Canadian Journal of

Volume 10 | Issue/numéro 1

pathology pathologie Revue canadienne de

OSCE mOdulE fOr pathOlOgy COmpEtEnCy aSSESSmEnt

PM 43490512

www.cap-acp.org

KEY TRUDA DA: ®

Pr

NOW FOR PA ATIENT TS WITH METASTA ATIC NSCLC WITH NO PRIOR SYSTEMIC CHEMOTHERAPY TREA T T TMENT 1 FOR METASTA AT TIC NSCLC N N EW

N NSCLC INDICATIO T ON ®

KEYTRU UDA (pembrolizumab) as monotherapy is indicated for the tr t eatment of metastatic NS SCLC in adults whose tumourss have high PD-L1 expressio on [Tumour Proportion Score (TPS T ) ≥50%] as determined by b a validated test, with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for f metastatic NSCLC.1

MELANOMA KEYTRUDA® is indicated for f the treatment of patients with unresecta able or metastatic melanoma who have not received prior treatment with ipilimumab. b. Subjects with BRAF V600 mutant melanoma noma may have received prior BRAF inhibitor bitor therapy.1

Pembrolizumab is RECOMMENDED as a FIRST-line treatment of metastatic NSCLC, in patients with PD-L1+ expression ( TPS ≥50%) and EGFR-, ALK- in the NCCN guidelines.2 Please see e the NCCN guidelines for complete recommendations

Relevant warrnings g and p precautions: • Immune-me ediated adverse reactions including: Pneumonittis Colitis Hepatitis Nephritis and a renal dysfunction Endocrinopathies including hypophysitis, type 1 diab betes mellitus and thyroid disorders Severe skin n reactions, including Stevens-Jo Stevens Jo ohnson syndrome and toxic epidermal necrolysis

• Other immune-mediated adverse events, including uveitis, arthritis, myositis, bullous pemphigoid, higoid, myasthenic syndrome,, vasculitis, litis, Guillain-Barré syndrome, hemolytic ic anemia, pancreatitis, and partial seizures arising in a patient with inflammatory focii in brain parenchyma Solid organ transplant rejection Myocarditis • Severe infusion-related reactions, including hypersensitivity and anaphylaxis • Embryofetal toxicity • Not recommended in pregnant w women • In nursing women, a decision sho ould be made whether to discontinue breast-feeding st-feeding or KEYTRUDA® taking t ki into account ntt the th benefit of breast-feeding for the cchild and the benefit of KEYTRUDA® th herapy for the woman

• Has not been studied ed in patients with moderate or severe hepatic impairment • Has H nott been b studied t died d in i patients ti t with ith severe renal impairment • Monitor liver and thyr hyroid function tests and electrolytes during ring treatment For more information: on: Before prescribing KE EYTRUDA®, please consult the product monograph available at https://health-products.canada.ca/dpd-bdpp/ ts.canada.ca/dpd-bdpp/ index-eng.jsp for important ortant information relating to adverse rea actions, drug interactions and dosing information on which have not been discussed in this docu ument. The product monograph raph is also available by calling us at 1-800-567-2594 0-567-2594 or by email at medinfocanada@mer m ck.com.

ALK=anaplastic lym mphoma kinase; EGFR=epidermal gro owth factor receptor; e NCCN=National Compre ehensive Cancer cer Network; NSCLC=non-small cell lung carcinoma; c oma; PD-L1=programme ed cell death ligand 1; TPS=tumour pro oportion score References: 1. KEY YTRUDA® Pro oduct Monograph. Merck Canada In nc. July 20, 2017. 2. National Compre ehensive Cancer ancer Network. Clinical Practice Guidelines in Oncology ncology. Non-small cell lung g cancer.. Version e 5.2017. Marcch 16, 2017. ®

Merck Sharp & D Dohme Corp. Used under license. © 2017 Merck Can nada Inc. All rights reserved. e

ONCO-1226035-0000

Clinical use: Safety and efficacy fi of KEYTRUDA® in pediatric di i patie ients have h not been b established. bli h d

Canadian Journal of

Volume 10 | issue 1 EdItOr-In-ChIEf George M Yousef, MD, PhD FRCPC (Path) EdItOr EmErItuS J. Godfrey Heathcote, MA, MB, BChir, PhD, FRCPC fOundIng EdItOr Jagdish Butany, MBBS, MS, FRCPC

pathology

Official Publication of the Canadian Association of Pathologists

table of Contents

4 9

managIng EdItOr Deborah McNamara EdItOrIal COntEnt managEr Heather Dow art dIrECtOr Sherri Keenan

Canadian Journal of Pathology is a peer-reviewed journal published four times per year, by Clockwork Communications Inc., on behalf of the Canadian Association of Pathologists.

13

34 24

We welcome editorial submissions to www.CanadianJournalOf Pathology.ca Publications Mail Agreement No. 43490512 ISSN 1918-915X (print) ISSN 1918-9168 (online) Return undeliverable Canadian addresses to: Clockwork Communications Inc PO Box 33145 Halifax, NS B3L 1K3

www.cap-acp.org

Cap-aCp neWs CAP-ACP Guidelines for Benign Endometrial Biopsy Interpretation and Reporting. Authors: Carlos Parra-Herran MD; Matthew Cesari MD, FRCPC; Bojana Djordjevic MD, FRCPC; Katherine Grondin MD, FRCPC; Mary Kinloch MD, FRCPC; Martin Köbel MD, FRCPC; Amrah Pirzada MD; Anna Plotkin MD, FRCPC; and C Blake Gilks MD, FRCPC.

CAP-ACP 69th Annual Meeting (held jointly with APQ) Schedule Overview.

Digital pathology An interactive objective structured clinical examination (OSCE) module for performance assessment in anatomical pathology. A Diagnosis not to Miss in Patients with Bowel Ischemia Authors: Elena Diana Diaconescu MD; Alex O. Salagean BSc; Eriny Tawedrous MD, MSc; Lorna Mirham MD, FRCPC; Adriana Krizova MD, MSc, FRCPC; Hala Faragalla MD, FRCPC; Shachar Sade MD, MSc, FRCPC; Martin Bullock MD, FRCPC; Andrea Grin MD; Catherine Streutker MD, MSc, FRCPC; Beverley Carter MD, FRCPC; Mark Lee MD, PhD, FRCPC; George M Yousef MD, MSc, PhD, FRCPC.

We cannot assume responsibility or commitment for unsolicited material. Any editorial material, including photographs, that are accepted from an unsolicited contributor, will become the property of the Canadian Association of Pathologists. Copyright Canadian Association of Pathologists (CAP-ACP). All rights reserved. Reprinting in part or in whole forbidden without express written consent from CAP-ACP.

Molecular Pathology Corner: Investigating DICER1 syndrome: the urgency to establish reliable diagnostic and molecular markers. Authors: Fabio Rotondo BSc., Luis V. Syro MD, Kalman Kovacs MD, PhD.

tranSlatIOn Jocelyne Demers-Owoka Éliane Fréchette publIShIng agEnCy Clockwork Communications Inc. PO Box 33145, Halifax, NS, B3L 4T6 902.442.3882 / [email protected]

Letter from the Editor-in-Chief: Challenging the peer review process. Are we heading the right direction?

36

Case RepoRt Social media eh? A Canadian perspective on social media use in pathology. Authors: Matthew J. Cecchini MD, PhD; Leslie M. Anderson MD, MEd; Elena Diana Salagean MD; Marcio M. Gomes MD, PhD, FRCPC.

54

RetRospeCtiVe stUDy Detection of sessile serrated adenomas from colonoscopies in a major Canadian city: a retrospective study Authors: Ehteshamul Chowdhury MSc; Leonard T. Nguyen PhD; and Christopher Naugler MD, CCFP, FCFP, FRCPC. Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

3

LETTER FROM THE EDITOR-IN-CHIEF

CHALLENGING THE PEER REVIEW PROCESS. ARE WE HEADING THE RIGHT DIRECTION?

F

or centuries peer-review has been considered the cornerstone of the scholarly publication process. It is the evaluation of scholarly work, by expert colleagues in the same field, to ensure the quality of academic journals.

A review process provides a number of positive aspects such as the filtering out of substandard or falsified work prior to publication. It provides beneficial feedback to authors regarding experimental design and scientific errors. And it allows Editors to select the most remarkable research findings for publication in order to ensure their journals are highly trusted by the scientific community. The three traditional versions of peer-review are single-blind (where the authors do not know the identity of the reviewers), double-blind (where neither reviewers nor authors know each other’s identities), and the more recent open-review (where all identities are known by all and reviewer comments are published with the article). Regardless of the type of peer-review there are some disadvantages. There is ongoing debate as to whether the peer-review process is really effective in detecting scientific weaknesses or plagiarism. The process can also result in longer delays between submission and publication dates due, in part, to the fact that the review process is a volunteer activity. Not all reviewers will conduct the process to the same standard and personal bias can lead to unfair rejection of high quality papers or limitations on new and cutting-edge topics. These concerns have resulted in new trends toward on-line alternatives to the conventional peer-review process. Examples of these new trends include Unpublished Preprints where a draft of an academic article is posted on-line immediately after submission and without peer-review. BioRxiv (pronounced bio-archive), operated by the Cold Spring Harbor Laboratory (a not-for-profit research and educational institution), offers an example of preprints. This option allows authors to make their findings immediately 4

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

available to the scientific community and to receive feedback on draft manuscripts before they are submitted to journals. It does not eliminate the future possibility of peer-reviewed publication of the article. Advantages of preprints include reduction in the delays associated with publication and providing diversity of feedback by readers. When considering preprint articles researchers should take into account various considerations. It is difficult to predict how preprints will be weighed by the scientific community and there is the possibility of the dissemination of pseudoscience before preprints are peer-reviewed. Another example is “post publication review”. For instance, F1000Research, launched by the founders of BioMed Central and Current Opinion journals, is an open access publisher that offers immediate publication after rapid scientific checks, with fully transparent, post-publication reviews that are public and citable. Authors are able to select their own reviewers and authors can submit revised versions of their work in response to feedback. And unlike the traditional publishing model, of accept or reject, the articles remain on the site permanently. This process helps to eliminate long delays in publishing times by ensuring the latest article is available in real time. It also eliminates potential bias from Editors (there are no Editors involved). The review process is author driven so it is up to the author to determine if feedback will result in revisions and to continue to revise as long as feedback is being received. The author takes the risk of paying the article submission fee without knowing if the article will receive reviewer feedback – and once submitted to F1000Research the article cannot be submitted to another Journal. The risk of it is a potential inability to filter low quality research. It is also still unknown as to how an article will be judged by the scientific community in terms of quality and impact. Collabra, an open-access journal program launched by the University of California, allows authors the option to request continued on page 6

LETTRE DU RÉDACTEUR EN CHEF

REMISE EN QUESTION DU PROCESSUS D’ÉVALUATION PAR LES PAIRS : ALLONS-NOUS DANS LA BONNE DIRECTION?

P

endant des siècles, l’évaluation par les pairs a été considérée comme la pierre angulaire du processus de publication scientifique. Ce terme renvoie à l’examen des travaux d’érudition à paraître par des collègues experts du domaine dans le but de garantir la qualité des revues spécialisées.

Un tel processus comporte un certain nombre d’avantages, y compris le filtrage des travaux falsifiés ou de piètre qualité avant la publication. Il permet également de fournir de la rétroaction utile aux auteurs du point de vue de la méthodologie expérimentale et des erreurs scientifiques. Enfin, l’évaluation par les pairs donne aux rédacteurs en chef l’occasion de sélectionner les résultats de recherche les plus remarquables de manière à renouveler la confiance de la communauté scientifique envers leur revue. Les trois variantes classiques de l’évaluation par les pairs sont l’évaluation à simple insu (les auteurs ne connaissent pas l’identité des évaluateurs), l’évaluation à double insu (les évaluateurs ne connaissent pas l’identité des auteurs, et viceversa) et, plus récemment, l’évaluation ouverte (l’identité de toutes les parties est connue et les commentaires des évaluateurs sont publiés avec l’article). Or, tous les types d’évaluation par les pairs présentent aussi des inconvénients. Un débat est d’ailleurs en cours à savoir si le processus d’évaluation par les pairs est réellement efficace pour mettre en évidence les faiblesses scientifiques ou détecter le plagiat. L’évaluation par les pairs peut également allonger les délais entre la soumission des articles et la publication en raison, notamment, du fait qu’il s’agit d’une activité bénévole. Par ailleurs, les évaluateurs ne sont pas tous soumis aux mêmes normes, et leurs préjugés personnels peuvent mener au refus d’articles de qualité supérieure ou au musellement de nouveaux sujets de pointe. Ces préoccupations ont donné lieu à l’émergence de nouvelles tendances; de plus en plus d’auteurs se tournent

désormais vers des solutions en ligne qui remplacent le processus d’évaluation par les pairs traditionnel. Parmi ces nouvelles options se trouve la prépublication, qui désigne la publication en ligne d’un article scientifique immédiatement après sa soumission, sans évaluation par les pairs. bioRxiv (prononcé « bio-archive »), un serveur exploité par le Cold Spring Harbor Laboratory (un établissement de recherche et d’enseignement à but non lucratif), offre des exemples de prépublications. Cette solution permet aux auteurs de rendre leurs conclusions accessibles à la communauté scientifique sur-le-champ et de recevoir de la rétroaction sur l’ébauche de leur manuscrit avant de soumettre leur article à des revues. La prépublication n’élimine pas la possibilité future de publication d’une version de l’article évaluée par des pairs. Les avantages associés à cette méthode regroupent la diminution des délais liés à la publication et l’émission de commentaires par une variété de lecteurs. Cela dit, les chercheurs qui envisagent d’avoir recours à la prépublication devraient tenir compte de certains éléments. En effet, il est difficile de prédire de quelle façon les prépublications seront perçues par la communauté scientifique. Il est aussi possible que de la pseudoscience soit diffusée avant que les prépublications soient évaluées par des pairs. Une autre option est l’« évaluation post-publication ». Par exemple, la plate-forme F1000Research, lancée par les fondateurs de BioMed Central et de la série de revues Current Opinion, est un éditeur en libre accès qui offre une publication immédiate à la suite d’une vérification scientifique rapide et des évaluations post-publication publiques pouvant être citées. Les auteurs peuvent choisir leurs évaluateurs et soumettre des versions révisées de leur travail en réponse à la rétroaction obtenue. De plus, contrairement au modèle de publication classique (acceptation ou refus), les articles publiés sur le site y demeurent en permanence. Cette façon de faire contribue à éliminer les longs délais associés à la publication traditionnelle en rendant accessible le dernier article paru en

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

5

lEttrE du rédaCtEur En ChEf (suite) temps réel. Elle permet aussi d’éradiquer les partis pris potentiels des rédacteurs en chef, puisqu’aucun ne participe aux démarches entourant la publication. Le processus d’évaluation est mené par les auteurs; ce sont donc eux qui déterminent si la rétroaction reçue engendrera des modifications ou non, et qui décident s’ils continueront de réviser leur article tant et aussi longtemps que des commentaires seront formulés à son endroit. Les auteurs prennent également le risque de payer les frais liés à la soumission de leur article sans savoir s’ils recevront de la rétroaction. Qui plus est, une fois soumis à F1000Research, un article ne peut être présenté à une autre revue. Une éventuelle incapacité à exclure les travaux de recherche de moindre qualité pourrait découler de cette approche. Finalement, la manière dont un article sera jugé par la communauté scientifique en ce qui concerne sa qualité et ses retombées reste à ce jour inconnue. Collabra, un programme de revue en accès libre lancé par l’Université de Californie, donne aux auteurs l’option de faire la demande d’une évaluation ouverte, dans le cadre du processus d’évaluation à simple ou à double insu. Dans ce cas, les commentaires des évaluateurs sont ouvertement

accessibles et, si l’article est accepté, sont publiés avec ce dernier. Si les évaluateurs choisissent de signer les révisions qu’ils proposent, leur nom est publié avec les commentaires. Il convient aussi de noter que les évaluateurs sont rémunérés pour leur travail. Bien que les évaluateurs aient la possibilité de demeurer anonymes, la plupart semblent opter pour une évaluation ouverte. Si cette formule assure la transparence du processus d’évaluation, elle soulève la question suivante : ce niveau de transparence garantira-t-il un processus d’évaluation honnête et exhaustif? Le fait de permettre aux évaluateurs de choisir s’ils veulent travailler dans l’anonymat ou non améliorera-t-il le processus ou créera-t-il plutôt un système de type « deux poids, deux mesures »? On dirait qu’un dialogue long et complexe, qui s’étalera certainement sur plusieurs années, s’amorce. Il sera intéressant de suivre l’évolution de cette discussion et de voir où elle nous mènera.

George M. Yousef, M. D., Ph. D., FRCPC(Path) Rédacteur en chef, Revue canadienne de pathologie

lEttEr frOm thE EdItOr-In-ChIEf (cont.) open-review, as part of the single-blind or double-blind review process. In this case the reviewer comments are openly available and, if the article is accepted, are published with the article. If reviewers have chosen to sign their reviews then the reviewer name is also published with the comments. Reviewers also receive payment for their reviews. Although it gives the option for the reviewers to remain anonymous the majority seem to opt for open review. While this ensures transparency of the review process it raises the question as to whether this level of transparency will guarantee a full and honest review process? Does allowing reviewers to opt in or opt out improve the process or create two sets of standards? It seems like we are at the beginning of a long and complex dialogue that will not be over in the near future. It will be interesting to follow the evolution of this discussion and where it will lead us.

George M. Yousef MD, PhD, FRCPC(Path) Editor-in-Chief, Canadian Journal of Pathology 6

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org










     
     
 
 Rural Incentives ~ Relocation Support ~ Diverse Practice Options

Interior Health Authority is currently recruiting for an experienced Canadian General Pathologist or anatomic and clinical pathologist (AP/CP). The ideal candidate will have 5 or more years of clinical practice experience, with strong skills in surgical pathology and laboratory diagnostics, and will be comfortable with independent practice in a small group environment. Additional fellowship training in surgical pathology and the ability to sign out cytology and bone marrow biopsies would be an asset. This position requires strong interpersonal and communication skills, including the ability to relate well with laboratory staff, clinicians, and administration.

Apply today: [email protected]       


Irvaym B. Barsoum MD, MSc, PhD; Michael Carter MD, PhD; Hala Faragalla MD, FRCPC; Louis Gaboury, M.D., Ph.D., F.R.C.P.(C), F.C.A.P.; John Gartner, MD CM, FRCPC; Laurette Geldenhuys, MBBCH, FFPATH, MMed, FRCPC, MAEd, FIAC; Zeina Ghorab MD, MSc; Nadia Ismiil, MBChB, FRCPC; Jason Karamchandani, MD; Adriana Krizova MD, MSc, FRCPC; David Munoz, MD, MSc, FRCPC; Christopher Naugler, MD, FRCPC; Tony Ng, MD, PhD FRCPC; Sharon Nofech-Mozes, MD; Maria Pasic, PhD, FCACB; Aaron Pollett, MD, MSc, FRCPC; Rola Saleeb MD; Harman Sekhon, MD, PhD, FCAP; Monalisa Sur, MBBS, FCPath, MMed., MRCPath, FRCPC; Aducio Thiesen, MD, PhD, MSc, FRCPC; Stephen Yip, MD, PhD, FRCPC.

IntErnatIOnal EdItOrIal bOard Emma H. Allott PhD, University of North Carolina, USA; Fredrik Bosman, MD, PhD, University of Lausanne, Switzerland; Daniel Chanm, PhD, DABCC, FACB, Johns Hopkins University School of Medicine, USA; Runjan Chetty, MB BCh, FRCPA, FFPath, FRCPath, FRCPC, FCAP, Dphil, University of Tornto, Canada; Kumarasen Cooper ,MBChB, Dphil, FRC path, University of Pennsylvania, USA; Brett Delahunt, BSc Hons BMedSc MB ChB MD FRCPA FFSc FRCPath, University of Otago, New Zealand; Sunil R Lakhani, BSc (Hon), MBBS, MRCPath, MD, FRCPath, FRCPA, The University of Queensland, Australia; Virginia A. LiVolsi, MD, MASCP, University of Pennsylvania, USA; Ricardo Lloyd, MD, PhD, University of Wisconsin, USA; Jesse Mckenney, MD, Cleveland Clinic, USA; Chris Meijer, MD, PhD, VU University, The Netherlands; George Netto, MD, PhD, Johns Hopkins University School of Medicine, USA; Isobel Scarisbrick, PhD, Mayo Clinic, USA; Manfred Schmitt, Dr. rer. nat., Dr. med. habil. (Ph. D., M.D. sci.), Dipl.-Biologist, Technical University, Munich, Germany; Iris Schrijver, MD, Stanford University, USA; Andreas Scorilas, PhD, University of Athens, Greece; Ming Tsao, FRCPC, MD, University of Toronto, Canada; Mark Wick, MD, University of Virginia, USA.

COmIté dE rédaCtIOn Irvaym B. Barsoum M. D., M. Sc, Ph.D; Michael Carter M. D., Ph. D; Hala Faragalla, M. D., FRCPC; Louis Gaboury, M. D., Ph. D., FRCPC, FCAP; John Gartner, M. D. CM, FRCPC; Laurette Geldenhuys, MBBCH, FFPATH, MMed, FRCPC, MAEd, FIAC; Zeina Ghorab M. D.; Nadia Ismiil, MBChB, FRCPC; Jason Karamchandani, M. D.; Adriana Krizova M. D., M. Sc, FRCPC; David Munoz, M. D., M. Sc, FRCPC; Christopher Naugler, M. D., FRCPC; Tony Ng, M. D., Ph. D., FRCPC; Sharon Nofech-Mozes, M. D.; Maria Pasic, Ph. D., FCACB; Aaron Pollett, M. D., M. Sc, FRCPC; Rola Saleeb M. D.; Harman Sekhon, M. D., Ph. D, FCAP; Monalisa Sur, MBBS, FCPath, MMed., MRCPath, FRCPC; Aducio Thiesen, M. D., Ph. D, M. Sc, FRCPC; Stephen Yip, M. D., Ph. D, FRCPC.

COmIté dE rédaCtIOn IntErnatIOnal Emma H. Allott Ph. D, Université de North Carolina, É.-U.; Fredrik Bosman, M. D., Ph. D., Université de Lausanne, Suisse; Daniel Chanm, Ph. D., DABCC, FACB, faculté de médecine de l’Université Johns Hopkins, É.-U.; Runjan Chetty, MB BCh, FRCPA, FFPath, FRCPath, FRCPC, FCAP, Dphil, Université de Toronto, Canada; Kumarasen Cooper ,MBChB, Dphil, FRC path, Université de la Pennsylvania, É.-U.; Brett Delahunt, B. Sc Hons BMedSc MB ChB MD FRCPA FFSc FRCPath, Université d’Otago, Nouvelle-Zélande; Sunil R Lakhani, B. Sc (Hon), MBBS, MRCPath, M. D., FRCPath, FRCPA, Université de Queensland, Australie; Virginia A. LiVolsi, M. D., MASCP, Université de la Pennsylvanie, É.-U.; Ricardo Lloyd, M. D., Ph. D, Université du Wisconsin, É.-U.; Jesse Mckenney, M. D., Clinique de Cleveland, É.-U.; Chris Meijer, M. D., Ph. D., Université VU, Pays-Bas; George Netto, M. D., Ph. D., faculté de médecine de l’Université Johns Hopkins, É.-U.; Isobel Scarisbrick, Ph. D., Clinique Mayo, É.-U.; Manfred Schmitt, Dr. rer. nat., Dr. med. habil. (Ph. D., M.D. sci.), Dipl.-Biologist, Université polytechnique, Munich, Allemagne; Iris Schrijver, M. D., Université Stanford, É.-U.; Andreas Scorilas, Ph. D., Université d’Athènes, Grèce; Ming Tsao, FRCPC, M. D., Université de Toronto, Canada; Mark Wick, M. D., Université de la Virginie, É.-U. 8

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

COmIté dE rédaCtIOn

EdItOrIal bOard

EdItOrIal bOard

MoleCUlaR pathology CoRneR This article was peer-reviewed.

KeyWoRDs: DICER1, mutation, neoplasms, pathology.

InvEStIgatIng DICER1 SyndrOmE: thE urgEnCy tO EStablISh rElIablE dIagnOStIC and mOlECular markErS author:

Fabio Rotondo1 BSc., Luis V. Syro2 MD, Kalman Kovacs1 MD, PhD

affiliations: 1Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital and 2 Department of Neurosurgery, Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia acknowledgement: Authors are grateful to the Jarislowsky and Lloyd Carr-Harris foundations for their continuous support.

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. All authors have provided CAP-ACP with non-exclusive rights to publish and otherwise deal with or make use of this article, and any photographs/images contained in it, in Canada and all other countries of the world.

E

Dicer, is an enzyme encoded by the DICER1 gene and part of the RNase III family in humans. It is responsible for cleaving double-stranded RNA (dsRNA) and premicroRNA (pre-miRNA) into small interfering RNA and microRNA (miRNA).

ndoribonuclease Dicer, or more commonly known as Dicer, is an enzyme encoded by the DICER1 gene and part of the RNase III family in humans. It is responsible for cleaving double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into small interfering RNA and microRNA (miRNA). These short fragments of RNAs bind to the 3′-untranslated region of target mRNAs and inhibit gene expression of many cellular proteins by preventing translation. This process is known as RNA interference or gene silencing. Through the regulation of expression of genes, Dicer is involved in many processes of cell proliferation and differentiation and has also been implicated in the development of various types of cancer due to its ability to alter miRNA expression profiles.

DICER1 syndrome is a rare, heritable disorder (autosomal dominant pattern of inheritance) characterized by germline DICER1 mutations that lead to tumours and dysplasias in childhood or adolescence. Germ-line DICER1 mutations have been documented in various benign and malignant tumours presenting in the lungs (pleuropulmonary blastoma (PPB)), kidney (cystic nephroma, anaplastic sarcoma of the kidney, Wilms tumour), central nervous system (pituitary blastoma, ciliary body medulloepithelioma), ovaries (sex cordstromal tumours), thyroid (multinodular goiter), and upper respiratory tract (nasal chondromesenchymal hamartoma). The exact incidence of DICER1 syndrome is unknown since the number of individual or familial cases are not Continued on Pg 11.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

9

RUbRiqUe De pathologie MoléCUlaiRe Veuillez noter que seuls les résumés des articles sont offerts en français.

rEChErChES Sur lE SyndrOmE DICER1 : lE bESOIn urgEnt d’établIr dES marquEurS dIagnOStIquES Et mOléCulaIrES fIablES auteurs :

Fabio Rotondo, B. Sc.1; Luis V. Syro, M.D.2; Kalman Kovacs, M.D., Ph. D.1

affiliations: 1 Département de médecine de laboratoire, Division de pathologie, Hôpital St. Michael, Toronto, Canada 2 Département de neurochirurgie, Hôpital Pablo Tobón Uribe et Clínica Medellín, Medellín, Colombie remerciements : Les auteurs souhaitent remercier la Fondation Jarislowsky et la Fondation Lloyd Carr-Harris pour leur soutien continu.

Les auteurs ne déclarent aucun conflit d’intérêts qui pourrait être perçu comme pouvant compromettre l’impartialité de l’étude présentée. Ils n’ont pas reçu de subvention particulière de la part d’organismes de financement du secteur public, commercial ou à but non lucratif. Enfin, ils ont tous accordé à la CAP-ACP le droit non exclusif de publier et d’utiliser cet article, et toute image ou photographie qu’il renferme, ou d’en disposer autrement, au Canada et partout ailleurs dans le monde.

L

’endoribonucléase Dicer, mieux connue sous le nom « Dicer », est une enzyme encodée par le gène DICER1 qui appartient à la famille des ribonucléases III chez les humains. Elle est responsable de la fragmentation des ARN double-brin (ARNdb) et des prémicroARN (pré-miARN) en ARN interférents courts (ARNic) et en microARN (miARN). Ces courts fragments d’ARN se fixent à la région 3’ non traduite (UTR) des ARNm cibles et inhibent l’expression génique de nombreuses protéines cellulaires en empêchant leur traduction. On qualifie ce processus d’« interférence ARN » ou de « silençage de l’expression génique ». Par l’entremise de la régulation de l’expression génique, Dicer intervient

10

dans bon nombre de processus de prolifération et de différenciation cellulaire. Qui plus est, en raison de sa capacité à modifier les profils d’expression des miARN, cette enzyme a été associée au développement de divers types de cancer. Le syndrome DICER1 est un trouble héréditaire rare (transmission autosomique dominante) caractérisé par des mutations germinales de DICER1 qui engendrent l’apparition de tumeurs et de dysplasies durant l’enfance ou l’adolescence. Des mutations germinales de DICER1 ont été observées dans diverses tumeurs bénignes et malignes des poumons (blastome pleuropulmonaire [BPP]),

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

des reins (néphrome kystique, sarcome anaplasique du rein, tumeur de Wilms), du système nerveux central (blastome pituitaire, médulloépithéliome du corps ciliaire), des ovaires (tumeurs des cordons sexuels et du stroma gonadique), de la glande thyroïde (goitre multinodulaire) et des voies respiratoires supérieures (hamartome chondromésenchymateux nasal). L’incidence exacte du syndrome DICER1 est inconnue, puisque les cas individuels ou familiaux ne sont pas toujours bien diagnostiqués. Si on peut soupçonner la présence d’une tumeur associée à une mutation de DICER1 en s’appuyant sur la présentation clinique de l’excroissance, l’imagerie médicale et les résultats pathologiques, seule

RUbRiqUe De pathologie MoléCUlaiRe rEChErChES Sur lE SyndrOmE dICEr1 (suite)

À l’heure actuelle, mis à part la détection d’une mutation germinale délétère de DICER1, il n’existe pas d’autres critères officiels pour diagnostiquer le syndrome DICER1.

l’identification d’une ou de plusieurs mutations germinales de DICER1 peut permettre l’établissement du diagnostic. À l’heure actuelle, mis à part la détection d’une mutation germinale délétère de DICER1, il n’existe pas d’autres critères officiels pour diagnostiquer le syndrome DICER1. Or, le dépistage précoce des mutations germinales pourrait avoir un impact sur le pronostic et le traitement de ces tumeurs. Les cliniciens et les pathologistes doivent faire preuve de prudence et envisager d’effectuer des analyses moléculaires si une patiente ou un patient présente une maladie de Cushing à un très jeune âge (blastome pituitaire); un enfant âgé de quatre ans ou moins présente une dyspnée et une perte de poids accompagnées ou non d’un pneumothorax par rupture kystique (BPP); un jeune enfant présente une masse à l’abdomen/au flanc; ou une

adolescente ou un adolescent présente un goitre multinodulaire. Les travaux de recherche à venir qui porteront sur l’enzyme Dicer et la signalisation des miARN devraient être axés sur la façon dont ces derniers influencent la pathogenèse des différentes tumeurs déjà associées à des mutations de DICER1 et de celles qui pourraient être considérées comme un risque en lien avec ces affections. Des études et des publications sur DICER1 continuent d’émerger et un nouveau défi se pose – les cliniciens et les pathologistes se heurtent à la tâche suivante : décrypter la quantité colossale de données fournies par l’intermédiaire de ces parutions. Des marqueurs diagnostiques novateurs et fiables qui permettraient d’établir un pronostic chez les patients qui présentent des tumeurs associées à DICER1 pourraient mener à l’amélioration des options de traitement moléculaire ciblées.

InvEStIgatIng dICEr1 SyndrOmE (cont.)

At present, apart from identifying a deleterious germ-line mutation in DICER1, there are no other established diagnostic criteria for DICER1 syndrome.

properly recognized. A suspected DICER1 mutation-related tumour is based on imaging and pathologic findings as well as clinical presentation; diagnosis can only be confirmed by identifying germ-line DICER1 mutation(s). At present, apart from identifying a deleterious germ-line mutation in DICER1, there are no other established diagnostic criteria for DICER1 syndrome. Early diagnosis of the presence of germ-line mutations may impact the prognosis and treatment of these tumours. Clinicians and pathologists should be cautious and consider molecular testing when a patient presents with Cushing disease at a very early age (pituitary blastoma), a child four-years of age or younger presents with dyspnea and weight loss with or without pneumothorax with

cyst rupture (PPB), a young child presents with an abdominal flank mass, or an adolescent presents with a multinodular goiter. Future investigation on Dicer and miRNA signaling should focus on how they impact the pathogenesis of the various tumours already linked to DICER1 mutations and those that may also be considered as a risk for these conditions. Studies and publications on DICER1 continue to emerge and a new challenge presents as clinicians and pathologists face the task of deciphering the considerable amount of data streaming through those publications. Novel and reliable diagnostic markers that identify and predict prognosis in patients with DICER1- related tumours may lead to improved targetted molecular treatment options.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

11

Cap-aCp neWs Veuillez noter que seuls les résumés des articles sont offerts en français.

lIgnES dIrECtrICES dE la Cap-aCp Sur l’IntErprétatIOn dES bIOpSIES dE l’EndOmètrE Et la rédaCtIOn dES rappOrtS dIagnOStIquES auteurs :

Carlos Parra-Herran1, M.D., Matthew Cesari1, M.D., FRCPC, Bojana Djordjevic1, M.D., FRCPC, Katherine Grondin2, M.D., FRCPC, Mary Kinloch3, M.D., FRCPC, Martin Köbel4, M.D., FRCPC, Amrah Pirzada5, M.D., Anna Plotkin6, M.D., FRCPC, et C. Blake Gilks7, M.D., FRCPC.

affiliations: 1 Département de médecine de laboratoire et de pathobiologie de l’Université de Toronto et Centre des sciences de la santé Sunnybrook à Toronto (Ontario). 2 Département de pathologie, Centre hospitalier universitaire de Québec (Québec). 3 Département de pathologie et de médecine de laboratoire, Université de la Saskatchewan et Hôpital de Saskatoon (Saskatchewan). 4 Département de pathologie et de médecine de laboratoire, Université de Calgary et Institut du cancer Arnie Charbonneau à Calgary (Alberta). 5 Département de médecine de laboratoire, Université Memorial à Saint-Jean (Terre-Neuve-et-Labrador). 6 Département de médecine de laboratoire et de pathobiologie de l’Université de Toronto et Trillium Health Partners à Toronto (Ontario). 7 Département de pathologie, Université de la Colombie-Britannique et Hôpital général de Vancouver (Colombie-Britannique). remerciements : Les auteurs remercient le Dr Phillip Clement, M.D., FRCPC, de l’Université de la ColombieBritannique et les Drs R. Michael Shier, M.D., FRCS(C), Stéphane Laframboise, M.D., FRCSC, M. Sc., Lilian Gien, M.D., FRCSC, M. Sc., et Eric Leung, M.D., FRCSC, de l’Université de Toronto pour leur révision et leur approbation des lignes directrices.

RÉSUMÉ La normalisation des rapports de pathologie assure la prestation de soins aux patients adéquats, facilite la mise en œuvre d’initiatives d’assurance de la qualité à paliers multiples efficaces et favorise la recherche sur les populations. Or, les rapports qui confirment un diagnostic bénin à la suite d’une biopsie de l’endomètre ne sont actuellement pas assujettis à de telles normes. Une terminologie consensuelle à jour est également requise. À la lumière de ces renseignements, le Groupe d’intérêt spécial en pathologie gynécologique de la Canadian Association of 12

Pathologists/Association canadienne des pathologistes (CAP-ACP) a élaboré des lignes directrices sur la rédaction des rapports de biopsies bénignes de l’endomètre. Notre objectif est de présenter ces lignes directrices, le résultat d’une revue de la littérature évaluée par des pairs et d’un processus de discussion éclairé, dans un format qui s’applique à tous les milieux de pratique. Nous avons harmonisé la terminologie proposée avec les scénarios cliniques les plus couramment associés à la biopsie ou au curetage de l’endomètre. Nous avons également inclus des énoncés qui complètent chacun des termes suggérés et qui peuvent servir de lignes de

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

commentaires dans les rapports de diagnostic. Le document proposé (son contenu) peut être appliqué à la plupart des scénarios diagnostiques et a le potentiel d’avoir des répercussions positives sur les soins prodigués aux patients et de faciliter les initiatives d’assurance de la qualité et de recherche. Nous prévoyons que ces lignes directrices continuent d’évoluer au fil de leur mise en œuvre et de leur utilisation dans la recherche en pathologie. Finalement, il convient de noter que ces lignes directrices ne sont applicables qu’aux prélèvements bénins, et non pas à l’endomètre présentant des modifications précancéreuses ou cancéreuses.

Cap-aCp neWs This article was peer-reviewed.

KeyWoRDs: endometrial biopsy; guideline; benign; endometrium; structured reporting.

Cap-aCp guIdElInES fOr bEnIgn EndOmEtrIal bIOpSy IntErprEtatIOn and rEpOrtIng authors:

Carlos Parra-Herran1 MD; Matthew Cesari1 MD, FRCPC; Bojana Djordjevic1 MD, FRCPC; Katherine Grondin2 MD, FRCPC; Mary Kinloch3 MD, FRCPC; Martin Köbel4 MD, FRCPC; Amrah Pirzada5 MD; Anna Plotkin6 MD, FRCPC; and C Blake Gilks7 MD, FRCPC.

affiliations: 1Department of Laboratory Medicine and Pathobiology, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON. 2 Department of Pathology, Centre Hospitalier Universitaire de Quebec, Quebec, QC. 3 Department of Pathology and Laboratory Medicine, University of Saskatchewan and Saskatoon City Hospital, Saskatoon, SK. 4 Department of Pathology and Laboratory Medicine, University of Calgary and Arnie Charbonneau Cancer Institute, Calgary, AB. 5 Department of Laboratory Medicine, Memorial University, St John’s, NL. 6 Department of Laboratory Medicine and Pathobiology, University of Toronto and Trillium Health Partners, Toronto, ON. 7 Department of Pathology, University of British Columbia and Vancouver General Hospital, Vancouver, BC. acknowledgements: The authors thank Dr. Phillip Clement MD, FRCPC (University of British Columbia) and Drs. R Michael Shier MD, FRCS(C), Stephane Laframboise MD, FRCSC, MSc, Lilian Gien MD, FRCSC, MSc, and Eric Leung MD, FRCSC (University of Toronto) for reviewing and endorsing the guideline. The authors declare that there are no conflicts of interest regarding the publication of this paper. All authors have provided CAP-ACP with non-exclusive rights to publish and otherwise deal with or make use of this article, and any photographs/images contained in it, in Canada and all other countries of the world.

ABSTRACT Standardized pathologic reporting ensures adequate patient care, facilitates effective multi-level quality initiatives and supports population-based research. Reporting of benign diagnoses in endometrial biopsy currently lacks similar levels of standardization, and updated consensus terminology is needed. Consequently, the Special Interest Group in Gynecologic Pathology of the Canadian Association of Pathologists / l’Association canadienne des pathologistes (CAP-ACP) developed a guideline for benign endometrial biopsy reporting. Our current aim is to present this guideline, a result of peer-reviewed literature review and informed discussion process, in a format applicable to all practice settings. We align the proposed Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

13

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.)

Compared to other specimens, diagnosis of endometrial biopsies suffers from significant variation among pathologists, particularly in the setting of benign lesions8.

terminology with the most common clinical scenarios that prompt endometrial biopsy or curettage. In addition, we include statements that are complementary to each proposed term and can be used as a comment line in a diagnostic report. The proposed document can be applied to the majority of diagnostic scenarios, and has the potential to positively impact patient care and facilitate quality assurance and research initiatives. We anticipate continuous evolution of the guideline through its implementation and use in pathology research. Note that these guidelines are applicable only to benign samples, and not to endometrium with premalignant or malignant changes.

BACKGROUND Adequate clinical management requires consistency and clarity in the communication of the pathologic diagnosis. In addition, system-wide quality improvement programs need structured reporting data1. The benefits of implementing optimal levels of standardization in surgical pathology reports have been evidenced in cancer diagnosis2,3 and multiple organizations recommend such an approach for cancer resection specimens including the College of American Pathologists (CAP)4, the International Collaboration on Cancer Reporting (ICCR)5, the Canadian Association of Pathologists / l’Association canadienne des pathologistes (CAPACP)6, and the Canadian Partnership against Cancer7. The terminology used in benign endometrial pathology varies significantly between and within institutions. Compared to other specimens, diagnosis of endometrial biopsies suffers from significant variation among pathologists, particularly in the setting of benign lesions8. Such variability in interpretation and reporting can negatively impact patient care and quality assurance initiatives. Therefore, the benign endometrial biopsy is an ideal specimen to benefit from a standardized terminology approach. With the above background, the Gynecologic Pathology Interest Group (GPIG) of the CAP-ACP embarked in the elaboration of a simple, concise and updated list of diagnostic terminology for the diagnosis of benign endometrial pathology, aimed to provide clarity and uniformity in the diagnostic lexicon used

14

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

by pathologists and other healthcare providers. The process of guideline elaboration and initial implementation has been outlined in detail previously9. The initiative was first introduced to the GPIG in June 2016, and interested members (including the GPIG executive committee) were recruited to form the working group. This group represented a spectrum of gynecologic pathology practices across Canada. The elaboration step was led by two members of the GPIG (CPH and CBG), who jointly performed a systematic review of the peer-reviewed literature and extracted information from major reference textbooks in gynecologic pathology (evidence-based approach). Subsequently, several rounds of discussion were held within the working group (consensus-based approach). The resulting preliminary version of the document was then reviewed by gynecologists, the CAP-ACP executive committee and the CAP-ACP general membership. Feedback provided at these multiple review points was incorporated. The final version, an official CAP-ACP practice guideline, is presented here. Our current aim is to introduce the proposed guideline to the CAP-ACP membership and the Canadian Journal of Pathology readership. The terms presented here are accompanied by explanatory notes in a format suitable for pathologists to include them as a comment in a diagnostic report. We introduce them by discussing the most common clinical scenarios in which the guideline can prove useful. Lastly, we

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.) outline the next steps for consolidation and continuing improvement of this document.

cáÖìêÉ=NK=

CONSENSUS TERMINOLOGY The one-page list (Table 1) of recommended terms includes the type of procedure and a comprehensive range of histopathologic diagnosis: 17 in total, 6 of which have additional optional lines. See Table 1. The notes that follow are aimed to explain each diagnosis in a concise manner, suitable for routine pathology reports. Figure 1 shows examples of the pathologic scenarios covered in the guideline. A full set of accompanying images can be found at http://www.cap-acp.org/guidelines.php. APPROACH TO GUIDELINE USE: CLINICAL SCENARIOS The entities presented can be grouped by clinical presentation and / or indication for the biopsy procedure. That way, the pathologist can approach the benign endometrial biopsy with a narrowed differential diagnosis and a set of consensus and evidence-based criteria, which are outlined in the following paragraphs. The guideline is not intended to cover all diagnostic instances; however, we have previously demonstrated that it can successfully be applied to the vast majority of cases9. SCENARIO 1: POST-MENOPAUSAL BLEEDING (NOTES A-D) Sample in A is non-diagnostic (devoid of endometrial tissue). Sample in B has only strips of glandular endometrium; adequacy in this setting depends on the clinical scenario (post-menopausal versus pre-menopausal, indication for biopsy). C. Disordered proliferative endometrium with variation in glandular size and shape; note the absence of gland crowding (which would suggest non-atypical hyperplasia). D. Irregular secretory endometrium showing asynchrony in the secretory differentiation of the glandular and stromal components; compare to the normal mid-secretory endometrial sample in E. F. Chronic endometritis characterized by numerous plasma cells; gland in far right displays tubal metaplasia. G. Endometrium with high-dose progestin effect: notice the diffuse stromal pseudo-decidual change contrasting with the atrophic appearance of the glands. H. Panoramic view of an early gestation sample; notice the presence of abundant products of conception including villi (lower right), plate (lower left) and membranes (upper left), as well as endometrium with pregnancy-related changes (upper right).

In the setting of post-menopausal bleeding, the most important consideration is the exclusion of any premalignant or malignant lesions (which are beyond the scope of this document). If malignancy is not identified, the pathologist should establish: a) the adequacy of the sample, and b) the appropriate terminology to describe the benign findings observed. a. Sample adequacy Assessing sample adequacy is paramount,

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

15

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.)

!"#$%&'& ()*)+,)*&)--.(,)!,.*&./&0)!1.2.3,-!-&4&35,+62,*6-&/.7&6*+.86!7,)2&9,.0-:&760.7!,*3& 0)7!&,&4&96*,3*&;&*.*
. 16

D! =5,1/&'+.1,$03&

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.)

If sample adequacy is a concern, the diagnostic report can suggest that consideration be given to repeat sampling.

since sub-optimal or insufficient samples require strong consideration for repeated sampling10. However, the approach for such assessment varies greatly among pathologists11. A first attempt at standardization was described by McCluggage, who separates samples into inadequate (no endometrial tissue), unassessable (superficial strips of endometrial tissue) and adequate (intact, organized endometrial tissue fragments)12. If endometrial tissue is not identified at all, the specimen is considered nondiagnostic and repeated sampling can be explicitly recommended (see Note A). Reporting of adequacy in samples with endometrium present, but limited in quantity (considered unassessable as per McCluggage) has been recently addressed by Sakhdari et al, who propose that a sample is suboptimal if contains 30 strips13. Therefore, repeated sampling can be considered by the clinician when the biopsy contains less than 10 strips of endometrium. Importantly, repeated sampling should be considered in adequate biopsies if warranted by the clinical scenario (i.e. the hysteroscopic appearance of the endometrium, persistent abnormal bleeding, etc.)14. Of note, it has been shown that clinicians often perform follow-up biopsies if the pathologist raises concern for adequacy regardless of the terminology (inadequate, unassessable or suboptimal)15. Comment notes Note A. Endometrial tissue is not identified. Repeat sampling is recommended, if clinically indicated. Note B. Endometrial tissue is present, but is scant and suboptimal for

evaluation. The possibility of inadequate sampling cannot be entirely excluded. Correlation with clinical findings and consideration for repeated sampling is recommended. b. Benign findings Benign endometrial diagnoses in the context of post-menopausal bleeding include physiologic states (inactive endometrium) and abnormal findings (endometrial polyp, weakly proliferative endometrium). Inactive endometrium is a generic term for circumstances in which the endometrium lacks hormone-induced differentiation (pre-menarche, pharmacological effect, postmenopause). “Atrophic endometrium” refers to the physiologically inactive endometrium after menopause. The finding of cystic atrophy may correlate with a thick endometrium on ultrasound, and can be reported. The term "weakly proliferative endometrium" is proposed to represent samples from a perimenopausal or postmenopausal patient showing occasional glandular and / or stromal mitoses in an otherwise uniform endometrium with round to tubular, evenly spaced glands. Such findings reflect low-level estrogenic stimulation of the endometrium and requires clinical correlation. Comment notes Note C. Inactive glands and stroma are most frequently observed in the postmenopausal setting, but also may be encountered after exogenous hormonal therapy and associated with irregular cycles. Clinical correlation is recommended. Note D. Weak proliferative activity is identified in glands and/or stroma. In the post-menopausal setting this finding is indicative of low-level estrogenic stimulation of the endometrium; clinical correlation is suggested.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

17

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.) SCENARIO 2: PRE-MENOPAUSAL OR PERI-MENOPAUSAL ABNORMAL UTERINE BLEEDING (NOTES E, G-J, L)

imaging, as endometrial polyp; as secretory endometrium does not represent a true anatomic lesion, the term "functional polyp" is not recommended.

a. Sample adequacy

The term “irregular secretory endometrium” encompasses tissues with secretory differentiation that does not fit within the normal progression of the post-ovulatory period. These include disordered proliferative endometrium with subsequent ovulation, intrinsic luteal phase defects (weak or uneven secretory changes, breakdown) and changes secondary to exogenous hormonal therapy20.

In premenopausal women, the endometrial biopsy should contain fragments of intact endometrium (surface, glands and stroma). The adequacy of a sample composed of only superficial strips should be questioned. There should be functionalis present, and not just sampling of the lower uterine segment16. If sample adequacy is a concern, the diagnostic report can suggest that consideration be given to repeat sampling. b. Benign findings Disordered proliferative endometrium occurs secondary to unopposed estrogen stimulation, most frequently seen in the context of anovulation, obesity and exogenous estrogen administration. Histologically, there is variation in glandular size and shape with dilated, branching or stellate forms, patchy stromal breakdown and surface repair17,18. This pattern is distinguished from endometrial hyperplasia by the lack of significant glandular crowding. Endometrial polyp is usually a straightforward diagnosis in biopsy material; however, overlap with disordered proliferative endometrium exists. The diagnosis of endometrial polyp should be made only if stroma is altered relative to normal endometrial stroma (it is usually fibrotic-appearing). Thick-walled vessels may be present, particularly towards the surface. It is important not to confuse spiral arterioles, which are clustered, with the vascular component of an endometrial polyp. A useful marker of a polyp is the long axis of endometrial glands arranged parallel to the surface epithelium19. Furthermore, it is important not to misdiagnose secretory endometrium, which frequently appears polypoid on hysteroscopy and 18

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

Endometrium obtained during the menstrual phase of the cycle often includes an admixture of relatively intact late secretory endometrium, early proliferative endometrium and tissue with breakdown and neutrophilic infiltration. Sometimes, endometrial breakdown is extensive. The term “benign endometrium with diffuse stromal breakdown” is used by some to indicate menstrual-type breakdown of the endometrium that is so extensive that it is not possible to determine whether the menstrual-type changes are postovulatory i.e. occur in the setting of normal late secretory changes, or not. Diffuse stromal breakdown can be secondary to menstruation, cessation of exogenous hormonal therapy or intrinsic defects in normal follicle / corpus luteum progression (follicular / corpus luteum failure)21,22. Diffuse breakdown may obscure a relevant underlying process (e.g. hyperplasia, malignancy), and repeated sampling can be suggested (Notes H and I). The term "endometrial hyperplasia without atypia" appears in the most recent World Health Organization Classification of Tumours of Female Reproductive Organs, and is equivalent to benign endometrial hyperplasia23. Hyperplasia implies, by definition, gland crowding with gland to stroma ratio >1:1 (glands occupy more than 50% of the surface area). Sub-classification as

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.) simple or complex is no longer necessary as its reproducibility is poor. The spectrum of endometrial changes due to exogenous hormonal therapy is wide, and most agents produce nonspecific findings (atrophy, asynchronous patterns, disordered proliferative endometrium)24. The (arguable) exceptions to this are progestins (oral, levonorgestrel-releasing intrauterine device) and progesterone-receptor modulators; which have patterns recognizable on pathologic examination25–28. Documentation of history of exogenous hormonal therapy in the specimen requisition or in the medical records is helpful in the interpretation. If changes suggestive of exogenous hormonal effects are encountered but no clinical history is provided, a comment can be added to the diagnostic report (see Note L, below). Comment notes Note E. Findings are in keeping with a disordered proliferative (anovulatory) pattern. Clinical correlation is recommended. Note G. Non-physiologic secretory changes are observed; the differential diagnosis includes intrinsic luteal phase defects, anovulatory cycles with superimposed ovulation and exogenous hormonal therapy. Clinical correlation is recommended. Note H. If clinically indicated, further sampling performed outside of the menstrual phase of the cycle is suggested. Note I. Benign endometrium with diffuse non-physiologic breakdown can be seen in the context of cessation of exogenous hormonal therapy or after premature follicle / corpus luteum involution. Clinical correlation and consideration for repeated sampling is recommended. Note J. No significant cytologic atypia is identified in this sample. Sub-

classification as simple or complex is no longer part of the consensus terminology. Note L (history of hormonal therapy not provided). Findings raise the possibility of exogenous hormonal effect. Correlation with clinical history is recommended. SCENARIO 3: EARLY GESTATION (NOTES M-O) Samples submitted in the context of early gestation involve identification of products of conception, which are usually admixed with decidualized endometrium. In many practices, stating “products of conception” in the diagnostic line suffices. Nonetheless, listing the different types of products identified may provide useful information to the clinician about the completeness of the evacuation procedure: a. Pathologic confirmation of an intrauterine gestation is necessary in patients with suspected early gestation and an empty endometrial cavity on ultrasound, in which the differential diagnosis is missed abortion versus ectopic pregnancy. Confirmation of an intrauterine gestation is achieved by identifying implantation site trophoblast and chorionic villi and/or plate tissue. b. In cases of elective termination, the presence of chorionic membranes and embryonic tissues confirms disruption of the gestational sac. Pregnancy-related endometrial changes include diffuse stromal decidualization and persistent glandular secretory morphology, collectively known as decidua or decidualized endometrium20,22. Hypersecretory change, including Arias-Stella reaction, is also part of this spectrum. Recently instituted progestin therapy can cause a similar histologic appearance, which can be noted in a comment if history of concurrent gestation is not provided.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

19

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.) If, after thorough examination, intrauterine gestation cannot be confirmed, the pathologist is strongly advised to review the clinical notes, recent imaging and β-HCG levels in order to determine if an ectopic pregnancy is being clinically suspected or confirmed. If that is not the case, immediate notification of the findings to the clinician is warranted.

the secretory phase (early, mid or late) can be undertaken as an alternative. Early secretory endometrium is characterized by intracellular vacuolization; mid secretory endometrium is characterized by intraluminal secretions, gland dilation and stromal edema; late secretory endometrium is characterized by stromal decidualization.

Comment notes

Endometritis is an important finding in an endometrial biopsy, as it is treatable. There is some evidence that treatment of chronic endometritis with antibiotics can result in improved outcomes in patients with infertility35. Endometritis can be sub-divided as:

Note M. Findings are indicative of products of an intrauterine gestation. Note N. Outside of the context of pregnancy, the findings can be secondary to early-onset progestin therapy. Clinical correlation is recommended. Note O. No definitive products of conception are identified after careful macroscopic examination and extensive sampling. The possibility of ectopic gestation cannot be entirely excluded. Correlation with clinical findings and close follow-up is recommended. SCENARIO 4: INFERTILITY (Notes F and K) The main role of the endometrial biopsy in the diagnostic work-up of infertility is to identify anatomic causes (endometrial polyp, endometritis or leiomyoma)29,30. Conversely, endometrial evaluation to document physiologic progression of the ovulatory cycle is rarely performed nowadays, since ovulation can be readily documented based on urine or blood hormonal levels, and histological assessment of endometrial date does not correlate with infertility status31. Therefore, determination of the "date" in secretory endometrium is optional. This recommendation is further based on the fact that the reproducibility of dating of secretory endometrium is at most modest32–34. Assignment of endometrial “date” can be done when explicitly requested by the clinician. If precise dating is difficult to ascertain, approximation to the stage of 20

-

Chronic endometritis: This diagnosis should be considered if several to numerous plasma cells are identified, commonly associated with a fibrotic or edematous stroma and mucinous or tubal glandular metaplasia20,36. Chronic endometritis can be seen in association with sub-mucosal leiomyomas, post-partum or postabortion, or associated with chlamydial infection. Occasional, isolated plasma cells can be seen in endometrial polyp, disordered proliferative endometrium and with stromal breakdown, and therefore are not sufficient for the diagnosis of endometritis37. The use of special stains for plasma cells such as CD138 immunohistochemistry and Methyl Green Pyronin special stain are not recommended37,38. - Acute endometritis: It can be pregnancy-related (post-partum) and non-gestational. The latter is usually associated with acute pelvic inflammatory disease. Acute endometritis should only be considered if the biopsy contains abundant and confluent acute inflammation, micro-abscesses and/or necrotic debris20. Correlation with the clinical presentation is important (post-partum period, vaginal discharge, systemic signs of infection, distention of the endometrial cavity on imaging). In

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

-

addition, the presence of neutrophils in the endometrial surface and stromal plasma cells has been shown to highly correlate with concurrent upper genital tract infection and acute salpingitis39. The physiologic neutrophilic infiltration of the endometrium in pre-menstrual and menstrual periods can be distinguished from endometritis by the less prominent and non-confluent appearance of the inflammation and by the presence of late secretory changes. Granulomatous endometritis is rarely encountered. In most cases, granulomatous giant cell reaction is due to prior C-section or dilation and curettage. Infectious etiologies (tuberculosis, atypical mycobacteria, fungi) and sarcoidosis should be entertained if the reaction is diffuse40.

Comment notes Note F (dating). Estimation of exact endometrial date in the secretory phase can suffer from significant inter-observer variation. Note K (acute endometritis): Biopsy shows confluent abundant neutrophilic infiltrates; findings are in keeping with acute endometritis if there is a clinical correlate (signs of infection). Clinical correlation is recommended. Note K (granulomatous endometritis): Giant cell reaction within the endometrium can be seen after an invasive procedure (biopsy, C-section); however, a mycobacterial or fungal infection cannot be entirely excluded. Clinical correlation and further sampling for microbiology studies is recommended, if clinically indicated. SCENARIO 5: CRITICAL RESULT DUE TO FINDINGS INDICATIVE OF UTERINE PERFORATION (NOTE P) The last diagnostic term in the guideline is explained here, and can happen in any

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.)

Standardization of terminology and definitions is an effective way to decrease discrepancies and maintain an updated and relevant lexicon.

clinical context. The presence of uterine serosa, fat, fallopian tube, ovary or any other extra-uterine tissue in an endometrial biopsy indicates iatrogenic uterine perforation (if specimen contamination can be excluded). Given the possible life-threatening complications, review of recent clinical history must be undertaken to determine if this possibility is suspected or known to have occurred. If perforation is not suspected clinically, the treating physician must be notified immediately. Comment notes Note P. The above findings raise the possibility of uterine perforation. Prompt clinical correlation is recommended. SCENARIO 6: ENDOMETRIAL SAMPLING PRIOR TO GYNECOLOGIC SURGICAL INTERVENTION Biopsy of the endometrium is usually part of the pre-operative work-up of women undergoing salpingectomy, oophorectomy, myomectomy or simple hysterectomy for suspected benign reasons. The main objective is to rule out a malignant process, which may result in a change in the surgical approach. In this setting, virtually all the entities discussed previously can be encountered. Considerations about adequacy are important, as explained in scenario 1. DISCUSSION The initiative outlined here is an important first step towards uniformity and quality improvement in benign endometrial biopsy reporting. The negative effects of the heterogeneity in the wording of benign diagnoses are still to be fully documented; however it is known that diagnostic discrepancies are frequent in endometrial biopsy material8. Standardization of terminology and definitions is an effective way to decrease discrepancies and maintain an updated and relevant lexicon. When available, the proposed content was based on peer-

reviewed evidence (evidence-based approach). However, given the lack of research in the area, many definitions and terms are solely based on reference books and the experience of the GPIG members (consensus-based approach). This represents a limitation of this initiative, but also potential benefits as the consensus terminology can facilitate clinical research of benign endometrial disorders by providing a solid substrate for case identification and group analysis purposes. It is our goal to periodically update this guideline as new literature emerges. The document will be revised every three years by the GPIG, incorporating future peer-reviewed data. It is also our aim to extend this exercise to pre-malignant and malignant endometrial disorders. This document must be used along with proper clinical judgement. More than one diagnosis can be relevant for an individual biopsy, and all diagnoses should be listed in the report. Furthermore, the use of comments in the report is encouraged in cases where further information may be needed to explain the diagnosis and highlight its clinical implications. In summary, the GPIG presents a CAPACP consensus guideline for the interpretation and reporting of benign conditions observed in endometrial biopsy material. The guideline is a product of collegial and informed discussion between pathologists with diverse geographic and practice representation. It is also the product of critical appraisal of the peer-reviewed literature. We hope that, with this guideline as an instrument, new evidence-based knowledge in benign endometrial pathology will develop. This document has the potential to improve not only patient care but also monitoring and quality improvement programs. REFERENCES 1. Ellis DW, Srigley J. Does standardised structured reporting contribute to quality in diagnostic

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

21

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.)

the consensus terminology can facilitate clinical research of benign endometrial disorders by providing a solid substrate for case identification and group analysis purposes

pathology? The importance of evidence-based datasets. Virchows Arch Int J Pathol. 2016;468:51-9. 2. Lankshear S, Srigley J, McGowan T, Yurcan M, Sawka C. Standardized synoptic cancer pathology reports so what and who cares? A population-based satisfaction survey of 970 pathologists, surgeons, and oncologists. Arch Pathol Lab Med. 2013;137:1599-1602. 3. Srigley J, Lankshear S, Brierley J, McGowan T, Divaris D, Yurcan M, et al. Closing the quality loop: facilitating improvement in oncology practice through timely access to clinical performance indicators. J Oncol Pract. 2013;9:e255-61. 4. College of American Pathologists Cancer Protocols. Coll. Am. Pathol. Available at: http://www.cap.org/ web/oracle/webcenter/portalapp/ pagehierarchy/cancer_protocols. jspx. Accessed November 28, 2016. 5. International Collaboration on Cancer Reporting Datasets. Int. Collab. Cancer Report. Available at: http://www.iccr-cancer.org/datasets. Accessed November 28, 2016. 6. Canadian Association of Pathologists Guidelines. Can. Assoc. Pathol. - Assoc. Can. Pathol. Available at: http://www.capacp.org/guidelines.php. Accessed November 28, 2016.

22

9. Parra-Herran C, Cesari M, Djordjevic B, Grondin K, Kinloch M, Köbel M, et al. Canadian consensus-based and evidence-based guidelines for benign endometrial pathology reporting in biopsy material. Int J Gynecol Pathol 2018;Jan 24 [e-pub ahead of print]. 10. van Doorn HC, Opmeer BC, Burger CW, Duk MJ, Kooi GS, Mol BW; Dutch Study in Postmenopausal Bleeding (DUPOMEB). Inadequate office endometrial sample requires further evaluation in women with postmenopausal bleeding and abnormal ultrasound results. Int J Gynaecol Obstet. 2007;99:100-4. 11. Phillips V, McCluggage WG. Results of a questionnaire regarding criteria for adequacy of endometrial biopsies. J Clin Pathol. 2005;58:417-9. 12. McCluggage WG. My approach to the interpretation of endometrial biopsies and curettings. J Clin Pathol. 2006;59:801-12. 13. Sakhdari A, Moghaddam PA, Liu Y. Endometrial samples from postmenopausal women: a proposal for adequacy criteria. Int J Gynecol Pathol. 2016;35:525-30. 14. Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review. BJOG. 2002;109:313-21.

7. Canadian Partnership Against Cancer: Synoptic Reporting. Cancerviewca Brought Can. Partnersh. Cancer. Available at: http://www.cancerview.ca/treatment andsupport/synopticreportingms/ pathologystaging/pathologystaging standards/. Accessed November 28, 2016.

15. Ewies AA, Shaaban KA, Merard R, Zanetto U. Endometrial biopsy in women with abnormal uterine bleeding: inadequate and unassessable categorisation is not clinically relevant. J Clin Pathol. 2014;67:673-7.

8. Agarwal S, Wadhwa N. Revisiting old slides--how worthwhile is it? Pathol Res Pract. 2010;206:368-71.

16. Kandil D, Yang X, Stockl T, Liu Y. Clinical outcomes of patients with insufficient sample from

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

gUiDelines Cap-aCp EndOmEtrIal guIdElInES (cont.) endometrial biopsy or curettage. Int J Gynecol Pathol. 2014;33:500-6. 17. Clement PB, Young RH. Atlas of gynecologic surgical pathology: expert consult: online and print. 3rd edition. Elsevier Canada; 2013. 18. Nucci MR, Oliva E. Gynecologic pathology: a volume in the series: foundations in diagnostic pathology. 1st edition. Edinburgh: Elsevier Canada; 2009. 19. Kim K-R, Peng R, Ro JY, Robboy SJ. A diagnostically useful histopathologic feature of endometrial polyp: the long axis of endometrial glands arranged parallel to surface epithelium. Am J Surg Pathol. 2004;28:1057-62. 20. Mutter GL, Prat J. Pathology of the female reproductive tract. 3rd edition. Elsevier Canada; 2014. 21. Vakiani M, Vavilis D, Agorastos T, Stamatopoulos P, Assimaki A, Bontis J. Histopathological findings of the endometrium in patients with dysfunctional uterine bleeding. Clin Exp Obstet Gynecol. 1996; 23:236-9.

features of endometrial decidualization following long-term intrauterine levonorgestrel delivery. Hum Reprod. 1998;13: 1218-24. 26. Mutter GL, Bergeron C, Deligdisch L, Ferenczy A, Glant M, Merino M, et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod Pathol. 2008;21:591-8. 27. Williams ARW, Bergeron C, Barlow DH, Ferenczy A. Endometrial morphology after treatment of uterine fibroids with the selective progesterone receptor modulator, ulipristal acetate. Int J Gynecol Pathol. 2012;31:556-69. 28. Nogales FF, Crespo-Lora V, CruzViruel N, Chamorro-Santos C, Bergeron C. Endometrial changes in surgical specimens of perimenopausal patients treated with ulipristal acetate for uterine leiomyomas. Int J Gynecol Pathol. 2017;Sep 13 [E-pub ahead of print]. 29. Pavone ME, Hirshfeld-Cytron JE, Kazer RR. The progressive simplification of the infertility evaluation. Obstet Gynecol Surv. 2011;66:31-41.

22. Crum CP, Nucci MR, Lee KR. Diagnostic Gynecologic and Obstetric Pathology. 2nd edition. Philadelphia, PA: Elsevier Canada; 2011.

30. Alansari LM, Wardle P. Endometrial polyps and subfertility. Hum Fertil. 2012;15:129-33.

23. Kurman RJ, Carcangiu ML, Herrington CS, Young RH (eds.). World Health Organization Classification of tumours of female reproductive organs. Fourth Edition; WHO Press;2014.

31. Coutifaris C, Myers ER, Guzick DS, Diamond MP, Carson SA, Legro RS, et al. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril. 2004;82:1264-72.

24. Soslow RA, Longacre TA. Uterine Pathology. Cambridge University Press; 2012.

32. Murray MJ, Meyer WR, Zaino RJ, Lessey BA, Novotny DB, Ireland K, et al. A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril. 2004;81:1333-43.

25. Critchley HO, Wang H, Jones RL, Kelly RW, Drudy TA, Gebbie AE, et al. Morphological and functional

33. Duggan MA, Brashert P, Ostor A, Scurry J, Billson V, Kneafsey P, et al. The accuracy and interobserver reproducibility of endometrial dating. Pathology. 2001;33:292-7. 34. Fadare O, Zheng W. Histologic dating of the endometrium: accuracy, reproducibility, and practical value. Adv Anat Pathol. 2005;12:39-46. 35. Park HJ, Kim YS, Yoon TK, Lee WS. Chronic endometritis and infertility. Clin Exp Reprod Med. 2016;43:185-92. 36. Eckert LO, Hawes SE, WölnerHanssen PK, Kiviat NB, Wasserheit JN, Paavonen JA, et al. Endometritis: the clinical-pathologic syndrome. Am J Obstet Gynecol. 2002;186:690-5. 37. Gilmore H, Fleischhacker D, Hecht JL. Diagnosis of chronic endometritis in biopsies with stromal breakdown. Hum Pathol. 2007;38:581-4. 38. Vicetti Miguel RD, Chivukula M, Krishnamurti U, Amortegui AJ, Kant JA, Sweet RL, et al. Limitations of the criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease research. Pathol Res Pract. 2011;207:680-5. 39. Kiviat NB, Wølner-Hanssen P, Eschenbach DA, Wasserheit JN, Paavonen JA, Bell TA, et al. Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis. Am J Surg Pathol. 1990;14:167-75. 40. Almoujahed MO, Briski LE, Prysak M, Johnson LB, Khatib R. Uterine granulomas: clinical and pathologic features. Am J Clin Pathol. 2002;117:771-5.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

23

Digital pathology Veuillez noter que seuls les résumés des articles sont offerts en français.

un mOdulE d’EXamEn ClInIquE ObJECtIf StruCturé (ECOS) IntEraCtIf pOur évaluEr lE rEndEmEnt En anatOmIE pathOlOgIquE auteurs :

Elena Diana Diaconescu, M.D.1,2; Alex O. Salagean, B. Sc.2; Eriny Tawedrous, M.D., M. Sc.2; Lorna Mirham, M.D., FRCPC1,2; Adriana Krizova, M.D., M. Sc., FRCPC1,2; Hala Faragalla, M.D., FRCPC1,2; Shachar Sade, M.D., M. Sc., FRCPC1; Martin Bullock, M.D., FRCPC4; Andrea Grin, M.D.1,2; Catherine Streutker, M.D., M. Sc., FRCPC1,2; Beverley Carter, M.D., FRCPC3; Mark Lee, M.D., Ph. D., FRCPC5; George M. Yousef, M.D., M. Sc., Ph. D., FRCPC1,2.

affiliations : 1Département de médecine de laboratoire et de pathobiologie, Université de Toronto, Toronto, Ontario, Canada 2 Département de médecine de laboratoire et Centre de recherche Keenan en sciences biomédicales du Li Ka Shing Knowledge Institute, Hôpital St. Michael, Toronto, Ontario, Canada 3 À la retraite (au moment de la rédaction de cet article, l’auteure était affiliée à l’Hôpital Western Memorial, Corner Brook, Terre-Neuve-et-Labrador, Canada) 4 Département de pathologie, Université Dalhousie, Halifax, Nouvelle-Écosse, Canada 5 Département de médecine de laboratoire et d’anatomie pathologique, Hôpital Royal Alexandra, Edmonton, Alberta, Canada RÉSUMÉ Introduction : À l’aube d’une nouvelle ère de médecine de précision, le rôle du pathologiste connaît des transformations. Plus qu’un simple diagnosticien, il joue désormais un rôle actif dans la prise en charge des patients. L’évaluation des résidents en pathologie devrait permettre de mesurer les connaissances de base, la capacité à établir le bon diagnostic à partir de lames de verre et la capacité à gérer des cas de ces derniers. Ces compétences sont généralement évaluées par l’entremise d’examens oraux ou écrits. Or, certains problèmes sont associés aux examens oraux. Ils comprennent une potentielle variabilité ou incohérence au moment de poser ou de formuler les questions, tant du point de vue des examinateurs que de celui des candidats, de même qu’une variabilité au moment de verbaliser ou d’interpréter les réponses, en plus des coûts et du stress qui en découlent. Méthodes : Une application sur ordinateur visant à évaluer le rendement des résidents en anatomopathologie a été mise au point. Le simulateur d’examen oral sur le Web permet l’évaluation efficace des résidents relativement à un vaste éventail de sujets et de compétences de façon fiable et normalisée. Des scénarios ont été programmés; chacun d’entre eux représente un « thème 24

Canadian Journal of Pathology | Volume 9, Issue 4 | www.cap-acp.org

» qui peut être utilisé en tant que module autonome. Grâce à l’application, il est possible d’évaluer les connaissances des candidats dans les domaines suivants : techniques de macroscopie, microscopie, études connexes, notions cliniques, assurance de la qualité et considérations d’ordre éthique. Résultats : Les candidats ont été appelés à interagir en temps réel avec des lames histologiques numériques et des spécimens macroscopiques numérisés qui simulaient des situations de la vie réelle. Le module intègre différents niveaux d’évaluation en ce qui a trait aux renseignements cliniques et comporte les sections qui suivent : images radiologiques, lames immunohistochimiques et macroscopie interactive. L’examen est composé de questions à choix multiple, de choix de combinaisons, de questions à développement et de questions de type « arbre décisionnel ». Le système s’adapte aux équivalences terminologiques et aux fautes d’orthographe mineures. Conclusions : Une étude ayant pour but d’évaluer la pertinence et la facilité d’utilisation de l’application sur ordinateur pourrait éventuellement être menée auprès de plusieurs centres universitaires.

Digital pathology This article was peer-reviewed.

KeyWoRDs: digital pathology, digitalized gross specimen, education, digital whole scan images.

an IntEraCtIvE ObJECtIvE StruCturEd ClInICal EXamInatIOn (OSCE) mOdulE fOr pErfOrmanCE aSSESSmEnt In anatOmICal pathOlOgy authors:

Elena Diana Diaconescu1,2 MD; Alex O. Salagean2 BSc; Eriny Tawedrous2 MD, MSc; Lorna Mirham1,2 MD, FRCPC; Adriana Krizova1,2 MD, MSc, FRCPC; Hala Faragalla1,2 MD, FRCPC; Shachar Sade1 MD, MSc, FRCPC; Martin Bullock4 MD, FRCPC; Andrea Grin1,2 MD; Catherine Streutker1,2 MD, MSc, FRCPC; Beverley Carter3 MD, FRCPC; Mark Lee5 MD, PhD, FRCPC; George M Yousef1,2 MD, MSc, PhD, FRCPC.

affiliations:

1

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Department of Laboratory Medicine and the Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON, Canada. 3 Retired (at time of writing was at Western Memorial Hospital, Corner Brook, NL, Canada). 4 Department of Pathology, Dalhousie University, Halifax, NS, Canada. 5 Department of Laboratory Medicine and Pathology, Royal Alexandra Hospital, Edmonton, AB, Canada. 2

acknowledgement : Dr. Yousef’s research is supported by grants from the Canadian Institute of Health Research, Kidney Foundation of Canada, the Kidney Cancer Research Network of Canada, and Prostate Cancer Canada. non-standard abbreviations: OSCE: Objective Structured Clinical Examination; H & E: Hematoxylin and Eosin The authors declare that there are no undisclosed conflicts of interest regarding the publication of this paper. All authors have provided CAP-ACP with non-exclusive rights to publish and otherwise deal with or make use of this article, and any photographs/images contained in it, in Canada and all other countries of the world.

ABSTRACT Introduction: Approaching a new era of precision medicine, the role of the pathologist is evolving from being a diagnostician to becoming an active participant in patient management. Pathology resident assessment should be able to evaluate background knowledge, ability to reach the correct diagnosis on glass slides, and case management ability. The latter is usually captured by oral or written examinations. Problems associated Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

25

Digital pathology OSCE mOdulE (cont.)

The application can test knowledge in grossing techniques, microscopy, ancillary studies, clinical knowledge, quality assurance, and ethical considerations.

with an oral exam include potential variability/inconsistency in question delivery/phrasing for both examiner and examinee and also the variability in delivery/interpretation of the answers, in addition to cost and stress. Methods: A computer application for resident performance assessment in anatomical pathology was developed. The web-based oral examination simulator can efficiently examine residents on a broad range of subjects and skills in a reliable and standardized manner. Scenarios were programmed, each representing a “theme” that can be used as a stand-alone module. The application can test knowledge in grossing techniques, microscopy, ancillary studies, clinical knowledge, quality assurance, and ethical considerations. Results: Examinees were allowed to interact in real-time with digital histological slides and digitalized gross specimens, thus simulating real-life situations. The module incorporates various levels of testing for clinical information including radiological images, immunohistochemical slides and interactive grossing sections. Question styles included multiple choice questions, mix and match, free-text and decisiontree type questions. The system accommodates equivalent terminologies and minor spelling mistakes. Conclusions: In the future, a trial study including multiple academic centers to test the utility and ease of use of the computer-based application could be created.

INTRODUCTION The evolution of information technology has revolutionized the practice of pathology. After years of traditional glass slide-based practice, pathology is stepping into a new era of digital images and telepathology.1-3 This will necessitate the incorporation of digital pathology during pathology residency training.4-6 A number of initiatives are currently underway introducing online competency and diagnostic decision analysis using virtual microscopy.2,7,8 For educational purposes, digital whole scan images offer a number of advantages over glass slides including the use of small biopsy specimens and the availability of rare cases.9-11 Recent data indicate that there is an increasing interest in digital pathology for resident education.1,12 Approaching a new era of precision medicine, the role of the pathologist is 26

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

also evolving from a diagnostician to becoming an active participant in patient management.13 Resident assessment should thus include evaluation of background medical knowledge, the ability to reach the correct diagnosis on glass slides, and case management. The later includes the ability to collect and synthesize relevant clinical data,14 order appropriate ancillary testing and the integration of different types of information (gross pathology, microscopic results and clinical data) into a consolidated clinically meaningful diagnosis that can guide patient management. Testing theoretical knowledge can be achieved through written examination. Glass slides, or more recently, whole slide images15 are used to assess diagnostic competency. Case management is more problematic to evaluate. In some programs, this is superficially tested

Digital pathology OSCE mOdulE (cont.) through multiple-choice questions, whereas in others it is assessed through oral examination.

and standardized developed.

manner

was

MATERIALS AND METHODS Oral examination is useful to assess parameters that cannot be captured in a written or slide examination, such as the candidate’s ability to interpret clinical history in the context of the case, request consultation when appropriate, and use ancillary testing. Additionally, the ability of the candidate to interact with clinical colleagues and her/his role as a communicator can also be assessed.16 Shortcomings of an oral exam, however, include examiner’s subjectivity in question delivery/phrasing and in interpretation of the answers. Added to this is the variability in the time allocated for each question and an inability to test certain areas of practice. There is also the stress and the high cost associated with live oral examination, especially if nationally centralized.

The objective of this study was to develop a computer application that can be used for resident competency assessment in anatomical pathology.

Ideally, as in other clinical residency training programs, an Objective Structured Clinical Examination (OSCE) style exam16 is used for assessment of case management competency.17-19 Additionally, a “practical/bedside” examination that assesses the candidate’s ability to deal with complicated and challenging cases is important. Unfortunately, these are not feasible in pathology, due to a number of time and technical issues and the nature of pathology practice. It remains important that an ideal examination would test the examinee on a variety of skills; including slide interpretation, gross pathology skills, technical lab issues, quality assurance, communication and knowledge. The objective of this study was to develop a computer application that can be used for resident competency assessment in anatomical pathology. To achieve this, a web-based oral examination simulator that can efficiently examine residents on a broad range of subjects and skills in a reliable

Program software The web application was created using open-source web technologies such as HTML and JavaScript. The jQuery library was extensively used to create the interactive components of the application. This choice allowed for the creation of a stable, fast and very responsive interface for the user. Due to its broad compatibility, any modern browser can be used to access it. The user is presented with a wide range of familiar web elements and functions, allowing for a very quick learning curve. JQuery was chosen because it is a free, open source library that is backed up by a large development community. A wide range of plugins are available out of the box, and it is easy to add new features, or improve on the current ones (https://jquery.com/). Depending on the type of questions, a number of interactive effects and animations to dynamically show or hide information on the page in a decision tree type of format were used. Virtual imaging To obtain high resolution virtual images, gross surgical pathology specimens were photographed as high resolution images during dissection and the corresponding microscopic slides were scanned at 40x resolution whole slide scan using Aperio ScanScope console.20 Question design and strategy The web application incorporated a variety of question styles including, in addition to free-text answers, multiple choice questions, mix and match, and decision-tree type questions. Following the completion of each question, the examinee was prompted to submit the answers, which “locks” the answer, preventing further changes from being made.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

27

Digital pathology OSCE mOdulE (cont.) Results evaluation There are two options for the evaluation of trainee responses. The first is automatic marking of answers based on key words and phrases. In the second format, a document containing all answers is generated for manual evaluation. The model can accommodate spelling mistakes and the use of alternative terminologies can be also used in candidates’ responses. Module functionality and performance assessment To evaluate the application, 10 senior residents and fellows were asked to complete 3 cases using the program. After completing all three cases, they were asked to fill out a questionnaire to assess the level of standardization, ease of use, flexibility and limitations of the program in an anonymized fashion. RESULTS The Interactive Pathology OSCE Module An OSCE computer application, with a simple user-friendly interface including

text boxes, radio buttons, check boxes and drop-down menus, was developed. This allows for an easy-to-use, test taking environment. In addition, no training is required to use the system. All questions are self-explanatory with clear instructions. Three scenarios were programmed, each representing a “theme/case” that can be used as a stand-alone module. Each scenario included various aspects of a specific subject divided into sub-sections to test knowledge in grossing techniques, microscopy, choice of ancillary studies, clinical knowledge, quality assurance, and ethical considerations. To emulate conditions of real practice, examinees were asked to interact in realtime with digital simulations of virtual histological slides and digitalized gross specimens. Various levels of clinical information including radiological images, immunohistochemical stains and interactive history taking sections that were made available to the

examinee were incorporated. Virtual slides were provided at high resolution (x40) with the ability to zoom in and out and navigate through the different parts of the entire slide. Question styles were varied according to the scenario. The test format included multiple choice questions, mix and match, free-text and decisiontree type questions. The system’s response was carefully trained to accommodate for equivalent terminologies for the same meaning and also for minor spelling mistakes. Confirmation of receipt of the response was indicated after each question. There was no specific time for each case therefore giving the candidates the flexibility to move along the three cases at their own pace. However, the total time of the examination was fixed as was indicated by a digital watch/timekeeper on the computer screen. The modules are available through the principal investigator (PI) and will be publicly available shortly.

cáÖìêÉ=NK=

For the first scenario, the candidate is given the choice to retrieve clinical information before performing a frozen section. As seen to the left, once responses are submitted, the system provides immediate feedback, including a head CT image with the radiologist's interpretation (right). 28

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

Digital pathology OSCE mOdulE (cont.) cáÖìêÉ=OK=

(a) An image showing a smear specimen (left) and a frozen section (right). Either or both of the images will appear based on the keyword entered by the candidate

(b) a representative of a virtual slide image that is easy to navigate by using the keys at the bottom The first module The module started with an intraoperative neurosurgery consultation. The first question asked the candidate to list (in a free text format) potential reasons to request an intraoperative consultation. In the second question, the candidate was provided with an option, prior to obtaining the specimen, to retrieve relevant clinical information. The system then revealed available information based on the candidate’s response. History in this case

was “non-contributory”. If the candidate elected to request a CT scan, a CT scan image is provided with radiology interpretation (Figure 1). The candidate then received a small biopsy from the operating room (OR) and had to choose to proceed with up to two different procedures. The system database contained virtual slide images of both a smear and a frozen section. Either or both were available to the candidate

on request (Figure 2a). These were virtual slides of high resolution (x40) with easy to use navigation buttons (Figure 2b). This was followed by testing the ability of the candidate to communicate the nature of the lesion with the surgeon using multiple questions in a yes or no and multiple-choice question formats. Moving on with the cases, the trainee received a fractured femur from the same patient and was asked to list relevant

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

29

Digital pathology OSCE mOdulE (cont.) cáÖìêÉ=PK=

A virtual slide with questions focusing on three specific highlighted areas. This tests the candidate’s diagnostic ability and his/her ability to extract information from specific areas of the slide, including pathological patterns, tumour grades, as well as normal histological structures.

q~ÄäÉ=NK=

The first module assesses the ability of the candidate to: 1. 2. 3. 4.

Request and interpret relevant clinical information Effectively communicate intra-operative consult findings with clinicians Perform the appropriate pathology procedure for the case Accurately assess disease characteristics of clinical importance (e.g. tumour grade) 5. Reach correct microscopic diagnosis

q~ÄäÉ=OK= Main abilities assessed through the second module:

1. Candidate’s ability to provide the most appropriate microscopic diagnosis /differential diagnosis 2. Working up a case to reach diagnosis, including ordering the most appropriate immunostains and serology testing. 3. Interpret immunostaining results 4. Quality assurance 5. Interpretation of pathology findings in view of background of medical information 6. Understand the significance of ancillary pathology testing (e.g. prognostic factors)

30

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

clinical information to obtain before grossing the specimen. An x-ray showing a fractured femur was available, if requested. After asking for the provisional diagnosis, a virtual H&E slide was provided. The candidate was requested to list three main differential diagnoses (in free text format). The scenario continued with a radical prostatectomy. As shown in Figure 3, a unique opportunity to ask questions on three specific highlighted areas in the virtual slide was provided. This eliminated the probability of guessing in an oral examination. Clinicopathologic abilities assessed by this module are summarized in Table 1. The second module The second module started with asking the candidate to identify the main histopathological findings of a virtual slide. The candidate was then provided with informative highlights of the patient medical history and asked to provide two main differential diagnoses based on the combination of clinical information and histologic findings. The case proceeded with requesting appropriate ancillary testing that will help to reach a diagnosis. The scenario then moved on with a virtual slide of another lesion that the same patient developed three years later. The candidate was requested to provide the most likely diagnosis and grade the tumour. The candidate was then asked to list risk factors of this condition and order the most appropriate immunohistochemical stains (Figure 4a). This was followed by a guided discussion about problems in quality assurance of immunohistochemical staining (Figure 4b). In this scenario, if the candidate asked to see the positive control, it would show up as negative (Figure 4c). The main skills tested in this module are summarized in Table 2. The third module This module put more emphasis on the role of the pathologist in a multidisciplinary team, as summarized in Table 3. In this module one can navigate through a number of situations that face

Digital pathology OSCE mOdulE (cont.) cáÖìêÉ=QK=

Assessment of the candidate’s ability to perform and interpret ancillary testing. a) Testing the candidate’s ability to order the appropriate immunohistochemistry. The candidate is requested to pick the most appropriate stain to confirm the diagnosis of a neuroendocrine tumour from a drop-down menu. b) Testing the candidate’s ability to understand the importance of QC in pathology. If the candidate recognizes this is a false negative result, he/she will then be prompted to troubleshoot and determine the source of the problem. c) The positive control in this case was showing negative results. The candidate is expected to ask for and interpret the positive control slide. d) An example of equivocal Her2 testing (2+) in a breast cancer case. the pathologist in daily practice including gross assessment of pathology specimens (Figure 5) and radiological/pathological correlation. It is important to note that q~ÄäÉ=PK= the program was set in a such way that prevented selection of every possible Main qualities assessed through the third module. block in grossing section. 1. The candidate’s ability as a communicator in a multidisciplinary setting Module evaluation (e.g. correlating mammographic findings with the corresponding The web-based oral examination pathology) simulator modules were evaluated by 2. The gross pathology skills of the candidate including submitting optimal Canadian anatomical pathology sections for microscopic evaluation and ability to recognize how the gross residents and fellows. Resident feedback appearance can guide microscopic interpretation indicated that the main advantages of 3. The microscopic diagnostic ability of the candidate the application include an increased level 4. The ability to correctly order molecular tests, interpret their results, and of standardization between test takers, their significance in patient management ease of use and program flexibility. The incorporation of interactive images, Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

31

Digital pathology OSCE mOdulE (cont.) cáÖìêÉ=RK=

Testing the ability to gross pathology specimens. The candidate is asked to highlight the sections that they need to submit for microscopic evaluation.

histological and immunohistochemical slides, photographs of gross specimens, radiological images, and molecular pathology results were other advantages mentioned by the participants. Additional benefits of the computer application were the elimination of the examiner driven testing bias and oral examination stress. The most recognized limitations of the application included occasional slow image upload and the need to write long sentences in free text response questions. All participants indicated that the examination experience was similar to, or improved, relative to previous oral examinations that they have experienced. Overall, stress levels were significantly reduced when taking the examination using the computer application compared to standard oral examinations. 32

DISCUSSION This is, to our knowledge, the first OSCE computer application that enables the evaluation of candidates as pathology physician consultants, in an environment that simulates real clinical settings. In this new era of genomic medicine13 and with the fast advances in molecular pathology,21 the role of the pathologist extends far beyond being a diagnostic expert and there becomes an urgent need for a more thorough assessment of other parameters including quality control, communication with clinicians and appropriate ordering and interpretation of ancillary testing.22 There are many advantages to introducing this module in pathology resident assessment:

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

1) it allows remote examination administration to multiple trainees at the same time and eliminates the need to have live examiners. This fact translates into cost savings to the Royal College (examiners remuneration and rental of examining rooms) and to trainees (cost of examinations and travel); 2) the module eliminates important weaknesses of an oral examination by giving the candidate the opportunity to record histologic criteria on the spot without the need to rely on memory to recruit this information; 3) increased efficiency and exam standardization would be permitted by the fact that the program allows the administration of the examination without the need to have live examiners and manual reporting of the examinees’ responses by the examiners necessary in oral examination; 4) remote examination administration may increase examinee confidentiality and reduces their stress; and 5) this module can be used in the assessment of skills that cannot be evaluated in the setting of the traditional oral examination. The incorporation of interactive images of histological and immunohistochemical slides, digitized maps of gross specimens, radiological images,23 and molecular pathology results is a unique feature that allows assessment in areas that would be hard to evaluate in the traditional examination setting. It has to be noted, however, that there are a number of issues that should be considered before implementing such module. These include web security issues, proper equipment which must be universally accessible and the need for training the residents on handling high resolution digital images. CONCLUSION: In conclusion, the web-based oral examination simulator standardizes and facilitates the objective evaluation of resident competency in anatomical

Digital pathology OSCE mOdulE (cont.) pathology, providing a more precise measure of proficiency and an enhanced examination experience.

REFERENCES 1. Gabril MY, Yousef GM. Informatics for practicing anatomical pathologists: marking a new era in pathology practice. Mod Pathol. 2010;23(3):349-58. 2. Hamilton PW, Wang Y, McCullough SJ. Virtual microscopy and digital pathology in training and education. APMIS. 2012;120(4):305-15.

practice. Pathology. 2010;42(6):512-8. 9. Brachtel E, Yagi Y. Digital imaging in pathology--current applications and challenges. J Biophotonics. 2012;5(4):327-35. 10. Sivamalai S, Murthy SV, Gupta TS, Woolley T. Teaching pathology via online digital microscopy: positive learning outcomes for rurally based medical students. Aust J Rural Health. 2011;19(1):45-51. 11. Weinstein RS. Innovations in medical imaging and virtual microscopy. Hum Pathol. 2005;36(4):317-9.

3. Weinstein RS, Descour MR, Liang C, Barker G, Scott KM, Richter L, et al. An array microscope for ultrarapid virtual slide processing and telepathology. Design, fabrication, and validation study. Hum Pathol. 2004;35(11):1303-14.

12. Bellis M, Metias S, Naugler C, Pollett A, Jothy S, Yousef GM. Digital pathology: Attitudes and practices in the Canadian pathology community. J Pathol Inform. 2013;4:3.

4. Al-Janabi S, Huisman A, Van Diest PJ. Digital pathology: current status and future perspectives. Histopathology. 2012;61(1):1-9.

13. Pasic MD, Samaan S, Yousef GM. Genomic medicine: new frontiers and new challenges. Clin Chem. 2013;59(1):158-67.

5. Cross SS, Dennis T, Start RD. Telepathology: current status and future prospects in diagnostic histopathology. Histopathology. 2002;41(2):91-109.

14. Goldberg-Kahn B, Healy JC. Medical informatics training in pathology residency programs. Am J Clin Pathol. 1997;107(1):122-7.

6. Laurinavicius A, Raslavicus P. Consequences of "going digital" for pathology professionals entering the cloud. Stud Health Technol Inform. 2012;179:62-7. 7. Costello SS, Johnston DJ, Dervan PA, O'Shea DG. Development and evaluation of the virtual pathology slide: a new tool in telepathology. J Med Internet Res. 2003;5(2):e11. 8. Jara-Lazaro AR, Thamboo TP, Teh M, Tan PH. Digital pathology: exploring its applications in diagnostic surgical pathology

15. Mirham LM, Naugler C, Hayes M, Ismiil N, Belisle A, Sade S, et al. Performance of residents using digital images versus glass slides on certification examination in anatomical pathology: a mixed methods pilot study. CMAJ Open. 2016;25;4(1):E88-94. doi: 10.9778/cmajo.20140075. eCollection 2016 Jan-Mar. 16. Dwyer T, Wright S, Kulasegaram KM,Theodoropoulos J, Chahal J. Wasserstein D, et al. How to set the bar in competency-based medical education: standard setting after an Objective Structured Clinical

Examination (OSCE). BMC Med Educ. 2016;16(1):1. 17. Carraccio C, Englander R. The objective structured clinical examination: a step in the direction of competency-based evaluation. Arch Pediatr Adolesc Med. 2000;154(7):736-41. 18. Prislin MD, Fitzpatrick CF, Lie D, Giglio M, Radecki S, Lewis E. Use of an objective structured clinical examination in evaluating student performance. Fam Med. 1998;30(5):338-44. 19. Tervo RC, Dimitrievich E, Trujillo AL, Whittle K, Redinius P, Wellman L. The Objective Structured Clinical Examination (OSCE) in the clinical clerkship: an overview. S D J Med. 1997;50(5):153-6. 20. Slodkowska J, Pankowski J, Siemiatkowska K, Chyczewski L. Use of the virtual slide and the dynamic real-time telepathology systems for a consultation and the frozen section intra-operative diagnosis in thoracic/pulmonary pathology. Folia Histochem Cytobiol. 2009;47(4):679-84. 21. Diamandis M, White NM, Yousef GM. Personalized medicine: marking a new epoch in cancer patient management. Mol Cancer Res. 2010;8(9):1175-87. 22. Yorke RF. Informed evaluation of pathology residency programs. Arch Pathol Lab Med. 2000;124(6):853-8. 23. Velan GM, Goergen SK, Grimm J, Shulruf B. Impact of interactive elearning modules on appropriateness of imaging referrals: a multicenter, randomized, crossover study. J Am Coll Radiol. 2015;12(11): 1207-14.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

33

SCHEDULE OVERVIEW The Evolving Role of Pathologists in the Era of Predictive Biomarkers and Precision Medicine SATURDAY JULY 7

1700-1900

Assemblée générale annuelle de l’Association des pathologistes du Québec

0830-1730

Essential Pathology Skills Program

1800-2000

Pathologists’ Assistants Reception

0830-1200

Preconference Workshops

1800-2100

Residents’ Symposium and Dinner

• Breast Pathology: Challenges and Pitfalls • Statistics for Pathologists: Primer on Diagnostic Accuracy Statistics

SUNDAY JULY 8

• Histopathological Application of Staging and Grading Parameters in Medical Liver Diseases

0730-0830

Satellite Symposia Breakfasts

0830-0945

Opening Plenary Session: The Impact of Predictive Biomarker Testing on Patient Outcomes

1015-1215

Concurrent Sessions

• Tumours of the Salivary Glands / Well Differentiated Squamous Cell Carcinoma of the Upper Aerodigestive Tract – The Biopsy Challenge • Hematopathology

• Advanced Diagnostics Section Symposium

• Essential Pathology Skills Morning Workshop

• Gynecological Pathology Specialty Network Symposium: Emerging Trends in Gynecologic Pathology: Scientific Update and Discussion

1200-1400

Residents’ Networking Lunch

1400-1730

Preconference Workshops • Recent Advances in Common Diagnostic Dilemmas in Uterine Pathology • Are Your Residents Getting the Most of their Learning Experiences? Using Adult Learning Theories to Improve Teaching Effectiveness • Precision Medicine in Urology: Where Does the Pathologist Fit In? • GI Precision Oncology: Pathologists Needed! • Towards Increased Precision – Recent Developments in Renal Pathology • Essential Pathology Skills Afternoon Workshop

34

• Paediatric Section Symposium

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

• Workshop: A Practical Approach to Quality and Patient Safety in Anatomical Pathology 1215-1345

Lunch

1345-1515

Concurrent Sessions • Cytopathology Section Symposium Part I • Neuropathology Section Symposium: Neuropathology for Anatomic Pathologists • Canadian Society of Dermatopathology Specialty Network Symposium: Challenging Cases In Dermatopathology; Melanocytic and Non-melanocytic Tumours and Inflammatory Dermatoses • Workshop: Shifting the Focus From Professional Liability To Accountability

1515-1545 1545-1715

• Workshop: Pathological Assessment of Breast Cancer Post-neoadjuvant Therapy

Refreshment Break Concurrent Sessions • Cytopathology Section Symposium Part II

1730-1930

• Canadian Network of Uropathology Symposium: Practical Approaches to Problem Areas in GU Pathology

TUESDAY JULY 10

• Workshop: B-cell lymphomas: the WHO and WHAT in 2018

0730-0830

Satellite Symposia Breakfasts

0830-0945

Plenary Session: Dr. Cam Coady Symposium: From Bench to Bedside: Implementation of Predictive Biomarker Tests

1015-1215

Concurrent Sessions

• Workshop: How to Resolve Diagnostic Disagreement Between Physicians 1730-1800

CAP-ACP Junior Scientist Award Lecture

1800-1830

CAP-ACP William Boyd Award Lecture

1900-2200

President’s Reception at Le Parlementaire

Exhibit Hall Wine & Cheese Reception and Poster Presentations

• Hematopathology Section Symposium: Mimics and Pitfalls in Diagnosing Myeloid Neoplasms

MONDAY JULY 9

• Evidence-Based Medicine Section Symposium

0730-0830

Satellite Symposia Breakfasts

• Humanities and International Health Section Symposium

0830-0945

Plenary Debate: “Pathologists Should Stay Behind Their Microscopes and Let Oncologists Take Care of Biomarker Testing”

• Workshop: Glandular Lesions of the Cervix, Endometrium and Ovary: an Update for the Practicing Pathologist

1015-1215

Concurrent Sessions

1215-1345

CAP-ACP Annual General Meeting Lunch

• Workshop: The World of Ocular Pathology, Intraocular and Periocular Neoplastic and Non-neoplastic Lesions

1345-1515

Concurrent Sessions

• Workshop on the Expert Witness

• Education Section Symposium: Health Care is a Team Sport: Moving Beyond Individual Competence to Collective Competence Part I

• Platform Presentations A

• General Pathology Section Symposium Part I

• Platform Presentations B

• Workshop: Diagnostic Devils and Rogue Results in Molecular Pathology, OMPRN Part I

1215-1345

Lunch

1345-1515

Concurrent Sessions • Anatomical Pathology & Patient Safety and Quality Assurance Sections Combined Symposium Part I

• Informatics, Digital Resources & Social Media Special Interest Group Symposium 1515-1545

Refreshment Break

1545-1715

Concurrent Sessions

• Forensic Pathology Section Symposium: Detection and Documentation of Fractures in the Deceased Infant and Small Child & Unusual Child Deaths Part I

• Education Section Symposium: Health Care is a Team Sport: Moving Beyond Individual Competence to Collective Competence Part II

• Biobanking Special Interest Group Symposium: Biobanking: A Forum for Discussion and Networking

• Workshop: Diagnostic Devils and Rogue Results in Molecular Pathology, OMPRN Part II

• General Pathology Section Symposium Part II

• Workshop: Practice Approach to Mismatch Repair Testing

• Workshop: Lung 1515-1545

Refreshment Break

1545-1715

Concurrent Sessions • Anatomical Pathology & Patient Safety and Quality Assurance Sections Combined Symposium Part II

1730-1815

Closing Plenary: The Evolving Role of Pathology in Multidisciplinary Teams

1900-2200

Gala Banquet and Awards Presentations at Musée national des beaux-arts du Québec

• Forensic Pathology Section Symposium: Detection and Documentation of Fractures in the Deceased Infant and Small Child & Unusual Child Deathsa Part II

For more information or to register visit

• Workshop: NIFT-P of the Thyroid, Friend or Foe

Register by April 30th and save $50

www.cap-acp.com.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

35

ReVieW Veuillez noter que seuls les résumés des articles sont offerts en français.

médIaS SOCIauX, vOuS dItES? unE pErSpECtIvE CanadIEnnE Sur l’utIlISatIOn dES médIaS SOCIauX danS lE dOmaInE dE la pathOlOgIE auteurs :

Matthew J. Cecchini, M.D., Ph. D.1,6; Leslie M. Anderson, M.D., M.Ed.2,7; Elena Diana Salagean, M.D.3,8; Marcio M. Gomes, M.D., Ph. D., FRCPC4,5,9

affiliations: 1 Département de pathologie et de médecine de laboratoire, London Health Sciences Centre 2 Département de pathologie, Université du Manitoba 3 Département de médecine de laboratoire et de pathobiologie, Université de Toronto 4 Département de pathologie et de médecine de laboratoire, Université d’Ottawa 5 Éducateur clinicien, Collège royal des médecins et chirurgiens du Canada 6 @Path_Matt 7 @DrLesliesPath 8 @CAPACPResidents 9 @gomesmmg

perspective : Cet article explore le recours émergent aux médias sociaux dans le domaine de la pathologie à des fins de formation, de promotion et de sensibilisation, en plus d’examiner les répercussions importantes des différentes plates-formes sur les plans de l’éthique et du respect de la vie privée.

RÉSUMÉ Les médias sociaux jouent un rôle de plus en plus déterminant dans les communications en médecine. Partout à travers le monde, les pathologistes commencent à adopter ces technologies qui leur permettent d’échanger avec des collègues du monde entier. Dans cet article, nous mettons en lumière les principales plates-formes des médias sociaux (Twitter, Facebook et Instagram) et nous penchons sur leur rapport avec la pathologie. Les avantages que ces outils procurent aux pathologistes et aux internes canadiens en ce qui a trait à la formation, à l’autopromotion, au réseautage et à la sensibilisation du public sont analysés et mis en contraste

36

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

avec les obstacles éventuels liés aux préoccupations en matière d’éthique et de respect de la vie privée. En réponse à ces inquiétudes, nous proposons des lignes directrices relatives à l’éthique, à la protection de la vie privée et au professionnalisme qui ont pour but d’orienter les pathologistes quant à l’utilisation adéquate de ces technologies. Les médias sociaux peuvent être un outil précieux et permettre aux pathologistes et aux internes canadiens de tisser des liens les uns avec les autres et avec des collègues de partout dans le monde. Alors si ce n’est pas déjà fait, abonnezvous et rejoignez la communauté internationale de pathologie!

ReVieW This article was peer-reviewed.

KeyWoRDs: social media, pathology, education, ethics, public outreach

SOCIal mEdIa Eh? a CanadIan pErSpECtIvE On SOCIal mEdIa uSE In pathOlOgy authors:

Matthew J. Cecchini MD, PhD1,6; Leslie M. Anderson MD, MEd2,7; Elena Diana Salagean MD3,8; Marcio M. Gomes MD, PhD, FRCPC4,5,9.

affiliations: 1Department of Pathology and Laboratory Medicine, London Health Sciences Centre 2 Department of Pathology, University of Manitoba 3 Department of Laboratory Medicine and Pathobiology, University of Toronto 4 Department of Pathology and Laboratory Medicine, University of Ottawa 5 Clinician Educator, Royal College of Physicians and Surgeons of Canada 6 @Path_Matt 7 @DrLesliesPath 8 @CAPACPResidents 9 @gomesmmg disclosures: MJC, LMA and EDS have no relevant disclosures or conflicts of interest. MMG is a part-time employee of the of the Royal College of Physicians and Surgeons of Canada. MMG has received consulting fees/honorarium from Merck, Amgen and AstraZeneca, and educational grants from Merck, AstraZeneca, Boehringer-Ingelheim, Brystol Myers Squibb, Pfizer, Eli Lilly and Hoffman-La Roche. The authors declare that there are no undisclosed conflicts of interest regarding the publication of this paper. perspective: This review article explores the emerging utility of social media technologies in pathology for education, promotion and outreach while considering important ethical and privacy implications. All authors have provided CAP-ACP with non-exclusive rights to publish and otherwise deal with or make use of this article, and any photographs/images contained in it, in Canada and all other countries of the world.

ABSTRACT Social media (SoMe) is becoming an increasingly important communication tool in medicine. The international pathology community is beginning to embrace these technologies connecting pathologists from around the globe. In this review, we highlight and discuss the major SoMe platforms (Twitter, Facebook and Instagram) as they relate to pathology. The benefits for Canadian pathologists and trainees for education, self-promotion, networking and public outreach are discussed and contrasted with possible barriers related to privacy and ethical concerns. To address these concerns, we present some guidelines around ethics, privacy and Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

37

ReVieW SOCIal mEdIa Eh? (cont.)

SoMe can be a valuable tool to connect Canadian pathologists and trainees with each other and with colleagues around the world, so get connected to the global pathology village!

38

professionalism to inform pathologists on the appropriate use of these technologies. SoMe can be a valuable tool to connect Canadian pathologists and trainees with each other and with colleagues around the world, so get connected to the global pathology village!

INTRODUCTION Social media (SoMe) has revolutionized the way in which people around the world communicate. There are many evolving platforms for social media that vary in popularity and use. SoMe platforms often have overlapping functions but can be loosely grouped into social networking services and microblogging sites. Facebook (Facebook Inc, Menlo Park, California) is the world’s largest social networking service while Twitter (Twitter Inc, San Francisco, California) and Instagram (Facebook Inc, Menlo Park, California) are two of the major microblogging sites often used for sharing information. These three are the dominant platforms for social media especially in North America and in Europe. We will therefore focus this review on these networks and use their trade names throughout this paper.1–5 Of note, there are other emerging platforms, including ‘Figure 1’, which has been developed with a medical focus.6 Each platform is different in the way it allows user interactions and the types of content that can be shared. They have in common an ability to share user generated content with others who have similar interests. These platforms have resulted in a paradigm shift in media consumption by individuals. Media has become a personalized and tailored experience where an individual can develop a custom media ‘newsfeed’ that only displays content that they are interested in seeing. This has powerful applications in the field of pathology, as pathologists working in very subspecialized fields can find, connect and engage with individuals sharing the same interests from around the world.2,4,5,7,8

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

Social Media Platforms Twitter: Twitter is increasingly utilized by professionals and organizations to connect with very specific audiences.3 Twitter is defined as a microblogging social network that allows users to share short tweets (posts) with their followers from around the world. A tweet is limited to 280 characters but can also include images, links and even video. As shown in Figure 1, a tweet about a pathology case for example, is composed of a short description of the case followed by a hashtag (denoted by the # symbol) and the tagging of individuals (denoted by the @ symbol). The tweet shows a case of a middle-age individual with a history of (h/o) multiple gastrointestinal (GI) polyps. The images show a duodenal adenoma that when coupled with the history of multiple other GI polyps raises the suspicion for familial adenomatous polyposis (FAP). This was all elaborated in the comments and helped start a discussion around FAP and duodenal carcinoma, the second most common cause of cancer-related deaths in these patients. The description is followed by the hashtag #pathology and #gipath, which define the tweet as relating to GI pathology. A full list of pathology specific twitter hashtags is available at www.symplur.com/healthcarehashtags/ontology/pathology and a list of the most commonly used hashtags are presented in Table 1. The use of the hashtag is important because it allows users that are interested in a specific topic to find all the tweets relating to that topic.

ReVieW SOCIal mEdIa Eh?(cont.) cáÖìêÉ=NK=

Anatomy of a tweet, with relevant components annotated.

When a tweet is tweeted, it will go out and be visible to all a user’s followers on Twitter and to anyone who searches for any of the hashtags used in the tweet. A user just starting out on Twitter will likely have only a few followers, meaning there are only a few individuals that will see the tweet. By tagging other users in the tweet using the @ sign followed by the user’s twitter handle (Ex: @Path_Matt) this will send them a notification about that tweet. If they choose to, they can then re-tweet this to their followers and thus expand and amplify the reach of the original tweet. The power of retweets to amplify a message is demonstrated in Figure 2. Even if the original poster only has a few

followers, each time the tweet is retweeted it will be potentially seen by all the followers of the person who retweets the post. While there will be some overlap in the followers between different individuals, a few retweets by individuals with large numbers of followers can result in a significant increase in the number of users that view a tweet. Twitter can be a great tool even if you do not wish to post or contribute material. Many leaders in the field of pathology are on Twitter and by following these individuals it is possible to stay current with the most recent

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

39

ReVieW SOCIal mEdIa Eh? (cont.) q~ÄäÉ=NKM=^ÄÄêÉîá~íÉÇ=äáëí=çÑ=m~íÜçäçÖó=e~ëÜí~Öë

!"#"$%&' !"#$%%&'()* +#$%%*&'()$,$"-* ./'"0%* !&'()'#(* 1#(.%(.4*&'()$,$"-* ./'"0%* !67$$87.8013'()$,$".%(* 3'()$,$".%(*%0,9.0%* !3'()5$'#=%* !3'()A?* !C0#/&'()A?* !&'()$,$"-* !&'()$,$".%(%* !3'()G0%.=0! G1-H%!5667! :;I?! !

the transverse colon as well (176, 17.7%) and for these lesions, distinctions between the distal and proximal sides were not specified in the diagnostic reports. Less than 10% of SSAs were found in any individual segment of the distal colon. DISCUSSION Following initial screening by fecal immunochemical testing,22,23 colonoscopy is the standard method for detecting both cancerous and precancerous lesions.24 However, it suffers from a significant miss rate, especially providing less protection in the proximal than in the distal colon.25,26 As much as 7% of CRC patients are diagnosed between 6 and 36 months after receiving a cancer-negative colonoscopy, a condition termed interval cancer.19,27 Poor bowel prep, endoscopic technique and different polyp characteristics are contributing factors to the weaker performance of colonoscopies ! in the proximal colon.24

! !"#$%&'()!"#$%&'()!*&)$%(&#!&+!,,"-!(#!.$%(/#%-0!1(%2!./3)/#%$4/-!&#!%2/!3(42%!$5(-6!! !

! 58

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

!

RetRospeCtiVe stUDy dEtECtIOn Of SSaS In Calgary (cont.)

SSA lesions are slightly more prevalent in women than men; however age is a higher contributing factor.

Serrated adenomas, especially SSAs, have emerged as important precursor lesions of CRC that are underdiagnosed due to their indistinct flat appearance as well as their similarity to benign hyperplastic polyps. Roughly 30% of sporadic colorectal carcinomas develop through the serrated neoplastic pathway, yet serrated adenomas account for ≤ 5% of polyps detected in biopsies as observed here. SSAs were identified by Calgary pathologists according to AGA guidelines, which employ less discriminating criteria compared to those set by the WHO. Reported rates for SSAs from colonoscopies range from ≤ 1% for cohorts in Boston, MA,13 Seoul, Korea,28 and Sydney, Australia;29 1-5% for cohorts in Irving, TX,30 Cleveland, OH,31 Montreal, QC,32 Scottsdale, AZ,33 and Chicago, IL34 or as high as 10-15% for a cohort in Brisbane, Australia17 and a multicentre cohort in Australia.35 Different detection standards are likely to have a major influence on this variability, especially with the ongoing refinement of diagnostic criteria and growing vigilance among endoscopists for recognizing serrated adenomas.15 SSA lesions are slightly more prevalent in women than men; however age is a higher contributing factor. Serrated adenomas are most common in 60-79 year olds, in agreement with CRC incidence.16 The significant SSA counts in 40-59 year olds indicate a steadily increasing risk with age rather than the sharp age-related increase that is seen with conventional adenomas.28 The average serrated polyp size is relatively small, and less than 10% of SSAs are large polyps (> 10 mm) which pose elevated cancer risk.28 The low rate of invasive CRC in patients with SSAs is likely due to the latter being precursors to CRC, hence a low likelihood of their coexistence. One criterion for serrated polyposis syndrome as defined by the WHO is the presence of at least five serrated polyps proximal to the sigmoid colon with two or more being > 10 mm. 8 Of the nine patients observed here with five or more

SSAs, only one meets the size criterion. The higher risk of CRC for patients with this rare condition, which can be sporadic or hereditary, requires special consideration and management.20 The preference of SSAs to reside in the proximal colon is in agreement with several reports,27,36 although there is a broad distribution throughout the large intestine and SSAs have been detected at both ends of the large intestine, i.e. the terminal ileum and the anal canal. Hyperplastic polyps, the serrated lesions resembling SSAs that are 10-20 times more abundant, are more common in the distal colon.15 Mid-to-large sized serrated lesions proximal to the sigmoid colon are recommended for excision if possible, even when they are recognized as HPs.15,37 Nosho et al. have reported that SSAs from elderly patients (≥ 75 years) were located only in the proximal colon,38 however we could not find any clear correlation between age and SSA location. In fact, serrated adenomas were detected in the rectum and descending colon of several elderly patients. However, a rectal serrated polyp may occasionally be misdiagnosed as an SSA due to prolapse-induced changes.39 This study is limited by its retrospective nature. Another limitation is the detection and resection skills of the endoscopists performing the procedures, which may miss lesions in patient colons to varying degrees. This may also affect the polyp diagnoses and indeed, < 10% of the SSAs counted in this study were indicated as “likely” SSAs rather than definite diagnoses. Consensus recommendations from an expert panel advocate more inclusive criteria for detecting serrated adenomas because they are significantly under-diagnosed, especially in high risk patients with a history of polyps.15,40 CONCLUSIONS In summary, we report SSAs in 4.7% of colonoscopy results for patients in Calgary, AB, Canada. Our results highlight the patient demographics and

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

59

RetRospeCtiVe stUDy dEtECtIOn Of SSaS In Calgary (cont.)

ACKNOWLEDGEMENTS The authors would like to thank Jeannine Viczko for her efforts in the acquisition of the clinical data used in this study.

anatomic distribution of these lesions. This will serve to improve their detection and excision by colonoscopies in future CRC screening programs.

Snover D, Ahnen, D. J., Burt, R. W., Odze, R. D. Serrated polyps of the colon and rectum and serrated polyposis. In: Bosman FT, Carneiro, F., Hruban, R. H., Theise, N. D., ed. WHO Classification of Tumours of the Digestive System. Lyon, France: IARC; 2010:160-165.

9.

Bauer VP, Papaconstantinou HT. Management of serrated adenomas and hyperplastic polyps. Clin Colon Rectal Surg. 2008;21(4):273-9.

REFERENCES 1.

2.

3.

4.

5.

60

8.

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;36(1):11-30. Cancer Fact sheet N°297. World Health Organization, Geneva, Switzerland. 2015. http://www.who.int/mediacentre/ factsheets/fs297/en. Accessed on 27 July 2017. Canadian Cancer Statistics 2015. Canadian Cancer Society’s Advisory Committee on Cancer Statistics, Toronto, ON. 2015. http://www.cancer.ca/statistics. Accessed on 29 Aug 2016. Classification of Benign Polyps. National Colorectal Cancer Screening Network, Toronto, ON. 2011. http://www.cancerview.ca /idc/groups/public/documents/ webcontent/pathology_work_ report_dec11.pdf. Accessed on 27 July 2017. Crockett SD, Snover DC, Ahnen DJ, Baron JA. Sessile serrated adenomas: an evidence-based guide to management. Clin Gastroenterol Hepatol. 2015;13(1):11-26 e1.

10. Coriat R, Lecler A, Lamarque D, Deyra J, Roche H, Nizou C, et al. Quality indicators for colonoscopy procedures: a prospective multicentre method for endoscopy units. PLoS One. 2012;7(4):e33957. 11. Kahi CJ, Hewett DG, Norton DL, Eckert GJ, Rex DK. Prevalence and variable detection of proximal colon serrated polyps during screening colonoscopy. Clin Gastroenterol Hepatol. 2011;9(1):42-6. 12. Payne SR, Church TR, Wandell M, Rösch T, Osborn N, Snover D, et al. Endoscopic detection of proximal serrated lesions and pathologic identification of sessile serrated adenomas/polyps vary on the basis of center. Clin Gastroenterol Hepatol. 2014;12(7):1119-26.

6.

Bordacahar B, Barret M, Terris B, Dhooge M, Dreanic J, Prat F, et al. Sessile serrated adenoma: from identification to resection. Dig Liver Dis. 2015;47(2):95-102.

13. Hetzel JT, Huang CS, Coukos JA, Omstead K, Cerda SR, Yang S, et al. in the detection of serrated polyps in an average risk colorectal cancer screening cohort. Am J Gastroenterol. 2010;105(12):2656-64.

7.

Longacre TA, Fenoglio-Preiser CM. Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia. Am J Surg Pathol. 1990;14(6):524-37.

14. Lee CK, Shim JJ, Jang JY. Cold snare polypectomy vs. Cold forceps polypectomy using doublebiopsy technique for removal of diminutive colorectal polyps: a prospective randomized study. Am

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

RetRospeCtiVe stUDy dEtECtIOn Of SSaS In Calgary (cont.) J Gastroenterol. 2013;108(10): 1593-600. 15. Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, Burt RW, et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 2012; 107(9):1315-29; quiz 1314, 1330. 16. Strum WB. Colorectal adenomas. N Engl J Med. 2016;374(11):1065-75. 17. Bettington M, Walker N, Rosty C, Brown I, Clouston A, Wockner L, et al. Critical appraisal of the diagnosis of the sessile serrated adenoma. Am J Surg Pathol. 2014;38(2):158-66. 18. Rashtak S, Rego R, Sweetser SR, Sinicrope FA. Sessile serrated polyps and colon cancer prevention. Cancer Prev Res (Phila). 2017;10(5):270-8. 19. Shin SP. Sessile serrated adenoma; the hard-to-catch culprit of interval cancer. Clin Endosc. 2017;50(3):215-6. 20. Guarinos C, Sanchez-Fortun C, Rodriguez-Soler M, Alenda C, Paya A, Jover R. Serrated polyposis syndrome: molecular, pathological and clinical aspects. World J Gastroenterol. 2012;18(20):2452-61. 21. Hiraoka S, Kato J, Fujiki S, Kaji E, Morikawa T, Murakami T, et al The presence of large serrated polyps increases risk for colorectal cancer. Gastroenterology. 2010;139(5):1503-10, 1510 e1-3. 22. Crouse A, Sadrzadeh SM, de Koning L, Naugler C. Sociodemographic correlates of fecal immunotesting for colorectal cancer screening. Clin Biochem. 2015;48(3):105-9.

23. Crouse AL, De Koning L, Sadrzadeh SM, Naugler C. Sensitivity and specificity of community fecal immunotesting screening for colorectal carcinoma in a high-risk canadian population. Arch Pathol Lab Med. 2015;139(11): 1441-5. 24. Young PE, Womeldorph CM. Colonoscopy for colorectal cancer screening. J Cancer. 2013;4(3): 217-26. 25. Brenner H, Hoffmeister M, Arndt V, Stegmaier C, Altenhofen L, Haug U. Protection from rightand left-sided colorectal neoplasms after colonoscopy: populationbased study. J Natl Cancer Inst. 2010;102(2):89-95. 26. O’Connell BM, Crockett SD. The clinical impact of serrated colorectal polyps. Clin Epidemiol. 2017;9:113-25. 27. Cooper GS, Xu F, Barnholtz Sloan JS, Schluchter MD, Koroukian SM. Prevalence and predictors of interval colorectal cancers in medicare beneficiaries. Cancer. 2012;118(12):3044-52. 28. Kim HY, Kim SM, Seo JH, Park EH, Kim N, Lee DH. Age-specific prevalence of serrated lesions and their subtypes by screening colonoscopy: a retrospective study. BMC Gastroenterol. 2014;14:82. 29. Bariol C, Hawkins NJ, Turner JJ, Meagher AP, Williams DB, Ward RL. Histopathological and clinical evaluation of serrated adenomas of the colon and rectum. Mod Pathol. 2003;16(5):417-23. 30. Lash RH, Genta RM, Schuler CM. Sessile serrated adenomas: prevalence of dysplasia and carcinoma in 2139 patients. J Clin Pathol. 2010;63(8):681-6.

Revue canadienne de pathologie | volume 10, numéro 1 | www.cap-acp.org

61

RetRospeCtiVe stUDy dEtECtIOn Of SSaS In Calgary (cont.) 31. Sanaka MR, Gohel T, Podugu A, Kiran RP, Thota PN, Lopez R, et al. Adenoma and sessile serrated polyp detection rates: variation by patient sex and colonic segment but not specialty of the endoscopist. Dis Colon Rectum. 2014;57(9):1113-9. 32. Higuchi T, Sugihara K, Jass JR. Demographic and pathological characteristics of serrated polyps of colorectum. Histopathology. 2005;47(1):32-40. 33. Gurudu SR, Heigh RI, De Petris G, Heigh EG, Leighton JA, Pasha SF, et al. Sessile serrated adenomas: demographic, endoscopic and pathological characteristics. World J Gastroenterol. 2010;16(27): 3402-5. 34. Pai RK, Hart J, Noffsinger AE. Sessile serrated adenomas strongly

predispose to synchronous serrated polyps in non-syndromic patients. Histopathology. 2010;56(5):581-8. 35. Burgess NG, Pellise M, Nanda KS, Hourigan LF, Zanati SA, Brown GJ, et al. Clinical and endoscopic predictors of cytological dysplasia or cancer in a prospective multicentre study of large sessile serrated adenomas/polyps. Gut. 2016;65(3):437-46. 36. Yang JF, Tang SJ, Lash RH, Wu R, Yang Q. Anatomic distribution of sessile serrated adenoma/polyp with and without cytologic dysplasia. Arch Pathol Lab Med. 2015;139(3):388-93. 37. Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis.

Gastroenterology. 2010;138(6):2088-100. 38. Nosho K, Igarashi H, Ito M, Mitsuhashi K, Kurihara H, Kanno S, et al. Clinicopathological and molecular characteristics of serrated lesions in Japanese elderly patients. Digestion. 2015;91(1):57-63. 39. Huang CC, Frankel WL, Doukides T, Zhou XP, Zhao W, Yearsley MM. Prolapse-related changes are a confounding factor in misdiagnosis of sessile serrated adenomas in the rectum. Hum Pathol. 2013;44(4):480-6. 40. Lee J, Park SW, Kim YS, Lee KJ, Sung H, Song PH, et al. Risk factors of missed colorectal lesions after colonoscopy. Medicine (Baltimore). 2017;96(27):e7468.

All peer-reviewed articles appearing in this publication have undergone a double blind peer-review process. The views or opinions expressed in this Journal are those of the authors and contributors, and do not necessarily reflect those of this Journal, the editors, the editorial board, the publisher of this Journal, or the Canadian Association of Pathologists (CAP-ACP). Although the CAP-ACP has made reasonable efforts to ensure accuracy the articles herein, the Journal, the editors, the editorial board, the publisher of this Journal, or the CAP-ACP, take no responsibility whatsoever for any errors, omissions, or any consequences of reliance on any material or the accuracy of any information contained in this publication. In the event of a discrepancy, between the original and translated versions of the texts, the original version shall take precedence. The mention of trade names, commercial products or organizations, and the inclusion of advertisements in the Journal does not imply endorsement by this Journal, the editors, the editorial board, the publisher of this Journal or the CAP-ACP. This publication is copyright in its entirety. Material may not be reprinted, stored in a retrieval system, or copied without the written permission of CAP-ACP. Contact through www.cap-acp.org.

62

Canadian Journal of Pathology | Volume 10, Issue 1 | www.cap-acp.org

du 7 a PRE u 1 NE 0 j Z DA uil TE let 20 18

69e Cong grès annuel de l’Asssociation canadienne des paathologistes - Canadian Assocciation of Pathologists, en collaboration avec l’Association des pathologist t es du Québec

L’’é évoluttion du rôle des pathologistess face aux biomarrqueurs prédictif t s et à la méde ecine de précision Le congrès scientifique annuel se déroulera du 7 au 10 juillet 2018 à Québeec et présentera cette année un progr o amme scientifique m multidisciplinaire, des conffér érencierss de renom, une vaste gam mme d’exposants et un choix d’activvités sociales des plus intéressan e ts. Activités pré-conférences (samedi 7 juillet 2018) 18) érents domaines nes de la • Dix ateliers interactifs explorant diffffér pathologie, tout en utilisant des moyens variés d’appr a entissage • Les assistants-pa t thologistes invitent les résidents en pathologie à se joindre à eux pour la présentation du nouveau programme interproffessionnel essionnel : Compétences esseentielles en pathologie (les pathologistes sont également les bien b venus) • Déjeuner de réseautage pour les résidents et les chefs hefs de pathologie permettan p t d’ééchanger changer sur les opportuunités d’eemploi, mploi, less ffello ellowships et le mentorat • Assistez au symposium s des résidents dans une am mbiance détendue • Rencontrez d’anciens collègues lors des activités soociales des assistants-paathologistes

Hébergement : Hilton Québec

cap-acp.com/2018 o

Réunion annuellee (du dimanche 8 juillet au mardi 10 juillet 2018) Trois journées compplètes de conffér érences, incluant quatre sessions simultanées, abordant trois filières e d’apprentissage qui s’adressent à diff iffffér érents sujets d’intérêt, champs de pratiquee et besoins d’apprentissage des participan cipants : pratique en surspécialité, pratique générale et sujets spécifiquement liés à la pratique au Canada. • Quatre conffér érencces individuelles portant sur des sujetss généraux reliés au thème du congrès • Sessions éducativves préparées par chaque section, grouupe d’intérêt spécial et réseau de spécialitité de la CAP-ACP • Neuf ateliers en conf c fér érence, y compris des sessions de surspécialité sur les biomarqueurs prédic é tifs • Assemblées génér érales annuelles de la CAP-ACP et de l’’APQ A APQ • Remise des prix d’excellence, présentations des platefformes o ormes et affiches mettant en évidence la recheerche au Canada • Poursuite des parrtenariats avec l’’AAssociation canadienne ne de protection médicale et le Ontario Molec ecular Pathology Research Network • Séances éducativves avec petit déjeuner offffer erts par des commanditaires présents au congrès • La réception du président au Parlement de Québec aveec une visite de la Chambre des communes • La soirée de Gala - Banquet au Musée national des beaux aux-arts de Québec avec l’accès à l’Exposittion de Riopelle

Date limite de soumissioon des résumés : Le 28 fféévrier 22018

Ouverture de l’’inscription inscription : er Le 1 févrrier 2018

facebook ae . om/capac .c a p.or p g/ g

#capac a p2018 p

Ju SAV ly E T H 7-1 E D 0, ATE 20 S 18 69th Ann nual Meeting Canadian Association of Pathologists - Association canadieenne des pathologistes, held jointly with w the Association des pathhologistes du Québec

The Evolving o Role of Pathologists in the Era of Predictiv t e Biomarkerrs and Precisio on Medicine The 2018 Annual Scientific Meeting will be held July 7- 10 in Quebec City annd will fea feature a multi-disciplinarry scientific program, renowned guest speakers, an extensive trade show, and a greaat social program. Pre-Conference Activities (Saturdayy,, July 7) • TTen en interactive pre-conffer erence workshops exploringg diverse areas of pathology onn the diffffer erent learning tracks • Pathologists’ Assistan s ts invite Pathology trainees to the revamped interrproffessional essional PA program: Essential Pathology Skills (pathologgists are also welcome!) • Networking lunnch ffor or trainees and pathology leadeers to optimize employment, fello fellowship and mentorship opportunities • Unwind and learn arn at the Residents’ symposium • Catch up with old friends at the Pathologists’ Assistaants Social

[ Accommodation ] H on Quebec Hilt

cap-acp.com/2018 o

Annual Meeting ng (Sunday to Tuesdayy,, July 8-10) Three full conffer erenc e e days with four four concurrent sessioons in three diffffer erent learning tracks that will addr ddress the various content interests, scopes of practice, and learning styles off the audience: Subspecialty practice, General practice, and Canadian practice-related topics: • Four stand-alone one plenary lectures exploring overarching topics related to the annual theme • Educational sessions essions from all CAP-ACP Sections, Special p Interest Groups andd Specialt i lty Nettworks k • Nine in-conffer errence workshops, including sub-specialt cialty sessions on predictive biom markers • CAP-ACP and APQ A Annual General Meetings • Award lectures, platfform orm and poster presentationss showcasing Canadian reseearch • Continued parrtnerships with the Canadian Medical a Protective Association and the Ontario Molecular Pathology Research Nettwork • Daily industry-sponsored breakfast symposia • Presiden id t’’ss recception i at the h Quebec b Parliamen liament; tours to the h House off Commons • Gala Banquet at the Musée national des beaux-arts t du Québec with Riopelle’’ss expoosition

[ Abstract Deadline ] February 28, 20188

[ Registration t Opens ] Februarry 1, 2018

facebook ae . om/capac .c a p.or p g/ g

#capac a p2018 p