumor of uncertain malignant potential

9

36

9

Leiomyosarcoma

30

45

21

ALL SMT

23

37

14

Granulosa cell tumor

0

78

0

Sertoli-Leydig cell tumor

0

25

0

Fibroma

0

58

0

ALL SCST

0

67

0

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1145-1200

O208 Desorption Electrospray Ionization (DESI) Mass Spectrometry Imaging (MSI) Margin Assessment in Surgical Resections with Histologic Correlation

Kevin Yi Mi Rena, Martin Kaufmannb, Nicole Morsea, Amanda Shuo Xua, Gabor Fichtingerc, Zoltan Takatsd, John Rudana, David Bermana, Sonal Varmaa.

aDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

bDepartment of Surgery, Queen’s University, Kingston, Ontario, Canada

cSchool of Computing, Queen’s University, Kingston, Ontario, Canada

dImperial College, London, England, UK

Background: Intraoperative resection margin assessment by frozen section is a challenging aspect of pathology practice that would benefit from novel ancillary tests. DESI MSI is an emerging technique capable of tissue characterization based on metabolite profiling. It can be applied to frozen section slides to create tissue metabolite images topographically matching the histology. We present a pilot study assessing DESI’s ability to perform margin analysis in multiple solid organs.

Method: Seventeen tumor samples with adjacent non-neoplastic tissue were collected from breast (n=9), liver (n=4) and kidney (n=4) specimens containing grossly identifiable tumors histologically confirmed as invasive ductal, metastatic colorectal, and renal cell carcinomas respectively. Tissue edges of the specimens were defined as margins. Frozen section slides were subjected to DESI MSI, and subsequently stained by hematoxylin and eosin (H&E) for histologic correlation.

Results: Metabolites with distinct mass-to-charge ratios (m/z) had different relative abundance in tumor versus non-neoplastic tissue. DESI MSI accurately highlighted tumor at tissue edges in all samples with discrete tumor nests, and correlated correctly with the margin status defined by histology.

Conclusion: Our findings demonstrate that DESI MSI can be used to supplement histology in tumor identification, and therefore has the potential to improve intraoperative resection margin assessment.

Keywords: Mass spectrometry imaging, Frozen section, Margin