DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE DÉPARTEMENT DE PATHOLOGIE ET DE MÉDECINE DE LABORATOIRE JOURNÉE ANNUELLE DE LA RECHERCHE ANNUAL RESEARCH DAY 2017 ANNUAL RESEARCH DAY PROGRAM DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE UNIVERSITY OF OTTAWA Monday May 15th, 2017 ROGER GUINDON HALL ROOM 1007 HEALTH SCIENCES BUILDING 8:45 - 9:00 COFFEE 9:00 – 9:10 WELCOME 9:10 – 9:25 THE USE OF A TISSUE SAVING MULTIPLEX ANTIBODY (ADH5) WITH TTF 1 TO SUBTYPE NON-SMALL CELL LUNG CANCER ON CYTOLOGY SPECIMENS Jordan Sim, Shahid Islam. Department of Pathology and Laboratory Medicine, University of Ottawa and The Ottawa Hospital, Ottawa ON, Canada 9:25 –9:40 IFITM1 OUTPERFORMS CD10 IN DIFFERENTIATING LOW GRADE ENDOMETRIAL STROMAL SARCOMAS FROM SMOOTH MUSCLE NEOPLASMS OF THE UTERUS Aurelia Busca1, Previn Gulavita2, Carlos Parra-Herran3* and Shahidul Islam1*, 1 Department of Pathology and Laboratory Medicine, University of Ottawa and The Ottawa Hospital, Ottawa ON, Canada, 2 Department of Medical Biology, University of Ottawa and Montfort Hospital, Ottawa ON, Canada, 3 Department of Laboratory Medicine and Pathobiology, University of Toronto and Sunnybrook Health Sciences Centre, Toronto ON, Canada 9:40-9:55 NSCLC LYMPH NODE METASTASIS: DO CYTOMORPHOLOGICAL FEATURES CORRELATE WITH STANDARDIZED UPTAKE VALUE OF PET SCAN? Kianoosh Keyhanian, Harman Sekhon Department of Pathology and Laboratory Medicine, University of Ottawa/The Ottawa Hospital, Ottawa, Ontario 9:55-10:10 LIPOMATOUS TUMOURS WITH ATYPIA ARE NOT ALWAYS LIPOSARCOMA: IMMUNOHISTOCHEMICAL EVALUATION OF A SERIES OF LIPOMATOUS TUMOURS WITH ATYPIA, INCLUDING A RETROPERITONEAL PLEOMORPHIC LIPOMA Ashley N. Flaman a,b, Denis H. Gravel a,b, Chi K. Lai a,b, Susan J. Robertson a,b, Bibianna M. Purgina a,b a Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON; bUniversity of Ottawa, Ottawa, ON 10:10-10:25 VALUE OF EOSINOPHILIC ESOPHAGITIS HISTOLOGY SCORING SYSTEM Chernetsova, Elizaveta1, A Agarwal2, D El Demellawy1,2 University of Ottawa, Children’s Hospital of Eastern Ontario, Canada 10:25 – 10:45 COFFEE BREAK 10:45-11:00 THE HISTOPATHOLOGY AND THE PATHOGENESIS OF FLOPPY EYELID SYNDROME Chen, Henry1, 2; Brownstein, Seymour1, 2; Jordan, David R.1; Belliveau, Michel J.1; Gilberg, Steven1; Blanco, Paula2; Farmer, James2; Iacob, Codrin3 1. Ophthalmology, University of Ottawa, Ottawa, ON, Canada. 2. Pathology & Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada. 3. Pathology, New York Eye and Ear Infirmary, New York, NY, United States. 11:00-11:15 AN ANALYSIS OF MEDICAL ASSISTANCE IN DYING CASES IN ONTARIO: UNDERSTANDING THE PATIENT DEMOGRAPHICS OF CASE UPTAKE IN ONTARIO SINCE THE ROYAL ASSENT AND AMENDMENTS OF BILL C-14 Rosso, Alexandra E BHSc candidate, School of Health Sciences, University of Ottawa Dr Dirk Huyer MD, Chief Coroner for the Province of Ontario, Office of the Chief Coroner Dr Alfredo Walker MB.BS, FRCPath, DMJ (Path), MFFLM, MCSFS.Forensic Pathologist/Coroner – Ontario Forensic Pathology Service. Eastern Ontario Regional Forensic Pathology Unit – Ottawa. Department of Pathology and Laboratory Medicine, University of Ottawa 11:15-11:30 OOCYTE DONATION PREGNANCIES AND THE RISK OF PREECLAMPSIA OR GESTATIONAL HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS Masoudian, Pourya, BHSc1 , Ahmed NASR, MD, MSc2, Joseph De Nannasy, MD1,, Karen FUNG-KEE-FUNG, MD, MHPE3, Shannon A. BAINBRIDGE, PhD4, Dina EL DEMELLAWY, MD, PhD1 1Department of Pediatric Pathology, Children's Hospital of Eastern Ontario, Faculty of Medicine, University of Ottawa, Ottawa, ON 2Department of Pediatric Surgery, Children's Hospital of Eastern Ontario, Faculty of Medicine, University of Ottawa, Ottawa, ON 3Department of Obstetrics and Gynecology, The Ottawa Hospital, Faculty of Medicine, University of Ottawa, Ottawa ON 4Faculty of Health Sciences, University of Ottawa, Ottawa, ON. 11:30-11:45 TREATMENT MODALITIES OF TWIN ANEMIA POLYCYTHEMIA (TAPS): A SYSTEMATIC REVIEW Hill, Kevin1, Pourya Masoudian1, Karen Fung-Kee-Fung1,2, Dina El Demellawy1,3 1 University of Ottawa, Faculty of Medicine, 2Department of Obstetrics and Gynecology, The Ottawa Hospital, 3Department of Pediatric Pathology, Children's Hospital of Eastern Ontario, Ottawa, Ontario 11:45 – 13:45 LUNCH AND POSTER VIEWING Atrium (University) 13:45 – 14:45 KEYNOTE LECTURE - Dr. Fattaneh Tavassoli Professor of Pathology - Yale University, USA Lecture Title: “Correlation between GEP-based Molecular and Morphologic Classification of Breast Carcinomas” Objectives: To cover the morphology of multiple variants of triple negative carcinoma, evolution of molecular classification & some of the potential problems if one relies completely on molecular classification. 14:45 – 15:00 POSTER ORAL PRESENTATIONS (OPTIONAL) 14:45-14:50 PEDIATRIC BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM - A SYSTEMATIC LITERATURE REVIEW Jeong-Min Kim, Marie, Ahmed Nasr, Bilaal Kabir, Joseph de Nanassy, Ken Tang, Danielle Menzies-Toman, Donna Johnston, Dina El Demellawy University of Ottawa, Children’s Hospital of Eastern Ontario, Canada 14:50-14:55 DIAGNOSTIC VALUE OF MID ESOPHAGEAL BIOPSIES IN PEDIATRIC PATIENTS WITH EOSINOPHILIC ESOPHAGITIS Chernetsova, E, J Joo, A Agarwal, J Barkey, D El Demellawy University of Ottawa, Children’s Hospital; of Eastern Ontario, Canada 14:55-15:00 A RARE CASE OF PEDIATRIC LIPOMA WITH T(9;12)(P22;Q14) AND EVIDENCE OF HMGA2 NFIB GENE FUSION Lacaria, Melanie1, Dina El Demellawy2,3, Jean McGowanJordan1,4 Genetics Department, Children’s Hospital of Eastern Ontario; Pediatric Pathology Department, Children’s Hospital of Eastern Ontario; 3 Department of Surgery, University of Ottawa; 4 Department of Pathology and Laboratory Medicine, University of Ottawa 1 2 15:00 – 15:15 COFFEE BREAK 15:15 – 15:30 ANNOUNCEMENT OF PRIZE WINNERS AND CONCLUSION Nadia Mikhael Award for Best Paper presented by a Junior Resident 2nd Best paper by a Junior Resident Virbala Acharya Award for Best Presentation by a Senior Resident or Fellow 2nd Best paper by a Senior Resident or Fellow Best Poster Presentation by a Graduate Student 2nd Best Poster Presentation by a Graduate Student Best Poster Presentation by a Resident 2nd Best Poster Presentation by a Resident Dr. M. Orizaga Award for Best Teacher POSTERS 1. PEDIATRIC BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM A SYSTEMATIC LITERATURE REVIEW Jeong-Min Kim, Marie, Ahmed Nasr, Bilaal Kabir, Joseph de Nanassy, Ken Tang, Danielle Menzies-Toman, Donna Johnston, Dina El Demellawy University of Ottawa, Children’s Hospital of Eastern Ontario, Canada 2. THE EFFICIENCY OF ACTIVATING THE MasR/Ang1-7 PATHWAY TO REDUCE MUSCLE ATROPHY AND FUNCTION LOSS FOLLOWING DENERVATION Albadrani, H*1 and J.M Renaud*1 Department of the Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada 3. RNA-SEQ ANALYSIS OF REXINOID RESPONSIVE GENE EXPRESSION DURING EARLY MYOBLAST DIFFERENTIATION Khilji, Saadia, Qiao Li Department of the Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada 4. Retrospective, case-controlled stereological assessment of vascularization in placentas of HIV-exposed, uninfected (HEU) children. Wahba, Mary, Jenifer Bowes (BSc, MSc), Chris G. Ball (M.D.), Jason Brophy (M.D.), David Grynspan (M.D.) University of Ottawa, Children’s Hospital of Eastern Ontario, Canada 5. DIAGNOSTIC VALUE OF MID ESOPHAGEAL BIOPSIES IN PEDIATRIC PATIENTS WITH EOSINOPHILIC ESOPHAGITIS Chernetsova, E, J Joo, A Agarwal, J Barkey, D El Demellawy University of Ottawa, Children’s Hospital; of Eastern Ontario, Canada 6. DOUBLE HIT DIFFUSE LARGE B-CELL LYMPHOMA TESTING AT THE OTTAWA HOSPITAL Capitano, Mario, M.D., and Philip Berardi, M.D., Ph.D., FRCPC The Ottawa Hospital, General Campus, 501 Smyth Rd, Ottawa ON K1H 8L6 7. ADENOCARCINOMA EX-GOBLET CELL CARCINOID TUMOURS, PATHOLOGIC CLASSIFICATION AND CLINICAL BEHAVIOR: AN ANALYSIS OF CASE SERIES (FROM 2003-2017 FROM THE OTTAWA HOSPITAL PATHOLOGY GROUP Capitano, Mario, M.D., and Zohreh Eslami, M.D., Ph.D., FRCPC The Ottawa Hospital, General Campus, 501 Smyth Rd, Ottawa ON K1H 8L6 8. STROMAL TISSUE AS AN ADJUNCT TOOL IN THE DIAGNOSIS OF FOLLICULAR THYROID LESIONS BY FINE-NEEDLE ASPIRATION BIOPSY Hogan, Kevin, Kien T. Mai. The Ottawa Hospital and University of Ottawa, Pathology and Laboratory Medicine, Ottawa, ON, Canada 9. CHARACTERISTICS OF LYMPHOPROLIFERATIVE DISORDERS (LPD) WITH MORE THAN ONE ABERRANT CELL POPULATION AS DETECTED BY 10 COLOR FLOW CYTOMETRY Mahdi, Talal (1, 2), Amr Rajab (2,3) ,Ruth Padmore (1), *Anna Porwit (2,4) (1) Department of Pathology and Laboratory Medicine, The Ottawa Hospital and Eastern Ontario Regional Laboratory Association and University of Ottawa, ON, Canada. (2) Flow Cytometry Laboratory, Department of Laboratory Hematology, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada. (3) Present address: Flow cytometry department, Lifelabs Medical laboratory services-Toronto. (4) Present address: Department of Clinical Sciences, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden 10. EMERGENCY TRANSFUSION OF ONE UNCROSSMATCHED GROUP O Rh POSITIVE RED CELL UNIT TO A PATIENT WITH ANTI-D ANTIBODY IDENTIFY ONCE TYPE AND SCREEN WERE COMPLETED. A CASE REPORT Mahdi, Talal, MD, Ruth Padmore, MD The Ottawa Hospital and Eastern Ontario Regional Laboratory Association and University of Ottawa 11. A RARE CASE OF PEDIATRIC LIPOMA WITH T(9;12)(P22;Q14) AND EVIDENCE OF HMGA2 NFIB GENE FUSION Lacaria, Melanie1, Dina El Demellawy2,3, Jean McGowan-Jordan1,4 1Genetics Department, Children’s Hospital of Eastern Ontario; 2Pediatric Pathology Department, Children’s Hospital of Eastern Ontario; 3Department of Surgery, University of Ottawa; 4Department of Pathology and Laboratory Medicine, University of Ottawa 12. DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE HISTOLOGY CORE FACILITY J.P.Veinot1, C.A. Jodouin2, Z. Ticas3, L. Dong4, E. Labelle5, S. Faulkes6, M. Khalili7, M. Alazzabi8, O. Agah9 The University of Ottawa, Faculty of Medicine, Department of Pathology and Laboratory Medicine (PALM), Histology Core Facility WELCOME THE USE OF A TISSUE SAVING MULTIPLEX ANTIBODY (ADH5) WITH TTF 1 TO SUBTYPE NON-SMALL CELL LUNG CANCER ON CYTOLOGY SPECIMENS Jordan Sim, Shahid Islam. The Ottawa Hospital, Ottawa, ON, Canada Background: 70% of lung cancers present at an advanced stage, and subtyping of non-small cell lung cancers must therefore be done on cytologic specimens and small biopsies when possible. Many antibodies have been investigated for the subtyping of non-small cell lung carcinomas. Although the combination of p40 and TTF-1 is commonly used, this is not always sufficient and more markers must be used. Entering the era of personalized medicine, conservation of cell blocks for molecular studies is vital, and minimizing the number of immunohistochemical stains is important. The multiplex antibody ADH5 is frequently used in breast pathology, but to date has not been investigated for its use in lung cancer. ADH5 includes a panel of antibodies (CK5/14, CK7/18 and p63) all of which have been proven to aid in the subtyping of non-small cell lung carcinomas. The aim of this study is to assess the efficacy of the ADH5 multiplex antibody in combination with TTF-1 in subtyping non-small cell carcinomas. Design: A database search from January 2014 onwards was conducted for cases of cytologically diagnosed non-small cell lung cancer with subsequent surgical resection specimens. A total of 175 consecutive cases were retrieved, 83 of which had adequate cell blocks fixed in formalin. Immunohistochemistry for TTF-1 and ADH5 was performed on all 83 cases. Results: Of the 83 cases used in this study, final diagnoses on surgical resection included squamous cell carcinoma (25.3%), adenocarcinoma (71.1%) and adenosquamous carcinoma (3.6%). On cytology, 17 (20.5%) cases could not be subtyped. At the time of original cytologic diagnosis, immunohistochemistry was used to subclassify NCSLC in 32 (38.6%) cases. The number of stains performed ranged from 2 to 5 (mean 3.38). With the use of immunohistochemistry, 9 (11%) remained not subtyped. Using the combination of TTF-1 and ADH5 multiplex antibody, 80/83 (96%) cases were classified accurately, including 17 cases that were previously not subtyped and 1 case that was misdiagnosed. 3 (3.6%) cases of adenosquamous carcinoma could not be accurately subtyped using this panel. Conclusions: A multiplex antibody for CK5/14, CK7/18 and p63 in combination with TTF-1 is an effective combination for subtyping NSCLC on cytology specimens. This combination requires only 2 sections, therefore saving tissue for further ancillary studies. IFITM1 OUTPERFORMS CD10 IN DIFFERENTIATING LOW GRADE ENDOMETRIAL STROMAL SARCOMAS FROM SMOOTH MUSCLE NEOPLASMS OF THE UTERUS Aurelia Busca1, Previn Gulavita2, Carlos Parra-Herran3* and Shahidul Islam1* 1 Department of Pathology and Laboratory Medicine, University of Ottawa and The Ottawa Hospital, Ottawa ON, Canada 2 Department of Medical Biology, University of Ottawa and Montfort Hospital, Ottawa ON, Canada 3 Department of Laboratory Medicine and Pathobiology, University of Toronto and Sunnybrook Health Sciences Centre, Toronto ON, Canada * CP-H and SI contributed equally as senior authors Introduction: Distinguishing between uterine neoplasms of smooth muscle and endometrial stromal origin is a frequent diagnostic challenge. We investigated the staining pattern of interferon-induced transmembrane protein-1 (IFITM1), a novel endometrial stromal marker, in endometrial and smooth muscle uterine neoplasms and compared it to CD10 in its ability to differentiate between these two groups. Methods: Immunohistochemistry for IFITM1 and CD10 was performed in 20 cases of smooth muscle neoplasms (10 cases leiomyoma, 10 cases leiomyosarcoma), 14 cases of endometrial stromal sarcoma (12 cases low grade and 2 cases high grade) and 12 cases of carcinosarcoma. Staining was scored in terms of intensity and distribution (0=absent, 1=weak/less than 50%, 2=moderate/50-75%, 3=strong/more than 75%). A total score was obtained by adding intensity and distribution scores and classified as positive (score 3-6) or negative (score 0-2). Results: IFITM1 was positive in 10/12 (83%) low grade endometrial stromal sarcomas, 6/20 (30%) smooth muscle tumors (leiomyomas and leiomyosarcomas) and 11/12 carcinosarcomas (91.6%). The two cases of high grade endometrial stromal sarcoma were IFITM1 negative. While both IFITM1 (83%) and CD10 (91%) had high sensitivity in differentiating low grade endometrial stromal sarcomas from smooth muscle neoplasms, IFITM1 (70%) had higher specificity compared to CD10 (45%). Conclusions: In this study IFITM1 appears to be a more specific marker of endometrial stromal differentiation compared to CD10 in differentiating low grade endometrial stromal sarcomas from smooth muscle neoplasms. Thus, IFITM1 may be a valuable tool as part of an immunohistochemical evaluation panel in this diagnostic scenario. NSCLC LYMPH NODE METASTASIS: DO CYTOMORPHOLOGICAL FEATURES CORRELATE WITH STANDARDIZED UPTAKE VALUE OF PET SCAN? Kianoosh Keyhanian, Harman Sekhon Department of Pathology and Laboratory Medicine, University of Ottawa/The Ottawa Hospital, Ottawa, Ontario Background/Objective Positron emission tomography (PET) followed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the suspicious lymph nodes (LNs) is a standard procedure for pre-operative staging of lung cancer. The objective of this study is to correlate cytomorphological features of metastatic non-small cell lung carcinoma (mNSCLC) with maximal standardized uptake value (mSUV) of PET scan in LNs. Method(s) Positive EBUS-TBNA cytology slides were reviewed from patients with mNSCLC. Fifty-seven LNs were selected from 49 patients who had undergone PET study. Student t-test was used for statistical comparisons. Results Mean patients’ age was: 68.7, 67% male. LNs locations were as follows: mediastinum: 48 (24 subcarinal, 24 para-tracheal), lung hilum: 8, axilla: 1. Final diagnoses were: Adenocarcinoma: 41 LNs, squamous cell carcinoma: 13 LNs and NSCLC: 3 LNs. Within the Adenocarcinoma subgroup, we observed that histological patterns correlate with mSUV, with acinar and papillary (both mean values: 9.3) patterns associating with significantly lower mSUVs than solid pattern (Mean value: 13.8) (both P values <0.05). Similar difference exists between low and high grade Adenocarcinomas (Mean values: 9.4 and 13.2, respectively. P value <0.01). Interestingly, micropapillary pattern was associated with the lowest mSUV (Mean value: 4.7). Other features that correlated with higher mSUV: LN size (correlation coefficient: 0.51, P value: 0.006), presence of necrosis and moderate/severe nuclear atypia (both P values < 0.01), LN site (mediastinal vs. hilar Mean value: 11.6 vs. 7, respectively. P value: 0.01) as well as lower lymphoid tissue yield (Mean values: 7.7 vs. 11.4, P value: 0.04). Besides, presence of solid pattern was linked with significantly higher cell-block yield than acinar or papillary patterns (P values < 0.05). Conclusions In LNs with mNSCLC, certain cytomorphological features including histological pattern, grade, necrosis and moderate/severe nuclear atypia are associated with higher mSUV. These results are consistent with the prior studies examining primary lung tumours. Interestingly, more aggressive metastatic micropapillary carcinomas express lower SUV values; hence, a lower threshold should raise concerns for metastasis. LIPOMATOUS TUMOURS WITH ATYPIA ARE NOT ALWAYS LIPOSARCOMA: IMMUNOHISTOCHEMICAL EVALUATION OF A SERIES OF LIPOMATOUS TUMOURS WITH ATYPIA, INCLUDING A RETROPERITONEAL PLEOMORPHIC LIPOMA Ashley N. Flaman a,b, Denis H. Gravel a,b, Chi K. Lai a,b, Susan J. Robertson a,b, Bibianna M. Purgina a,b aDepartment of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON; b, University of Ottawa, Ottawa, ON Background: Pleomorphic lipoma/spindle cell lipoma (PL/SCL) is a benign lipomatous tumor that occurs most commonly in the neck/upper back. They may be diagnostically challenging because they contain pleomorphic or multinucleated floret-like cells (PL) and/or spindle cells (SCL) that may mimic well-differentiated liposarcoma (WDLPS). In contrast, WDLPS is most commonly found in the retroperitoneum and deep soft tissues of the extremities. While they rarely metastasize, WDLPS may recur locally or dedifferentiate. As a result, the current assumption is that all retroperitoneal or deep lipomatous tumors with atypia are considered to be WDLPS until proven otherwise. Using fluorescence in situ hybridization (FISH) for MDM2 amplification as the gold standard for diagnosis of WDLPS, we studied the utility of HMGA2, CD34 and S100, with a focus on the relatively new marker, HMGA2, in the evaluation of lipomatous tumors with atypia. Design: Using MDM2 FISH and IHC for CD34, S100 and HMGA2, we analyzed 10 cases of PL, 6 cases of SCL and 11 cases of WDLPS diagnosed since 2003. 3 PL occurred in unusual locations including the arm, forehead and one in the retroperitoneum (previously reported only once in an English-language journal without MDM2 analysis). Results: PL/SCL was CD34 positive (100%), and negative for S100 (100%) and HMGA2 (100%), while WDLPS was HMGA2 positive (100%) and negative for S100 (91%) and CD34 (55%); 5 cases of WDLPS showed aberrant staining with CD34. FISH for MDM2 demonstrated amplification in all tested cases of WDLPS (7/7) and was not amplified in tested cases of PL/SCL (5/5). The case of retroperitoneal PL shared the same morphology and IHC pattern as its usual counterparts, and MDM2 was not amplified via FISH. Conclusion: All PL/SCL were negative for HMGA2 and positive for CD34. All WDLPS were HMGA2 positive with 45% also CD34 positive. CD34 in WDLPS was difficult to interpret because of increased background staining in many cases. Because of its tidy nuclear staining and ease of interpretation, as well as its superior performance at differentiating PL/SCL and WDLPS, the combination of HMGA2 and CD34 may be particularly useful. In addition, while anatomic location may be suggestive of a particular diagnosis, ultimately, the morphology, IHC and molecular pathology should be used in concert in the diagnosis of difficult lipomatous tumors. Finally, retroperitoneal PL/SCL do exist and must be considered for lipomatous tumors with atypia in this location. VALUE OF EOSINOPHILIC ESOPHAGITIS HISTOLOGY SCORING SYSTEM Chernetsova, Elizaveta1, A Agarwal2, D El Demellawy1,2 University of Ottawa, Children’s Hospital of Eastern Ontario, Canada Background: EoE is a chronic immune-mediated disorder characterized by the presence of ≥15 eosinophils/HPF in esophageal biopsies in the absence of other causes of esophageal eosinophilia. The eosinophilic infiltrate in EoE tends to be patchy and variable. A new scoring method, the histology scoring system (HSS), evaluates pediatric patients with EoE using multiple histologic parameters including their severity (grade) of pathology and the extent (stage). It was proposed by Collins and her colleagues in 2016 [1]. Study aim: to assess if there is a difference between the traditional histologic assessment used by pediatric pathologists at CHEO and the HSS for EoE diagnosis and monitoring. Study design: the study was granted CHEO REB approval. We conducted a retrospective chart review of patients with EoE who presented at CHEO from 2014 – 2016. We included all patients ≤ 18 years old with a clinical, endoscopic and histological diagnosis of EoE, as well as available initial and follow-up endoscopies reports and esophageal biopsy slides for review. We excluded patients with a diagnosis of eosinophilic gastroenteritis, eosinophilic proctitis, gastroesophageal reflux disease and parasitic infections. Clinical symptoms were assessed for nausea, vomiting, heartburn, chest or abdominal pain, food impaction, dysphagia, and symptom dynamic (improvement vs no improvement). Treatment was also assessed. Endoscopic parameters included trachealization, edema, strictures, white flecks, and mucosal furrowing. As per the traditional CHEO pathologists’ assessment, the histologic parameter scoring was conducted solely on the peek eosinophilic count, in the proximal, middle and distal esophageal biopsies. The same patients were then scored using the HSS. This assessment included the following histologic parameters: peak eosinophilic density, eosinophilic abscess, surface eosinophil layering, basal cell hyperplasia, lamina propria fibrosis, surface epithelial alterations, spongiosis (dilated intercellular spaces), and dyskeratotic epithelial cells. For each of the parameters assessed, a grade and a stage score was assigned, for each location of the esophageal biopsy (proximal, middle, and distal). Final grade and stage scores were achieved by the summation of scores across the parameters for each of the locations. From this, the highest score across the three locations was used to identify one score per patient, for both grade and stage. Additionally, an overall combined score per patient was obtained, by summing their overall grade and stage score. All scoring was completed for both the initial and follow-up biopsies, and from this, the change in overall combined score was also computed. Statistical Analysis: Demographic, clinical characteristics and the histological scores of patients with both scoring systems were summarized using descriptive statistics. Univariate logistic regression models were created to assess whether the change in overall combined score predicted endoscopic or symptom improvement in patients with EOE. All analyses were computed for the HSS, and then for the CHEO scoring system. All statistics were computed using R Version 1.0.136. Results: A total of 40 patients were identified and included in the study, of which 9 (25%) were female and 27 (75%) were male. The main symptoms at initial presentation included vomiting (2.5%), heartburn (5%), chest or abdominal pain (5%), food impaction/sensation of the food sticking (22.5%), and dysphagia (25%). 35 (87.5%) of patients demonstrated symptom improvement at the time of the follow up assessment. Of the 40 patients, 39 (97.5%) had a diagnostic abnormality on the initial endoscopy; and 33 (82.5%) patients had an abnormality that persisted on the follow-up endoscopy. All patients received treatment with PPI and 23 (57.5%) of patients received treatment with oral steroids as well. 39 (97.5%) of patients were on milk-free diet. HSS: The mean overall grade score on the initial biopsy was 12.5 (±5.1), while on the follow-up biopsy it was 7.4 (±5.6). The mean overall stage score at the time of the initial biopsy was 11.7 (±4.5), while on the follow-up biopsy it was 7.3 (±5.4). The mean overall combined score at the time of the initial biopsy was 24.2 (±9.1), while on the follow-up biopsy it was 14.8 (±10.9). The change in the overall combined histological score from the initial to follow-up biopsy, as determined by the HSS, significantly predicted endoscopic improvement (OR=0.93, p=0.05) and symptom improvement (OR=0.87, p=0.01) in the follow-up assessment. CHEO pathologists’ semi quantitative system: The mean eosinophil count on the initial biopsy was 86.2 (±53.6), while on the follow-up biopsy it was 43.2 (±52.4). In contrast to the HSS, the eosinophil count by itself did not significantly predict endoscopic improvement (OR=0.99, p=0.34) or symptom improvement (OR=0.99, p=0.45). Conclusion: our study shows that in contrast to maximum intraepithelial eosinophilic count that is traditionally used to evaluate EOE histologically, HSS is of value in predicting endoscopic and symptom improvement in pediatric patients with EOE. Reference list. 1. Collins MH, Martin LJ, Alexander ES. Et al. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Dis Esophagus. 2017 Feb 1;30(3):1-8. doi: 10.1111/dote.12470. BREAK THE HISTOPATHOLOGY AND THE PATHOGENESIS OF FLOPPY EYELID SYNDROME Chen, Henry1, 2; Brownstein, Seymour1, 2; Jordan, David R.1; Belliveau, Michel J.1; Gilberg, Steven1; Blanco, Paula2; Farmer, James2; Iacob, Codrin3 1. Ophthalmology, University of Ottawa, Ottawa, ON, Canada. 2. Pathology & Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada. 3. Pathology, New York Eye and Ear Infirmary, New York, NY, United States. Purpose: Floppy eyelid syndrome (FES) is an uncommon, but distressing condition, characterized by a constellation of symptoms and signs that include an easily everted upper eyelid, papillary conjunctivitis, nonspecific ocular irritation, and a rubbery, malleable eyelid. The pathogenesis of FES has not been fully elucidated. We performed an observational case series to further explore the pathogenesis of FES by studying the degree of association of elastic tissue loss, adipose tissue accumulation, and scarring in the tarsus. Methods: Twenty specimens of FES were obtained from the Ocular Pathology Registry of the University of Ottawa. Sections from each formalin-fixed paraffin-embedded specimen were stained with hematoxylin and eosin, periodic acid-Schiff, Masson’s trichrome, Verhoeff-Van Gieson elastica, and S100. Each slide was analyzed by light microscopy. Scores of 1 to 4+ were assigned for the amount of elastic tissue, number of adipocytes, and degree of fibrovascular scarring in the tarsus. In each specimen, the number of adipocytes can readily be counted, while the degree of changes in the elastic tissue and amount of fibrovascular scarring were compared to selected test slides. Specimens of eyelids with a normal tarsus served as controls. Results: The amount of elastic tissue, number of adipocytes, and fibrovascular scarring will be evaluated pending controls (p<0.05). Conclusions: Our study documents the possibility of decreased elastic tissue, the presence of increased adipocytes, and the presence of fibrovascular scarring and their potential role in the pathogenesis of FES. Our results further characterize the pathological processes involved in FES. AN ANALYSIS OF MEDICAL ASSISTANCE IN DYING CASES IN ONTARIO: UNDERSTANDING THE PATIENT DEMOGRAPHICS OF CASE UPTAKE IN ONTARIO SINCE THE ROYAL ASSENT AND AMENDMENTS OF BILL C-14 Rosso, Alexandra E BHSc candidate, School of Health Sciences, University of Ottawa Dr Dirk Huyer MD, Chief Coroner for the Province of Ontario, Office of the Chief Coroner Dr Alfredo Walker MB.BS, FRCPath, DMJ (Path), MFFLM, MCSFS. Forensic Pathologist/Coroner – Ontario Forensic Pathology Service Eastern Ontario Regional Forensic Pathology Unit – Ottawa Department of Pathology and Laboratory Medicine, University of Ottawa On June 17, 2016, the Canadian government legalized medical assistance in dying (MAID) across the country by giving Royal Assent to Bill C-14. This Act made amendments to the Criminal Code and other Acts relating to MAID, allowing physicians and nurse practitioners to offer clinician-administered and self-administered MAID in conjunction with pharmacists being able to dispense the necessary medications. The eligibility criteria for MAID indicates that the individual (i) must be a recipient of publicly funded health services in Canada, (ii) be at least 18 years of age, (iii) be capable of health-related decision-making, and (iv) has a grievous and irremediable medical condition Because this is a new practice in Canadian health care, there are no published Canadian statistics on MAID cases to date and this paper constitutes the first analysis of MAID cases in both the province of Ontario and Canada. Internationally, there are only a few jurisdictions with similar legislation already in place (USA, the Netherlands, Belgium, Luxembourg, Switzerland, Columbia, Japan and the United Kingdom). The published statistics on MAID cases from these jurisdictions were reviewed and used to establish the current global practices and demographics of MAID and will provide useful comparisons for Canada. This analysis will (i) outline the Canadian legislative approach to MAID, (ii) provide an understanding of which patient populations in Ontario are using MAID and under what circumstances and (iii) determine if patterns exist between the internationally published MAID patient demographics and the Canadian MAID data. Selected patient demographics of the first 100 MAID cases in Ontario were reviewed and analyzed using anonymized data obtained from the Office of the Chief Coroner for Ontario so that an insight into the provision of MAID in Ontario was obtained. Demographic factors such as age, sex, the primary medical diagnosis that prompted the request for MAID and patient rationale for making a MAID request, the place where MAID was administered, the nature of MAID drug regimen used and the status/specialty of medical personnel who administered the MAID drug regimen were analyzed. The analysis revealed that the majority of the first 100 MAID recipients were older adults (only 5.2% of patients were aged 35 - 54 years with no younger adults between ages 18-34 years) who were afflicted with cancer (64%) and had opted for clinician-administered MAID (99%) which had been delivered in either a hospital (38.8%) or private residence (44.9%). Although the cohort was small, these Ontario MAID demographics reflect similar observations as those published internationally but further analysis of both larger and annual case uptake in both Ontario and Canada will be conducted as the number of cases increase. OOCYTE DONATION PREGNANCIES AND THE RISK PREECLAMPSIA OR GESTATIONAL HYPERTENSION: SYSTEMATIC REVIEW AND META-ANALYSIS OF A Masoudian, Pourya, BHSc1 , Ahmed NASR, MD, MSc2, Joseph de Nanassy, MD1,, Karen Fung-Kee-Fung, MD, MHPE3, Shannon A. Bainbridge, PhD4, Dina El Demellawy, MD, PhD1 1Department of Pediatric Pathology, Children's Hospital of Eastern Ontario, Faculty of Medicine, University of Ottawa, Ottawa, ON 2Department of Pediatric Surgery, Children's Hospital of Eastern Ontario, Faculty of Medicine, University of Ottawa, Ottawa, ON 3Department of Obstetrics and Gynecology, The Ottawa Hospital, Faculty of Medicine, University of Ottawa, Ottawa ON 4Faculty of Health Sciences, University of Ottawa, Ottawa, ON OBJECTIVE: To determine whether pregnancies achieved via oocyte donation, compared to pregnancies achieved via other assisted reproductive technology methods or natural conception demonstrate increased risk of preeclampsia or gestational hypertension. DATA SOURCES: PubMed, MEDLINE, Embase and CENTRAL (from 1989 to 2015); bibliographies, Google Scholar. STUDY ELIGIBILITY CRITERIA: Comparative studies of pregnancies achieved with oocyte donation versus other methods of assisted reproductive technology or natural conception, with preeclampsia or gestational hypertension included as one of the measured outcomes. Abstracts and unpublished studies were excluded. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently selected studies, assessed for quality using Methodological Index for Non-Randomized Studies, and extracted the data. Statistical analysis was conducted using Review Manager 5.3. RESULTS: Of 523 studies initially reviewed, 19 comparative studies met the pre-defined inclusion and exclusion criteria and were included in the meta-analysis, allowing for analysis of a total of 86,515 pregnancies. Our pooled data demonstrated that the risk of preeclampsia is higher in oocyte donation pregnancies compared to other methods of assisted reproductive technology (OR: 2.54 [1.98, 3.24], p<0.0001) or natural conception (OR: 4.34 [3.10, 6.06], p<0.0001). The risk of gestational hypertension was also significantly increased in oocyte donation pregnancies in comparison with other methods of assisted reproductive technology (OR: 3.00 [2.44, 3.70], p<0.0001) or natural conception (OR: 7.94 [1.73, 36.36], p=0.008). Subgroup analysis conducted for singleton and multiple gestations demonstrated similar risk for preeclampsia and gestational hypertension in both singleton and multiple gestations. CONCLUSIONS: This meta-analysis provides further evidence supporting that egg donation increases the risk of preeclampsia and gestational hypertension compared to other assisted reproductive technology methods or natural conception. TREATMENT MODALITIES OF TWIN ANEMIA POLYCYTHEMIA (TAPS): A SYSTEMATIC REVIEW Hill, Kevin1, Pourya Masoudian1, Karen Fung-Kee-Fung1,2, Dina El Demellawy1,3 1University of Ottawa, Faculty of Medicine, 2Department of Obstetrics and Gynecology, The Ottawa Hospital, 3Department of Pediatric Pathology, Children's Hospital of Eastern Ontario, Ottawa, Ontario Objective: Twin anemia-polycythemia sequence (TAPS) is a complication of monochorionic twin or multiple gestation pregnancies with a variety of management options. Our objective was to evaluate the effects of various interventions on perinatal outcomes associated with pregnancies complicated with TAPS. Methods: A literature search in PubMed, MEDLINE, EMBASE and CENTRAL (until 2016) was performed to identify cases of TAPS which were diagnosed antenatally and for which the perinatal outcomes were reported. We included both comparative and non-comparative studies (including case reports and case series). Abstracts and unpublished studies were excluded. Articles were screened and the data was extracted by two reviewers independently. Results: Of 936 articles initially screened, 22 studies met our pre-defined inclusion criteria. We identified 54 cases of TAPS from case studies and 61 pregnancies with TAPS from two comparative studies. In the 7 included cases managed with laser ablation therapy there was a mortality of 20%, a live-birth morbidity of 0% and a 12.4% rate of adverse perinatal outcomes. Of the 21 studies which used any combination of intrauterine transfusion (IUT) and partial exchange transfusion (PET), a mortality of 16.7%, morbidity of 25.6% and rate of adverse perinatal outcomes of 43.6% were reported. Finally, the 18 cases managed expectantly demonstrated an 11% mortality, 23.5% morbidity and a rate of adverse perinatal outcomes of 73.5%. In addition, the percent of cases requiring emergent caesarean section for laser ablation, IUT/PET and expectant management were 28.6%, 65% and 71.4%, respectively. Conclusion: Laser ablation therapy appears to have the lowest rates of morbidity, occurrence of adverse perinatal outcomes and emergent caesarean sections compared to IUT and expectant management. However, due to presence of bias associated with using non-comparative studies, it is difficult to draw conclusions and more prospective comparative studies are needed in the future. LUNCH AND POSTER VIEWING (ATRIUM) GUEST SPEAKER DR. fattaneh tavassoli Professor OF PATHOLOGY YALE UNIVERSITY USA TITLE: “Correlation between GEP-based Molecular and Morphologic Classification of Breast Carcinomas” POSTERS (ORAL PRESENTATIONS) PEDIATRIC BLASTIC PLASMACYTOID DENDRITIC NEOPLASM - A SYSTEMATIC LITERATURE REVIEW CELL Jeong-Min Kim, Marie, Ahmed Nasr, Bilaal Kabir, Joseph de Nanassy, Ken Tang, Danielle Menzies-Toman, Donna Johnston, Dina El Demellawy University of Ottawa, Children’s Hospital of Eastern Ontario, Canada Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive hematologic malignancy characterized by frequent skin involvement that most commonly affects older patients. BPDCN is known to have a poor prognosis. Our objective was to assess if outcome and disease prognosis were independently influenced by age when evaluated with clinical presentation, sex, and treatment regimens. We conducted a systematic review to identify BPDCN cases, in order to compare pediatric BPDCN cases with adult cases. A total of 125 publications were identified detailing 356 cases. Including one pediatric case from our institution, 74 were children, and 283 were adults aged 19 or over. Age was shown to be an independent prognostic factor predictive of more favorable outcomes across measures including initial response to therapy, likelihood of relapse, and overall survival at follow-up. The distribution of affected organs at diagnosis was similar across children and adults and type of clinical presentation did not disproportionately influence one age group’s prognosis over the other. Acute Lymphoblastic Leukemia (ALL)-type chemotherapy regimens were shown to be superior to other chemotherapy regimens (Acute Myeloid Leukemia, Lymphoma, ALL/Lymphoma, other, or none) in inducing complete remission. Allogeneic stem cell transplantation was shown to increase mean survival time. Future research may be directed towards elucidating the further morphologic, cytogenetic, and cytochemical differences between younger and older BPDCN patients. DIAGNOSTIC VALUE OF MID ESOPHAGEAL BIOPSIES PEDIATRIC PATIENTS WITH EOSINOPHILIC ESOPHAGITIS IN Chernetsova, E, J Joo, A Agarwal, J Barkey, D El Demellawy University of Ottawa, Children’s Hospital; of Eastern Ontario, Canada Background: Eosinophilic esophagitis (EOE) is a chronic immune-mediated disorder characterized by the presence of ≥15 eosinophils/HPF in esophageal biopsies in the absence of other causes of esophageal eosinophilia. The esophageal eosinophilic infiltrate is patchy and levels of eosinophilia can vary between the distal, middle and proximal esophagus. Studies have shown that increasing numbers of biopsies (6–9 biopsies) improve the diagnostic sensitivity. However, studies comparing different biopsy protocols for diagnosis of EOE, particularly in pediatric patients, have not been conducted. Design: We performed a retrospective study of pediatric patients with EOE presenting at our institute from 2007 – 2015. Our inclusion criteria included patients’ ≤ 18 years old with clinical, endoscopic and histological diagnosis of EoE and available initial and follow-up upper GI endoscopies and esophageal biopsies. Our exclusion criteria included syndromic conditions, parasitic infections, diagnosis of reflux esophagitis on biopsy and history of medication at the time of initial presentation. Endoscopic parameters evaluated were linear furrows, edema/decreased vascularity/mucosal stiffness, white papules/exudate, trachealization/rings, stricture and crêpe-paper mucosa. Histologic parameters evaluated were eosinophils number, basal cell hyperplasia, lamina propria fibrosis, eosinophilic abscess and spongiosis. The McNemar chi-square test was used to identify a statistically significant difference in signal detection of various parameters across the proximal or distal versus the mid esophageal biopsies. SPSS version 24 was used for the statistical analysis. Results: A total of 100 patients were identified. At the initial diagnostic visit, for the proximal/distal versus mid esophageal biopsies, there was a statistically significant difference in identifying intraepithelial eosinophils (p<0.001), lamina propria fibrosis (p=0.008), crust and erosion (p<0.001), esophageal thickening/nodularity (p=0.004), furrowing/striation (p=0.01) and white flecks/exudates (p=0.031) In all significant cases, the proximal or distal biopsy detected more signals as compared to the mid esophageal biopsies. There was no statistically significant difference between the proximal/distal versus mid esophageal biopsies in identifying basal cell hyperplasia (p=0.063), eosinophilic abscess (p=0.824), erosive changes/ulceration (p=0.250), spongiosis (p=0.481), trachealization (p=0.375), edema/loss of vascular pattern/stiffening (p=0.219), strictures (p=0.625), impacted food content (p=1.000), and friability (p=0.250). For any follow-up biopsies, for the proximal/distal versus mid esophageal biopsies, there was a statistically significant difference in identifying eosinophilic abscess (p=0.027), spongiosis (p<0.001), crust and erosion (p=0.024), furrowing/striations (p=0.001), edema/loss of vascular pattern (p=0.001), white flecks, exudates (p=0.008), and impacted food content (p=1.000). In all significant cases, the proximal or distal biopsy detected more signals as compared to the mid esophageal biopsies. There was no statistically significant difference between the proximal/distal versus mid esophageal biopsies in identifying intraepithelial eosinophils (p=0.238), basal cell hyperplasia (p=0.581), lamina propria fibrosis (p=0.092), esophageal thickening/nodularity (p=0.180), erosive changes/ulcerations (p=1.000), trachealization (p=1.000), erythema (p=0.125), strictures (p=0.250) and friability of tissue (p=0.250) Conclusion: Our study demonstrated that biopsies of the proximal/distal esophagus show superior diagnostic value compared to the mid esophageal biopsy at the initial presentation of EOE in children with identifying intraepithelial eosinophils (≥15 eosinophils/HPF). Similarly the proximal/distal esophagus show additional information compared to the mid follow up esophageal biopsies with significantly identifying eosinophilic abscesses, crust/erosions and spongiosis. The mid esophagus did not show additional gross or microscopic pathology on the initial or follow up presentations in pediatric patients with EOE. However, severity of pathological findings was not assessed in the current study. A RARE CASE OF PEDIATRIC LIPOMA WITH T(9;12)(P22;Q14) AND EVIDENCE OF HMGA2 NFIB GENE FUSION Lacaria, Melanie1, Dina El Demellawy2,3, Jean McGowan-Jordan1,4 1Genetics Department, Children’s Hospital of Eastern Ontario; 2Pediatric Pathology Department, Children’s Hospital of Eastern Ontario; 3Department of Surgery, University of Ottawa; 4Department of Pathology and Laboratory Medicine, University of Ottawa Abstract Lipoma is a benign tumor, typically of adulthood, with characteristic cytogenetic findings including rearrangement of 12q13-15; these rearrangements often lead to the fusion of the HMGA2 gene at this locus to the transcriptional regulatory domain of its fusion partner, resulting in neomorphic activity that presumably facilitates the neoplastic process. Herein, we report a rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion in a 9 year-old boy. This case provides further evidence of the link between NFIB rearrangement and early-onset, deep-seated lipomatous tumors. Key Words: HMGA2, NFIB, FISH, lipoma COFFEE BREAK ANNOUNCEMENT OF PRIZE WINNERS AND CONCLUSION POSTERS PEDIATRIC BLASTIC PLASMACYTOID DENDRITIC NEOPLASM - A SYSTEMATIC LITERATURE REVIEW CELL Jeong-Min Kim, Marie, Ahmed Nasr, Bilaal Kabir, Joseph de Nanassy, Ken Tang, Danielle Menzies-Toman, Donna Johnston, Dina El Demellawy University of Ottawa, Children’s Hospital of Eastern Ontario, Canada Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive hematologic malignancy characterized by frequent skin involvement that most commonly affects older patients. BPDCN is known to have a poor prognosis. Our objective was to assess if outcome and disease prognosis were independently influenced by age when evaluated with clinical presentation, sex, and treatment regimens. We conducted a systematic review to identify BPDCN cases, in order to compare pediatric BPDCN cases with adult cases. A total of 125 publications were identified detailing 356 cases. Including one pediatric case from our institution, 74 were children, and 283 were adults aged 19 or over. Age was shown to be an independent prognostic factor predictive of more favorable outcomes across measures including initial response to therapy, likelihood of relapse, and overall survival at follow-up. The distribution of affected organs at diagnosis was similar across children and adults and type of clinical presentation did not disproportionately influence one age group’s prognosis over the other. Acute Lymphoblastic Leukemia (ALL)-type chemotherapy regimens were shown to be superior to other chemotherapy regimens (Acute Myeloid Leukemia, Lymphoma, ALL/Lymphoma, other, or none) in inducing complete remission. Allogeneic stem cell transplantation was shown to increase mean survival time. Future research may be directed towards elucidating the further morphologic, cytogenetic, and cytochemical differences between younger and older BPDCN patients. THE EFFICIENCY OF ACTIVATING THE MasR/Ang1-7 PATHWAY TO REDUCE MUSCLE ATROPHY AND FUNCTION LOSS FOLLOWING DENERVATION Albadrani, Hind*1 and Renaud, JM1 Department of the Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada Muscle atrophy involved a sequence of events including loss of muscle mass, reduction in fiber diameter, disorganization of intracellular structures and decrease in force generation. Muscle atrophy occurs with spinal cord injury (SCI), neural denervation and space travel as well as chronic diseases such as heart and renal failure. Recent studies reported that activation of MasR/Ang1-7 pathway reversed muscle atrophy in skeletal muscle wasting disease. It remains to be determined, however, whether Ang 1-7 can also reduce the atrophy process and force loss following muscle denervation. So, the objective was to test the hypothesis that “an activation the MasR/Ang1-7 pathway reduces the atrophy and function loss following denervation in skeletal muscle”. Mouse extensor Digitorum Longus (EDL) and soleus were denervated by removing 3-4 mm of the sciatic nerve at the thigh level. Denervated mice were divided into 4 groups: i) denervated; ii) denervated and treated with Ang 1-7 at a rate of 100 ng/kg body weight/ min; and iii) denervated and treated with diminazene aceturate (DIZE), a ACE2 activator to locally increase Ang 17 levels, administrated by oral gavage at 15 mg/kg body weigh/day, iv) denervated group receiving 1 g/kg/day of sucrose by oral gavage. A 5 th group was used as control; i.e., normal innervated mice. Angiotensin 1-7 and DIZE fully prevented the decrease in isometric force in EDL and soleus muscle that occurred after 2 and 4 week denervation period. It also partially reduced the decrease in muscle fiber cross sectional area. This study is thus providing strong evidence that Ang 1, 7 has therapeutic potential to prevent function loss following a denervation. RNA-SEQ ANALYSIS OF REXINOID RESPONSIVE GENE EXPRESSION DURING EARLY MYOBLAST DIFFERENTIATION Khilji, Saadia, Qiao Li Department of the Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada The development of skeletal muscle is regulated by complex coordinated signaling pathways. We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor, promotes the specification and differentiation of the muscle lineage. Here, we examine the genome-wide impact of rexinoid action on myogenic expression through RNA-seq transcriptome profiling. We found that bexarotene promotes myogenic differentiation in a time specific manner. In addition, we show that bexarotene promotes myoblast differentiation via the simultaneous coordination of exit from the cell cycle to the activation of muscle-related genes. Our future work will focus on characterizing the mechanism of bexarotene action, in addition to, using a combination of RNA-seq and ChIP-seq datasets to discern functionally novel myogenic targets. These studies will allow for further dissection of signaling pathways in myogenesis, in search for developing cell-based therapies for skeletal muscle-related diseases. Retrospective, case-controlled stereological assessment of vascularization in placentas of HIV-exposed, uninfected (HEU) children. Wahba, Mary, Jenifer Bowes (BSc, MSc), Chris G. Ball (M.D.), Jason Brophy (M.D.), David Grynspan (M.D.) University of Ottawa, Children’s Hospital of Eastern Ontario, Canada Background: To prevent vertical human immunodeficiency virus (HIV) transmission, HIV+ pregnant women are treated with combination antiretroviral therapy (cART). Increased rates of preterm delivery have been found in HIV+ women, in some studies linked to protease inhibitor (PI) based cART treatment, although the underlying mechanism is not clear. Hypothesis: cART increases placental vessel formation, leading to adverse pregnancy outcomes. Materials and methods: Placentas were available for 40 HIV+ women from July 2014 – December 2016; with pathology slides available for 27. Slides were retrieved for 21 term HIV+ cases and 22 HIV-negative controls; preterm cases were excluded (5/27, 18.5%). 7/21 cases had received a PI. Vessel volume fractions (VVFs) and length densities (LDs) were calculated (Stereology Analyzer, ADCIS). Results: Mean VVFs for cases and controls were both 0.21. Mean LD was 335/mm2 (cases) versus 359/mm2 (controls). For PI-treated cases, mean VVF was 0.23 and mean LD was 324/mm2. Stereology measurements were not significantly different between groups. Mean placental weight was 471.2g (cases) versus 675g (controls) (p<.0001). Conclusion: Vessel measurements were not significantly different between term cases and controls. The difference in placental weight between cases and controls raises the possibility of confounding factors which will be addressed with a larger cohort. Future work will include examination of preterm placentas. DIAGNOSTIC VALUE OF MID ESOPHAGEAL BIOPSIES PEDIATRIC PATIENTS WITH EOSINOPHILIC ESOPHAGITIS IN Chernetsova, E, J Joo, A Agarwal, J Barkey, D El Demellawy University of Ottawa, Children’s Hospital; of Eastern Ontario, Canada Background: Eosinophilic esophagitis (EOE) is a chronic immune-mediated disorder characterized by the presence of ≥15 eosinophils/HPF in esophageal biopsies in the absence of other causes of esophageal eosinophilia. The esophageal eosinophilic infiltrate is patchy and levels of eosinophilia can vary between the distal, middle and proximal esophagus. Studies have shown that increasing numbers of biopsies (6–9 biopsies) improve the diagnostic sensitivity. However, studies comparing different biopsy protocols for diagnosis of EOE, particularly in pediatric patients, have not been conducted. Design: We performed a retrospective study of pediatric patients with EOE presenting at our institute from 2007 – 2015. Our inclusion criteria included patients’ ≤ 18 years old with clinical, endoscopic and histological diagnosis of EoE and available initial and follow-up upper GI endoscopies and esophageal biopsies. Our exclusion criteria included syndromic conditions, parasitic infections, diagnosis of reflux esophagitis on biopsy and history of medication at the time of initial presentation. Endoscopic parameters evaluated were linear furrows, edema/decreased vascularity/mucosal stiffness, white papules/exudate, trachealization/rings, stricture and crêpe-paper mucosa. Histologic parameters evaluated were eosinophils number, basal cell hyperplasia, lamina propria fibrosis, eosinophilic abscess and spongiosis. The McNemar chi-square test was used to identify a statistically significant difference in signal detection of various parameters across the proximal or distal versus the mid esophageal biopsies. SPSS version 24 was used for the statistical analysis. Results: A total of 100 patients were identified. At the initial diagnostic visit, for the proximal/distal versus mid esophageal biopsies, there was a statistically significant difference in identifying intraepithelial eosinophils (p<0.001), lamina propria fibrosis (p=0.008), crust and erosion (p<0.001), esophageal thickening/nodularity (p=0.004), furrowing/striation (p=0.01) and white flecks/exudates (p=0.031) In all significant cases, the proximal or distal biopsy detected more signals as compared to the mid esophageal biopsies. There was no statistically significant difference between the proximal/distal versus mid esophageal biopsies in identifying basal cell hyperplasia (p=0.063), eosinophilic abscess (p=0.824), erosive changes/ulceration (p=0.250), spongiosis (p=0.481), trachealization (p=0.375), edema/loss of vascular pattern/stiffening (p=0.219), strictures (p=0.625), impacted food content (p=1.000), and friability (p=0.250). For any follow-up biopsies, for the proximal/distal versus mid esophageal biopsies, there was a statistically significant difference in identifying eosinophilic abscess (p=0.027), spongiosis (p<0.001), crust and erosion (p=0.024), furrowing/striations (p=0.001), edema/loss of vascular pattern (p=0.001), white flecks, exudates (p=0.008), and impacted food content (p=1.000). In all significant cases, the proximal or distal biopsy detected more signals as compared to the mid esophageal biopsies. There was no statistically significant difference between the proximal/distal versus mid esophageal biopsies in identifying intraepithelial eosinophils (p=0.238), basal cell hyperplasia (p=0.581), lamina propria fibrosis (p=0.092), esophageal thickening/nodularity (p=0.180), erosive changes/ulcerations (p=1.000), trachealization (p=1.000), erythema (p=0.125), strictures (p=0.250) and friability of tissue (p=0.250) Conclusion: Our study demonstrated that biopsies of the proximal/distal esophagus show superior diagnostic value compared to the mid esophageal biopsy at the initial presentation of EOE in children with identifying intraepithelial eosinophils (≥15 eosinophils/HPF). Similarly the proximal/distal esophagus show additional information compared to the mid follow up esophageal biopsies with significantly identifying eosinophilic abscesses, crust/erosions and spongiosis. The mid esophagus did not show additional gross or microscopic pathology on the initial or follow up presentations in pediatric patients with EOE. However, severity of pathological findings was not assessed in the current study. DOUBLE HIT DIFFUSE LARGE B-CELL LYMPHOMA TESTING AT THE OTTAWA HOSPITAL Capitano, Mario, M.D., and Philip Berardi, M.D., Ph.D., FRCPC The Ottawa Hospital, General Campus, 501 Smyth Rd, Ottawa ON K1H 8L6 Introduction: Double-hit diffuse large B-cell lymphomas (DH-DLBCL) are more aggressive variants of DLBCL characterized by MYC translocation plus translocations in BCL2 and/or BCL6. This diagnosis is made by expensive fluorescent in-situ hybridization (FISH) testing. Current screening practices suggest only testing cases of germinal center B-celllike (GCB) DLBCL that overexpress MYC and BCL2 and/or BCL6 (dual expressors) as opposed to non-GCB DLBCL cases, since GCB DLBCL are more likely to be double-hit cases when they are dual expressors. However, non-GCB DLBCL are more likely to be dual expressors compared to GCB cases. Design and Results: Cases of de novo diffuse large B-cell lymphomas that were tested for MYC and BCL2 and/or BCL6 translocations by FISH were searched in PowerPath from 2010-2016 (inclusive) using variations of “diffuse large B-cell lymphoma”, “lymphoma”, and “MYC”. Cases were excluded if they were transformed from a lower grade lymphoma, were a primary central nervous system lymphoma, or had not had FISH testing for MYC and BCL2 and/or BCL6 translocations. This resulted in 39 cases of at least dual expressor DLBCL that had FISH testing. Fourteen cases (35.9%) were GCB DLBCL and 25 cases (64.1%) were non-GCB DLBCL. There were 11 cases of DH-DLBCLs. 7/14 (50%) of GCB DLBCL cases were DH-DLBCLs and 4/25 (16%) of the non-GCB DLBCL cases were DHDLBCLs. Overall, 7/11 (63.6%) of DH-DBLCL cases were GCB DLBCLs and 4/11 (36.4%) cases were non-GCB DLBCLs. CONCLUSION: This retrospective study of DH-DLBCLs cases at The Ottawa Hospital corroborates previous evidence showing that non-GCB DLBCLs are more likely to be dual expressors while GCB DLBCLs are more likely to actually harbour double-hit translocations. However, given that a substantial number of DH-DLBCLs cases may be missed if only GCB dual expressor cases undergo FISH testing, further research with a large retrospective study or a prospective study with strict criteria for FISH testing for MYC and BCL2 and/or BCL6 translocations should be done to better determine an effective screening algorithm for DH-DLBCL cases . ADENOCARCINOMA EX-GOBLET CELL CARCINOID TUMOURS, PATHOLOGIC CLASSIFICATION AND CLINICAL BEHAVIOR: AN ANALYSIS OF CASE SERIES (FROM 2003-2017 FROM THE OTTAWA HOSPITAL PATHOLOGY GROUP Capitano, Mario, M.D., and Zohreh Eslami, M.D., Ph.D., FRCPC The Ottawa Hospital, General Campus, 501 Smyth Rd, Ottawa ON K1H 8L6 Introduction: Adenocarcinoma ex-goblet cell carcinoids are poorly characterized, rare appendiceal tumours that histologically appear as a mix of goblet cell carcinoid tumour with a high grade adenocarcinoma. These tumours tend to occur more often in females who present with advanced clinical stage with gynecologic tract metastases, making it an important entity for gynecologic pathologists to be aware of. Design and Results: Here we report nine cases of adenocarcinoma ex-goblet cell carcinoid from 2003-2017. Tumours occurred predominantly in females (7/9), median age of 57 years, and advanced stage disease (7/9). Patients presented as acute appendicitis (3/9), bowel obstruction (4/9), or pelvic masses (2/9). Morphologically these tumours had a component of mucinous/signet ring cells admixed with well-formed glands. Limited IHC shows positivity for CK20, CDX-2, focal positivity for synaptophysin and chromogranin, and negative for CK7, PAX8, TTF-1. Most patients were treated surgically with right hemicolectomy or subtotal colectomy (6/9) and variations of bilateral salping-oophoerectomy and omentectomy. Five of nine cases had follow-up greater than three years. Four underwent standard chemotherapy for colonic adenocarcinoma. Four had disease progression to peritoneal carcinomatosis and one had no recurrence after 5 years. CONCLUSION: This study reveals that the high-grade entity of goblet cell carcinoid is a unique tumor with fairly specific morphologic and immunohistochemical features of gastrointestinal origin unique to the appendix, and has a variety of distinguishing clinicopathologic characteristics. Our results corroborate previous studies that show that these high grade tumors are seen predominantly in females in their early to mid-fifties, and have a predilection for transcoelomic dissemination with frequent gynecologic tract involvement. STROMAL TISSUE AS AN ADJUNCT TOOL IN THE DIAGNOSIS OF FOLLICULAR THYROID LESIONS BY FINE-NEEDLE ASPIRATION BIOPSY Hogan, Kevin, Kien T. Mai. The Ottawa Hospital and University of Ottawa, Pathology and Laboratory Medicine, Ottawa, ON, Canada Background: The stroma in fine-needle aspiration biopsy (FNAB) of thyroid lesions has not been well investigated. Design : We studied 256 consecutive cases of thyroid FNAB prepared with traditional smear technique. The stroma was categorized: Type 1a consisted of long (more than 3 mm), broad bands composed of mesh containing collagen fibrils thickened by entrapped blood components and follicular cells. Type 1b consisted of dense strands/bands. Type 2 was similar to Type 1a but with shorter (<2 mm) and looser stromal strands. Results : Types 1a and b showed straight/curved/circular branching patterns suggestive of incomplete frameworks of nodular/papillary architectures or fragments of capsule. Type 1b stroma likely represented thick/collagenized fibrous septae. Incomplete or complete rings of small encapsulated tumor were occasionally identified. These frameworks of stroma were frequently associated with multinodular goiters (MNGs) which are often hypocellular and follicular neoplasms/papillary thyroid carcinoma with increased cellularity. Type 2 was associated with microfollicles in encapsulated neoplasms or with macrofollicles in MNG. Follicular lesions of unknown significance (n = 41) either negative (n = 26) or positive (n = 15) for carcinoma in subsequent follow-up were frequently associated with stroma characteristic of MNG and carcinoma, respectively. Conclusion : The preservation of the in vivo architecture of Type 1 is likely due to its elasticity. Recognition of the stromal architecture will likely facilitate the diagnosis. CHARACTERISTICS OF LYMPHOPROLIFERATIVE DISORDERS (LPD) WITH MORE THAN ONE ABERRANT CELL POPULATION AS DETECTED BY 10 COLOR FLOW CYTOMETRY Mahdi, Talal (1, 2), Amr Rajab (2,3) ,Ruth Padmore (1), *Anna Porwit (2,4) (1) Department of Pathology and Laboratory Medicine, The Ottawa Hospital and Eastern Ontario Regional Laboratory Association and University of Ottawa, ON, Canada. (2) Flow Cytometry Laboratory, Department of Laboratory Hematology, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada. (3) Present address: Flow cytometry department, Lifelabs Medical laboratory services-Toronto. (4) Present address: Department of Clinical Sciences, Division of Oncology and Pathology, Faculty of Medicine, Lund University, Lund, Sweden Background: We have evaluated the frequency of lymphoproliferative disorders with more than one aberrant population of monotypic B-cells detected during routine hematopathological diagnostics. Materials and Methods: 2600 samples peripheral (blood, bone marrow, fine needle aspirate, lymph node and pleural fluid cell suspensions) were analyzed with flow cytometry using a ten-color B-cell panel and a tencolor T-cell panel. A ten-color plasma cell/lymphoplasmacytic panel was performed when appropriate. Results: 790/2600 samples (30%) showed at least one aberrant B-cell population and 27(1%) showed an aberrant T-cell population. 41/790 samples (5.1%) showed two aberrant B-cell populations. Thirteen patients had two B-cell populations with different surface immunoglobulin restriction (one kappa+ and one lambda+), most with B-cell chronic lymphocytic leukemia-like phenotype. Five cases showed two B-cell populations with the same light chain restriction but distinctly different immunophenotypes. In 23 cases, two populations had the same light chain restriction and differed by expression of one or 2 markers, thus, a possibility of intraclonal variation could not be excluded. Cases with possible intraclonal variation had a significantly higher proportion of aberrant B-cells than those with two coexisting aberrant B-cell populations (49.9% vs. 27.7%, p = 0.008). In only one sample one population of clonal B-cell and one clonal T-cell population with large granular lymphocyte related phenotype were found. Conclusion: Using our panels 5.1% of cases with LPD-associated aberrant findings show two aberrant lymphoid and/or plasma cell populations. EMERGENCY TRANSFUSION OF ONE UNCROSSMATCHED GROUP O Rh POSITIVE RED CELL UNIT TO A PATIENT WITH ANTI-D ANTIBODY IDENTIFY ONCE TYPE AND SCREEN WERE COMPLETED. A CASE REPORT Mahdi, Talal, MD, Ruth Padmore, MD The Ottawa Hospital and Eastern Ontario Regional Laboratory Association and University of Ottawa Introduction: Patient blood management programs aim to transfuse group O Rh negative red cells (RCs) only to Rh negative recipients. At the Ottawa Hospital, the CODE BLEED policy for trauma patients specifies that if uncross matched RC units are required for patients with unknown blood group, only female patients less than 45 years of age receive group O Rh negative RC units. All other patients receive group O Rh positive RC units. We report a patient who was transfused one unit of uncross matched group O Rh positive RC and in whom anti-D antibody was identified once the type and screen were completed. Case Report: The patient was an 87-year-old female trauma patient with pelvic fracture. The patient was initially transported to a community hospital; 2 hours later she was transferred to the Ottawa Hospital (TOH) Civic Campus Trauma Centre (day 0). On arrival the patient was unstable and a CODE BLEED was initiated. One unit of uncross matched group O Rh positive RC was transfused. Half an hour after transfusion the patient complained of nausea and back pain. One hour after transfusion, the transfusion medicine (TM) laboratory reported the patient was group B Rh negative with positive antibody screen; subsequently anti-D and anti-E alloantibodies were identified. The clinical team was notified, and no further group O Rh positive RCs were transfused. Following transfusion of the incompatible RC unit the hemoglobin stayed the same, 90 g/L pre and post transfusion and the post transfusion DAT anti-IgG was only weakly positive. Surgical open reduction and internal fixation were performed on day +6. The patient was discharged to rehabilitation on day +32. In retrospect, the community hospital TM lab results of group B negative with a positive antibody screen were available approximately at time of transfer to TOH, but there was no forward feeding of this information. Conclusion: Transfusion of uncross matched RCs has a low but definite risk for incompatible transfusion. Elderly Rh negative females whose childbearing years pre-date the universal introduction of RhIg might have increased incidence of anti-D antibody. Forward feeding of TM laboratory results is important for trauma transfusion protocols. A RARE CASE OF PEDIATRIC LIPOMA WITH T(9;12)(P22;Q14) AND EVIDENCE OF HMGA2 NFIB GENE FUSION Lacaria, Melanie1, Dina El Demellawy2,3, Jean McGowan-Jordan1,4 1Genetics Department, Children’s Hospital of Eastern Ontario; 2Pediatric Pathology Department, Children’s Hospital of Eastern Ontario; 3Department of Surgery, University of Ottawa; 4Department of Pathology and Laboratory Medicine, University of Ottawa Abstract Lipoma is a benign tumor, typically of adulthood, with characteristic cytogenetic findings including rearrangement of 12q13-15; these rearrangements often lead to the fusion of the HMGA2 gene at this locus to the transcriptional regulatory domain of its fusion partner, resulting in neomorphic activity that presumably facilitates the neoplastic process. Herein, we report a rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion in a 9 year-old boy. This case provides further evidence of the link between NFIB rearrangement and early-onset, deep-seated lipomatous tumors. Key Words: HMGA2, NFIB, FISH, lipoma DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE HISTOLOGY CORE FACILITY J.P.Veinot1, C.A. Jodouin2, Z. Ticas3, L. Dong4, E. Labelle5, S. Faulkes6, M. Khalili7, M. Alazzabi8, O. Agah9 The University of Ottawa, Faculty of Medicine, Department of Pathology and Laboratory Medicine (PALM), Histology Core Facility The Histology Core Facility (HCF) is a full-service research histology laboratory, located in the Department of Pathology and Laboratory Medicine of the University of Ottawa. The HCF has served the University and the Ottawa Region by providing histology services to faculty, researchers, clinicians, and students. Currently the HCF provides histology service to over 70 researchers from the University of Ottawa (Neuroscience, CMM, and BMI) and its partners at the Ottawa Hospital Research Institute (OHRI), University of Ottawa Heart Institute (UOHI), The Ottawa Hospital Cancer Centre (TOHCC), Children's Hospital of Eastern Ontario (CHEO), and the Eastern Ontario Regional Laboratory Association (EORLA). The HCF also provides service to special projects of the Public Health Agency of Canada (PHAC), Health Canada, the National Research Council (NRC), and Canadian Nuclear Labs in Deep River Ontario which contribute to the University of Ottawa's goal of excellence in research. The Histology Core Facility services offered include: Paraffin processing and embedding; Paraffin, frozen, and RNAse free sectioning; Histological stains for general morphology, carbohydrates, connective tissue, lipids, microorganisms, and intracellular granules. Immunohistochemistry services include: optimization of new antibodies, staining of routine and new antibodies, chromogenic and single or dual colour immunofluorescence. Digital whole slide scanning on the Zeiss Mirax Midi Slide scanner can scan all brightfield slides containing one or multiple tissue sections at resolution magnification of 40X. The Histology Core Facility provides training, education and assistance with course content and set-up for first and second year medical students and graduate students. We participate in the Faculty of Medicine program that provides high school student tours throughout the year. In 2016 the Histology Core Facility implemented an online system to streamline the processing of client service requests, invoicing, tracking of equipment training requests and usage of common area equipment as part of our services. The iLAB system optimizes the processing of service requests and improves turnaround times for our Internal, External, and Commercial clients. Monthly microtome and cryostat training is also offered with registration via the iLab system. Consultation services are available to direct and coordinate research, develop protocols, provide teaching or carry out clinical work. Project service requests are offered on an individual basis to accommodate the specific needs of our research clients to include protocol development, preliminary costing services, and protocol technical information. The HCF is equipped with two automatic LOGOS tissue processors for paraffin processing, and microtomes to section paraffin blocks. Cryostats are available for sectioning frozen tissues for lipid and enzyme demonstration, and for immunohistochemical or immunofluorescence service requests. In 2016, the HCF acquired a Thermo-VWR NX-70 Cryostar Cryostat and a Thermo-Fisher Slide-Mate Slide Printer. A fully automated Leica Bond III automated immunostainer will be operational in the very near future. The Leica Bond III is able to perform automated immunohistochemistry (IHC), in-situ hybridization (ISH), and Immunofluorescence (IF). This together with other existing instruments, services, and staff expertise is will allow the HCF to expand its menu of available services and provide reproducible, consistent, high-quality staining and increased throughput.
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