canadian journal of volume 4, issue 1 spring 2012...
TRANSCRIPT
Pathology Recruitment in Canada
In Situ Mantle Cell Lymphoma: A New Entity in Hematopathology
Canadian Journal of
Pathology
Publications Agreement Number 40025049 • ISSN 1918-915X
Official Publication of the Canadian Association of Pathologists
www.cap-acp.org
Volume 4, Issue 1 • Spring 2012
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VOLUME 4, ISSUE 1 2012
About the Cover
4
5
Editorial: Of Infection, Inflammation, and IgG4J. Godfrey Heathcote, MA, MB BChir, PhD, FRCPC
Éditorial : De l’infection, de l’inflammation et des IgG4J. Godfrey Heathcote, MA, MB BChir, PhD, FRCPC
Thank You to Reviewers
EDITOR-IN-CHIEFJ. Godfrey Heathcote, MA, MB BChir, PhD, FRCPC
EDITORIAL BOARDManon Auger, MD, FRCPC, Cytopathology;
Calvino Cheng, BSc, MD, FRCPC, Pathology Informatics and Quality Management;
Eleftherios Diamandis, BSc, MD, PhD, FRCPC, Medical Biochemistry; David K. Driman, MB ChB, FRCPC, Anatomical Pathology;
Todd F. Hatchette, BSc, MD, FRCPC, Medical Microbiology; Michael J. Shkrum, MD, FRCPC, Forensic Pathology;
Louis D. Wadsworth, MB ChB, FRCPath, FRCPC, Hematopathology
C AP A SSOCIATION MANAGER Danièle Saintonge
MANAGING EDITORSusan Harrison
COPY EDITORS Michael Peebles, Scott Bryant
PROOFREADERScott Bryant
ART DIRECTORAndrea Brierley, [email protected]
TR ANSL ATORMarie Dumont
SALE S AND CIRCUL ATION COORDINATORBrenda Robinson, [email protected]
ACCOUNTINGSusan McClung
GROUP PUBLISHERJohn D. Birkby, [email protected]
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––Canadian Journal of Pathology is published four times annually by
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Canadian Journal of Pathology • Volume 4, Issue 1, 2012
Contents
Original Articles
For Instructions to Authors, please visit http://www.andrewjohnpublishing.com/CJP/instructionstoauthors.html
The cover image shows a diagnosis of in-situ mantle cell lymphoma confirmed by immunohistochemistry for cyclin D1 and fluorescence in situ hybridization. Two interphase cells show IGH/CCND1 dual fusions with orange/green (yellow) FISH signals (arrows).
18
CAP-ACP News
9
7 Message from the President: Mapping Out Our FutureVina Alexopoulou, MD, FRCPC
Pathology Recruitment in Canada: Does Medical School Education in Pathology Influence Student Career Choice?Lawrence Lee, MASc, Marcio M. Gomes, MD, PhD, Jason C. Ford, MD, FRCPC
Notes on the History of the Canadian Association of Pathologists – Association canadienne des pathologistesGuillermo Quinonez, MD, MS, MA, FRCPC, Laurette Geldenhuys, MB BCh, MAEd, FRCPC
Canadian Immunohistochemistry Quality Control: A 3-Year Review of an Academic Program Providing Proficiency Testing to Canadian Clinical Immunohistochemistry LaboratoriesMaria A. Copete, DDS, MS, John Garratt, RT (Cytology), Greg Young, BScH, Carol Cheung, MD, PhD, FRCPC, Blake Gilks, MD, FRCPC, John Costa, MSc, Anup Saseendran, BSc, Dragana Pilavdzic, MD, FRCPC, Jagdish Butany, MBBS, MS, FRCPC, Emina Torlakovic, MD, PhD
In Situ Mantle Cell Lymphoma: Case Report of a New Entity in HematopathologyMara Caragea, MD, Pat Allevato, MD, FRCPC, Caroline Hamm, MD, FRCPC, Jie Xu, PhD, FCCMG, Kamilia Rizkalla, MD, FRCPC
Neighbourly Collaboration to Improve Breast Predictive Factors Testing in North AmericaM. Elizabeth H. Hammond, MD, FCAP, Wedad Hanna, MB, ChB, FRCPC, Sharon Nofech-Mozes, MD, FRCPC
Opinion
11
Recruiting Medical Students into Pathology: The Consequences of FailureJason C. Ford, MD, FRCPC
FOUNDING EDITORJagdish Butany, MBBS, MS, FRCPC
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Book Reviews38 Manual of Pediatric Hematology and Oncology, Fifth Edition
Reviewed by Jason C. Ford, MD, FRCPC
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38
Professional Development/Employment Opportunities8173739
Interior HealthMcGill Cytopathology Review CourseCAP Advanced Practical Pathology ProgramsMolecular Oncologic Pathology Fellowship Program
Canadian Journal of P athology 3Spring 2012
Spring 20124 Canadian Journal of P athology
EDITORIAL
In the day-to-day activities of surgical pathologists, therecognition of tumours as benign or malignant and theirappropriate classification are of paramount importance.Indeed, much of the public concern about the standard ofdiagnostic pathology in this country and others has beencentred on these two aspects of pathologists’ work. With thisfocus on tumour pathology, it is easy to overlook thedifficulties that infectious and inflammatory conditions cancreate for the general surgical pathologist, and these conditionsinevitably tend to accumulate on the desks of subspecialists.Histopathology has proved vital in the understanding of manyinfectious diseases; the examples of legionnaires’ disease andhuman immunodeficiency virus/acquired immune deficiencysyndrome during the span of my career in laboratory medicineimmediately spring to my mind. Yet, infectious diseases posespecial challenges for histopathologists, and some of these arediscussed in a recent briefing paper prepared for the RoyalCollege of Pathologists (UK) by Professor Sebastian Lucas ofthe University of London.1 Lucas emphasizes the importantrole of the histopathologist in diagnosing infections in tissuesthrough recognition of the characteristic features of the host-parasite interaction. All pathologists understand that thepresence of a micro-organism in a tissue specimen does notmean it is the cause of a patient’s disease, and the absence of ademonstrable infectious agent does not mean it is not presentwithin the tissue. Although many common infectious diseasesare readily diagnosable, such as a Helicobacter pylori infectionin the stomach, there are many that may be quite challenging,including tuberculosis and syphilis. Lucas closes his article witha thought-provoking quotation from one of his NorthAmerican colleagues in infectious disease pathology: “Why arepathologists more interested in learning about the tumour theywill never see than … the infection they will likely miss?”1
Similar considerations apply to many inflammatoryconditions, in particular those that involve multiple systemsor organs. In my professional practice as an ophthalmicpathologist, I have become used to the frustrations of dealingwith inflammatory conditions of obscure etiology, given thatthey are common occurrences in the vitreous, conjunctiva, andorbit. Idiopathic orbital inflammation (orbital inflammatorypseudotumour) has always been particularly intriguing: Arethe lesions with a heavy lymphoplasmacytic infiltrate differentfrom those with more fibrous tissue? Does the degree of
fibrosis influence the natural history? Why are there often somany eosinophils present in the tissue, particularly inchildhood? If granulomatous inflammation is present, is thelesion really a manifestation of sarcoidosis? Above all, why dosome patients with idiopathic orbital inflammation haveretroperitoneal fibrosis, Riedel’s thyroiditis, or sclerosingcholangitis?2 The answers to some of these questions arebeginning to emerge.Autoimmune pancreatitis was first described in 1961 but onlybecame an established entity in the 1990s. In 2001, Hamanoet al. reported the association of autoimmune pancreatitis withelevated serum concentrations of IgG4, and subsequentlyextra-pancreatic lesions were described.3,4 From theseobservations, the concept of IgG4-related disease (IgG4-RD)as a systemic fibro-inflammatory disease characterized bytissue infiltration of IgG4-positive plasma cells has becomeestablished.5 It is now recognized that almost all organs maybe involved, and, for the most part, the lesions have very similarhistopathological features: a dense lymphoplasmacyticinfiltrate, fibrosis (usually in a storiform pattern), and phlebitis,often obliterative. Although IgG4-positive plasma cells arepresent within the inflammatory infiltrate, in some cases theserum IgG4 concentration is not elevated. In October 2011, an International Symposium on IgG4-RD inBoston, organized by Dr. John Stone of the Division ofRheumatology at Massachusetts General Hospital, broughttogether a group of experts from nine countries, representinga variety of medical disciplines, of which rheumatology andpathology were numerically the most prominent. The purposeof the symposium was to
• create a standardized nomenclature for the organ-specificmanifestations of IgG4-RD;
• establish histopathological criteria for the diagnosis of IgG4-RD that would be recognizable by all practising pathologists, irrespective of the frequency with which theywere likely to see such lesions; and
• develop further understanding of the pathobiology of IgG4 and IgG4-RD.
It is anticipated that one outcome of this symposium will be apublication in 2012 of recommendations for the nomenclatureof the organ- and system-based manifestations of IgG4-RD.
Of Infection, Inflammation, and IgG4
Competing interests: J. Godfrey Heathcote was a member of the Organizing Committee for the 2011 Symposium on IgG4-RD in Boston and received free hotel accommodationfor the duration of the symposium.
In addition, a consensus statement on the histopathology is inpreparation. In a pre-symposium exercise, there was a highlevel of concordance in the diagnosis of IgG4-RD amongpathologists, despite the lack of defined criteria for thediagnosis. The role of IgG4 itself in this condition remainssomething of an enigma, and it is perhaps concerning that ourknowledge is still so rudimentary that the condition is namedafter what may be nothing more than a biomarker. IgG4 maybe pathogenic in some conditions, for example, bullous skinlesions such as pemphigus vulgaris, but it is by no meanscertain that it has a pathogenic role in IgG4-RD. It is of interestthat evidence has started to emerge that there may be acausative link to infectious agents in some cases of IgG4-RD.5
J. Godfrey HeathcoteEditor-in-Chief
References1. Lucas S. UK infectious diseases and diagnostic cellular pathology: remit,
constraints and capacities. Bull R Coll Pathol 2011;156:238–42.
2. Comings DE, Skubi KB, Van Eyes J, Motulsky AG. Familial multifocal
fibrosclerosis. Findings suggesting that retroperitoneal fibrosis, mediastinal
fibrosis, sclerosing cholangitis, Riedel’s thyroiditis and pseudotumor of the
orbit may be different manifestations of a single disease. Ann Intern Med
1967;66:884–92.
3. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in
patients with sclerosing pancreatitis. N Engl J Med 2001;344:732–8.
4. Kamisawa T, Funata N, Hayashi Y, et al. Close relationship between
autoimmune pancreatitis and multifocal fibrosclerosis. Gut 2003;52:683–7.
5. Cheuk W, Chan JKC. IgG4-related sclerosing disease. A critical appraisal of
an involving clinicopathologic entity. Adv Anat Pathol 2010;17:303–32.
Canadian Journal of P athology 5Spring 2012
HEATHCOTE
La différenciation des tumeurs selon leur caractère bénin
ou malin et leur classification appropriée sont des
activités professionnelles du médecin spécialiste en
pathologie chirurgicale qui revêtent une importance
primordiale. De fait, quand le public se préoccupe de la
qualité ou des normes en matière de diagnostic
pathologique, ici au pays ou ailleurs dans le monde, il
s’attarde à ces deux aspects du travail du pathologiste. La
pathologie tumorale occupant ainsi le devant de la scène, les
difficultés que posent les maladies infectieuses et
inflammatoires pour le pathologiste généraliste peuvent
facilement passer inaperçues, et la tâche de procéder à ces
examens tend à revenir inévitablement au surspécialiste.
L’histopathologie s’est révélée vitale dans la connaissance des
mécanismes de nombre de maladies infectieuses; ne serait-
ce qu’au cours de ma carrière en biologie médicale, je peux
citer, à titre d’exemple, la maladie du légionnaire, l’infection
due au virus de l’immunodéficience humaine et le sida.
Pourtant, les maladies infectieuses conservent encore et
toujours une part de mystère en histopathologie; c’est
d’ailleurs le sujet abordé par le professeur Sebastian Lucas
de l’Université de Londres dans un exposé récent sur l’état
de la question destiné au Collège royal des pathologistes du
Royaume-Uni1. Le professeur fait valoir l’importance de
l’histopathologiste dans le diagnostic de l’infection par
l’examen histologique, car il sait détecter les traits
caractéristiques de l’interaction entre l’hôte et le parasite.
Les pathologistes savent bien que le microorganisme présent
dans un prélèvement ne constitue pas forcément la cause de
la maladie du patient et que l’impossibilité de déceler la
présence d’un tel microorganisme ne peut être assimilée à
son absence dans les tissus. Alors que de nombreuses
infections courantes comme l’infection gastrique due à
Helicobacter pylori sont faciles à diagnostiquer, beaucoup
posent d’énormes défis à l’instar de la tuberculose et de la
syphilis. Le professeur termine son article en citant un
collègue nord-américain spécialiste de la pathologie des
maladies infectieuses : « Comment se fait-il que le
pathologiste s’intéresse davantage à une tumeur qu’il ne
verra jamais… qu’à l’infection qu’il ne détectera peut-être
pas? »1
Il en va de même à peu de choses près des maladies
De l’infection, de l’inflammation et des IgG4
Conflit d’intérêts : Le docteur J. Godfrey Heathcote a fait partie du comité organisateur du Symposium 2011 sur la maladie systémique associée aux immunoglobulines IgG4 àBoston; il a bénéficié de l’hébergement gratuit le temps du symposium.
inflammatoires, plus particulièrement de celles qui touchent
de multiples systèmes ou organes. Dans l’exercice de ma
profession dans le domaine ophtalmique, je connais bien la
frustration qui naît de l’examen de troubles inflammatoires
d’étiologie obscure, car ils sont chose courante dans le corps
vitré, la conjonctive et la cavité orbitaire. L’inflammation
orbitaire idiopathique (pseudotumeur inflammatoire) reste
une énigme : les lésions caractérisées par l’infiltration
lymphoplasmocytaire massive sont-elles différentes de celles
où la fibrose prédomine? L’étendue de la fibrose influe-t-elle
sur l’histoire naturelle de la maladie? Pourquoi les
éosinophiles sont-ils si souvent présents en grand nombre,
particulièrement chez l’enfant? Si la lésion inflammatoire
présente des traits granulomateux, est-elle une manifestation
de la sarcoïdose? Par-dessus tout, pourquoi l’inflammation
orbitaire idiopathique s’accompagne-t-elle de fibrose
rétropéritonéale, de thyroïdite de Riedel ou de cholangite
sclérosante dans certains cas?2 Mais voici que des réponses
à ces questions commencent à émerger.
Décrite pour la première fois en 1961, la pancréatite auto-
immune accède à la désignation d’entité distincte dans les
années 1990. En 2001, Hamano et ses collègues constatent
l’élévation de la concentration sérique des immuno-
globulines IgG4 en présence de pancréatite auto-immune,
et par la suite, des lésions extrapancréatiques reliées au
même phénomène sont observées3,4. De là est issu le concept
de maladie associée aux IgG4 (syndrome d’hyper IgG4),
essentiellement une maladie fibro-inflammatoire
systémique caractérisée par l’infiltration tissulaire de
plasmocytes IgG4 positifs5. Nous savons maintenant que
tous les organes peuvent être touchés et que, pour la plupart,
les lésions ont des traits quasi identiques : un infiltrat
lymphoplasmocytaire dense, la fibrose (de motif storiforme
habituellement) et la phlébite souvent oblitérante. Bien que
les lésions inflammatoires contiennent des plasmocytes IgG4
positifs, la concentration sérique d’IgG4 n’augmente pas
toujours.
En octobre 2011, un symposium international sur la maladie
systémique associée aux IgG4, organisé par le
docteur John Stone du service de rhumatologie de l’Hôpital
général du Massachusetts, a rassemblé des experts de
diverses disciplines médicales, principalement la
rhumatologie et la pathologie, en provenance de neuf pays.
Les objectifs du symposium consistaient à :
• établir une nomenclature uniforme des manifestations
organiques de la maladie systémique associée aux IgG4;
• déterminer les critères histopathologiques du diagnostic
de la maladie systémique associée aux IgG4 qui
deviendront la norme en vigueur dans la profession;
• approfondir les connaissances sur les aspects
biopathologiques des IgG4 et de la maladie qui leur
est associée.
Le symposium sera vraisemblablement suivi en 2012 de la
publication de recommandations sur la nomenclature des
manifestations organiques et systémiques de la maladie
associée aux IgG4. En outre, des experts préparent un exposé
consensuel sur l’histopathologie de cette maladie. Un
exercice tenu avant le symposium révèle un haut degré de
concordance entre les pathologistes présents quant au
diagnostic de la maladie associée aux IgG4, quoique les
critères diagnostiques ne soient pas établis encore. Le rôle
des IgG4 dans cette maladie demeure un mystère et il est
troublant de constater que nos connaissances sont à ce point
rudimentaires que la maladie est désignée du nom de ce qui
n’en sera peut-être qu’un biomarqueur. Les IgG4 peuvent
être pathogènes dans certaines affections, comme le
pemphigus vulgaire et ses lésions bulleuses, mais rien n’est
certain quant à leur rôle pathogène dans la maladie qui leur
est associée. Fait à noter, des données probantes émergentes
semblent établir un lien causal entre des agents infectieux et
certains cas de maladie systémique associée aux IgG45.
J. Godfrey HeathcoteRédacteur en chefe
Références1. Lucas S. UK infectious diseases and diagnostic cellular pathology: remit,
constraints and capacities. Bull R Coll Pathol 2011;156:238–42.
2. Comings DE, Skubi KB, Van Eyes J, Motulsky AG. Familial multifocal
fibrosclerosis. Findings suggesting that retroperitoneal fibrosis, mediastinal
fibrosis, sclerosing cholangitis, Riedel’s thyroiditis and pseudotumor of the
orbit may be different manifestations of a single disease. Ann Intern Med
1967;66:884–92.
3. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in
patients with sclerosing pancreatitis. N Engl J Med 2001;344:732–8.
4. Kamisawa T, Funata N, Hayashi Y, et al. Close relationship between
autoimmune pancreatitis and multifocal fibrosclerosis. Gut 2003;52:683–7.
5. Cheuk W, Chan JKC. IgG4-related sclerosing disease. A critical appraisal of an
involving clinicopathologic entity. Adv Anat Pathol 2010;17:303–32.
Spring 20126 Canadian Journal of P athology
É DITORIAL
Canadian Journal of P athology 7Spring 2012
CAP-ACP NEWS
Dear CAP/ACP Members,
The 2011 annual meeting in Vancouver was an outstanding
success; more than 440 members and 150 exhibitors
attended, one of the highest attendances in recent memory.
If you did not attend, you missed a great lineup of speakers
and workshops as well as a chance to meet old friends and
make some new ones. The excitement from the Stanley Cup
finals in Vancouver was surpassed only by the enthusiasm
of our trainees presenting their research and by their proud
supervisors, silently glowing as they anticipated the bright
future of our new generation of Canadian laboratory
physicians.
The 2011 meeting was a milestone for me. My 30 years of
experience in pathology was recognized by my being selected
by my peers as the new president of our national association,
the ultimate honour. What a fantastic opportunity to put
my efforts toward solving both old and emerging challenges
of our profession. Although my predecessors, Jagdish Butany
(2006–2009) and Laurette Geldenhuys (2009–2011), are
tough acts to follow, the stage has been set, and we are ready
to continue the vision.
Our Canadian health care system is under pressure. Our
pathologists are overworked and often stressed by decisions
imposed by hospital administration without their input.
While the news media are ready to point fingers at
laboratory physicians for laboratory errors, the public is
finally recognizing our quiet but crucial contributions to
health care. “The chasm separating what is needed from
what is provided is only going to widen.”1 Our strength as a
national association is you – the members – and your expert
understanding of our specialty. We need each and every one
of you to participate in our sections and special interest
groups. Encourage your colleagues who are not members to
join us. Governments recognize and value numbers, and our
strength lies in our membership numbers.
Let us map out our future together. We have what we need.
We have a vision, a good strategy, and the right people.
Previous executives created key processes to ensure our voice
is heard in national bodies such as the Royal College of
Physicians and Surgeons of Canada, the Canadian
Partnership Against Cancer (CPAC), the College of
American Pathologists, the Canadian Medical Association
(CMA), and the Canadian Medical Protective Association
(CMPA), just to mention a few. But land mines at the local,
provincial, or national levels lie in our path and threaten to
make us deviate from our goals; we will carefully manage
each and every one of them as they arise. We are here to
advise and support those affected and to present a united,
well-focused perspective while upholding excellence in
patient care rather than seeking quick political wins or
personal gains.
We can already celebrate some victories won in 2011. The
Ontario Ministry of Health sought our advice and
participation in the expert panel deliberations related to the
“Windsor Report.” The creation of the Canadian Alliance of
Laboratory Medicine was a first in Canadian laboratory
medicine history. Thanks to the efforts of Laurette
Geldenhuys, this body will be participating in future
deliberations affecting the profession as the Canadian
Leadership Council on Laboratory Medicine, under the
auspices of the Royal College and the Canadian Association
of Pathologists. Our collaboration with the College of
American Pathologists is also a first worth celebrating. We
are co-developing courses by providing accreditation
suitable for Canadian fellows, and members of our
association with subspecialty expertise are now invited to
contribute to the ongoing development of College of
American Pathologists cancer checklists.
Our Pathologists’ Assistants section is finalizing the
proposed certification process for its members. Our Patient
Safety and Quality Assurance section is working closely with
the CMPA to develop guidelines. Our first annual Residents’
Review Course for PGY4s and PGY5s was an outstanding
success and a humbling experience for the course directors
and the scientific advisory committee. More than 60 trainees
gathered in Hamilton for 2 days in March 2011. The future
practitioners of Canadian pathology were united under one
roof, preparing for the ultimate challenge in their training,
the Royal College examination. Let me assure you that the
future of Canadian pathology is very bright! All teaching
faculty members were volunteers, Canadian, and among our
best educators. We are aiming for an even better course in
2012, including sessions for trainees in general pathology.
Message from the PresidentMapping Out Our Future
DISPLAY CLASSIFIED
Pathologists
CranbrookKamloops
Trail
It’s the best of both worlds.
Career success and a great lifestyle.
I can work hard, and then play like there’s no tomorrow.
achieve freedom and balance. My patients
We are seeking general or anatomical pathologists in some of Interior Health’s most desirable communities. The successful candidates’ main responsibility will be in anatomic pathology and to a lesser degree in hematopathology, chemistry and transfusion medicine. The Laboratory services in Interior Health is an integrated laboratory system with full professional support.
Interior Health communities offer exceptional recreational activities including
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Life’s better here. Find out why.
Life’s better here for...Life’s better here for...
Spring 20128 Canadian Journal of P athology
MESSAGE FROM THE PRESIDENT
Finally, please remember that, unlike the case of any other
specialty, no patient is cared for in hospital without being
touched by our laboratory services in some way. So I urge
you to continue to practise quality laboratory medicine,
train the young ones well, and be proud of your work. At the
same time, be aware of what’s happening, be involved; be an
active CAP/ACP member.
Thank you all for allowing me to be your president. I am
committed, enthusiastic, and counting on your ongoing
support and ideas.
Vina AlexopoulouPresident
Reference1. Haggie J. President’s message. Ottawa (ON): Canadian Medical Association,
2012; http://www.cma.ca/multimedia/CMA/Content_Images/
Inside_cma/Media_Release/PresidentsMessage/President-Sept2011_en.pdf.
Accessed February 14, 2011.
Canadian Journal of P athology 9Spring 2012
OPINION
Recruiting Medical Students into Pathology:The Consequences of Failure
Jason C. Ford, MD, FRCPC is with the Department of Pathology and Laboratory Medicine, University of British Columbia, andthe Division of Hematopathology, BC Children’s Hospital, in Vancouver, British Columbia. He can be contacted by e-mail [email protected] opinion expressed in this article is that of the author and is not necessarily shared by CAP-ACP, the editor and editorialboard, or the publisher.This article has been peer reviewed.Competing interests: None declared
Jason C. Ford, MD, FRCPC
The last decade has not been kind to the practice of
pathology in Canada – or to the patients we serve.
Thanks to extensive coverage in the lay press, the scandals
that have afflicted our specialty are well known to Canadians
and to Canadian pathologists:
• In Newfoundland in 2005, public officials revealed
serious deficiencies in the laboratory analysis of breast
cancer specimens affecting hundreds of patients.1
• In New Brunswick in 2008, a series of complaints about
misdiagnoses led to a public inquiry into the practice of
pathology at Miramichi Regional Hospital.2
• In Manitoba in 2009, a public review into pathology
practices followed allegations by a pathologist about
excessive workload.3
• In Quebec in 2009, the pathological assessment of more
than 2,000 breast cancer specimens was called into
question after a study suggested the original results may
have been inaccurate.4
• In Ontario in 2010, questions about a pathologist’s errors
led to a public inquiry focused on hospitals in the Essex
County region.5
• In Saskatchewan in 2011, a pathologist was fired after
blowing the whistle on controversial laboratory
management practices at the provincial level.6
In every one of these cases, an inability to hire enough
adequately trained pathologists was cited as a contributing
factor.
As Tolstoy famously noted at the beginning of Anna
Karenina,7 “Happy families are all alike; every unhappy family
is unhappy in its own way.” It is certainly the case that each
of these Canadian laboratory scandals was “unhappy in its
own way,” and it would be a mistake to try to attribute these
events to a single cause. But the extent to which an
inadequate supply of pathologists – and by extension the
inadequate recruitment of medical students into pathology
– has been identified as a common contributor is remarkable.
Three of these scandals led to official public reviews: the
Cameron report in Newfoundland,8 the McLellan report in
Ontario,9 and Justice Creaghan’s report of the provincial
commission of inquiry in New Brunswick10 summarize the
findings. It is worth noting what each of these reports has to
say about pathologist availability and recruitment from
medical school:
• “Given the shortage of pathologists, faculties of Medicine
are encouraged to promote interest in pathology as a
specialty by exposing students to pathology in the early
years of their program. Faculties of Medicine are also
encouraged to expand their curriculum to ensure that all
medical students are educated as to the important,
underlying role of pathology in the practice of
medicine.”8
Spring 201210 Canadian Journal of P athology
RECRUITING MEDICAL STUDENTS INTO PATHOLOGY
• “There is currently a shortage of pathologists. This
shortage needs to be addressed to build an optimal
province-wide system based on improved peer
assessment and second opinion consultation … It is
recommended that: The Ministry of Health and Long-
Term Care support the development and imple-
mentation of a provincial quality assurance system
for pathology that includes … a human resource review
of the number of pathologists … required to support
the provincial system.”5
• “That there is a shortage of pathologists in Canada is
beyond dispute. Nor can there be any question that the
students at Canadian medical schools and residency
programs have not to now seen pathology as a desirable
specialty. We … must take steps to increase the number
of pathologists trained in Canada.”2
• “I can but call on universities and the Medical Council
of Canada to develop programs designed to encourage
medical students to consider pathology as a career.”2
Several authors have demonstrated severe pathologist
understaffing in laboratories across Canada,9,10 and as the
above public inquiries indicate, the inadequate recruitment
of medical students into pathology is almost certainly a
major contributor to this alarming situation. Pathology
recruitment is not of merely academic interest but, rather,
an urgent public policy concern.
The unpopularity of pathology among medical students has
been analyzed for several decades, starting at least with
Coombs’ 1967–1971 survey results11 (as summarized by
Vance12) that medical students generally viewed pathologists
as “insecure, uncomfortable, and ill at ease with others, and
inept in interpersonal communication, shy, introverted,
aloof, and cold.”
The specific reasons for pathology’s recruitment failures are
not clear, but interestingly many of the usual suggestions
appear to be incorrect. There is evidence that the likelihood
of a student choosing (or avoiding) pathology is not related
to
• whether the medical school favours problem-based
learning (PBL) or lectures,13
• how much lecture time students have in pathology,14
• whether there is a pathology course in medical
school,14 or
• the expected availability of pathology jobs.15
Most medical students seem not to reject pathology so much
as ignore it.16 Strategies to remove pathology’s cloak of
invisibility are difficult to devise, but several possible options
exist: Should medical students have more clinical
experiences in pathology? Do medical schools need to
incorporate pathology into medical or surgical clerkships?
Do medical school admission criteria need to be revised in
order to accept more pathology-friendly candidates?
Many academic pathologists will be familiar with dismissive
institutional attitudes toward pathology. As an internal
medicine representative on one university committee
recently queried, “Why should the recruitment problems of
pathology be of any significance to this medical school?” The
answer is that pathology recruitment matters because
patient safety matters. Six Canadian provinces have already
seen how patient care is affected when pathologists are in
short supply. How many more scandals do we need?
It will be up to pathologists to show leadership on this
important issue. Canadian pathologists should develop
strategies to improve recruitment into our field: this may
require more academic work to better define influences on
student recruitment. We must drive this issue at a national
level and develop a network of local champions across the
country. If Canadian medical schools are resistant to the idea
that pathology recruitment deserves their attention, it is up
to us to change their minds.
References1. CanWest MediaWorks Publications Inc. St. John’s Telegram. Newfoundland
falls short in pathology department: report. 4 April 2008;
http://www.canada.com/topics/news/national/story.html?id=9394967d-bde0-
44fc-bad1-8f457551e804&k=94030. Accessed 22 Sept 2011.
2. Creaghan PS. A Report with Recommendations of a Commission of Inquiry
into Pathology Services at the Miramichi Regional Health Authority, Vol 1.
Commissioner’s Report. Fredericton (NB): New Brunswick Department of
Health; 2008.
3. CBC News. Pathology program put under review. 11 December 2009;
http://www.cbc.ca/news/canada/manitoba/story/2009/12/11/mb-pathology-
review-workloads-winnipeg.html. Accessed 22 Sept 2011.
4. Fidelman C. Breast cancer: anatomy of a scandal. Montreal Gazette, 5 June
2009; http://www.bcam.qc.ca/content/breast-cancer-anatomy-scandal.
Accessed 22 Sept 2011.
Continued on page 31
Canadian Journal of P athology 11Spring 2012
ORIGINAL ARTICLE
Pathology Recruitment in Canada: Does Medical School Education in Pathology
Influence Student Career Choice?
Lawrence Lee, MASc, and Jason C. Ford, MD, FRCPC, are members of the Department of Pathology and Laboratory Medicine,University of British Columbia. M. M. Gomes, MD, PhD, is a member of the Department of Pathology and Laboratory Medicine,University of Ottawa. Correspondence may be directed to [email protected] article has been peer reviewed.Competing interests: None declared
Lawrence Lee, MASc, Marcio M. Gomes, MD, PhD, Jason C. Ford, MD, FRCPC
ABSTRACTPurpose: Poor recruitment of medical students into pathology residency programs contributesto a clinically significant shortage of pathologists in Canada. This study compares Canadian
medical schools to determine if different approaches to pathology education influence
pathology recruitment.
Methods: We surveyed pathology directors to compare quantitative features of preclinical
pathology teaching at Canadian medical schools. We next determined the proportion of each
medical school’s graduating class that opted for any laboratory medicine residency program,
to identify any correlations with survey responses.
Results: There is no statistically significant association between any quantitative feature ofpathology education and the likelihood that a medical student will select pathology. The amount
of preclinical pathology teaching did not strongly influence pathology recruitment. Schools
with a separate pathology course were no more likely to recruit medical students into pathology
than schools with integrated pathology teaching.
Conclusions: Poor recruitment of medical students into pathology cannot be attributed to
limited preclinical pathology contact hours or to the absence of a separate pathology course.
National variation in medical student recruitment into pathology is likely due to other
curricular features that differ among schools or to different features of the medical school classes
themselves.
RÉSUMÉBut : Le peu d'étudiants en médecine qui choisissent la résidence en pathologie est à l’originede la pénurie de ces professionnels en pratique clinique au Canada. La présente étude examine
les modalités d’enseignement de la pathologie dans les facultés de médecine canadiennes pour
en déterminer l’influence sur le recrutement de médecins résidents.
Méthode : Nous avons interrogé les directeurs de programme d’études en pathologie à proposd’aspects quantitatifs de l’enseignement préclinique de la pathologie dans les facultés de
médecine canadienne. Nous avons ensuite relevé la proportion des diplômés en médecine qui
optent pour une résidence en biologie médicale dans les facultés de médecine afin de cerner les
Spring 201212 Canadian Journal of P athology
PATHOLOGY RECRUITMENT IN CANADA
The present international shortage of pathologists
adversely affects patient care.1–4 One contributor to this
shortage is the consistently poor recruitment of medical
students into pathology residency programs.5–9 The ability
to recruit medical graduates into pathology programs differs
greatly among Canadian medical schools.10 A recently
published survey of pathology education in Canadian
medical schools revealed other important differences.11 For
example, total preclinical pathology contact time (lectures
plus small-group teaching) ranged from 10 to 300 hours. It
has been suggested that the amount of pathology teaching
in medical school is linked to the likelihood of a medical
student’s choosing to enter a pathology residency
program.12,13 It is quite common, for example, to hear
pathologists blame poor recruitment directly on limited
pathology contact hours.13
This study was undertaken to identify any correlations
between Canadian medical schools’ approaches to pathology
education and their ability to recruit medical students into
the field of pathology.
MethodsAfter receiving institutional ethical approval, we contacted
pathology educators at 17 Canadian medical schools (13
English, one bilingual, and three French).11 Each educator
was asked to participate in a 27-question survey about their
own medical school curriculum, modeled on a previously
published survey of American pathology educators.14
Residency match data were obtained from the Canadian
Resident Matching Service (CaRMS).15 These data reveal the
proportion of each school’s graduating class that opted for
any pathology or laboratory medicine residency program
(i.e., anatomical pathology, general pathology, laboratory
medicine, hematopathology, medical microbiology, medical
biochemistry, or neuropathology).
Data were tabulated with Microsoft Excel (Microsoft,
Seattle, Washington).
ResultsSurvey ResponsesResponses were received from 16 of the 17 schools (a 94%
response rate). One school, Queen’s University, provided
survey feedback describing a new curriculum in pathology
that was being implemented. Because residency-choice data
from Queen’s University reflected the previous curriculum
and could not be correlated with the new curricular data
provided, survey results from Queen’s University were
excluded. The French schools were also excluded because
their students generally do not use CaRMS to select
residency positions. This left 12 English or bilingual medical
schools in the analysis. Survey responses from these 12
schools are summarized in Table 1.
Residency-Choice DataAs reported previously,11 88% of survey respondents
reported significant changes in the medical curricula at their
schools during the previous 10–20 years. To minimize this
confounder, only residency-choice data from the recent 5-
corrélations entre les réponses du sondage et ces chiffres.
Résultats : Il n’y a pas de lien statistiquement significatif entre les aspects quantitatifs de
l’enseignement de la pathologie et la probabilité qu’un étudiant en médecine choisisse la
résidence en pathologie. L’étendue de l’enseignement préclinique en pathologie n’influe pas
véritablement sur le recrutement. Les facultés offrant un cours de pathologie distinct ne sont
pas avantagées dans le recrutement d’étudiants dans la résidence en pathologie par rapport aux
facultés où l’enseignement de la pathologie est intégré à d’autres cours.
Conclusion : Le faible nombre d’étudiants en médecine qui choisissent la pathologie ne peut êtreimputé au nombre d’heures d’enseignement préclinique de la pathologie ou à l’absence d’un
cours de pathologie en bonne et due forme. La variabilité du recrutement au pays est
probablement due à d’autres aspects du programme d’études qui diffèrent d’une faculté à une
autre ou à des caractéristiques particulières des facultés de médecine.
Canadian Journal of P athology 13Spring 2012
LEE ET AL.
year period (2006–2010) were used to assess survey results.
During that period, 7,966 students from the responding
English or bilingual medical schools used CaRMS to select
a Canadian residency position. Of these, 114 chose a
pathology or laboratory medicine residency program
(hereafter referred to simply as “pathology”), an overall
selection percentage of 1.4%.
Table 2 shows the average likelihood that a student
graduating from each medical school would rank pathology
first in the CaRMS match during the 2006–2010 period.
Data from the 2001–2005 period is also shown for
comparison. Values are expressed as the average percentage
of each school’s graduating classes during the years
indicated.
Correlations between Quantitative Survey Results and Residency-Choice DataThere is no statistically significant association between the
response to any quantitative survey question and the
likelihood that a student will choose to enter pathology.
Some responses showed limited, non-significant
associations or trends whereas others showed no association
or a negative association:
• Pathology as a separate course: not associated with
increased pathology recruitment. Four of the top 6
recruitment schools do not have a separate pathology
course whereas 4 of the bottom 6 recruitment schools
do.
• Hours of preclinical pathology instruction: an almost
flat relationship (if borderline positive, R2 = 0.0029)
between hours of instruction and recruitment (Figure 1).
Table 1. Summary of Quantitative Survey Responses
Survey Question Response SummaryWhat are the preclinical pathology lecture hours? Mean 45 hours; range 5–140 hours*What are the preclinical pathology small-group hours? Mean 34 hours; range 0–250 hours*What are the total preclinical pathology contact hours? Mean 81 hours; range 10–300 hours*Does pathology “control” its own preclinical curriculum? 50% “significant” control, 50% “total” controlAre there separate pathology examinations? 42% yes, 58% noHow much influence does the department of 25% minimal influence, 58% some influence, 17% major influencepathology have on “overall curricular design”? Do pathology residents teach preclinical students? 100% yesDo pathology residents receive formal instruction in teaching? 42% yes, 58% noIs pathology “recognizable” as a career 58% definitely yes, 17% possibly yes, 25% mostly nochoice to your medical students?Does your pathology department have a medical 50% yes, 50% limited outreach or recruitmentstudent outreach or recruitment program?Does your program have preclinical pathology electives? 58% yes, 42% noDoes your program have clerkship pathology electives? 100% yesIs there a mandatory elective/selective in pathology? 17% yes, 83% noDo you promote pathology electives to students? 50% yes, 42% no, 8% no answerWhat is the overall medical school class size? Mean 172; range 64–250*One school did not answer this question.
Table 2. Medical Students Ranking Pathology First in the2006–2010 and 2001–2005 Canadian Resident MatchingService Matches
Students Ranking Pathology First(%)*
Medical School 2006–2010 2001–2005U. of British Columbia 2.7 3.2U. of Saskatchewan 1.7 1.1McGill U. 1.6 1.7U. of Toronto 1.5 1.8U. of Western Ontario 1.5 0.8U. of Alberta 1.4 2.0Dalhousie U. 1.3 1.7U. of Calgary 1.3 1.1Memorial U. of Newfoundland 1.0 0.0U. of Ottawa 0.9 2.5U. of Manitoba 0.6 1.1McMaster U. 0.3 0.2*Percentage of the graduating class at each institution, averaged over the timeperiod.
Spring 201214 Canadian Journal of P athology
PATHOLOGY RECRUITMENT IN CANADA
• Pathology’s “control” of its own curriculum: no apparent
association with recruitment. Schools in the top half of
Table 2 (2006–2010) were just as likely as schools in the
bottom half to exercise “total” control over the
pathology curriculum.
• Separate pathology examinations: limited positive
association with recruitment. Schools that had a
separate preclinical pathology examination were slightly
more likely, on average, to recruit students into
pathology (i.e., an average recruitment of 1.6%,
compared to 1.1% for schools with no pathology
examination).
• Pathology’s influence on overall curricular design: no
evidence of association with increased recruitment. The
top three and bottom three recruiters all declared
“some” influence. Both of the schools claiming “major”
curricular influence were in the bottom half of Table 2.
• Pathology outreach or medical student recruitment
program: no evidence that this leads to improved
recruitment. Only 2 of the top 6 recruiters had “well
defined” recruitment efforts, compared to 4 of the 6
bottom recruiters.
• Preclinical electives in pathology: negatively (if
minimally) associated with recruitment. Three of the
top 6 recruiters have preclinical pathology electives
whereas 5 of the bottom 6 recruiters have these electives.
• Clinical electives in pathology: provided by all schools.
• Mandatory rotations/selectives in pathology: no evidence
that these lead to improved recruitment. The only
schools providing these were in the bottom half of Table 2.
• Promotion of pathology electives to medical students: no
evidence that this increases recruitment. Only 2 of the
top 6 recruitment schools promote pathology electives
whereas 4 of the bottom 5 schools promote their
electives. (One school did not answer.)
• Class size: no evidence of association with recruitment.
There was a positive (if limited) association between
pathology recruitment and the respondents’ feeling that
pathology was recognized as a career choice by the students
of their institutions. All of the top 6 recruiters reported that
students were aware of pathology as a career, compared to
only 3 of the 6 recruiters in the bottom half of Table 2.
Figure 1. Relationship between preclinical pathology contact hoursand the percentage of the medical graduating class recruited intopathology.
DiscussionThe relatively large literature on medical students’ career
choices includes studies focused on general career influences
as well as those relating to specific specialties. A wide variety
of career influences outside of pathology have been
identified, including the presence16 and timing17 of clerkship
electives, sociodemographic features of the student
population,18 and the “cultural” characteristics of different
medical schools.19 This study was designed to identify
pathology-specific career influences.
Although pathology is generally not a popular career choice
for medical students, it is not equally unpopular at every
Canadian medical school. Across a 5-year average of student
career choice (2006–2010), students at the top recruiting
school were nine times as likely as students in the bottom
school to select pathology. If every Canadian school
recruited as many medical students into pathology as the
top school, the total number of students choosing to become
pathologists from 2006 to 2010 would have been 215 rather
than 114. This increase would have exceeded the number of
unfilled pathology residency spots across the country during
this period, and the “excess” demand would ideally have
driven an increase in the number of residency positions in
pathology.
There are many assumptions about the reasons for
pathology’s poor recruitment. Medical students are said to
reject pathology because “students no longer take second-
Canadian Journal of P athology 15Spring 2012
LEE ET AL.
year pathology courses”13 or because of medical schools’
“enthusiasm for problem-based learning”20 or because of “a
reduction in the total amount of time devoted to pathology,
and [even] a disproportionate reduction in pathology when
compared with other subjects.”21 These suggestions seem
reasonable, but they are often made without evidence.
It is already clear that a problem-based learning curriculum
does not reduce pathology recruitment.10 The current study
allows us to test some other theories. Our analysis considers
such variables as the presence or absence of the traditional
pathology course, the amount of total pathology
instructional time for preclinical medical students (i.e., years
1 and 2 in most medical schools), the extent of the pathology
department’s influence or control over the medical school
curriculum, the availability of pathology electives, and the
extent of pathology recruitment efforts. The data show that
there is no statistically significant association between
pathology recruitment and any one of these variables.
Given a sample size of only 12 medical schools, it is
important to consider not just statistically significant
associations but also trends. Even with this approach, none
of the variables appears to have a meaningful positive
association with pathology recruitment, except for a small
positive trend observed with stand-alone pathology
examination. Schools with a separate pathology course,
preclinical electives, active promotion of clerkship electives
in pathology, or robust pathology curricular input seem no
more likely than other schools to recruit medical students
into pathology residencies.
The demonstrated association between better recruitment
and pathologists’ belief that students recognize pathology as
a potential career may simply reflect a correct inference on
the part of pathology educators (pathologists presumably
can recognize whether their students are more or less likely
to choose pathology). It may also represent a more general
opinion about whether pathology is respected or valued at
their various medical schools. The one other demonstrable
positive association – namely, the presence of a stand-alone
pathology examination – is difficult to explain. The
suggestion that writing a preclinical multiple-choice
examination in pathology could cause medical students to
preferentially choose pathology residencies strains credulity.
However, the existence of such an examination could be
correlated with curricular features that may favour
pathology recruitment, such as an emphasis on pathology
in the overall preclinical curriculum. A slight positive
recruitment trend was identified with increasing pathology
contact time, but this relationship was so trivial that it is
hard to believe it could be educationally important. As
Figure 1 illustrates, the relationship between contact time
and recruitment appears essentially flat. It seems safe to
conclude that medical students are not rejecting pathology
simply because of too limited contact with pathologists in a
preclinical pathology course.
The generally negative results of this study suggest three
possible explanations for the observed interschool variability
in pathology recruitment:
1. The apparent range in pathology recruitment is a “data
noise” artefact arising from the small numbers of
students.
2. Recruitment differences among schools arise from
many different influences; no single factor explains
significant variation.
3. Recruitment differences among schools arise from
features not assessed by this study.
There is certainly a great deal of “noise” in year-to-year
recruitment statistics.10 However, when averaged over longer
periods, pathology recruitment is more stable. If we
arbitrarily divide pathology recruitment into three tiers
(0–1.0%, 1.1–2.0%, and >2.0%), we find that the majority
of schools stayed in the same tier from the 2001–2005 period
to the 2006–2010 period (see Table 1) and that all but one
of the rest changed by only a single tier. It is clear that there
are “pro–family practice” schools22; it is reasonable to suggest
that there are “pro-pathology” schools as well.
Career choice among medical students is a complex
multifactorial process; the relatively limited sample size in
this study may obscure small but important factors.
However, we looked not only for statistically significant
findings but also for nonsignificant associations. The fact
that career-choice influences are multifactorial does not
mean they are invisible. Recruitment into family practice
must be as multifactorial as recruitment into pathology, and
there are clearly demonstrable career influences for family
Spring 201216 Canadian Journal of P athology
PATHOLOGY RECRUITMENT IN CANADA
medicine.22 If pathology contact hours are a meaningful
influence on career choice, this should be observable in
isolation, even if it is only one of several interrelated factors.
It is worth remembering that this study evaluates the career
decisions of 7,966 students, of whom 114 chose pathology.
Although this study is not powerful enough to exclude
pathology contact hours (or any of the other above
variables) as an influence on pathology recruitment, we can
conclude that preclinical contact hours are likely not a major
influence. The widespread opinion (among pathologists)
that the amount of preclinical pathology teaching drives
recruitment does not have strong evidentiary support. The
relatively wide differences in how (and how much)
preclinical pathology is taught in different Canadian medical
schools show almost no meaningful association with
recruitment. There is evidence that students find preclinical
pathology teaching to be a very important part of their
education.11 However, there is no convincing evidence that
the quantity of this teaching is a major influence on
pathology recruitment.
If there are major influences on pathology recruitment, they
are most likely not included in the variables we tested.
Previous studies into the career choices of non-pathology
medical students divided career influences into two broad
categories: (1) personal characteristics of the student,
including personality and demographic factors, and (2)
experiential features, such as medical school rotations and
other outside influences.18 Both of these types of influence
likely play a role in pathology career choice. This study does
not include analysis of any personal features of the different
medical schools’ students, such as age, sex, area of
premedical study, interest in research, or personality type.
Perhaps the schools with better pathology recruitment
simply admit a slightly different cohort of students than the
schools with lower pathology recruitment.
The study also does not explore several experiential features
of the different medical schools. The medical education
literature is full of references to the so-called “hidden
curriculum,” defined as “the set of influences [on medical
students] that function at the level of organizational
structure and culture.”23 The hidden curriculum is what
teaches medical students that pathology is morbid and
boring.6,24 It may be that there is a more pro-pathology
culture at the higher-recruitment schools; perhaps the non-
pathology clinical instructors are more likely to speak
positively of pathology, or the pathologists themselves are
more welcoming or encouraging of students. Schools that
are more pro-pathology might have more or stronger role
models in pathology and laboratory medicine. Higher-
recruitment schools may also have more concrete
advantages, including more student elective time (and
therefore more opportunity to pursue a noncore rotation
such as pathology) or encouragement to pursue pathology
experiences within other rotations (such as the chance for a
student on a surgery rotation to follow a specimen through
the anatomical pathology laboratory). Some of these
personal and experiential features may be difficult to
measure, but others (such as the sociodemographic features
of medical students at different schools) seem amenable to
further research.
The issue of recruitment into pathology residencies is not
merely of academic interest. Several recent scandals in
laboratory medicine in Canada have been blamed partly on
a shortage of Canadian-trained pathologists.25 According to
the Canadian Association of Pathologists, an additional 500
pathologists will be needed in Canada in the next 10 years.4
If current recruitment trends are maintained, fewer than 250
students will decide to become pathologists in the next
decade. There are already too few pathologists in Canada;26
we need to understand better what recruitment strategies
are working now, so they can be more widely implemented.
References1. Mahoney R, Katona C, McParland M, et al. Shortage specialties: changes in
career intentions from medical student to newly qualified doctor. Med Teach
2004;26:650–4.
2. Graves D. The impact of the pathology workforce crisis on acute health care.
Aust Health Rev 2007;31 Suppl 1:S28–30.
3. Furlow B. Cancer inquiry unveils Canada’s troubled health system. Lancet
Oncol 2008;9:823–4.
4. Chorneyko K, Butany J. Canada’s pathology. CMAJ 2008;178:1523–6.
5. Lambert TW, Goldacre MJ, Turner G, et al. Career choices for pathology:
national surveys of graduates of 1974-2002 from UK medical schools. J Pathol
2006;208:446–52.
6. Hung T, Jarvis-Selinger S, Ford JC. Residency choices by graduating medical
students: why not pathology? Hum Pathol 2011;42:802–7.
7. Lambert TW, Goldacre MJ, Turner G. Career choices of United Kingdom
medical graduates of 2002: questionnaire survey. Med Educ 2006;40:514–21.
8. Lambert TW, Goldacre MJ, Turner G. Career choices of United Kingdom
medical graduates of 1999 and 2000: questionnaire surveys. BMJ
2003;326:194–5.
Canadian Journal of P athology 17Spring 2012
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9. Lambert TW, Goldacre MJ. Career destinations seven years on among doctors
who qualified in the United Kingdom in 1988: postal questionnaire survey.
BMJ 1998;317:1429–31.
10. Ford JC. Influence of a problem-based learning curriculum on the selection
of pathology as a career: evidence from the Canadian match of 1993-2004.
Hum Pathol 2005;36:600–4.
11. Ford JC, Gomes MM. Pathology education in Canada: results of a national
survey. Can J Pathol 2010;2:23–7.
12. Weedon D. Whither pathology in medical education? Med J Aust
2003;178:200–2.
13. Glauser W. Saskatchewan regulation breach linked to pathologist shortage.
CMAJ 2011;183:E715.
14. Taylor CR, DeYoung BR, Cohen MB. Pathology education: quo vadis? Hum
Pathol 2008;39:1555–61.
15. Reports and statistics: R-1 match reports. Canadian Resident Matching
Service; http://www.carms.ca/eng/operations_R1reports_e.shtml. Accessed
October 24, 2011.
16. Mihalynuk T, Leung G, Fraser J, et al. Free choice and career choice: clerkship
electives in medical education. Med Educ 2006;40:1065–71.
17. Coffeng LE, Visscher AJ, Ten Cate OT. The influence of early clinical
experiences on career preference of male and female medical students.
Med Teach 2009;31:e323–6.
18. Sobral DT. Influences on choice of surgery as a career: a study of consecutive
cohorts in a medical school. Med Educ 2006;40:522–9.
19. Tandeter H, Granek-Catarivas M. Choosing primary care? Influences of
medical school curricula on career pathways. Isr Med Assoc J 2001;3:969–72.
20. Herdson PB. Pathology, pathologists and problem-based learning. Pathology
1998;30:326–7.
21. Nash JRG, West KP, Foster CS. The teaching of anatomic pathology in England
and Wales: a transatlantic view. Hum Pathol 2001;32:1154–6.
22. Meurer LN. Influence of medical school curriculum on primary care specialty
choice: analysis and synthesis of the literature. Acad Med 1995;70:388–97.
23. Lempp H, Seale C. The hidden curriculum in undergraduate medical
education: qualitative study of medical students’ perceptions of teaching. BMJ
2004;329:770–3.
24. Ford JC. If not, why not? Reasons why Canadian postgraduate trainees chose
– or did not choose – to become pathologists. Hum Pathol 2010;41:566–73.
25. Ford JC. Recruiting medical students into pathology: the consequences of
failure. Manuscript submitted for publication. Can J Pathol 2012;4(1):9–10.
26. Pollett AF, Lajoie G, Colgan T. Canadian laboratory physician supply: falling
behind. Can J Pathol 2011;3:1–6.
DISPLAY CLASSIFIED
Cytopathology Review CourseApril 21 – 24, 2012
Montréal, Québec, CanadaCourse Director: Dr. Manon Auger
For further information contact:Email: [email protected] University Health CentreContinuing Education Office
Tel: (514) 934-8253Fax: (514) 934-1779
www.muhc-cme.mcgill.ca
Spring 201218 Canadian Journal of P athology
Notes on the History of the CanadianAssociation of Pathologists – Association
canadienne des pathologistes
Guillermo Quinonez, MD, MS, MA, FRCPC, is with the Department of Pathology, University of Manitoba, in Winnipeg, Mani-toba, and also has an office in Ancaster, Ontario. Laurette Geldenhuys, MB BCh, MAEd, FRCPC, is with the Department ofPathology, Dalhousie University, in Halifax, Nova Scotia. Correspondence can be directed to [email protected] article has been peer reviewed.Competing interests: Dr. Quinonez is the founder of the Humanities in Pathology Club and an emeritus member of CAP-ACP.Dr. Geldenhuys is past-president of CAP-ACP.
Guillermo Quinonez, MD, MS, MA, FRCPC, Laurette Geldenhuys, MB BCh, MAEd, FRCPC
ABSTRACTThe history of the first 45 years of the Canadian Association of Pathologists–Association
canadienne des pathologistes is well documented in an essay published by Henry Letts and John
Jacques in 1994. The authors of this article have written an updated essay, focusing instead on
the role that the association has played in promoting pathology to the national and international
health care communities and to Canadian society.
RÉSUMÉL’essai de Henry Letts et de John Jacques publié en 1994 relate l’histoire des 45 premières années
de l’Association canadienne des pathologistes dans ses moindres détails. Les auteurs publient
un complément d’information à cet essai, qui se penche sur le rôle de l’Association dans la
promotion de la pathologie auprès du public canadien et des communautés de la santé du pays
et de l’étranger.
This article is dedicated to Harry Walter Vincent Letts, historian of Canadian pathology, and to all
those members of the association who made this story possible.
ORIGINAL ARTICLE
EmergenceThe initial attempt to create a national organization by a
group of pathologists within the Canadian Medical
Association (CMA) occurred in September 1907 in
Montreal. As a separate section, it was named the
“Laboratory Section” and lasted until 1932 when it was
united with the “Section of Medicine.” A further attempt was
made by Louis Berger (1895–1948) from l’Université Laval,
who began to promote the idea of a new independent
organization after the interruption of professional activities
during World War II. Unfortunately, Berger died in 1948;
but he had transmitted his ideas to John Drennan Hamilton
(1911–2002), at that time a pathologist from Queen’s
University, in Kingston, Ontario.
Berger’s idea became reality with the verbal support of the
nascent Association des pathologistes du Québec, founded
in 1946, and the assistance of the Ontario Association of
Pathologists (OAP), founded in 1937. The active
participation of members of the OAP and other provincial
pathologists’ organizations culminated in the first meeting
of the new Canadian Association of Pathologists (CAP-
ACP) at the University of Saskatchewan on June 15, 1949.
Canadian Journal of P athology 19Spring 2012
QUINONEZ AND GELDENHUYS
The meeting was held concurrently with the annual meeting
of CMA. Fifteen members from Newfoundland, New
Brunswick, Ontario, Manitoba, Saskatchewan, and Alberta
were present and became the founding members of the new
association.
Since its beginnings, the administration of CAP-ACP has
consisted of a council with representatives from the
provincial associations, an executive, sections, and
committees. Members of the executive are elected by a
general assembly. The sections – with their years of
foundation – are presented in Table 1. The committees of
CAP-ACP are presented in Table 2.
There are also standing committees and task forces
appointed by the executive. Sections and committees have
changed names through the years to serve better the interests
of the association’s membership, and a secretariat, now
located in Ottawa, was established in 1990. In the past few
years, special interest groups have developed in areas such
as education, informatics, international health, tissue
banking, and semen analysis. There is also a Medical
Humanities in Pathology Club.
The association officially represents the pathology
community to federal and provincial authorities and other
national and international professional organizations such
as CMA, the Royal College of Physician and Surgeons of
Canada (RCPSC), the American Society of Clinical
Pathologists (ASCP), the College of American Pathologists
(CAP), the International Academy of Pathology (IAP), the
World Association of Societies of Pathology and Laboratory
Medicine (WASPaLM), and the International Liaison
Committee of Presidents (ILCP). It also works closely with
other groups related to laboratory medicine such as the
Canadian Chairs of Pathology and Laboratory Medicine
(CCPLM), the Canadian Society of Medical Laboratory
Science (CSMLS), and the recently formed Canadian
Alliance of Laboratory Medicine (CALM).
Status of PathologistsCAP-ACP supports the community of pathologists and
constantly reviews its objectives to fulfill their needs. One
permanent activity is the bringing of provincial societies
under a common umbrella with the intent to minimize
differences of provincial jurisdiction. The association
responds to comments by the media and politicians, making
balanced recommendations that defend the interests of
pathologists but without ignoring those of society.
One of the initial aims of the association was “to study the
various schedules of fees, pension plans, and the general
situation of pathologists.” Publication of annual income
reports and workforce requirements has been an activity of
the association since the very beginning. From the early
1970s, it became an important source of information for
those looking to obtain employment and/or willing to
relocate. In the early 1980s, this information became a CAP-
ACP databank used to establish workforce requirements in
Canada.
When the federal and provincial hospital and medical care
insurance programs were introduced in the 1950s and 1970s,
CAP-ACP carefully evaluated the impact that such
legislation would have on the economic status of its
members and advised them accordingly. The association
played a successful role in opposing Bill 320 in 1968 (“The
Hospital Insurance and Diagnostic Act”) whereby the
federal government proposed to remove pathology and
radiology services from the act. More recently, in 2002, it
Table 1. Sections and Years of Foundation
Section YearCytopathology 1961 (Canadian Society of Cytology, CSC)Experimental Pathology 1979Laboratory Genetics 1981 Clinical Pathology 1983 Residents 1986 Hematological Pathology 1990 Anatomical Pathology 1990 Neuropathology 2007 Pathologists’ Assistants 2007 Forensic Pathology 2007 Patient Safety and Quality Assurance 2009
Table 2. CAP-ACP Committees and Years of Foundation
Committee YearNominating 1949 Membership 1950 Professional Affairs 1950 Local Organizing 1954 Continuing Professional Development 1960 Special Archives 1975 Annual Meeting 1978 Awards 1990 Resource Development 1990 Workload 2009
Spring 201220 Canadian Journal of P athology
NOTES ON THE HISTORY OF CAP-ACP
also opposed Bill 114 in the province of Quebec that
threatened to damage the profession and quality patient
care.
The association has worked diligently in guiding its
members to adapt to changes in the practice of medicine so
evident in recent years. Such support received special
attention in the early 1990s with the creation of a
Consortium on the Future of Pathology/Laboratory
Medicine in Canada, aimed at identifying problems in
Canadian pathology and their solutions. Sections have also
played a role as lobby groups for several subspecialties of
pathology and in creating guidelines in areas such as
workforce planning, workload standards, quality assurance,
and ethical operation of private clinical laboratory practices.
Status of Laboratory TechnologistsCAP-ACP has worked to support and elevate the status of
laboratory technologists, in co-operation with CMA, the
Canadian Hospital Association (CHA), CSMLS, and CSC.
The association has supported technologists’ training and
has been an active participant in the inspection and
accreditation of laboratory technology training programs in
co-operation with CSMLS. Since the 1960s, CAP-ACP has
supported the idea of pathologists’ assistants, and in 2006 it
set out a position statement that would guarantee adequate
training conditions for these professionals. This statement
became the basis for creating a new Section of Pathologists’
Assistants. Since 1986, it has recognized annually the
contribution of CSMLS to the continuing education of its
members by a technologist award.
Laboratory ManagementCAP-ACP has been a leader in laboratory management, with
members of the association participating in successive
attempts to develop workload units for pathologists and
technologists. The initial ones were based on systems
developed in Great Britain and by the College of American
Pathologists, with other health care disciplines under the
control of the Canadian federal government adopting a
similar approach to that of our organization. Unfortunately,
in spite of modifications, attempts to apply these units to
everyday work were unsuccessful, and it was several years
before new systems of evaluation were introduced. In the
1960s and 1970s, CAP-ACP became an active participant in
the creation of the Systematized Nomenclature in Pathology
(SNOP) and the Systematized Nomenclature for Medical
Terminology (SNOMED).
CAP-ACP has been a leader in workforce issues and quality
assurance and laboratory safety. Since its very beginning, the
association has maintained committees that provide
guidelines to address these issues and increased professional
awareness by including such topics in annual educational
activities. In 2009, the Section of Patient Safety and Quality
Assurance was formed to promote education in quality
assurance and to develop guidelines related to this field.
This section has under its umbrella Canadian
Immunohistochemistry Quality Control (cIQc), an
immunohistochemistry proficiency-testing program, and
the National Standards Committee on High Complexity
Laboratory Testing, which has developed immuno-
histochemistry guidelines and checklists. The organization
has also set guidelines for the practice of pathology, such as
cytology, retention times for human material and reports,
surgical reporting protocols and guidelines, blood donor
systems, the importance of autopsies, and consultation
between pathologists. It has further advocated for the
leadership role of pathologists as laboratory directors.
Continuing Professional Development and Post-graduateEducationContinuing professional development (CPD) in the form of
scientific sessions and workshops for its members during
annual meetings is one of the main activities of CAP-ACP.
These activities are frequently presented in collaboration
with sister organizations such as the Canadian Society of
Clinical Chemistry (CSCC) and the Canadian Association
of Medical Biochemists (CAMB). Scientific sessions were
introduced in Vancouver in 1954 and have become
progressively more elaborate, with national and
internationals speakers as participants. Workshops
introduced in the1962 annual meeting held in Winnipeg are
now among the most important activities of the association,
having a similar format to those offered by IAP. In 2008,
CAP-ACP also became a Royal College Accredited Provider
of CPD and accredits its own and other educational events.
CAP-ACP has committed educational support for pathology
Canadian Journal of P athology 21Spring 2012
QUINONEZ AND GELDENHUYS
residents. The Residency Training Committee began in 1950,
and successive committees have worked closely with RCPSC
supporting these programs. For instance, the association
effectively negotiated the creation of a Fellowship in
Pathology. Since 1972, CAP-ACP has provided financial
assistance for residents to attend and present at the annual
meetings. Such assistance is given in the form of awards
honouring distinguished members of the association. The
Residents’ Section organizes annual meetings where
professional issues affecting residents are discussed. In 2011,
an annual Resident's Review Course was introduced in
preparation for the Royal College examination.
CAP-ACP, as an institution and through several of its
members, strongly supported the activities of the Canadian
Reference Centre for Cancer Pathology (CRCCP). It has also
promoted assistance for pathologists in the developing
world.
Relation with the Royal CollegeThroughout the years, CAP-ACP has represented the
interests of the pathology community to RCPSC, while
maintaining its independence. It has played an advisory role
on matters of residency training, clinical pathology, CPD,
recertification, and maintenance of competence. In 1952,
and again in the early 1970s and 1990s, CAP-ACP advocated
that pathology become a separate Division of Laboratory
Medicine within the Royal College.
CytopathologyIn 1962, CSC began its activities as an affiliated society. The
organization meets annually at the CAP-ACP Annual
Meeting and offers a scientific program. In addition it offers
advice to the CAP-ACP Executive, CMA, and RCPSC in
matters of professional practice and training programs. CSC
is also active in developing cytotechnologist training
programs across Canada and quality assurance programs in
cytopathology.
ResearchThe objectives of CAP-ACP as stated in the constitution and
bylaws extend beyond service and administration. By
establishing an annual research award in 1965, the
association began to recognize outstanding contributions by
its members in basic and clinical research. It plays a role in
promoting and lobbying national organizations for this
activity. Indicating its commitment to research in general,
the Canadian Journal of Pathology was established in 2009.
HumanitiesCAP-ACP gives special attention to humanities in pathology.
In 1953, the Code of Ethics of the CMA and additional
canons were officially adopted. The topic is a frequent theme
in internal debates. The association also recognizes the status
of women pathologists with equal participation in the
executive and sections, and female presidents were
appointed in 1985, 1997, 2009, and 2011.
CAP-ACP established a newsletter in 1958 and an Archives
Committee in 1975. In 2009, Canadian Journal of Pathology
replaced the newsletter as the official publication of the
association. A seminar called “Humanities in Pathology”
initially supported by Associated Medical Services (the
Hannah Foundation) is currently held annually, ensuring a
commitment to excellence in this field.
The FutureMore than 60 years later, the vision of the founders is still
alive and carried on by members of the association. In 2011,
CAP-ACP, together with other Canadian laboratory
physician national specialty societies, became a founding
member of CALM in order to collaborate on matters of
common interest. The association is also working with
RCPSC to form a Canadian Leadership Council on
Laboratory Medicine to work on issues such as workload
measurement and manpower, national standards in quality
assurance, and subspecialty training through the
development of Royal College diplomas in the subspecialties
of laboratory medicine. A working group on the media and
public relations was formed in 2011 to raise the profile of
laboratory medicine. These activities make CAP-ACP truly
representative of the interests of its members and society in
general.
AcknowledgementsMaterial for this essay has been obtained from Henry Letts
and John Jacques, A History of the CAP-ACP, 2nd ed.,
Kingston, ON: Allan Graphics Ltd, 1994; archives of the
secretariat, CAP-ACP; and the memories of Daniel
Saintonge and the co-authors.
Spring 201222 Canadian Journal of P athology
Canadian Immunohistochemistry Quality Control: A 3-Year Review of an Academic Program Providing Proficiency Testing to Canadian Clinical Immunohistochemistry
Laboratories
Maria A. Copete, DDS, MS, and Emina Torlakovic, MD, PhD, are members of the Department of Pathology, University ofSaskatchewan, in Saskatoon, Saskatchewan. John Garratt, RT (Cytology), is a member of the Department of Pathology, LionsGate Hospital, in North Vancouver, British Columbia. Greg Young, BScH, Carol Cheung, MD, PhD, FRCPC, Jagdish Butany,MBBS, MS, FRCPC, and Emina Torlakovic, MD, PhD, are members of the Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, in Toronto, Ontario. Blake Gilks, MD, FRCPC, is a member ofthe Department of Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, in Vancouver, British Columbia. John Costa, MSc, and Anup Saseendran, BSc, are members of the Information Technology Services Division, College of Medicine, University of Saskatchewan, in Saskatoon, Saskatchewan. Dragana Pilavdzic, MD,FRCPC, is a member of the Department of Pathology, Jewish General Hospital, McGill University, in Montreal, Quebec. Correspondence may be directed to [email protected] article has been peer reviewed.Competing interests: None declared
Maria A. Copete, DDS, MS, John Garratt, RT (Cytology), Greg Young, BScH, Carol Cheung, MD, PhD, FRCPC, Blake Gilks, MD, FRCPC, John Costa, MSc, Anup Saseendran, BSc, Dragana Pilavdzic, MD, FRCPC, Jagdish Butany, MBBS, MS, FRCPC, Emina Torlakovic, MD, PhD
ABSTRACTQuality control includes all processes designed to detect, reduce, and correct deficiencies in a
particular product through proper analysis and evaluation. Quality assurance evaluates these
processes to ensure that the goal of delivering patient care is achieved while a certain level of
excellence is maintained. Although proficiency testing in immunohistochemistry (IHC)
primarily evaluates the technical aspects of a laboratory protocol and compares it with the
results of reference laboratories and/or other participants (peer comparison), it also evaluates
the delivery of IHC products to patients and is an important component of quality control and
quality assurance. In 2007, the Canadian Immunohistochemistry Quality Control (cIQc)
program was established as a voluntary academic initiative to improve proficiency testing in
clinical IHC for all Canadian laboratories. We report the past, present, and future components
of the cIQc program, including methodology, results, and future directions.
RÉSUMÉLe contrôle de la qualité s’entend des processus de détection, de réduction et de correction des
défaillances d’un produit par l’analyse et l’évaluation. L’assurance de la qualité évalue ces
processus pour vérifier que la prestation des services de santé est conforme à un certain degré
d’excellence. Bien que la vérification de la compétence en immunohistochimie consiste
essentiellement en l’évaluation des aspects techniques d’un protocole de laboratoire en le
comparant avec les résultats obtenus aux laboratoires de référence ou par d’autres professionnels
ORIGINAL ARTICLE
Canadian Journal of P athology 23Spring 2012
Immunohistochemistry (IHC) has developed rapidly to
become an integral part of diagnostic surgical
pathology.1,2 More recently, as targeted therapies have
evolved, IHC has also aided in the determination of
prognostic and predictive markers.3,4 The Canadian
Association of Pathologists/Association canadienne des
pathologistes (CAP/ACP) National Standards Committee/
Immunohistochemistry has classified all IHC tests into two
groups according to their use.5 Class I IHC test results are
used by pathologists to determine lineages or to characterize
lesions beyond morphology and are never reported on their
own. Class II IHC test results are used by clinicians to direct
patients toward appropriate therapies.3,4 Class II tests are
performed not only for breast cancer cases but also for cases
in transplant pathology, gastrointestinal pathology, and
hematopathology.3,4,6–14 (Some class I and class II tests are
listed in Table 1.)
Quality control (QC) is defined by the College of American
Pathologists as “the aggregate of processes and techniques
so derived to detect, reduce and correct deficiencies in an
analytic process.”15 QC focuses on the evaluation of a
product that has been developed. Quality assurance (QA)
evaluates processes to ensure that the delivery of patient care
(1) meets its objectives and (2) is of excellent quality.16–19 QC
is a product-oriented approach that ensures the accuracy of
results whereas QA examines the correctness of the processes
involved in the testing.15
External QA programs often use proficiency testing as a tool
to monitor interlaboratory concordance. Although
proficiency testing primarily evaluates the results of IHC
staining, it also addresses IHC procedures to a degree and is
therefore part of both QC and QA. While proficiency testing
for breast carcinoma markers has been developed by several
international providers, proficiency testing for all other class
II tests is lagging behind.20–24 Despite the efforts of various
programs to broaden IHC modules, it is not possible to
include several hundred class I tests that are currently used
clinically by pathologists. For instance, the United Kingdom
National External Quality Assurance Scheme, one of the
largest providers of proficiency testing in IHC, offers about
30 class I markers per year. Also, for some tissue types (such
as those obtained from bone marrow biopsies), there are no
existing proficiency testing programs.25
In 2007, the Canadian Immunohistochemistry Quality
Control (cIQc) program was established as an academic
initiative to support proficiency testing in clinical IHC. This
program was created by two academic pathologists (Emina
Torlakovic and Blake Gilks) and is mostly run by volunteers.
It is hosted by the University of Saskatchewan and the
University of British Columbia and is not contracted by any
accreditation body. It provides proficiency-testing tissue
samples in accordance with scientific principles and national
and international guidelines for diagnostic IHC. The cIQc
program provides proficiency testing on selected class I and
class II markers, as well as human epidermal growth factor
receptor 2 (HER2) in situ hybridization (ISH). In this article,
we discuss all components of the cIQc program, including
the results of IHC runs and challenges.
cIQc Program HistoryThe cIQc program was created in 2007 to support external
QC and QA for clinical IHC testing at a national level; it was
intended to facilitate participation by any Canadian IHC
laboratory regardless of jurisdiction or existing accreditation
requirements. The program has received support from (1) the
CAP/ACP, which has endorsed the program since its
inception; (2) the College of Medicine at the University of
Saskatchewan, which provided server space and information
technology expertise in designing and maintaining the
website at www.ciqc.ca; and (3) the Canadian Partnership
Against Cancer (CPAC), which awarded the program a 3-year
operating grant in April 2009.
COPETE ET AL.
(comparaison entre pairs), elle porte également sur les produits d’immunohistochimie offerts
aux patients, et elle constitue un volet important du contrôle et de l’assurance de la qualité.
L’initiative scientifique volontaire de contrôle de la qualité en immunohistochimie à l’échelle
du pays, mise sur pied en 2007, a pour objectif d’améliorer la vérification de la compétence en
immunohistochimie clinique des laboratoires canadiens. Nous présentons les éléments de
l’initiative, passés, présents et futurs, notamment sa méthodologie, ses résultats et ses objectifs
futurs.
Spring 201224 Canadian Journal of P athology
CANADIAN IMMUNOHISTOCHEMISTRY QUALITY CONTROL
The cIQc program aims to provide additional means for
monitoring and improving the quality of IHC testing in
clinical IHC laboratories on the national level. Any Canadian
clinical IHC laboratory may join by completing an online
registration form at www.ciqc.ca. The program is voluntary
and currently free due to the generous support of the
University of Saskatchewan and CPAC. Participation is
anonymous, and the results of each laboratory’s performance
are disclosed to a third party only at the special request of the
participant.
The cIQc program started by inviting 13 laboratories to
participate in its inaugural run. Since then, a total of 16 IHC
runs have been completed, including 56 various IHC
challenges and two HER2 ISH runs. Currently 89 laboratories
participate in the program, including occasional participants
from the United States and the European Union. Although
the exact number of laboratories that perform IHC testing in
Canada is unknown, information received from IHC reagent
suppliers allows us to estimate that the program is used by
more than half of the clinical IHC laboratories in Canada and
that it continues to grow in use.
cIQc Program MethodsTest SamplesTissue microarray (TMA) technology is used for creating
test samples.26 TMAs are made with multiple tissue samples
from normal and cancerous tissues and are constructed in
such a manner that the cIQc is able to provide participants
with the following statistically meaningful calculations:
(1) participant laboratory agreement with peer consensus
results, reference laboratory results, and reference method
results; (2) kappa value; and (3) sensitivity and specificity of
the class II tests. Unstained slides from TMA blocks are sent
to participants to be tested for various antigens; the
participants perform the designated IHC assay and return
the slides to the cIQc.
Assessment of ResultsReturned slides are assessed and scored by a panel of at least
four experienced pathologists or technologists at a
multiheaded microscope. Class II tests (which currently
include tests for estrogen receptor, progesterone receptor,
and HER2) are scored as either positive, negative, or
unsatisfactory (referring to the absence of a core or lesion
on the slide). In rare instances, the term “not interpretable”
is used for results that show high background staining or
unacceptable hematoxylin staining; these samples are not
Table 1. Canadian Immunohistochemistry Quality ControlIHC Runs, 2007–2010
Suboptimal and Run (Class) Participants Challenge Poor Results1 (I) 13 PanCK 8/13
LMWCK 4/11Vimentin 12/13
S-100 3/12HMB-45 1/12
EMA 9/102 (II) 18 ER 1/18
PR 1/18HER2 1/18
3 (II) 23 ER 8/23PR 3/23
4 (II) 25 ER 2/25PR 3/25
HER2 1/185 (II) 33 ER 2/33
PR 1/33HER2 1/24
6 (I) 29 CD45 8/28CD20 3/28Ki-67 2/28CD3 7/28
Cyclin D1 2/25Bcl-2 12/28CD30 4/28Bcl-6 11/20
7 (II) 56 ER 2/56PR 6/56
HER2 0/438 (I) 61 PanCK 1/55
LMWCK 25/45HMWCK 33/59
CK7 4/59CK20 12/58
9 (II) 53 ER 3/53PR 0/53
HER2 0/5310 (I) 25 S-100 4/23
Melan-A 0/21HMB-45 3/19
11 (I) 60 ER 2/60PR 3/60
HER2 0/41CK = cytokeratin; EMA = epithelial membrane antigen; ER = estrogen receptor;HER2 = human epidermal growth factor receptor 2; HMWCK = high-molecular-weight cytokeratin; LMWCK = low-molecular-weight cytokeratin; PR = progesteronereceptor.
Canadian Journal of P athology 25Spring 2012
COPETE ET AL.
scored. For class I tests, results are scored as "optimal" if no
improvement was recommended. If results appear to be
clinically useful, but some component of the test should still
be improved, the results are scored as "good." The results are
scored as "suboptimal" if it is suspected that clinical utility
may be limited. Finally, results are labelled "poor" if they
indicate definite evidence of false-positive results or false-
negative results or both. IHC protocols that produced poor
results should be considered for optimization. However,
proficiency testing is only one component of the QC/QA
system in clinical IHC. Therefore, an internal audit of results
with the specific marker scored as “poor” is recommended
before the protocol is significantly altered. The appropriate
selection and daily performance monitoring of tissue
samples as positive controls and the appropriate observation
of negative controls are essential for interpreting the results
of proficiency testing in IHC laboratories. Results of
proficiency testing have been shown in some cases to help
improve the design of daily QC. However, individual
laboratory results when internal patient tissues are used are
occasionally better than results achieved in proficiency
testing.
Online Reporting of ResultsAll results – including digital slides, calculations, composite
images, and tabulated summaries of results
(“garrattograms”) – are presented at www.ciqc.ca. This
transparency enables quick assessment of the overall success
of the participants and a nationwide comparison of
concordance. The display of results is anonymous because
each laboratory has its own code.
Digital slides are created for all runs and challenges. The
stained slides are scanned with an Aperio ScanScope CS slide
scanner, and the scans are available online to be viewed and
evaluated. Digital slides from runs 1 to 3 can be viewed with
MultiViewer whereas run 4 and all other runs can be viewed
only by ImageScope; both enable viewers to compare slides
side by side at any magnification. MultiViewer is limited to
four slides at a time but works well on both PC and Mac
platforms. ImageScope software may be downloaded at no
charge from Aperio but is available only for the PC platform.
Mac users can open cIQc digital slides one at a time,
although multiple separate images can be opened
simultaneously. ImageScope provides a “snapshot” function
by quickly creating high-quality images, allowing the user
to save areas of choice for individual laboratories to record
and discuss.
Protocols are available on the website and can be linked to
digital slides, composite images, and garrattograms by
laboratory code. This enables participants to determine
which protocols produced optimal results and which did
not. Only registered participants can view slides and
protocols. Protocols are also tabulated, and these can be
viewed online, saved, or printed by the participants. One of
the cIQc program’s special features is the garrattogram
(named after John Garratt, who was the first to apply
tabulated summaries of results for the evaluation of
nationwide concordance for class II tests). This allows for
evaluation of each laboratory’s success and concordance on
individual tests. Furthermore, garrattograms identify
individual laboratories that use unnecessarily harsh antigen-
retrieval procedures (marked by an abnormally high
number of lost tissue cores).
Composite images are generally used for class I IHC tests to
display the results of the most informative tissue cores,
allowing insight into the parameters used by the assessors
to score the results. They also enable quick comparisons of
IHC staining with the results of reference laboratories and
other participants in the program. Composite images
usually show the results of tissues to be considered when a
laboratory is designing external positive controls.
cIQc Program Development: Growing for the FutureProficiency testing programs are important for calibrating
tests and comparing protocols with those of peers. They
provide a standard against which clinical laboratories can
align themselves – a practice that ultimately results in
improved patient safety. In recognition of this, as of
December 2010, the cIQc program has been affiliated with
the CAP/ACP’s newly established Section for Patient Safety
and Quality Assurance.
The cIQc program is now in beta testing of a new web tool,
the TMA Scorer, that will allow laboratories to enter their
self-assessment results online and enable them to review
their results and the results (garrattograms) of other
laboratories and a reference site immediately. Other features
Spring 201226 Canadian Journal of P athology
CANADIAN IMMUNOHISTOCHEMISTRY QUALITY CONTROL
in development include links to reference images for each
run and the viewing of staining protocols from participating
laboratories immediately upon submission.
An important cIQc development is the launch of a question-
and-answer (Q&A) page on the cIQc website, which will
facilitate group discussion of important IHC laboratory
issues. Both questions and answers will be submitted
anonymously to the Q&A editor, who will then prepare
submissions for posting. The cIQc site is also building an
education page that will feature tools for improving
competencies in diagnostic IHC. Canadian and
international experts, both pathologists and technologists,
will be asked to prepare short comments on how IHC can
be used most effectively in their area of expertise and how
to approach and solve specific technical problems.
Improving Quality for Canadian LaboratoriesSince its creation in 2007, the cIQc program has provided
proficiency testing of both class I and class II IHC markers,
as well as ISH, for Canadian laboratories at a national level.
At present, 16 IHC runs (including 56 challenges) and two
ISH runs for HER2 have been completed. The results show
that greater attention to internal QC/QA measures for
Figure 1. Run 6. Garrattogram summarizes the overall performanceof participants. Ki-67 and CD20 testing was consistently optimal inalmost all laboratories. Bcl-2 and Bcl-6 testing was mostproblematic, with only 20% and 26% optimal results, respectively.CYD1 = cyclin D1; LAB = laboratory.
Figure 3. Run 9. There were no false-positive or false-negative results for human epidermal growth factor receptor 2 (HER2) in this cIQcchallenge with 40 tumour samples. FISH = fluorescence in situ hybridization.
HER2
Canadian Journal of P athology 27Spring 2012
COPETE ET AL.
clinical IHC and a regular comprehensive proficiency
program improve laboratory performance. As an example,
12 of 13 laboratories in run 1 produced at least some false-
negative results for the S-100 protein. With the use of our
follow-up testing protocols, there was significant
improvement; by run 10, only 4 of 25 laboratories produced
false-negative results. Similarly, results for intermediate
filament staining were improved in the second round of
testing for pancytokeratin and low-molecular-weight
cytokeratin.27 We have found that one of the major reasons
for poor results with frequently used class I markers is the
lack of known standardized calibrators; the currently used
positive controls and tissues employed for protocol
optimization are not standardized. The cIQc program
instructed participants to use liver and kidney for pankeratin
and low-molecular-weight keratin positive controls; using
these enabled laboratories to properly calibrate their
protocols and improve their results, irrespective of their
detection platforms. Such success bodes well for the future.
As the importance of class II markers continues to grow, the
demonstrated success of a national proficiency testing
program such as the cIQc program will instill confidence
that Canadian laboratories are issuing reliable results for
patient care that transcend provincial geographic
boundaries. Further developments are needed to provide
proficiency testing material at the national level for new class
II IHC tests, in addition to ISH and other molecular testing
techniques.
cIQc Program Test ResultsSixteen IHC runs have been completed since the creation of
the cIQc program. Run 5 has been described and run 8
Figure 4. Run 2 (in situ hybridization): human epidermal growth factor receptor 2 (HER2). Tumour samples with borderline results aroundclinically relevant cutoff points (i.e., difficult cases were used for the challenge). In protocols that use both HER2 gene probe and internalchromosome 17 centromeric probe (Cep17), the results are expressed as a ratio of HER2 signals to chromosome 17 signals or the numberof HER2 signals to nucleus for those test systems without an internal Cep17. The results were interpreted as positive if the HER2/Cep17ratio was >2.2 or if the HER2 gene copy number was >6; equivocal if the HER2/Cep17 ratio was 1.8–2.2 or the HER2 gene copy numberwas 4–6; and negative if the HER2/Cep17 ratio was <1.8 or the HER2 gene copy number was <4. Patients with a HER2 gene amplificationof ≥2 may be eligible for trastuzumab treatment. CISH = chromogenic in situ hybridization; FISH = fluorescence in situ hybridization;ISH = in situ hybridization; SISH = silver in situ hybridization. (No results are listed for core 2 from laboratories 108, 190, and 111. Site102 uses a single probe system and could not provide the HER2:Cep17 ratio.)
HER2:CEP17 RATIO
RAT
IO H
ER2:
CEP
17
Dako
pharmDX
Spring 201228 Canadian Journal of P athology
CANADIAN IMMUNOHISTOCHEMISTRY QUALITY CONTROL
partly described in other articles.23,27 Results of IHC runs 1
to 11 are summarized in Table 1, and some specific results of
three of the runs are illustrated in Figures 1 to 3. (Figure 2
can be viewed online at http://www.andrewjohn
publishing.com/CJP/CJPhome.html.) Results of ISH run 2
are illustrated in Figure 4.
AcknowledgementsCIQC is supported by a grant from the Canadian Partnership
Against Cancer. The College of Medicine of the University of
Saskatchewan provides a server and maintenance for the
www.ciqc.ca website. Companies sponsoring the website and
educational activities may have their logos placed at
www.ciqc.ca. Such companies have no influence on the
methods, results, or conclusions of cIQc operations and
publications. The authors have no commercial interests in
the subject of study. There is no conflict of interest with any
test or evaluation discussed in this article. All figures in this
article were previously published at www.ciqc.ca and are
included here with minor modifications.
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pathologist. Philadelphia: Saunders, 2005: 26–8.
2. Taylor CR, Shi S-R, Barr NJ, et al. Techniques of immunohistochemistry:
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3. Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical
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immunohistochemical testing of estrogen and progesterone receptors in breast
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tests. Am J Clin Pathol 2010;133:354–65.
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findings. Am J Transplant 2006;6:1829–40.
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mediated rejection of cardiac allografts by C4d staining of interstitial
capillaries. Exp Mol Pathol 2009;86:41–5. Epub 2008 Dec 9.
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European MCL Network. J Hematop 2009 Jun 16. Epub ahead of print.
13. Pettengell R, Linch D, Haemato-Oncology Task Force of the British Committee
for Standards in Haematology. Position paper on the therapeutic use of
rituximab in CD20-positive diffuse large B-cell non-Hodgkin's lymphoma.
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15. College of American Pathologists. Standard for laboratory accreditation.
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pathology. Adv Pathol Lab Med 1994;7:59–105.
17. Taylor CR. An exaltation of experts: concerted efforts in the standardization
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19. Taylor CR. The total test approach to standardization of
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20. Rhodes A, Jasani B, Balaton AJ, et al. Immunohistochemical demonstration
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21. Rhodes A, Jasani B, Anderson E, et al. Evaluation of HER-2/neu
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22. Vyberg M, Torlakovic E, Seidal T, et al. NordiQC immunohistochemical
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Association of Pathologists (CAP) National Standards
Committee/Immunohistochemistry. Appl Immunohistochem Mol Morphol
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24. Rüdiger T, Höfler H, Kreipe HH, et al. Quality assurance in
immunohistochemistry: results of an interlaboratory trial involving 172
pathologists. Am J Surg Pathol 2002;26:873–82.
25. Torlakovic EE, Naresh K, Kremer M, et al. Call for a European programme in
external quality assurance for bone marrow immunohistochemistry; report
of a European Bone Marrow Working Group pilot study. J Clin Pathol
2009;62:547–51.
26. Hsu F, Nielsen TO, Alkushi A, et al. Tissue microarrays are an effective quality
assurance tool for diagnostic immunohistochemistry. Mod Pathol
2002;15:1374–80.
27. Copete M, Garratt J, Gilks B, et al. Inappropriate calibration and optimization
of pan-keratin (pan-CK) and low molecular weight keratin (LMWCK)
immunohistochemistry (IHC) tests; Canadian Immunohistochemistry
Quality Control (CIQC) experience. J Clin Pathol 2011;64:220–5.
Canadian Journal of P athology 29Spring 2012
ORIGINAL ARTICLE
In Situ Mantle Cell Lymphoma: Case Report of a New Entity in Hematopathology
Mara Caragea, MD, and Kamilia Rizkalla, MD, FRCPC, are members of the Department of Pathology, London Health SciencesCentre, University of Western Ontario, in London, Ontario. Pat Allevato, MD, FRCPC, is a member of the Department of Pathol-ogy, Windsor Regional Hospital (metropolitan site), University of Western Ontario, in Windsor, Ontario. Caroline Hamm, MD,FRCPC, is a member of the Windsor Regional Cancer Centre, University of Western Ontario, in Windsor. Jie Xu, PhD, FCCMG,works at the Cytogenetics Laboratory, London Health Sciences Centre, University of Western Ontario, in London. Correspon-dence may be directed to [email protected] article was peer reviewed.Competing interests: None declared
Mara Caragea, MD, Pat Allevato, MD, FRCPC, Caroline Hamm, MD, FRCPC,Jie Xu, PhD, FCCMG, Kamilia Rizkalla, MD, FRCPC
ABSTRACTIn situ mantle cell lymphoma is an early lesion of lymphoid neoplasms in nodal tissues that
has been described recently. This entity is quite rare and can be difficult to diagnose during
routine histological examination. Clinical management of the disease can be problematic, and
extensive investigations are usually required to completely rule out an associated aggressive
lymphoma. This paper describes a case of in situ mantle cell lymphoma, reviews the associated
literature, and discusses implications for histopathological diagnosis, prognosis, and patient
care.
RÉSUMÉLe lymphome à cellules du manteau in situ est une forme initiale, rare, connue depuis peu et
qui peut être difficile à diagnostiquer à l’examen histologique usuel, de tumeurs lymphoïdes
des ganglions lymphatiques. La prise en charge de la maladie peut être problématique, et il est
habituellement nécessaire de procéder à une investigation approfondie pour écarter la possibilité
d’un lymphome d’évolution rapide. Nous présentons ici un cas de lymphome à cellules du
manteau in situ, nous passons en revue la documentation sur le sujet et nous abordons le
diagnostic histopathologique, le pronostic et la prise en charge du patient.
Case ReportA 68-year-old man had a 2-year history of intermittent groin
pain and enlarged right inguinal lymph nodes, the largest of
which measured 2.9 cm in maximum dimension. The result
of an initial biopsy was nondiagnostic, and the results of
blood chemistry analysis and a bone marrow biopsy were
unremarkable. A second lymph node biopsy was performed.
MethodsThe lymph node was fixed for 24 hours in 10% neutral
buffered formalin. Immunohistochemistry was performed
with the Ventana BenchMark XT automated slide
preparation system for CD3, CD5, CD10, CD20, CD23,
CD79a, BCL2, and BCL6, as well as a cyclin D1 immuno-
stain. An interphase fluorescence in situ hybridization
(FISH) study was performed, using the IGH (14q32)/
CCND1(11q13) dual-colour, dual-fusion translocation
probe set (Vysis) on paraffin-embedded tissue of the
patient’s lymph node, in parallel with a normal control.
ResultsLight microscopy revealed open sinuses containing
Spring 201230 Canadian Journal of P athology
IN SITU MANTLE CELL LYMPHOMA
histiocytes, and primary and secondary follicles were
present. Some histiocytes contained brown pigment with
features resembling dermatopathic lymphadenopathy. There
was no evidence of mantle zone expansion or frank
malignancy. An initial diagnosis of reactive
lymphadenopathy was entertained (Figure 1A).
Immunohistochemical studies indicated that the follicles
were CD20 and CD79a positive with CD23 expressed in the
dendritic meshwork. BCL2 was negative in the germinal
centres. CD5 and CD3 were strongly positive in the T
lymphocytes. However, weaker expression of CD5 was seen
in occasional clusters and ring-shaped collections of small
lymphocytes, which were also CD20 and cyclin D1 positive
(see Figure 1B–D).
IGH/CCND1 dual-fusion FISH signals were detected in 17
of 200 cells of the patient’s sample (see insert in Figure 1D)
but not in the 200 control cells. The diagnosis of in situ
mantle cell lymphoma was confirmed.
Follow-UpThe patient received six cycles of cyclophosphamide,
doxorubicin, oncovin, prednisone, and rituximab, followed
by maintenance treatment with rituximab. Computed
tomography scans of the chest, abdomen, and pelvis showed
no evidence of lymphadenopathy at the 2-year follow-up.
DiscussionMantle cell lymphoma (MCL) is an uncommon aggressive
Figure 1. A, Low power shows reactive lymph node with open sinuses and histiocytic infiltrate. B, CD20 highlights the primary andsecondary follicles; the arrows point to the CD5-positive cells. C, Identical fields showing the abnormal, weakly stained CD5-positivepopulation. D, Cyclin D1 immunostain highlights the ring-shaped collection of positive cells; inset shows two interphase cells displayingIGH/CCND1 dual fusions with orange/green (yellow) signals. FISH = fluorescence in situ hybridization.
A B
C D
Canadian Journal of P athology 31Spring 2012
CARAGEA ET AL.
B-cell neoplasm, making up 5–10% of all non-Hodgkin
lymphomas. It is characterized by t(11;14)(q13;q32), which
leads to the overexpression of cyclin D1. Very few cases of
the disease are indolent.1 In situ MCL is extremely rare, and
fewer than 10 cases have been reported in the English
literature to date.2–4 By definition, the disease is limited to
the primary follicles or the mantle zone of the secondary
follicles. The lymph node architecture is preserved with only
minimal or no expansion of the mantle zone. Consequently
the changes can be very subtle and can thus be overlooked
on hematoxylin and eosin–stained slides.
In situ MCL expresses CD5, CD20, CD79, Bcl2, and cyclin
D1. CD5-negative cases have been reported,4 but cyclin D1
positivity is required. Translocation 11;14 leading to the
overexpression of cyclin D1 is a prerequisite for diagnosis of
in situ and conventional MCL. The translocation may be
thought to take place within the follicle, where cyclin D1–
positive cells are seen; however, pre–germinal centre B-cell
origin cannot be excluded.5 Two reported cases were
associated with widespread disease2 whereas another case
arose in a background of follicular lymphoma.3 Roullet et
al. reported a case of coexisting mantle and follicular
lymphoma, each having an in situ component.4
A clinical suspicion of lymphoma warrants the use of a
battery of immunohistochemical stains on sections of
lymph node. This should include CD3, CD5, CD20, BCL2,
and cyclin D1, and pathologists should pay particular
attention to the intensity of the staining pattern. Our case
had very subtle morphological changes (compared with the
cases of in situ MCL that were described previously) and
had no expansion of the mantle zone. It is crucial to use CD5
along with CD3 as pan T-cell markers to identify in situ
MCL, and aberrant or weak expression of CD5 should be
followed with immunohistochemistry for cyclin D1.
In situ MCL is considered an early stage of conventional
MCL; it can be easily missed on histological examination,
given that the lymph node architecture is preserved. The
disease may progress into aggressive lymphoma and can also
coexist with a conventional MCL in nonsampled lymph
nodes. The prognosis of in situ MCL is not clear, given the
small number of published cases. The type of treatment and
the clinical outcome depend on the disease’s behaviour and
the presence or absence of conventional MCL.
References1. Nodit L, Bahler DW, Jacobs SA, et al. Indolent mantle cell lymphoma with
nodal involvement and mutated immunoglobulin heavy chain genes. Hum
Pathol 2003;34:1030–4.
2. Richard P, Vassallo J, Valmary S, et al. “In situ-like” mantle cell lymphoma: a
report of two cases. J Clin Pathol 2006;59:995–6.
3. Aqel N, Barker F, Patel K, Naresh KN. In-situ mantle cell lymphoma – a report
of two cases. Histopathology 2008;52:239–62.
4. Roullet MR, Martinez D, Ma L, et al, Coexisting follicular and mantle cell
lymphoma with each having an in situ component: a novel, curious, and
complex consultation case of coincidental, composite, colonizing lymphoma.
Am J Clin Pathol 2010;133:584–91.
5. Welzel N, Le T, Marculescu R, et al. Templated nucleotide addition and
immunoglobulin JH-gene utilization in t(11;14) junctions: implications for
the mechanism of translocation and the origin of mantle cell lymphoma.
Cancer Res 2001;61:1629–36.
5. McLellan B, McLeod R, Srigley J. Report of the Investigators of Surgical and
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13. Ford JC. Influence of a problem-based learning curriculum on the selection
of pathology as a career: evidence from the Canadian match of 1993–2004.
Hum Pathol 2005;36:600–4.
14. Lee L, Gomes MM, Ford JC. Pathology recruitment in Canada: does medical
school education in pathology influence medical student career choice? Can J
Pathol 2012;4(1):11–17.
15. Rich P. Bleak job outlook in some specialties sparking concern. Canadian
Medical Association News, 9 Sept 2011; http://www.cma.ca/
index.php/ci_id/203366/la_id/1.htm. Accessed 28 Sept 2011.
16. Hung T, Jarvis-Selinger S, Ford JC. Residency choices by graduating medical
students: why not pathology? Hum Pathol 2011;42:802–7.
Continued from page 10
Spring 201232 Canadian Journal of P athology
ORIGINAL ARTICLE
Neighbourly Collaboration to Improve Breast Predictive Factors Testing
in North America
M. Elizabeth H. Hammond, MD, FCAP, is a member of the Department of Pathology at the University of Utah School of Med-icine, in Salt Lake City, Utah. Wedad Hanna, MB, ChB, FRCPC, and Sharon Nofech-Mozes, MD, FRCPC, are members of theDepartment of Pathobiology and Laboratory Medicine at the University of Toronto, in Toronto, Ontario. Correspondence maybe directed to [email protected] article has been peer reviewed.Competing interests: Dr. Hammond has received consulting fees from Amirsys Inc. Dr. Hanna has received honoraria fromRoche Canada and Roche International.
M. Elizabeth H. Hammond, MD, FCAP, Wedad Hanna, MB, ChB, FRCPC, Sharon Nofech-Mozes, MD, FRCPC
ABSTRACTA Canadian version of the College of American Pathologists’ Advanced Practical Pathology
Program on testing for predictive factors in breast cancer is described. Guidelines for the testing
of HER2 and estrogen and progesterone receptors are summarized.
RÉSUMÉIl s’agit de la description d’une version canadienne du volet du dépistage des indicateurs
prévisionnels du cancer du sein du programme de pathologie pratique avancée du College of
American Pathologists. Nous résumons les lignes directrices sur le repérage de HER2 et des
récepteurs de l’œstrogène et de la progestérone.
Over the past decade, it has become obvious to
pathologists and oncologists that the accuracy of
breast predictive factors testing needs improvement. Reports
of central pathology review associated with three large
clinical trials indicate a 13–18% discrepancy in the diagnosis
of human epidermal growth factor receptor 2 (HER2)–
positive breast cancers, involving both methods commonly
in use (fluorescence in situ hybridization and
immunohistochemistry).1,2 Studies on the accuracy of
estrogen receptor (ER) and progesterone receptor (PgR)
testing in both the United States and Canada have shown
that there is a significant discrepancy between centrally
reviewed and locally diagnosed breast cancers in multiple
locations and practice settings.3–5 These observations are
based on data collected prior to the standardization of
testing processes. The issues of accuracy in these test types
are serious because treatments defined by the testing are
highly dependent on test results and are highly effective in
controlling these subtypes of cancer.6–10
To improve these tests for patients, the American Society of
Clinical Oncology (ASCO) and the College of American
Pathologists (CAP) convened international panels of experts
to produce guideline recommendations for HER2, ER, and
PgR testing.11,12 Recommendations involved changing the
specimen handling, testing, quality assurance, monitoring,
interpretation, and reporting of breast predictive factors
testing. Similar guidelines in Canada were also produced
with the creation of Cancer Care Ontario’s guideline on
hormone receptor testing in breast cancer and the updated
recommendations from the Canadian National Consensus
Meeting on HER2/neu testing in breast cancer.13,14 In an
effort to enhance laboratory practices that ensure
appropriate quality processes, the Canadian Association of
Pathologists/Association canadienne des pathologistes
(CAP/ACP) has developed recommendations for high-
complexity laboratory testing.15 Although these elements
were clearly described, it became obvious to the panellists
that there was a need for associated education and problem
Canadian Journal of P athology 33Spring 2012
HAMMOND ET AL.
Table 1. Breast Predictive Factors Testing (BPFT): Canada Program Agenda
Workshop Day 1: BPFT Interpretation and Patient Treatment ImplicationsPatient Perspective Patient perspective on the important role of the pathologist in Diana Rowden, Susan Komen Foundation (video) diagnosing breast cancer (via video from CAP 2009 annual meeting)ER/PgR and HER2 Test Interpretation Overview Overview of interpretation issues in ER/PR and HER2 testingDr. Wedad HannaChallenging Case Reviews Challenging BPFT cases with glass slidesDr. Wedad HannaPatient Treatment/Oncologist Perspective Patient treatment of ER+ and HER2+ breast cancer patients from the Dr. Philippe Bedard oncologist point of view and how breast cancer predictive factors guide treatment
decisionsTumour Board Discussion Four pre-planned cases from US workshop, with audience response questionsDrs. Wedad Hanna, Elizabeth Hammond, Philippe Bedard
Workshop Day 2: BPFT Risk Mitigation and Multidisciplinary Communications
Risk Mitigation Process Steps to identify, define, act upon, and monitor common risks of BPFTDr. Sharon Nofech-MozesValidation and Verification of Predictive and Validation and verification definedPrognostic Biomarkers by IHC Technical validationDr. Elizabeth Hammond • When to validate
• Sample sets and sample sizes for validationOngoing monitoringProficiency testingInterpretative competency assessment
Importance of Effective Communication Why communication is importantDr. Elizabeth Hammond Building and maintaining credibility as a pathologist on the patient care teamDialogue Skills Balancing advocacy and inquiry
Effective listeningManaging resistance in conversationInfluencing skills and strategies
Online Learning*BPFT self-study Overview of ASCO-CAP guidelines
Critical research findings in BPFTMolecular analysis research and findings
HER2 IHC test interpretation accuracy Interpretation criteria and scoring Integration of staining patterns with clinical and morphological findingsExclusion criteria and artifactsCase studies
HER2 FISH test interpretation accuracy Interpretation criteria and scoringCase studies
ER IHC test interpretation accuracy Interpretation criteria and scoringIntegration of staining patterns with clinical and morphological findingsCase studies
BPFT reporting ASCO-CAP guidelines for HER2 and ER reportingRemediating inconsistent data and providing a resolution in an integrated reportReport formatting best practices
ASCO = American Society of Clinical Oncology; CAP = College of American Pathologists; ER = estrogen receptor; FISH = fluorescence in situ hybridization; HER2 = human
epidermal growth factor receptor 2; IHC = immunohistochemistry; PgR = progesterone receptor.
*Self-assessment modules.
solving by pathologists and other laboratorians who
performed these tests. The CAP therefore embarked on an
educational program to improve pathologists’ ability to
implement the guideline’s recommendations. The Advanced
Practical Pathology Program was created and marketed to
pathologists. The program involves nine separate
educational activities; three are conducted live over a
weekend, and the remainder are conducted online.
Following the education activities, a cognitive examination
and practical performance assessment are administered. To
date, 100 pathologists have completed this program in the
United States. In the meantime, the CAP/ACP was also
seeking ways to improve the performance of breast
predictive factors testing in Canada. The desire of both
organizations was to create common educational
opportunities and a naturally collaborative environment.
Challenges to this goal were handled smoothly because both
CAP/ACP president Laurette Geldenhuys and CAP
president Stephen Bauer were interested in creating
programs with common elements that served the slightly
different needs of the two communities. A steering
committee was formed to create a version of the CAP’s
Advanced Practical Pathology Program that was tailored to
a Canadian audience. This article summarizes what was
learned from this activity, the program’s perceived benefits,
and plans for the future.
Table 2. Summary of HER2 and ER/PgR Guideline Elements According to ASCO-CAP Guidelines, 2007 to 2011
Specimen Handling Considerations for HER2 and for ER and PgR (Combined, 2011)Required to keep time to fixation short (ideally less than an hour from tissue removal to fixation)Required that three time points be recorded and available when the report is signed out
• Cold ischemic time: time tissue is removed (OR staff to record) to time formalin is added• Fixation time: time tissue is placed in fixative to time alcohol is introduced on the tissue processor (includes the time to grossing
and the time the cassettes in formalin are loaded on the tissue processor)Required tissue bisection through the tumour immediately before tissue is placed in neutral buffered formalin, especially if sample isobtained remotely Required fixation time: >6 to <72 hours in 10% neutral buffered formalin
Analytic Requirements for HER2 and ER/PgR TestingUse external controls with each batch, including weakly positive controls for each analyte. Review internal acinar elements on each case if they are present:
• Should be positive with ER and PgR• Should be negative for HER2
Stain control tissues as on slide controls with each test if possible.
Quality Assurance Requirements for HER2, ER, and PgR AssaysValidate all assays before offering the testing in the laboratory, using 40 known positive (including weakly positive) cases and 40known negative cases.Revalidate assay if any major modification in the assay procedure is done, using the same number of cases.Monitor each assay run with batch controls.Monitor laboratory performance by the following benchmarks:
• ER-negative rate range is 15–30%, depending on patient age distribution.• PgR rate is about 15% less than ER-positive rate, depending on patient age distribution.• HER2 3+ rate range is 11–14% in early breast cancer.
Engage in external proficiency testing for both assays.Engage in external or internal laboratory accreditation, depending on standards in region.Conduct careful review of any monitoring shifts, and plan and execute an appropriate intervention.Verify assay when minor modifications occur, using 20 known positive (including weakly positive) cases and 20 known negative cases.
Interpretation GuidelinesHER2 IHC category of 3+ refined to assure that 95% would be FISH amplified if tested; 30% of cells must show homogeneous darkcircumferential staining (chicken-wire pattern).Exercise caution in interpreting HER2 IHC when the following apply:
• Nonformalin fixatives (alcohol-based fixatives used for FNA)• Excessive delay from collection to fixation• Overfixed tissue –– Friday cases (>48–72 hours in formalin)• Inadequately fixed tissue (<6–8 hours NBF)• Excessive artifacts• Edge, crush, disruption, necrosis• Decalcified blocks• Overexpression in benign elements
HER2 in situ hybridization must be scored on area of tumour defined by the pathologist. If IHC is performed, FISH should be scored inthe area of highest IHC staining.Exercise caution in interpreting HER2 FISH when the following apply:
• Nonformalin fixatives• Excessive delay from collection to fixation• Inadequately fixed tissue (<6–8 hours NBF)• Decalcified blocks• Weak or variable signal intensity across areas of tumour
Exercise caution in interpreting ER and PgR IHC when the following apply:• Nonformalin fixatives• Excessive delay from collection to fixation• Inadequately fixed tissue (<6-8 hours NBF) or excessively fixed tissue• Decalcified blocks• Weak or negative staining of internal glandular elements
Spring 201234 Canadian Journal of P athology
BREAST PREDICTIVE FACTORS TESTING IN NORTH AMERICA
Canadian Journal of P athology 35Spring 2012
HAMMOND ET AL.
LogisticsThe format of the program in Canada was planned through
a series of conference calls, beginning with a call between
the course director (Dr. Elizabeth Hammond) and a staff
educator from the CAP (Christina Tushman) and the
president of the CAP/ACP. The content and format of the
existing US program were shared with the Canadians, and a
discussion was held about which aspects of the course would
be most useful in Canada. The Canadian association worked
on arranging for appropriate continuing professional
development (CPD) credits and proposed the faculty
members for the Canadian course. The workshop was led
by Dr. Wedad Hanna from Sunnybrook Health Sciences
Centre, lead author of the updated recommendations from
the Canadian National Consensus Meeting on HER2 testing
in breast cancer; Dr. Sharon Nofech-Mozes, also from
Sunnybrook Health Sciences Centre, lead author of Cancer
Care Ontario’s Guideline on Hormone Receptor Testing in
Breast Cancer; and Dr. Elizabeth Hammond from
Intermountain Healthcare, co-author of the ASCO-CAP
guidelines for ER/PgR and HER2 testing. Dr. Hanna invited
her colleagues in breast cancer pathology all over Canada to
attend the program. Thirty-three experienced breast
pathologists met in Toronto in October 2011 to participate
in the final program, which consisted of a 2-day workshop
and 10 hours of online learning. Table 1 outlines the
program’s agenda.
Key LearningsThe key elements of the predictive factor guidelines were
discussed throughout the course; selected items are
summarized in Table 2. Live sessions were highly interactive,
especially because the participants from across Canada have
focused practice on breast pathology and are actively
involved in breast predictive factors testing. Dr. Wedad
Hanna led a microscope session, using glass slides from
selected challenging cases to highlight problems and pitfalls
in the interpretation of ER/PR and HER2 by
immunohistochemistry (IHC) and bright-field in situ
hybridization technique. Issues related to quality assurance,
such as the evaluation of concordance with surrogate
histopathological parameters and controls, were discussed.
The importance of the integration of histopathology and
scoring by pathologists, the advantage of bright-field
methodology, and various issues related to HER2 scoring
(such as the use of absolute HER2 gene copy number) were
highlighted. These insights will be useful in drafting the next
version of the ASCO-CAP guideline for HER2 testing.
Participating in specific case discussions was oncologist
Philippe Bedard from the University of Toronto, who led a
spirited discussion of patient care issues, using actual
problematic breast cancer cases.
A session discussing potential problems in breast predictive
factors testing illustrated the wide variation in specimen
handling practices across Canada. Although most specimens
Table 3. Overall Evaluation Results for Breast Cancer Predictive Factors Program in Canada
Average Rating Question (Out of 5)Overall, how would you rate the BPFT workshop in terms of ...
providing practical and useful content? 4.72offering up-to-date and timely 4.72information on BPFT?the overall quality of the education? 4.56
BPFT = breast predictive factors testing.
Final Reporting Considerations for HER2, ER, and PgR TestingER/PR expression correlates with low-grade and well-differentiated histology.HER2 is more likely in high-grade and poorly differentiated tumours.Low-grade tumours typically are ER/PR positive and HER2 negative, including the following:
• Classic infiltrating lobular • Mucinous carcinoma• Tubular carcinoma
A test result that does not fit the histological picture suggests the following:• The assay may be invalid• Repeat testing may be indicated
ASCO = American Society of Clinical Oncology; CAP = College of American Pathologists; ER = estrogen receptor; FISH = fluorescence in situ hybridization; FNA = fine-needleaspiration; HER2 = human epidermal growth factor receptor 2; IHC = immunohistochemistry; NBF = neutral buffered formalin; OR = operating room; PgR = progesterone re-ceptor.
Spring 201236 Canadian Journal of P athology
BREAST PREDICTIVE FACTORS TESTING IN NORTH AMERICA
are eventually placed in neutral buffered formalin, the
process by which this fixation occurs is highly variable. In
remote regions, the tumour may be placed in fixative
without appropriate preparation, which produces less than
optimal fixation results. Few places in Canada currently
record the time of removal, time of immersion in fixative,
and fixation interval, all of which are critical to defining
what part of the specimen handling process is out of
compliance with the guideline. In Canada (as opposed to the
United States), the major fixation issue is prolonged fixation
rather than shortened fixation time. Specimens commonly
are fixed for at least 24 hours, but in 16% of the practices
represented by the participants, samples are fixed for longer
than 72 hours. Most breast predictive factors testing is done
on resection specimens, for which issues of specimen
handling are more acute. Participants debated the value of
switching to needle core biopsies for these tests (a strategy
popular in the United States) in order to avoid specimen
handling issues. Concerns were raised about the financial
impact of retesting resection specimens in situations where
a repeat test might be needed.
Another topic of discussion concerned resource availability
in different provinces and highlighted local variations in
practice. Many provinces have a shortage of pathologists and
associated staff, leading to delays in processing and
reporting. Limited staff also makes it difficult to gather
information about the quality of practices, so analysis of the
issues is made more difficult. For example, 38% of
participants attending this workshop did not know how
much time passed before breast samples were fixed in their
practice settings. Dr. Hanna led discussions about these
issues, and participants expressed a strong desire to work
together and share their successful strategies.
During the sessions, it was obvious that participants had a
high level of expertise and understanding of guideline
elements and problematic issues in predictive factor testing.
The discussions on risk mitigation led by Dr. Nofech-Mozes
highlighted the importance of periodic trend analysis of
results per site and per reader. Methods of resolving various
issues were discussed. It became clear that pathologists need
to assume a leadership role in their community of practice
beyond the pathology department and encourage surgeons,
operating-room nurses, and laboratory information system
analysts to record ischemic and fixation times. Another
session focused on communication strategies to help
pathologists in their discussions with clinical colleagues and
patients. Participants felt it would be highly useful to have
sessions in which both pathologists and technical staff
participated in order to define and resolve handling and
technical issues.
Future PlansParticipants felt the course was very valuable and rated the
overall quality of the program as excellent (Table 3). There
was a strong interest among participants to have
mechanisms for further collaboration on issues and best
practices regarding these tests. The faculty agreed to
implement a process for ongoing communication about
breast predictive factors testing through an online discussion
group. Future educational collaborations between the CAP
and the CAP/ACP are being discussed. The CAP/ACP is
already collaborating with the CAP on the new CAP
Learning Portal, which provides tools and resources for the
professional development of pathologists. Additionally, the
program’s online learning materials related to ER test
interpretation, HER2 test interpretation, and the ASCO-
CAP guidelines for HER2 and ER/PgR testing are now
available and can be accessed through the Learning Portal
at www.cap.org.
The collaboration that started with breast predictive factors
testing paves the way for future opportunities for
pathologists across North America to share information and
develop a common understanding of new tests that will
predict therapeutic responses in many tumour sites. As
molecular targeted therapy becomes more common, such
collaborations will benefit patients throughout our
continent.
References1. Paik S, Bryant J, Tan-Chiu E, et al. Real-world performance of HER2 testing –
– National Surgical Adjuvant Breast and Bowel Project experience. J Natl
Cancer Inst 2002;94:852–4.
2. Perez EA, Suman VJ, Davidson NE, et al. HER2 testing by local, central, and
reference laboratories in specimens from the North Central Cancer Treatment
Group N9831 Intergroup adjuvant trial. J Clin Oncol 2006;24:3032–8.
3. Badve SS, Baehner FL, Gray RP, et al. Estrogen- and progesterone-receptor
status in ECOG 2197: comparison of immunohistochemistry by local and
central laboratories and quantitative reverse transcription polymerase chain
reaction by central laboratory. J Clin Oncol 2008;26:2473–81.
4. Regan MM, Viale G, Mastropasqua MG, et al. Re-evaluating adjuvant breast
cancer trials: assessing hormone receptor status by immunohistochemical
versus extraction assays. J Natl Cancer Inst 2006;98:1571.
5. Terry J, Torlakovic E, Garratt J, et al. Implementation of a Canadian External
Quality Assurance Program for Breast Cancer Biomarkers. Appl
Immunohistochem Mol Morphol 2009;17:375–82.
6. Bezwoda WR, Esser JD, Dansey R, et al. The value of estrogen and progesterone
receptor determinations in advanced breast cancer. Estrogen receptor level but
not progesterone receptor level correlates with response to tamoxifen. Cancer
1991;68:867.
7. Bartlett JM, Brookes CL, Robson T, et al. Estrogen receptor and progesterone
receptor as predictive biomarkers of response to endocrine therapy: a
prospectively powered pathology study in the
Tamoxifen and Exemestane Adjuvant
Multinational Trial. J Clin Oncol 2011;29:1531.
8. Pritchard KI, Shepherd LE, O’Malley FP, et al.
HER2 and responsiveness of breast cancer
to adjuvant chemotherapy. N Engl J Med
2006;354:2103–11.
9. Romond EH, Perez EA, Bryant J, et al.
Trastuzumab plus adjuvant chemotherapy for
operable HER2-positive breast cancer. N Engl
J Med 2005;353:1673–84.
10. Piccart-Gebhart MJ, Procter M, Leyland-Jones
B, et al: Trastuzumab after adjuvant
chemotherapy in HER2-positive breast cancer.
N Engl J Med 2005;353:1659–72.
11. Wolff AC, Hammond ME, Schwartz JN, et al.
American Society of Clinical Oncology/
College of American Pathologists guideline
recommendations for human epidermal
growth factor receptor 2 testing in breast
cancer. Arch Pathol Lab Med 2007;131:18.
12. Hammond ME, Hayes DF, Dowsett M, et al.
American Society of Clinical Oncology/
College of American Pathologists guideline
recommendations for immunohistochemical
testing of estrogen and progesterone receptors
in breast cancer (unabridged version). Arch
Pathol Lab Med 2010;134:e48.13.
13. Nofech-Mozes S, Vella E, Dhesy-Thind B,
Hanna W. Guideline on hormone receptor
testing in breast cancer. Program in evidence-
based care; Evidence-Based Series #22-1.
Cancer Care Ontario; http://www.cancercare.on.ca/
common/pages/UserFile.aspx?fileId=98566.
Accessed April 8, 2011.
14. Hanna W, O’Malley FP, Barnes P. Updated recommendations from the
Canadian National Consensus Meeting on HER2/neu testing in breast cancer.
Curr Oncol 2007;14:149–53.
15. Torlakovic EE, Riddell R, Banerjee D, et al. Canadian Association of
Pathologists – Association canadienne des pathologistes National Standards
Committee/Immunohistochemistry: best practice recommendations for
standardization of immunohistochemistry tests. Am J Clin Pathol
2010;133:354–65.
Canadian Journal of P athology 37Spring 2012
HAMMOND ET AL.
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Spring 201238 Canadian Journal of P athology
BOOK REVIEW
Manual of Pediatric Hematology and Oncology, Fifth Edition
This comprehensive manual provides a well-organized, highly readable
summary of the broad spectrum of hematologic and oncologic diseases
that afflict pediatric patients. It begins with a useful summary of anemia and
proceeds through more detailed discussions of specific types of anemia,
disorders of white blood cells and platelets, hemostatic and thrombotic
disorders, and hematologic and nonhematologic malignancies. It concludes
with chapters on the oncologic management and psychosocial impact of
pediatric cancer.
The book’s major strength is in its detail; each chapter contains many helpful
lists, tables, and diagrams to summarize key concerns such as the causes of
neutropenia or the specific diagnostic criteria for antiphospholipid syndrome.
Information is up to date (many references are as recent as 2009), and the
index is excellent.
The major weakness of this manual – from a hematopathologist’s perspective
– is that the book is so clearly targeted at clinicians. There is copious detail
devoted to treatment; unfortunately, less attention is paid to diagnosis. For
example, the details of diagnosis in congenital dyserythropoietic anemia are
relegated to a very brief summary in one table. Many of the manual’s 38
authors would be featured in a “who’s who” of pediatric hematology and
oncology, but there appears to be only a single pathologist among them.
This book would likely be a welcome addition to the libraries of clinicians
and trainees in the field of pediatric hematology and oncology or to those of
general pediatricians with a special interest in the field. For pathologists
looking for guidance in making diagnostic decisions, it may not be the best
fit.
Jason C. Ford, MD, FRCPCDivision of HematopathologyBC Children’s HospitalVancouver, British Columbia
Philip Lanzkowsky, editorAcademic Press, 2011ISBN-13: 978-01237515461,058 pages
Thank You to ReviewersTHE CJP EDITORIAL BOARD WISHES TO ACKNOWLEDGE THE FOLLOWING PATHOLOGISTS
AND SCIENTISTS WHO REVIEWED ARTICLES SUBMITTED TO THE JOURNAL IN 2011:
C. ArmstrongP. BarnesA. BoagK. ChorneykoB. Dickson
L. DiFrancescoH. C. EttlerJ. FernandesJ. GomezC. Howlett
W. HuangM. G. JosephD. LeBrunS. J. RaphaelC. Ross
H. SappB. SheridanM. TrotterN. van der Westhuizen
PARTNERING WITHGAMMA-DYNACAREALLOWS YOU TO FOCUSON WHAT YOU DO BEST
Leadership
ConfidenceConvenienceValue
Make our laboratories an extension of your hospital; our pathologists a part of your team.
www.gamma-dynacare.com
As your partner, we bring you:
For more information: Phone: 800.668.2714Email: hospital [email protected]