DEPARTMENT OF PATHOLOGY AND
LABORATORY MEDICINE
DÉPARTEMENT DE PATHOLOGIE ET
DE MÉDECINE DE LABORATOIRE
JOURNÉE ANNUELLE
DE LA RECHERCHE
ANNUAL RESEARCH DAY
2015
ANNUAL RESEARCH DAY PROGRAM
DEPARTMENT OF PATHOLOGY AND
LABORATORY MEDICINE
UNIVERSITY OF OTTAWA
Friday, May 15th, 2015
OHRI SEMINAR ROOM
Critical Care Wing Building Room 5225
TOH – GENERAL CAMPUS
9:00 – 9:10
COFFEE
9:10 – 9:15
WELCOME
9:15 – 9:30
MYELOID, LYMPHOID, BOTH, OR NEITHER? THE
DIAGNOSTIC CHALLENGE OF ACUTE
UNDIFFERENTIATED LEUKEMIA
Tariq M. Roshan, Manisha Lamba, A. Rajput, Luke Shier
9:30 – 9:45
DIFFERENTIATED SQUAMOUS INTRAEPITHELIAL
NEOPLASIA ASSOCIATED WITH SQUAMOUS CELL
CARCINOMA OF THE ANAL CANAL
Jason K. Wasserman, Christopher G. Ball, Justin Bateman,
Fawaz Halwani, E. Celia Marginean, Kien T. Mai
9:45 – 10:00
PREDICTING THE HISTOLOGIC SUBTYPE OF LUNG
ADENOCARCINOMAS USING CYTOLOGIC SPECIMENS
Jordan Sim, Nina Chang, Marcio Gomes, Chi Lai, Harman
Sekhon
10:00 – 10:15
FLAT UROTHELIAL NEOPLASIA EXHIBITING DIFFUSE
IMMUNOREACTIVITY FOR CD44 AND CYTOKERATIN 5
(UROTHELIAL STEM CELL/BASAL CELL MARKERS): A
VARIANT OF INTRA-UROTHELIAL NEOPLASIA
COMMONLY ASSOCIATED WITH MUSCLE-INVASIVE
UROTHELIAL CARCINOMA
Aurelia Busca, Trevor Flood, Eric C. Belanger, Kien T. Mai
10:15 – 10:30
COFFEE BREAK
10:30 – 10:45
SECONDARY
CORNEAL
AMYLOIDOSIS
FOLLOWING
PERFORATING
CORNEAL
TRAUMA: A SERIES OF 5 CASES AND
REVIEW OF THE LITERATURE
Solin Saleh, Seymour Brownstein, Joshua S.
Manusow, André Jastrzebski, Kay Lam, Joseph
W. Sassani, George Mintsioulis, Steven Gilberg
10:45-11:00
ESTIMATING RECURRENCE IN LOBULAR BREAST
CANCER USING MAGEE EQUATIONS
Nina Chang, Amelia Parrott, Angel Arnaout, Mark Clemons,
Susan J Robertson
11:00 – 11:15
CLEAR
CELL
UROTHELIAL
CELL
CARCINOMA: A STUDY OF EIGHT CASES
Christopher G. Ball, Justin Bateman, Trevor A.
Flood, Eric C. Belanger, Kien T. Mai
Department of Anatomical Pathology,
The Ottawa Hospital and Ottawa University,
Ottawa, Ontario, Canada
11:15 – 11:30
DEVELOPMENT OF A COMPREHENSIVE REGISTRY OF
GASTROINTESTINAL STROMAL TUMOUR (GIST)
PATIENTS AT A SINGLE CANADIAN INSTITUTION
Jason K. Wasserman & E. Celia Marginean
11:30 – 13:30
LUNCH AND POSTER VIEWING
PALM Rooms A & B (CCW Room 4137)
13:30 – 14:30
Keynote lecture
Dr. Simon Chiosea
Associate Professor of Pathology
University of Pittsburg Medical Center
Presbyterian Hospital
Pittsburg, PA
Title: “Update on Salivary Duct Carcinoma”
14:30 – 14:45
VALUE OF HISTOPATHOLOGY FOR PREDICTING THE
POSTOPERATIVE COMPLICATIONS OF ILEO-ANAL
ANASTOMOSIS (J-POUCH) PROCEDURE IN CHILDREN
WITH REFRACTORY ULCERATIVE COLITIS
Soufiane El Hallani, Joseph de Nanassy, James Young Lee,
Emily Chan, Juan Bass, David Mack, Ahmed Nasr, Dina El
Demellawy
14:45 – 15:00
IMMUNOHISTOCHEMISTRY IN THE DIAGNOSIS OF
MUCINOUS NEOPLASMS INVOLVING THE OVARY: THE
ADDED VALUE OF SATB2 AND BIOMARKER
DISCOVERY THROUGH PROTEIN EXPRESSION
DATABASE MINING
Sarah Strickland, Jason K. Wasserman, Ana Giassi, Bojana
Djordjevic, Carlos Parra-Herran
15:00 – 15:15
EVALUATION OF QUANTITATIVE TISSUE PATHOLOGY
IN THE ASSESSMENT OF BARRETT’S ESOPHAGUS
ASSOCIATED DYSPLASIA
Soufiane El Hallani, Martial Guillaud, Jakoda Korbelik, E.
Celia Marginean
15:15 – 15:45
COFFEE BREAK
15:45 – 16:00
ANNOUNCEMENT OF PRIZE WINNERS AND
CONCLUSION
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18:00 – 21:00
Nadia Mikhael Award for Best Paper presented
by a Junior Resident
2nd Best paper by a Junior Resident
Virbala Acharya Award for Best Presentation
by a Senior Resident or Fellow
2nd Best paper by a Senior Resident or Fellow
Best Poster Presentation by a Graduate
Student
2nd Best Poster Presentation by a Graduate
Student
Best Poster Presentation by a Resident
2nd Best Poster Presentation by a Resident
Dr. M. Orizaga Award for Best Teacher
DINNER AT MILESTONES
325 Marche Way (at Exhibition Way)
Ottawa, ON K1S 5J3
(613)-695-1669
POSTERS
1. MECHANISMS
OF
ENHANCER-MEDIATED
GENE
EXPRESSION
DURING
EARLY
MYOGENIC
DIFFERENTIATION
Katherine Dixon, Munerah Hamed, Hamood Al-Sudais, Qiao Li
Department of Pathology and Experimental Medicine,
Department of Cellular and Molecular Medicine, University of
Ottawa
2. MICRORNA SIGNATURE IN THE PREVENTION OF SKIN
CANCER STEM CELLS BY POLYPHENOL-ENRICHED
BLUEBERRY PREPARATION (PEBP)
Nawal Alsadi1, Jean-François Mallet1, Emilie Graham2 and
Chantal Matar1,2
1. Cellular and Molecular Medicine, Faculty of medicine,
University of Ottawa, Ottawa, Canada 2. Nutrition Sciences,
Faculty of Health Sciences, University of Ottawa, Ottawa,
Canada
3. MACROPHAGE FUNCTION MEDIATED THROUGH A MIR-92A
MECHANISM BY A COLLAGEN MATRIX
Zachary Lister, Helene Chiarella-Redfern, A. Chiu, Nick J. R. Blackburn,
Marc Ruel, M. Brand, Katey J. Rayner, Erik J. Suuronen
4. DEVELOPMENT OF HUMAN RECOMBINANT COLLAGEN TYPE I AND
TYPE III INJECTABLE HYDROGELS FOR CARDIAC THERAPY
James E. Podrebarac, Marc Ruel, Erik J. Suuronen, Emilio I. Alarcon
5. A NOVEL ROLE FOR SLK IN TGFΒ-INDUCED EPITHELIAL-TOMESENCHYMAL TRANSITION
Jillian Conway, Khalid Al-Zahrani, Luc Sabourin
6. ENDOTHELIAL CELL REACTION IN VASCULAR INVASION IN WELL
DIFFERENTIATED THYROID CARCINOMA IS MORE COMMONLY
ASSOCIATED WITH LOCO-REGIONAL RECURRENCE THAN
DISTANT METASTASIS
Christopher G. Ball, Bernhard Olberg, Chi K. Lai, Bibiana Purgina, Kien T.
Mai
7. PERINEURAL INVASION (PNI) AS A RISK FACTOR FOR LOCAL
RECURRENCE (LR) IN EARLY SQUAMOUS CELL CARCINOMA OF
THE ORAL TONGUE
Aurelia Busca, Chi Lai, Susan J. Robertson, Simon Chiosea, Raja
Seethala, Lester D. R. Thompson, Margaret S. Brandwein-Gensler,
Jessica H. Maxwell, Umamaheswar Duvvuri, Seungwon Kim, Jonas T.
Johnson, Robert L. Ferris, E. Celia Marginean, Bibianna Purgina
8. CANMEDS SPECIFIC COMPETENCY MILESTONES IMPLEMENTED IN
SURGICAL PATHOLOGY TRAINING IN ANATOMICAL PATHOLOGY
RESIDENCY TRAINING AT THE UNIVERSITY OF OTTAWA
Aurelia Busca, Sarah Strickland, Shahidul Islam
9. THE ACCELERATED CLINICAL COURSE OF PANCREATIC
NEUROENDOCRINE TUMORS: AN ANALYSIS OF CLINICAL,
IMAGING AND PATHOLOGIC PROGNOSTIC FACTORS
Nina Chang, Wayne S. Kendal, Wael Shabana, Alfredo Walker, Fady K
Balaa, Christine Nyiraneza, Yvonne Dawkins, Avijit Chatterjee, Rachel
Goodwin, Timothy Asmis, Terence N. Moyana
10. DIRECT AUTOFLUORESCENCE VISUALIZATION TO GUIDE KIDNEY
SPECIMEN GROSSING: A PROOF-OF-CONCEPT
Soufiane El Hallani, Trevor Flood, Previn Gulavita, Eric Belanger
11. PREDICTORS OF TUMOR UPGRADING OR UPSTAGING AFTER
RADICAL PROSTATECTOMY IN PATIENTS WITH GLEASON SCORE
3+4=7 PROSTATE CANCER (PCA) AT TRANSRECTAL ULTRASOUND
(TRUS) GUIDED NEEDLE BIOPSY
Soufiane El Hallani , Trevor Flood, Kien T. Mai, Eric Belanger, Nicola
Schieda
12. UNSUSPECTED AND MISDIAGNOSED CILIARY BODY AND
CHOROIDAL MELANOMA AFTER ENUCLEATION AND
EVISCERATION: REVIEW OF CASES IN THE OTTAWAGATINEAU REGION FROM 1996-2012
Saleh, Solin1, 2; Brownstein, Seymour1, 2; Jastrzebski, André1,
2; Jordan, David1; Gilberg, Steven1; Leonard, Brian1; Hurley,
Bernard1
1. Ophthalmology, University of Ottawa, Ottawa, ON, Canada.
2. Pathology, University of Ottawa, Ottawa, ON, Canada
13. THERAPEUTIC PLASMA EXCHANGE WITH OR WITHOUT RITUXIMAB
TO TREAT THROMBOTIC THROMBOCYTOPENIC PURPURA:
SIGNIFICANTLY DIFFERENT TREATMENT EFFICIENCIES
Vito Sanci, Elianna Saidenberg, Alan Tinmouth
14. GATA-3 EXPRESSION IS NOT ASSOCIATED WITH COMPLETE
PATHOLOGICAL RESPONSE IN TRIPLE NEGATIVE BREAST
PATIENTS TREATED WITH NEOADJUVANT CHEMOTHERAPY
Jason K. Wasserman, Phillip A. Williams, Shahidul Islam, Susan J.
Robertson
15. LABORATORY REQUISITION FORMS OFTEN LACK CRITICAL
INFORMATION: A QUALITY IMPROVEMENT INITIATIVE TO
ENHANCE COMMUNICATION AND PATIENT SAFETY AT THE
OTTAWA HOSPITAL
Jason K. Wasserman, Iris Teo, Darren Tse, John P. Veinot, Bibianna
Purgina
16. MAPPING OF UROTHELIAL CARCINOMA IN RADICAL CYSTECTOMY
SPECIMENS
Kien T Mai, Muhanad Hassan,Trevor Flood, Eric C Belanger
WELCOME
MYELOID, LYMPHOID, BOTH, OR NEITHER? THE DIAGNOSTIC
CHALLENGE OF ACUTE UNDIFFERENTIATED LEUKEMIA.
Roshan Tariq M., Lamba M., Rajput A. and Shier L.
Department of Pathology and Laboratory Medicine, Eastern Ontario
Regional Laboratory Association & The Ottawa Hospital, Faculty of
Medicine, University of Ottawa.
Introduction: Acute undifferentiated leukemia (AUL) is a rare ambiguous
lineage leukemia lacking sufficient lineage-specific markers to be
characterized as myeloid or lymphoid.
Findings: A 51-year-old male presented with pneumonia, weight loss, and
diffuse lymphadenopathy. Bone marrow examination showed a
hypercellular marrow with 60% blasts with rare granulation but no Auer
rods. Immunophenotyping showed strong expression of CD2, CD7, and
CD33, with weak expression of CD4, CD56, CD123 and HLA-DR. Blasts
were negative for all other myelomonocytic (MPO, CD11c, CD14, CD15),
erythroid (CD235a), megakaryoblastic (cytoplasmic CD41/CD61), B-cell
(CD10, CD19, CD20, cytoplasmic CD22 and CD79a), and T-cell (surface
and cytoplasmic CD3, CD5, CD8) markers. The phenotype was too
ambiguous for lineage assignment. Weak expression of CD4, CD56, and
CD123 did not support diagnosis of plasmacytoid dendritic cell leukemia.
Thus, the case was classified as AUL. Molecular studies were negative for
t(9;22), t(8;21), t(15;17), t(16;16), and TCR gene rearrangement.
Cytogenetic studies showed a complex karyotype with deletion of 5q,
which has been associated with AUL. Lymph node biopsy showed sheets
of blasts with similar ambiguous phenotype. Blasts were positive for CD4,
CD7, CD56, and CD99. TdT was positive by immunohistochemistry. Blasts
were negative for CD1a, CD3, CD10, CD15, CD30, CD34, PAX5, MUM1,
and MPO.
Conclusion: Because AUL is associated with poor outcomes, recognition
is critical to tailor therapy appropriately. Differentiation from myeloid or
lymphoblastic leukemia with aberrancy is not always clear. Because our
case expressed only CD33 as a myeloid marker and only CD2 and CD7 at
T-cell markers without cytoplasmic CD3, the leukemia could not be
confidently classified as either myeloid or T-lymphoblastic. AUL must be
differentiated from minimally differentiated myeloid leukemia lacking MPO,
which will typically expresses more than a single myeloid marker.
Comprehensive immunophenotyping is required to exclude erythroid,
megakaryoblastic, basophilic, NK-cell, and dendritic cell lineages.
Key words: Undifferentiated leukemia, ambiguous lineage.
DIFFERENTIATED SQUAMOUS INTRAEPITHELIAL NEOPLASIA
ASSOCIATED WITH SQUAMOUS CELL CARCINOMA OF THE ANAL
CANAL
Jason K. Wasserman, Christopher G. Ball, Justin Bateman, Fawaz
Halwani, E. Celia Marginean, Kien T. Mai
University of Ottawa, Pathology & Laboratory Medicine, Ottawa, Ontario,
Canada
Background: Differentiated squamous intraepithelial neoplasia (DSIN)
with atypical cells limited to the basal/parabasal layers has been described
in several sites including the oral cavity and the vulva, however, it has not
been studied in the anal canal.
Methods: Eighty-six consecutive cases of squamous cell carcinoma (SCC)
of the anal canal from the database of the Department of Anatomical
Pathology at the Ottawa Hospital were included in this study. Routine H&E
stained slides from each case were reviewed for features consistent with
DSIN.
Results: Of the 86 cases of SCC, 13 cases (15%) exhibited features
consistent with DSIN; 10 were 'pure' DSIN and 3 were 'mixed' DSIN and
squamous intraepithelial lesion (SIL). DSIN was characterized by atypical
keratinocytes limited to the basal/parabasal layers, acanthosis, and a
'cobble-stone' appearance. In specimens with pure DSIN, the surface was
flat in 8 cases. DSIN was identified below the anal transition zone (ATZ) in
8 cases, with extension to the ATZ in 3 cases and located only in the ATZ
in 2 cases. In 6 cases, the DSIN was extensive, associated with deeply
invasive SCC requiring radical surgical resection. The remaining 7 cases
were
successfully
treated
with
chemo-radiotherapy.
Immunohistochemically, all the epithelia demonstrating changes consistent
with DSIN were negative for p16 reactivity while the invasive component
was positive for p16 reactivity in 9 cases.
Conclusions: We describe for the first time the features of DSIN in the
anal canal associated with invasive SCC. The atypical cells were limited to
the basal/parabasal layers and were consistently p16 negative; a fact that
may account for the negative diagnoses by anal cytopathology and a poor
cytological/surgical correlation. The recognition of anal DSIN is important
to in order to avoid under-diagnosis in superficial biopsies.
PREDICTING
THE
HISTOLOGIC
SUBTYPE
ADENOCARCINOMA USING CYTOLOGIC SPECIMENS
OF
LUNG
Jordan Sim MD1, Nina Chang MD1, Marcio Gomes MD FRCPC1, Harman
Sekhon MD FRCPC1
1University of Ottawa, Pathology and Laboratory Medicine, Ottawa,
Ontario, Canada
Background: The 2011 IASLC/ATS/ERS guidelines on classification of
lung adenocarcinoma (ADC) have identified histologic grades which
correlate with tumour biological behaviour and prognosis: low (nonmucinous lepidic), intermediate (acinar and papillary) and high
(micropapillary and solid). While histologic grading is assessed on resected
lung tumours, subtyping ADCs on cytology may benefit patient
management, by selecting for early stage low grade ADCs that may be
followed rather than resected and prioritizing high grade ADCs for
resection in cases of synchronous tumours. Furthermore, in nonresectable/inoperable cases, subtyping may offer prognostic information
and allow the identification of histologic features associated with molecular
markers. Here we identify criteria that may allow the differentiation of the
histologic subtypes of lung ADC on cytologic specimens.
Design: Lung ADCs from 2012-2014 with cytologic specimens and
subsequent resections were reviewed and 104 cases were identified for
inclusion. Mucinous ADCs and those with pleomorphic and neuroendocrine
components were excluded. The cytologic smears (CS) and cell blocks
(CB) from 104 cases were reviewed by a pathologist and two trainees who
were blinded to final histologic subtype as an initial step to identify useful
histologic criteria. Criteria were correlated with histologic subtypes in
resection specimens using the Spearman correlation coefficient (ρ). The
presence of any high grade component >20% (alone or in combination)
was used as a cut-off for “high-grade patterns.” Diagnostic algorithms were
generated using the Classify-Tree function in SPSS v20.
Results: Individual patterns which correlated with high grade patterns on
smears included cytoplasmic inflammatory cells (ρ = 0.300, p = 0.002),
nuclear membrane irregularities (ρ = 0.320, p = 0.002), nuclear atypia (ρ =
0.511, p >0.001) and overlapping nuclei (ρ = 0.425, p < 0.001).
Individually, none of these had a sufficiently high sensitivity or specificity,
so a diagnostic algorithm was made to differentiate high grade from low
grade patterns of lung adenocarcinoma. The individual criteria within this
algorithm were cellularity, nuclear atypia, cribiform glands, nuclear
inclusions, and strips of cells. These criteria had a combined sensitivity of
80.4% and sensitivity of 82.5% for predicting high grade patterns of lung
adenocarcinoma.
Conclusion: We report for the first time a diagnostic algorithm which
allows cytologic criteria to be used to differentiate HGP of ADC on
cytologic specimens. The ability to characterize a patient’s disease may
provide prognostic and predictive information early in the disease course
and in unresectable cases. Although individual criteria do not have
adequate sensitivity or specificity to exclude HGP, good sensitivity and
specificity are achieved by using the cytologic criteria in combination in the
form of a diagnostic algorithm.
FLAT
UROTHELIAL
NEOPLASIA
EXHIBITING
DIFFUSE
IMMUNOREACTIVITY FOR CD44 AND CYTOKERATIN 5 (UROTHELIAL
STEM CELL/BASAL CELL MARKERS): A VARIANT OF INTRAUROTHELIAL NEOPLASIA COMMONLY
ASSOCIATED WITH
MUSCLE-INVASIVE UROTHELIAL CARCINOMA
Aurelia Busca, Kien T. Mai, Trevor Flood, Eric C. Belanger
The Ottawa Hospital and University of Ottawa, Pathology and Laboratory
Medicine, Ottawa, ON, Canada
Background: Immunoreactivity for CD44 and cytokeratin 5 (CK5)
(urothelial stem/basal cell markers) are documented as being
decreased/negative in the common type of intra-urothelial neoplasia (IUN)
and increased to full/nearly full thickness in reactive urothelium.
Methods: Consecutive cases of non-papillary urothelial carcinoma (UC)
were submitted for immunostaining for CD44, CK5 and CK20.
Immunostaining for CK5/CD44 was scored as high for staining of more
than 25% thickness of the urothelium and low for lesser immunoreactivity.
Results: 109 consecutive cases were grouped into: urothelial carcinoma in
situ (CIS) (n=11), pT1 (n=14) and pT2-4 (n=84) with surface urothelium
available for study. Forty-four cases including CIS (n=9), pT1 (n=12) and
pT2-4 (n=23) showed IUN with low/negative CD44/CK5 reactivity and
strong CK20 reactivity in 40 cases. Sixty-two cases including CIS (n=2),
pT1 (n=2) and pT2-4 (n=58) showed extensive IUN exhibiting a high
CD44/CK5 reactivity and reactive CK20 in only 30 cases. IUN lesions with
high CD44/CK5 reactivity scores were associated with urothelial dysplasia
or CIS and were rarely preceded by a history of papillary UC. Most
invasive UC associated with IUN with high CD44/CK5 reactivity also
exhibited extensive CD44/CK5 reactivity. The remaining 3 cases of nonpapillary UC showed only reactive urothelium. Of interest, 4 cases with IUN
showed negative CD44/CK5/CK20 reactivity.
Conclusions: Existence of CD44/CK5-immunoreactive (or basal-like) flat
IUN is consistent with the recent distinction of basal and luminal subtypes
of UC. This type of IUN is often associated with UC with progression to
high stage disease without a history of recurrent papillary UC.
BREAK
AND
POSTER
VIEWING
(PALM ROOMCCW Room 4137)
SECONDARY CORNEAL AMYLOIDOSIS FOLLOWING PERFORATING
CORNEAL TRAUMA: A SERIES OF 5 CASES AND REVIEW OF THE
LITERATURE
Solin Saleh, Seymour Brownstein, Joshua S. Manusow, André
Jastrzebski, Kay Lam, Joseph W. Sassani, George Mintsioulis, Steven
Gilberg
Purpose: Corneal amyloidosis is an infrequent condition that occurs when
normally soluble autologous proteins are deposited as abnormal insoluble
fibrils. Amyloidosis may be classified into two main groups, primary and
secondary, each of which is further divided into systemic or localized.
Secondary localized amyloidosis is uncommon and secondary amyloid
deposition following corneal trauma and wound healing has been rarely
reported. Our aim is to report and highlight the clinicopathological
correlations of five cases of secondary localized corneal amyloidosis
following perforating trauma to the cornea, and to present our proposal for
the pathogenesis of this relatively rare condition.
Methods: We retrospectively reviewed the clinical and surgical histories of
five patients with secondary localized corneal amyloidosis following either
surgical (in 1 patient) or nonsurgical (in the other 4 patients) perforating
corneal trauma. Three specimens were obtained by perforating
keratoplasties and two by excision of the cornea during evisceration of the
ocular contents. The histopathologic features of all five corneas are
outlined.
Results: All the corneal specimens showed full-thickness scars of a prior
perforating wound with congophilic amyloid deposits that exhibited applegreen birefringence under polarized light and dichroism. Variable degrees
of predominantly chronic nongranulomatous inflammation were noted in all
5 cases. Ultrastructural examination in one patient disclosed 8 nm
diameter fibrils in disarray consistent with amyloid. Amyloid P (AP)
immunostaining was positive in the three patients tested for this protein.
Conclusion: Secondary localized corneal amyloidosis is a relatively rare
sequela of surgical and nonsurgical perforating corneal trauma. The type of
corneal degeneration that occurs following trauma with chronic
inflammation, whether it is amyloid, elastotic, fibromatous, myxomatous, or
of another type, may be determined by a patient’s genetic predisposition.
ESTIMATING RECURRENCE IN LOBULAR BREAST CANCER USING
MAGEE EQUATIONS
Nina Chang MD1, Amelia Parrott MD1, Angel Arnaout MD2, Mark Clemons
MD3, Susan J Robertson MD1
1Department
of Pathology and Laboratory Medicine, University of Ottawa,
Ottawa, ON, Canada
2Department of Surgery, University of Ottawa, Ottawa, ON, Canada
3 Department of Medical Oncology, University of Ottawa, Ottawa, ON,
Canada
Background: Invasive lobular carcinoma (ILC) accounts for 5-15% of
invasive breast carcinomas, but its incidence and importance is increasing.
Compared to invasive ductal carcinoma (IDC), classic ILC more frequently
shows ER/PR positivity, HER2 negativity, and a narrow range in
proliferation index and Nottingham histologic score (SBR). Current
predictive/prognostic scores and assays have been validated using
populations where IDC is the predominant subtype. There is recent interest
in using proliferation markers to predict outcome in IDC, but
predictive/prognostic variables for IDC may not be extrapolated to ILC.
Clinical factors that predict recurrence in ILC include lymph node
metastasis (LNM) and tumor size. Here we examine the relationship of
Ki67 index and Magee Equation (ME) 1 score with LNM as prognostic
indicator in ILC.
Methods: Patients with resected classic ILC without neoadjuvant therapy
were identified: 24 cases without and 23 cases with LNM. Ki67 labelling
was performed on formalin-fixed paraffin embedded sections and counted
by a pathologist and two trainees who were blinded to LNM. Tumour
features and markers were reviewed. Modified ME 1-3 scores were
calculated, incorporating SBR, Ki67, tumour size and previously validated
surrogate ER/PR H-scores derived from the Allred score. Statistical
analysis was performed using SPSS v20.
Results: While SBR correlated with Ki67 index, ρ(45)=0.38, p<0.01, LNM
did not significantly correlate with Ki67 index, nor was there a significant
association between LNM and high versus low Ki67 index using the 14%
cut-off used to stratify IDC. Tumour size (p<0.001) differed significantly
between patients with (M=4.77, SD=3.56) and without (M=2.28, SD=1.47)
LNM, as did the presence of lymphovascular invasion (LVI, p=0.048). LNM
did not significantly correlate with SBR or ER/PR. While there was no
significant difference for ME 2 (excludes Ki67) or 3 (excludes tumour size),
there was a significant difference in the ME 1 score between patients with
(M=20.64, SD=4.37) and without (M=17.84, SD=3.79) LNM, p=0.02.
Conclusion: Although Ki67 index alone did not correlate with LNM, it may
offer predictive/prognostic value when combined with other tumour
parameters. Other tumour features used to predict outcome in IDC
(ER/PR, HER2 and SBR) did not correlate with LMN in ILC, likely due to a
narrow range in variability. Long-term follow-up is needed for further
validation of estimated Magee scores as a prognostic indicator.
CLEAR CELL UROTHELIAL CELL CARCINOMA: A STUDY OF EIGHT
CASES
Christopher G. Ball, Justin Bateman, Trevor A. Flood, Eric C. Belanger,
Kien T. Mai
Department of Anatomical Pathology,
The Ottawa Hospital and Ottawa University, Ottawa, Ontario, Canada
Introduction: Due to the rarity of clear cell urothelial carcinoma (CCUC),
its histopathogenesis and clinical significance have not been well
elucidated or documented. We study the largest single series of CCUC.
Materials and Methods: All consecutive cases of urothelial carcinoma over
a 5-year period were reviewed to identify cases of clear cell urothelial
carcinoma, as described in the medical literature.
Results: Of the total 826 cases of urothelial carcinoma, including 352
cases of invasive urothelial carcinoma, there were a total of 8 cases of
clear cell urothelial carcinoma at stage pT3 (n=7) and pT1 (n=1). Local
recurrence and/or distant metastasis occurred in 5 cases, with a follow-up
period of 1 to 5 years (2.4 ± 1.5) with patient death in 4 cases. The clear
cell component accounted for 50-90 % of invasive urothelial carcinoma.
The intra-urothelial component was flat and inverted with or without minor
papillary structures; it displayed intra-urothelial CCUC in 3 cases. Of the
remaining cases, at least 50 % non-invasive or invasive urothelial
carcinoma showed focal areas of clear cell change (CCC) with accounted
for less than 5 % of neoplastic cells. Immunohistochemically, 8 CCUC
exhibited positive reactivity for CK5/CD44 (n=7), CK20 (n=5), pax8 (n=4),
and GATA/CK7 (n=8).
Conclusions: Clear cell urothelial cell carcinoma can be distinguished
from non-CCUC by its extensive CCC in more than 50 % of cells; it is often
under-diagnosed. This variant is associated with aggressive clinical
course with rapid progression to muscle invasion, metastasis, and patient
death. Of interest, expression of CK5/CD44 is suggestive of basal cell
features of most CCUC; furthermore, expression of PAX8 is suggestive of
differentiation as a possible mechanism for extensive CCC.
DEVELOPMENT
OF
A
COMPREHENSIVE
REGISTRY
OF
GASTROINTESTINAL STROMAL TUMOUR (GIST) PATIENTS AT A
SINGLE CANADIAN INSTITUTION
Jason K. Wasserman and E. Celia Marginean
University of Ottawa, Pathology & Laboratory Medicine, Ottawa, Ontario,
Canada
Background: Current opportunities for adjuvant therapies for GIST have
necessitated an accurate diagnosis and risk stratification of patients. The
goal of this observational research study is to establish a registry of
information regarding clinicopathological profile and long-term outcome in
patients with GISTs.
Methods: A retrospective search of patients diagnosed with GIST at a
single institution between 2004- 2013 was performed. Collected data
included clinicopathological characteristics: tumour size, location, histologic
type, mitoses; demographics, outcomes and therapy. A standard
immunohistochemical (IHC) panel was performed: CD117, DOG1, CD34,
vimentin, S100, desmin, SMA, caldesmon, and Ki-67. Biological risk was
assessed using modified NIH criteria. PCR amplification and sequencing
was done for exons 9, 11, 13, 17 of KIT and exons 12 and 18 of PDGFRA
genes.
Results: 167 patients were included; 161 had surgery, 5 received
neoadjuvant imatinib and 49 received adjuvant imatinib; median follow-up
was 41 months (range 0–162). The majority (60%) were located in the
stomach. The median tumour size was 7.23 cm (range 0.3–35 cm) and
68% were spindle-type. By IHC, 99% and 94% were CD117 and DOG1
positive, respectively and Ki67 (n=113) positivity was median 2( range 050). Biologic risk included: 19 (11%) very low risk, 71(43%) low risk, 20
(12%), intermediate risk, and 52 (31%) high risk. Of 71 GIST sequenced,
mutations included 44 in KIT and 12 in PDGFRA genes, 15 wild-type.
Progressive disease included 27 metastases and 8 local recurrences; 10
patients had metastatic disease at presentation. Of 29 patients who died,
16 died of GIST. Ki-67 was correlated with the NIH biological risk
categories (p=0.008), tumour size (p=0.006), and mitotic index (p=0.002),
but not tumour location (p=0.32).
Conclusions: In this report we describe the clinicopathological
characteristics of GIST patients at a single Canadian institution with longterm follow-up. In our cohort, Ki-67 was significantly correlated with
modified NIH biological risk categories, tumour size and mitotic index. The
role of Ki-67 as independent prognostic factor merits exploration as it may
improve ability to predict disease recurrence or death.
LUNCH
AND
POSTER
VIEWING
(PALM ROOMCCW 4137)
GUEST SPEAKER
DR. simon chiosea
Associate Professor
university of pittsburg medical
center, Presbyterian hospital
pittsburg, pa, Usa
TITLE: “UPDATE ON SALIVARY
DUCT CARCINOMA”
VALUE
OF
HISTOPATHOLOGY
FOR
PREDICTING
THE
POSTOPERATIVE COMPLICATIONS OF ILEO-ANAL ANASTOMOSIS
(J-POUCH) PROCEDURE IN CHILDREN WITH REFRACTORY
ULCERATIVE COLITIS
Soufiane El Hallani MD PhD1*, Joseph de Nanassy MD1*, James Young
Lee*, Emily Chan2*, Juan Bass MD2*, David Mack MD3*, Ahmed Nasr MD2*,
Dina El Demellawy MD PhD1*,
Departments of 1Pediatric Pathology, 2Pediatric Surgery and 3Pediatrics,
*University of Ottawa and Children’s Hospital of Eastern Ontario, Ottawa,
Ontario, Canada
Background: The J-pouch is a surgical procedure offered to children with
refractory ulcerative colitis (UC) who have undergone subtotal colectomy to
reconstruct a reservoir function with ileo-anal anatomosis. Unfortunately,
postoperative complications are common and can compromise the pouch
function. We here evaluated the value of histopathology to determine the
risk factors or predictive parameters for complications.
Material and Methods: We retrospectively reviewed the histopathology of
all colectomy specimens from paediatric J-pouch procedures during the
period of 2000 – 2013 using an objective grading system that assess the
chronicity and activity of the UC disease. We analysed the parameters for
association with the post-operative complications. A decision tree algorithm
was generated to predict the risk of complication based on histopathology.
Results: A total of 28 paediatric patients were selected and 10 developed
postoperative complications (35%). The activity score at the recto-anal
margin was significantly higher among the patients with postoperative
complications (mean 7.3 ±3.1 versus 4.8±3.1; p-value = 0.04). The
involvement of more than 5% colonic crypts with epithelial neutrophilic
infiltration at the recto-anal margin was found to be an independent
parameter that would stratify the patients into low-risk or high-risk group for
developing complications (17% versus 64%; p-value = 0.04) with 70%
sensitivity, 78% specificity, 64% PPV and 83% NPV.
Conclusion: An association between UC disease activity at the recto-anal
margin and postoperative complications was determined. Potentially, this
association suggests that a histopathological assessment of the recto-anal
transitional zone may have a value in guiding the surgeon on the risk of
postoperative complications.
IMMUNOHISTOCHEMISTRY IN THE DIAGNOSIS OF MUCINOUS
NEOPLASMS INVOLVING THE OVARY: THE ADDED VALUE OF
SATB2 OF BIOMARKER DISCOVERY THROUGH PROTEIN
EXPRESSION DATABASE MINING
Sarah Strickland MD CCFP1,2, Jason K Wasserman MD PhD1,2, Ana
Giassi PhD1, Bojana Djordjevic MD FRCPC, FCAP 1,2 and Carlos ParraHerran MD FCAP1,2
1 Department of Pathology and Laboratory Medicine, University of Ottawa.
Ottawa, ON, Canada
2 The Ottawa Hospital and Eastern Ontario Regional Laboratory
Association. Ottawa, ON, Canada
RUNNING TITLE: SATB2 and immunohistochemistry of ovarian mucinous
neoplasms
ABSTRACT
Immunohistochemistry is frequently used to identify ovarian mucinous
neoplasms as primary or metastatic; however, there is significant overlap
in expression patterns. We compared traditional markers (CK7, CK20,
CDX2, PAX8, ER, β-Catenin, MUC1, MUC2 and MUC5AC) to two novel
proteins identified through mining of the Human Protein Atlas expression
database: SATB2 and POF1B. The study cohort included 49 primary
gastrointestinal mucinous adenocarcinomas (19 colorectal, 15 gastric, 15
pancreatobiliary), 60 primary ovarian mucinous neoplasms (19
cystadenomas, 21 borderline tumors, 20 adenocarcinomas), and 19
metastatic carcinomas to the ovary (14 lower and 5 upper gastrointestinal
primaries). Immunohistochemistry was performed on tissue microarrays,
scored and interpreted as negative (absent or focal / weak) or positive.
Metastatic tumors were frequently unilateral (42.1%) and ≥10 cm (84.2%).
CK7 was positive in 88.5% upper gastrointestinal and 88.3% primary
ovarian compared to 24.3% lower gastrointestinal neoplasms. CK20 and
CDX2 were positive in 84.8% and 100% of lower gastrointestinal tumors,
respectively; however, expression was also common in upper
gastrointestinal (CK20 42.8%, CDX2 50%) and primary ovarian neoplasms
(CK20 65.7%, CDX2 38.3%). Conversely, SATB2 was more specific for
lower gastrointestinal origin, being positive in 78.8% lower gastrointestinal
but only 11.5% upper gastrointestinal and 1.7% primary ovarian
neoplasms. PAX8 expression was common in primary ovarian neoplasms
(75% of all neoplasms, 65% of carcinomas); only one (1.5%) pancreatic
tumor was positive. MUC2 and β-Catenin were frequently positive in lower
gastrointestinal tumors (96.9% and 51.5% respectively). ER expression
was only seen in primary ovarian neoplasms (13.3%). Nuclear POF1B
expression was seen in malignant lesions regardless of their origin. A
panel including CK7, SATB2 and PAX8 separated primary from secondary
gastrointestinal neoplasms with up to 77.1% sensitivity and 99% specificity,
outperforming tumor laterality and size. Second line markers such as
CDX2, MUC2, ER, MUC1 and β-Catenin increased the sensitivity of
immunohistochemistry in excluding lower gastrointestinal origin to 93.3%.
Biomarker search using proteomic databases has a value in diagnostic
pathology, as shown with SATB2; however, as seen with POF1B,
expression profiles in these databases are not always reproduced in larger
cohorts.
EVALUATION OF QUARANTITATIVE TISSUE PATHOLOGY IN THE
ASSESSMENT
OF
BARRETT’S
ESOPHAGUS
ASSOCIATED
DYSPLASIA
Soufiane El Hallani (1), Martial Guillaud (2), Jakoda Korbelik (2),
Esmeralda Celia Marginean (1)
1) University of Ottawa, Department of Pathology and Laboratory
Medicine, Ottawa, ON
2) British Columbia Cancer Research Centre, Integrative Oncology Cancer Imaging Unit, Vancouver, BC,
OBJECTIVES: Barrett’s esophagus (BE) is a precursor lesion that confers
an increased risk of esophageal adenocarcinoma. Two issues confront the
diagnosis of BE patients: (1) sampling error at the time of endoscopy and
(2) variability among pathologists in grading dysplasia. The purpose of our
study was to evaluate Quantitative Tissue Phenotype (QTP) as a marker of
dysplasia and malignant progression in BE.
METHODS: Sixty one esophageal biopsies with BE were selected and
divided into six groups according to the dysplasia grade. QTP image
analysis was carried out by an in-house automated quantitative system on
sections. The values of 110 nuclear features that analyze the morphology
and chromatin texture were generated for each nucleus.
RESULTS: A progressive correlation was found between nuclear
morphometric features and chromatin features with BE dysplasia. The
chromatin texture was found to be the best discriminator of the class
diagnosis. There was a significant difference between the chromatin
features of isolated low-grade dysplasia versus low-grade dysplasia that
was associated with higher grade lesions in other biopsy tissue fragments.
CONCLUSION: QTP is a promising tool in the new era of digital pathology.
Pending clinical validation studies, analysis of chromatin texture could
contribute in the differential diagnosis of BE class and the detection of
concomitant high-grade lesions if not sampled.
COFFEE
BREAK
POSTERS
MECHANISMS OF ENHANCER-MEDIATED GENE
DURING EARLY MYOGENIC DIFFERENTIATION
EXPRESSION
Katherine Dixon, Munerah Hamed, Hamood Al-Sudais, Qiao Li
Department of Pathology and Experimental Medicine, Department of
Cellular and Molecular Medicine, University of Ottawa
Cellular differentiation is guided by highly regulated patterns of gene
expression, which are often achieved through complex interactions
between cell type-specific transcription factors and cis-regulatory elements.
Among the various regulatory DNA elements are enhancers, which are
particularly challenging to identify due to their distance from active
transcription start sites, but whose function has been linked to the
regulation of cell type-specific gene expression. We performed chromatin
immunoprecipitation followed by next-generation sequencing (ChIP-seq)
for the transcriptional co-activator p300 to identify potential enhancers in
C2C12 myoblasts and associate its histone acetyltransferase activity with
the chromatin marks H3K18ac and H3K27ac. We observed distinct
genome-wide patterns of chromatin modifications and found that levels of
enrichment in H3K18 acetylation showed the greatest variability across
genomic loci and between cell stages. H3K18ac also showed a specific
association with p300, suggesting that this mark may be an essential factor
in enhancer-mediated regulation of cellular differentiation. In addition, we
used chromosome conformation capture (3C) to examine candidate
enhancer-promoter interactions at the locus of the muscle regulatory factor
Myogenin and asses their role in the regulation of Myogenin gene
expression. Ultimately, insight into how these elements function to regulate
early myogenic differentiation may allow us to discover novel molecular
pathways that can be exploited to enhance the process of muscle
regeneration.
MicroRNA SIGNATURE IN THE PREVENTION OF SKIN CANCER
STEM
CELLS
BY
POLYPHENOL-ENRICHED
BLUEBERRY
PREPARATION (PEBP)
Nawal Alsadi1, Jean-François Mallet1, Emilie Graham2 and Chantal
Matar1,2
1. Cellular and Molecular Medicine, Faculty of medicine, University of
Ottawa, Ottawa, Canada 2. Nutrition Sciences, Faculty of Health Sciences,
University of Ottawa, Ottawa, Canada
Photochemoprevention with natural products is an effective strategy in the
control of cutaneous neoplasia. In particular, polyphenols have been
proven to help prevent skin cancer and to control the growth of cancer
stem cells.
Our goal is to analyze how Polyphenol-Enriched Blueberry Preparation
(PEBP) differentially regulates several micoRNA associated with
inflammatory responses and tumor progression. Therefore, we postulate
that PEBP inhibits CSC-dependent survival/stemness pathways by
inducing epigenetic-specific changes through modulating microRNA
regulatory networks.
Our preliminary results demonstrated that PEBP possesses potent
anticancer and anti-metastatic potentials and can be used as a novel
complementary therapy against skin cancer.
MACROPHAGE FUNCTION MEDIATED THROUGH
MECHANISM BY A COLLAGEN MATRIX
A miR-92 A
Zachary Lister,1 Helene Chiarella-Redfern,1 A. Chiu,2 Nick J. R.
Blackburn,1 Marc Ruel,1 M. Brand,2 Katey J. Rayner3 and Erik J.
Suuronen1
1Division of Cardiac Surgery, University of Ottawa Heart Institute; 2Ottawa
Hospital Research Institute; 3Atherosclerosis, Genomics and Cell Biology
Group, University of Ottawa Heart Institute
Background: Biomaterials are promising as a therapy to improve cardiac
repair and regeneration after myocardial infarction (MI). Notably, we have
shown that collagen matrix treatment at 3h post-MI leads to less
inflammation, reduced scar size and improved cardiac function.
MicroRNAs are emerging as key players in the regulation of the post-MI
environment. The goal of this study was to elucidate potential microRNA
mechanisms involved in the anti- inflammatory/pro-wound healing effect of
matrix treatment post-MI.
Methods/ Results: C57BL/6J mice underwent LAD ligation to induce MI.
Three hours post-MI, mice received intra-myocardial injections of PBS or a
type I collagen-based matrix. A
microRNA (miRNA) microarray was performed on infarct and peri-infarct
tissue isolated 2 days after treatment. Of the ~2000 known miRNAs, 120
had expression differences within +/- 0.3 log2 fold change. Interestingly,
miR-92a, a miRNA that is up-regulated after MI, was identified and
confirmed (by PCR) as being significantly down-regulated in the matrixtreated hearts compared to PBS treated hearts (p<0.0005). Since matrixtreated hearts had reduced numbers of M1 inflammatory macrophages at 2
days post-MI, bone marrow-derived macrophages
(BMDMs) were used in vitro to further evaluate matrix regulation of miR92a-mediated pathways. Integrins α5 (ITGα5) and αV (ITGαV), involved in
cell-matrix interactions, were identified as putative miR-92a targets.
Preliminary results showed that BMDMs cultured on the collagen matrix
had decreased expression of miR-92a compared to those cultured on
TCPS, while miR-92a target genes integrins α5 and αV were significantly
up-regulated. Forced over- expression of miR-92a in matrix-cultured
BMDMs caused a decrease in integrin expression. Finally, the matrix also
enhanced the differentiation of M2 wound healing macrophages as
indicated by increased expression of IL-10.
Conclusion: We report that matrix treatment positively regulated
inflammation, and
significantly preserved cardiac function when delivered at 3h post-MI. The
matrix effects may be mediated, at least in part, through its ability to
regulate miR-92a and integrin-related mechanisms in macrophages. These
results present the matrix as a novel non-pharmacological approach to
regulate miRNAs in vivo for protecting the myocardium post-MI.
DEVELOPMENT OF HUMAN RECOMBINANT COLLAGEN TYPE I AND
TYPE III INJECTABLE HYDROGELS FOR CARDIAC THERAPY
James E. Podrebarac, Marc Ruel, Erik J. Suuronen and Emilio I. Alarcon
Division of Cardiac Surgery, University of Ottawa Heart Institute
Purpose: Injectable hydrogel biomaterials have emerged as promising
therapies for treating myocardial infarction (MI). Our collagen type I based
matrix has been shown to reduce inflammation and fibrosis and improve
neovascularization and cardiac function in the ischemic heart of mice and
pigs. However, these materials cannot be used in humans due to the
rodent/porcine source of collagen. In the present study, we aimed to
develop and characterize novel materials intended for future translation
applications. To this end, the materials are comprised of recombinant
human collagen (rHC) type I and type III, and are made following standard
operating protocols adapted for good manufacturing practice (GMP).
Methods/results: Solutions of 1% collagen were prepared for rHC type I,
rHC type III, and TheraCol (porcine control) using TFF filtered and
lyophilized collagen dissolved in ultrapure water over a 7-day period.
Collagen solutions were tested to ensure the proteins were stable and
conserved over time, particularly in batch-to-batch comparison; this
included an assessment of pH, protein conformation and size, surface
charge, and protein content. Collagen hydrogels were prepared following
an optimized protocol using a de-novo T-piece mixing, which provides a
closed environment, minimizing the formation of air bubbles and uniformly
mixing the hydrogel’s components. The use of this system in the future will
also allow clinical translation. The material crosslinking degree was
assessed by differential scanning calorimetry (DSC), which displayed
differences in denaturation temperatures for the hydrogels. The hydrogels
were stable above 37oC. Toxicity of the material (unreacted EDC and NHS
chemical agents) was evaluated by testing the supernatant (PBS layer on
hydrogels) washes with absorbance spectroscopy. Over a period of 3h
post-gelation (6 time-points tested), the presence of chemical agents
diminished significantly.
Conclusions: We demonstrate that the physical and chemical properties
of the rHC type I and type III injectable hydrogels are suitable for use in
vitro and in vivo at physiological conditions. The injectable collagen matrix
is efficiently prepared using a T-piece system appropriate for clinical
applications. It is anticipated that, based on previous work on collagen
biomaterials in our lab, the rHC hydrogels will positively regulate
inflammation, fibrosis and remodeling in the MI heart.
A NOVEL ROLE OF SLK IN TGFβ-INDUCED EPITHELIAL-TOMESSENCHYMAL TRANSITION
Jillian Conway1,2, Khalid Al-Zahrani 1,2 & Dr. Luc Sabourin1,2
1. Centre for Cancer Therapeutics, Ottawa Hospital Research Institute
2. Department of Cellular and Molecular Medicine, University of Ottawa
Abstract
Cancer metastasis is the cause of 90% of all cancer deaths in patients. In
addition, 30% of breast cancer patients overexpressing an epidermal
growth factor receptor called HER2 have been shown to present with a
more invasive and metastatic form of cancer. Metastasis can be stimulated
by a process called EMT (epithelial-to-mesenchymal transition), where
epithelial cells located on the periphery of tumors transition into a migratory
phenotype and break free into the body’s blood and lymph systems. The
Ste20-like kinase, SLK, has been highly implicated in the process of cell
migration and has been shown to be involved in signaling pathways
downstream of the HER2 receptor. Immunofluorescence analyses as well
migration and invasion assays were used to elucidate the potential
relationship between SLK and the EMT process. It was determined that in
SLK knockdown conditions, there is a decrease in the cell’s ability to
progress into EMT, indicating that SLK activity is involved in downstream
EMT signaling. In addition, complete loss of SLK results in a significant
decrease in the migratory and invasive capacities of cells when EMT is
induced using transforming growth factor β. Further studies will continue to
investigate the role of SLK in the Smad-dependent pathway of EMT.
Preliminary data suggests that SLK lies upstream of the Smad proteins
and is involved in their signaling pathway. This study identifies SLK as a
molecular target in TGFβ-induced epithelial-to-mesenchymal transition.
ENDOTHELIAL CELL REACTION IN VASCULAR INVASION IN WELL
DIFFERENTIATED THYROID CARCINOMA IS MORE COMMONLY
ASSOCIATED WITH LOCO-REGIONAL RECURRENCE THAN DISTANT
METASTASIS
Christopher G. Ball, Bernhard Olberg, Chi K. Lai, Bibiana Purgina, Kien
T. Mai
Department of Anatomical Pathology, The Ottawa Hospital and Ottawa
University, Ottawa, Ontario, Canada
We studied the histopathological changes of vascular invasion in 96 cases
of encapsulated thyroid carcinoma (ETC) with a follow-up period of onehalf to nine years.
Vascular invasion is categorized as being intra- or extra-capsular with
tumor groups completely enveloped by endothelium (complete endothelial
reaction) (n=22), or as having tumor cell groups with or without focal
endothelial covering (incomplete or absent endothelial reaction) (n=18).
Intra-tumoral vascular invasion was identified in 14 cases of ETC with
intra/extracapsular vascular invasion mainly with incomplete or absent
endothelial reaction. This study also included ETC with only capsular
invasion (CI) (n=39) and without vascular invasion or capsular invasion
(n=17), including two tumors but with distant metastasis. Intra-tumoral
vascular invasion was more frequently associated with vascular invasion
with either absent or incomplete endothelial reaction. Large vessel
vascular invasion was present in fewer than half of the cases with vascular
invasion. Encapsulated thyroid carcinoma with complete endothelial
reaction developed distant metastasis and local recurrence in about 4.5 %
and36 % of cases; whereas ETC with absent or incomplete endothelial
reaction in 28.5 % and 3 % of cases, respectively. Loco-regional
recurrence often occurred in large vessel vascular invasion.
In conclusion, vascular invasion not associated with incomplete or absent
endothelial reaction was associated with a high incidence of distant
metastasis whereas complete endothelial reaction involving large vessels
likely develops loco-regional recurrence.
PERINEURAL INVASION (PNI) AS A RISK FACTOR FOR LOCAL
RECURRENCE (LR) IN EARLY SQUAMOUS CELL CARCINOMA OF
THE ORAL TONGUE
Aurelia Buscaa M.D. Ph.D., Chi Laia M.D., Susan J. Robertsona M.D.,
Simon Chioseab, M.D., Raja Seethalab, M.D., Lester D. R. Thompsonc,
M.D., Margaret S. Brandwein-Genslerd, M.D., Jessica H. Maxwellb M.D.,
M.P.H, Umamaheswar Duvvurib M.D., Ph.D., Seungwon Kim b M.D., Jonas
T. Johnsonb M.D., Robert L. Ferrisb M.D., Ph.D., E. Celia Margineana M.D.,
Bibianna Purginaa M.D.
a
University of Ottawa, Ottawa, ON, CAN
University of Pittsburgh Medical Center, Pittsburgh, PA, USA
c Southern California Permanente Medical Group, Woodland Hills, CA,
USA
d The University of Alabama at Birmingham, Birmingham, AL, USA
b
Background: The significance of PNI as a predictor of LR or as an
indication for post-operative radiotherapy (PORT) remains controversial in
early oral tongue squamous cell carcinoma (OTSCC). However, the
histologic characteristics of PNI in OTSCC are rarely considered. The
purpose of this study is to evaluate the prognostic utility of histological
patterns of PNI.
Methods: Patients with pT1-2, pN0 OTSCC were retrospectively identified
in four institutions. PNI was assessed according to nerve size, number of
foci, and location subgroups (intratumoral PNI (IT), peripheral PNI (P), and
extratumoral PNI (ET)). These subgroups were merged into groups A = P
and ET and B = no PNI and IT. Mood’s median nonparametric test and
Kaplan Meier analysis were used to calculate and compare median times
to local recurrence.
Results: Of 256 cases, 82 (32%) showed PNI [25 IT (9.8%), 38 P (14.8%)
and 19 ET (7.4%)]. All but one PNI foci were ≤ 1 mm. Irrespective of
PORT, the presence or absence of PNI or the number of PNI foci did not
correlate with time to LR. Patients with IT behaved similarly to those
without PNI. Median times to LR were not significantly different between
patients with PNI (33 months) vs no PNI (40 months) (p=0.197 by Mood’s
median test). Patients were then grouped into A (n=57; P or ET) and B
(n=199; no PNI or IT) and analyzed controlling for PORT. Without PORT,
PNI location groups A (29 months) and B (40 months) showed a
statistically significant difference in median times to LR (p=0.03). With
PORT, median times to LR were not statistically significant (group A=32
months, group B=26.5 months, p=0.82). Irrespective of PORT, Kaplan
Meier survival analysis did not show a significant difference in the curves of
time to LR within the 4 PNI subcategories and between PNI location
groups A and B.
Conclusions: For the first time, recently suggested histopathological
features of PNI were correlated with LR and time to LR in early OTSCCs.
Cases with P or ET were associated with shorter time to LR only in the
absence of PORT, suggesting that the use of adjuvant PORT in cases with
P or ET may be associated with a reduction the risk of LR. Thus, when
reporting oral tongue SCC, PNI location relative to the tumor should be
reported.
CANMEDS SPECIFIC COMPETENCY MILESTONES IMPLEMENTED IN
SURGICAL PATHOLOGY TRAINING IN ANATOMICAL PATHOLOGY
RESIDENCY TRAINING AT THE UNIVERSITY OF OTTAWA
Aurelia Buscaa, Sarah Stricklanda, Shahidul Islama
aDepartment of Pathology and Laboratory Medicine, The Ottawa Hospital
and University of Ottawa, Ottawa, ON, Canada
Objective As part of the shift towards competency based postgraduate
medical training, the new 2015 CanMEDS framework has added the
concept of “milestones”, which defines specific abilities at each stage of
training. In Anatomical Pathology Residency Training, the bulk of training is
developing complex skill sets in Surgical Pathology, which poses additional
challenges as a speciality with little clinical contact, where learning involves
individual study, with daily sign-outs with staff within one or two blocks of
subspecialty training.
Methods The pathology program at the University of Ottawa has
developed specialty specific milestones and competencies for each
postgraduate year of training, available on the department website. Based
on these documents, resident in-training evaluation reports (ITERs) were
generated with pathology specific CanMEDS framework format to be used
as end of rotation assessment tools. In addition, a checklist document for
resident feedback has also been created, to be used at the end of daily
sign-out sessions or midrotation.
Results Theses evaluation methods are ongoing for evaluation of
residency training in the Anatomical Pathology Residency program at the
University of Ottawa. It is expected that the provided documents will
standardize resident expectations and the evaluation process across all
levels of training, as evaluation of competency is performed according to
milestones specific for each PGY level. In addition, it will provide an
objective tool for self-directed assessment and learning.
Conclusion The use of pathology specific milestones, ITERs and
checklists during resident evaluation is expected to facilitate better
feedback for professional development.
THE ACCELERATED CLINICAL COURSE OF
NEUROENDOCRINE TUMORS
AN ANALYSIS OF CLINICAL, IMAGING AND
PROGNOSTIC FACTORS
PANCREATIC
PATHOLOGIC
Nina Chang MD1, Wayne S. Kendal MD PhD2, Wael Shabana MD3,
Alfredo Walker MBBS1, Fady K Balaa MD4, Christine Nyiraneza PhD5,
Yvonne Dawkins MBBS6, Avijit Chatterjee MD6, Rachel Goodwin MD7,
Timothy Asmis MD7, and Terence N. Moyana MD1
1Dept
of Pathology & Lab Medicine, 2Division of Radiation Oncology, 3Dept
of Radiological Sciences, 4Division of Hepatobiliary Surgery, 5Dept of
Epidemiology & Community Medicine, 6Division of Gastroenterology,
7Division of Medical Oncology.
The Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada.
BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) generally
behave indolently even with metastases. However, some manifest an
accelerated clinical course (ACC) with poor prognosis. It is not clear
whether this is due to intrinsic tumor aggressiveness, dedifferentiation, or
simply silent progressive tumor accumulation that then triggers
complications. This study analysed the features of PNETs to gain further
insight into their biology.
METHODS: A retrospective clinicopathologic review of 74 PNETs using
Kaplan-Meier and Cox proportional hazard analyses.
RESULTS: Median overall survival was 117 months; 5 year survivals were
92% where the PNETs were resected versus 35% for those not resected
(p<0.001). Liver metastases developed in 33/74 (18/33 synchronous
metastases; 15/33 metachronous). There was a significant difference in
Ki67 grade between metastatic and non-metastatic tumors (p<0.001).
However, there was considerable overlap of grades between synchronous
and metachronous tumor groups with 5/10 (50%) of synchronous PNETs
being well-differentiated. Most patients with metachronous metastases
(10/15; 67%) showed non-progressive disease whereas the majority with
synchronous metastases (15/18; 83%) manifested progressive disease
(p=0.01). On Cox analysis, synchronous metastases and inoperability were
significant predictors of survival whereas metachronous metastases, Ki67
grade and T/N stage were not.
CONCLUSIONS: The ACC for PNETs was associated with synchronous
metastases and inoperability. By multivariate analysis, the strongest
adverse prognostic factor was synchronous metastases and this was
related to the ACC over and above what was indicated by metachronous
metastases or the Ki67 grade on univariate analysis. These findings
suggest that the presence of synchronous metastases may reflect intrinsic
tumor aggressiveness.
KEYWORDS:
Pancreatic neuroendocrine tumors;
tumor biology;
surgery;
accelerated clinical course;
synchronous metastases;
metachronous metastases.
DIRECT AUTOFLUORESCENCE VISUALIZATION TO GUIDE KIDNEY
SPECIMEN GROSSING: A PROOF-OF-CONCEPT
Soufiane El Hallani, Trevor Flood, Previn Gulavita, Eric Belanger
Department of Pathology and Laboratory Medicine, The Ottawa Hospital,
Ottawa, ON
BACKGROUND: A proper examination of nephrectomy specimens is
detrimental to accurately stage the kidney cancers and guide the postsurgical treatment. Traditional gross examination relies on naked eye
visualization. In many situations; however, macroscopic extension of the
tumor into the renal vein or its segmental (muscle containing) branches
(stage pT3a) is under-recognized due to the difficulty of distinguishing the
anatomy of the renal vessels in the hilum or differentiating the vein wall
from the collecting calyceal system. A simple method to accurately identify
and examine the major renal vessels is proposed.
METHODS: A hand-held device that delivers blue excitation light was
employed to induce green fluorescence from endogenous fluophores (i.e.
elastin) present in the wall of the blood vessels. Three representative
nephrectomy specimens (non-tumoral kidney with hydronephrosis; renal
cell carcinoma with renal vein invasion; papillary urothelial carcinoma of
the renal pelvis) were selected during routine gross examination and
examined with the DAV device. Digital images of tissue white-light
reflectance and fluorescence of the kidney slices were recorded and
compared to selected H&E tissue sections. Verhoeff elastic stain was used
to highlight the blood vessel wall during microscopic examination.
RESULTS: In non-tumoral kidney with hydronephrosis, application of DAV
was able to specifically generate fluorescence from the wall of blood
vessels and highlight the renal vein and its branching network even when
they are not visualized with naked eye. In the other hand, the wall of
dilated calices did not fluoresce making DVA valuable for differentiation
between the two structures. In tumoral kidney, DAV highlighted
successfully the tumor-invaded renal vein wall. Using histology and Verhoff
stain as the gold standard for the diagnosis of renal vein invasion, we
found that the pattern of fluorescence is correlated to the level of the
vessel wall invasion. We also present a representative case in which occult
invasion into a branch of renal vein would have been missed, even after
extensive sampling of the hilum, without the application of DAV which
successfully detected the wall of the vessel wall surrounding a tumoral
nodule.
CONCLUSION: We believe that DAV technology has a potential
application in guiding the gross examiner to identify the renal vein and its
branches in the renal hilum and perform precise examination for the
diagnosis of renal vein invasion. Ultimately, this will improve the accurate
staging of kidney cancer and therapeutic outcome.
PREDICTORS OF TUMOR UPGRADING OR UPSTAGING AFTER
RADICAL PROSTATECTOMY IN PATIENTS WITH GLEASON SCORE
3+4=7 PROSTATE CANCER (PCa) AT TRANSRECTAL ULTRASOUND
(TRUS) GUIDED NEEDLE BIOPSY
Soufiane El Hallani Trevor A Flood, Kien T Mai, Eric C Belanger, Nicola
Schieda The Ottawa Hospital, Ottawa, ON, Canada; University of Ottawa,
Ottawa, ON, Canada
Background: Select patients with TRUS guided biopsies containing
Gleason Score 3+4=7 PCa may be considered candidates for active
surveillance. The purpose of this study was to determine if there are
features that predict PCa upstaging and/or upgrading after radical
prostatectomy (RP) in patients with 3+4=7 PCa diagnosed on TRUS
guided biopsies.
Design: We searched our institution's database for patients with Gleason
Score 3+4=7 PCa diagnosed on TRUS guided biopsy and who underwent
RP between January 2012 and May 2014. One hundred and four (104)
patients were identified. Two blinded genitourinary pathologists
independently reviewed the biopsies and assessed: a) nuclear size,
nucleolar size, and distribution of macronucleoli of PCa which were
subjectively graded using a semi-quantitative scale from 1 to 3, b) extent of
Gleason Pattern 4, and c) PCa with cribriform morphology. Patient age and
serum PSA were also recorded. The Gleason Score and stage (presence
or absence of organ confined disease [OCD]) was retrieved from RP
reports. Comparisons were performed between groups using the chisquare test and Spearman correlation.
Results: The mean age and PSA at diagnosis was 64 years (±5.77) and
8.34 ng/mL (±5.14) respectively. Gleason Scores were upgraded in 28
patients (27%) and 46 patients (44%) did not have OCD after RP. PSA
correlated with tumor upgrading (r=0.43, p=0.002) but not with absence of
OCD (p=0.28). The median extent of Pattern 4 was 20% (10-30 IQR) and
this was associated with tumor upgrading after RP (r=0.32, p=0.03). Ten
patients had cribriform morphology on core biopsy of which 70% were
upgraded after RP (p=0.009). Eighty percent of tumors with cribiform
morphology did not have OCD and this difference was not significant
(p=0.06). There was no association between age, nuclear size, nucleolar
size, and/or distribution of macronucleoli with upgrading and/or absence of
OCD (p>0.05).
Conclusions: A proportion of patients with Gleason Score 3+4=7 PCa at
needle biopsy do not have OCD or are upgraded to higher Gleason Scores
after RP. Features on needle biopsy that are associated with Gleason
Score upgrading after RP include PSA, extent of Pattern 4, and the
presence of cribriform morphology. Gleason Score 3+4=7 biopsies with
cribriform morphology are associated with tumor upgrading after RP and
may be considered a contraindication to active surveillance.
UNSUSPECTED AND MISDIAGNOSED CILIARY BODY AND
CHOROIDAL
MELANOMA
AFTER
ENUCLEATION
AND
EVISCERATION: REVIEW OF CASES IN THE OTTAWA-GATINEAU
REGION FROM 1996-2012
Saleh, Solin1, 2; Brownstein, Seymour1, 2; Jastrzebski, André1, 2;
Jordan, David1; Gilberg, Steven1; Leonard, Brian1; Hurley, Bernard1
1. Ophthalmology, University of Ottawa, Ottawa, ON, Canada.
2. Pathology, University of Ottawa, Ottawa, ON, Canada.
Purpose: There is little in the recent literature on the topic of clinically
unsuspected and misdiagnosed ciliary body and choroidal melanomas with
a calculation of the frequency of these events for a set geographical area.
We present 2 cases unexpectedly diagnosed with a melanoma of the
ciliary body and choroid after evisceration and enucleation, respectively,
and 2 cases of clinically misdiagnosed ciliary body and choroidal
melanoma. As the only ophthalmic pathology laboratory in our region
serving a population of 1,236,300, we determine the rate of these
outcomes over a period of 16 years.
Methods: We carried out a retrospective single centred, population based
case review in the Ottawa-Gatineau region. 3,320 total cases, of which 98
were ciliary body and choroidal melanomas, were reviewed. Four cases
were included in the study group. We calculate the frequency of clinically
unsuspected melanoma of the ciliary body and choroid in enucleated and
eviscerated eyes and of clinically misdiagnosed melanoma of the ciliary
body and choroid in enucleated eyes in our region. We also determine the
rate of uveal melanoma undergoing enucleation in our region by
calculating the annual population and the mean number of cases within
this area over a 16-year-span.
Results: Out of 98 diagnoses of ciliary body and choroidal melanoma, we
identified 2 cases where the diagnosis was clinically unsuspected. We also
identified 2 cases clinically misdiagnosed as a ciliary body or choroidal
melanoma, with one of these being a non-neoplastic lesion. The clinical
and pathological findings of all 4 Cases will be demonstrated. In our
region, 2.0% of ciliary body and choroidal melanomas were clinically
unsuspected and 2.0% of clinically diagnosed ciliary body and choroidal
melanomas were misdiagnosed. We also calculate a rate of uveal
melanoma
undergoing
enucleation
in
our
region
of
5.4
cases/1,000,000/year.
Conclusions: We present the first and only single centred, population
based data on the rate of unsuspected ciliary body and choroidal
melanoma in the current era of modern diagnostic imaging. Unsuspected
melanoma of the ciliary body or choroid is a rare occurrence, with a rate
significantly lower than previously published. The rate of clinically
misdiagnosed ciliary body or choroidal melanoma at our centre is within
the range of recent reports of this encounter.
Commercial Relationships Disclosure: Nil for all authors
THERAPEUTIC PLASMA EXCHANGE WITH OR WITHOUT RITUXIMAB
TO TREAT THROMBOTIC THROMBOCYTOPENIC PURPURA:
SIGNIFICANTLY DIFFERENT TREATMENT EFFICIENCIES
Vito Sanci, Elianna Saidenberg, and Alan Tinmouth
The Ottawa Hospital and the University of Ottawa, Ottawa, Ontario,
Canada
PURPOSE: The purpose of this study is to describe our single-center
experience in the treatment of thrombotic thrombocytopenic purpura (TTP)
using plasma exchange (PLEX) with or without rituximab.
METHODS: The charts of all patients presenting with TTP and treated with
PLEX at The Ottawa Hospital from January 2002-present were
retrospectively reviewed. Time-to-relapse was defined as the time (in
months) from the last PLEX treatment to the first day of an episode of
relapsed TTP.
RESULTS: This single-center study includes data on 19 patients (Figure
1). The average age at first diagnosis of TTP in our cohort was 50.9 ± 17.3
years. We observed a female predominance. The majority of patients had
idiopathic TTP, but one patient each presented with TTP in the context of
pancreatitis, the immediate post-partum period, HIV and active cancer.
Figure 1 demonstrates graphically that, in our small cohort, there was no
clear association between rituximab therapy and time to next relapse. All
patients presenting with relapse were treated with rituximab during at least
one episode of relapse. Patients receiving PLEX plus rituximab had
significantly increased numbers of PLEX as compared to those with PLEX
only (31.5 ± 11.4 versus 9.0 ± 5.3; t-test, p<0.05) but no difference in the
number of months to the next relapse (41.3 ± 17.5 versus 29.1 ± 25.6; ttest, p>0.05).
CONCLUSIONS: Significantly more patients with recurrent TTP received
PLEX plus rituximab, as compared to those with a one-time episode with
no relapse, which is consistent with the emerging evidence that rituximab
improves response rates, reduces the risk of relapse, and increases the
relapse-free duration (e.g. J Clin Apher 2013; 28:390-4). However, in
patients with recurrent TTP, no difference was found in the duration of
remission between those who received PLEX only versus PLEX plus
rituximab. Within individual patients who suffered multiple relapses, only
some of which were treated with rituximab, there appears to be a longer
duration following PLEX plus rituximab therapy than when PLEX is the sole
treatment modality.
In summary, the results of this single-centre, retrospective analysis of
patients calls into question the role of rituximab therapy in the treatment of
relapsed TTP. It further identifies the need to improve testing algorithms to
better categorize patients presenting with thrombotic microangiopathies to
help determine which patients are most likely to benefit from the addition of
rituximab therapy.
FIGURE 1. GRAPHIC REPRESENTATION OF POPULATION
TREATMENT AND RELAPSE
*For this chart only, the 1st documented episode of TTP in our charts for
Patient # 3 and Patient #10 were considered as the 1st occurrences,
despite the fact that they are known relapses. Otherwise, data points
indicate initial TTP episode at time 0, followed recurrent TTP episodes,
sequence. Data points with a red circle followed by a red line indicate that
PLEX plus rituximab was used during that TTP episode. Black dot
indicates patient is deceased.
GATA-3 EXPRESSION IS NOT ASSOCIATED WITH COMPLETE
PATHOLOGICAL RESPONSE IN TRIPLE NEGATIVE BREAST
PATIENTS TREATED WITH NEOADJUVANT CHEMOTHERAPY
Jason K. Wasserman, Phillip A. Williams, Shahidul Islam, Susan J.
Robertson
University of Ottawa, Pathology & Laboratory Medicine, Ottawa, Ontario,
Canada
Background: Triple negative breast cancer (TNBC) is defined by the lack
of estrogen, progesterone, and HER-2 expression. Even with optimal
management, most patients with TNBC will experience early relapse.
However, 1 in 5 patients with TNBC will demonstrate complete pathological
response (pCR) to chemotherapy and will remain disease free for many
years. GATA-3 is a protein normally expressed in breast tissue in response
to estrogen stimulation although it is still present in a subset of TNBC,
possibly under the influence of the androgen receptor (AR). Prior studies
have suggested that GATA-3 expression may be a negative predictor for
pCR in breast cancer although it is unclear if these results apply to TNBC.
In this study, we examine for the first time the relationship of the
expression of GATA in both AR positive and negative TNBC.
Methods: All patients diagnosed at The Ottawa Hospital between January
2005 and March 2014 with TNBC who underwent surgery for locally
advanced breast cancer after neoadjuvant chemotherapy were identified.
Immunohistochemical analysis was performed for GATA-3 and AR. Both
were scored using a composite of staining intensity and percentage cells
stained. The primary outcome was pCR, defined as the absence of
invasive disease in both breast and lymph nodes. Clinicopathological
parameters and the expression of GATA-3/AR were compared in patients
with and without pCR.
Results: Twenty-four patients were included in this study. The median age
at diagnosis was 48 years (range, 30–70 years) and the median time of
follow-up was 17.5 months (range, 1–88 months). Prior to chemotherapy
the median tumour size was 54 mm (range, 8–130 mm); 18 patients had
lymph node positive disease. Seven patients achieved pCR. There was no
difference in the pre-chemotherapy tumour size (44 ± 28 mm vs. 54 ± 30
mm; p=0.764) or lymph node status (86% vs. 71%; p=0.629) between
patients with and without pCR. GATA-3 expression was present in 20
cases (83%) while AR was present in 6 cases (25%). No AR expression
was seen in 15 cases (63%) with GATA-3 positivity. There was no
difference in either GATA-3 (4.3 ± 2.7 vs. 3.6 ± 2.5; p=0.549) or AR (1.4 ±
2.5 vs. 1.1 ± 2.4; p=0.778) expression between patients with and without
pCR.
Conclusions: GATA-3 expression is frequent in TNBC even in the
absence of AR expression. In contrast to previous studies expression of
GATA-3 or AR is not associated with pCR after neoadjuvant chemotherapy
in TNBC.
LABORATORY REQUISITION FORMS OFTEN LACK CRITICAL
INFORMATION: A QUALITY IMPROVEMENT INITIATIVE TO ENHANCE
COMMUNICATION AND PATIENT SAFETY AT THE OTTAWA
HOSPITAL
Jason K. Wassermanac, Iris Teoac, Darren Tsebc, John P. Veinotac, and
Bibianna Purginaac
aDepartment of Pathology and Laboratory Medicine
bDepartment of Otolaryngology
cThe Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada
Background: Every specimen submitted for pathological analysis is
accompanied by a laboratory requisition form (LRF). Despite the fact that
this LRF is often the only documentation provided to the pathologist, many
lack critical information. As part of an initiative to enhance patient safety,
we sought to identify areas in which the current LRF could be improved.
Methods: The Anatomical Pathology database was searched for all cases
accessioned in 2014. Mandatory fields in our LRF were assessed
including: specimen site, collection time and date, most responsible
physician (MRP), physician signature, and clinical history. In 100
consecutive finalized cases the 'clinical history' provided was reviewed and
compared with the patient's electronic medical record for completeness
and accuracy.
Results: 51,722 cases were accessioned: 273 (0.5%) were missing
anatomical site/laterality, 739 (1.4%) were missing the collection date and
time, and 6031 (12%) did not include a clinical history. Of the 100 LRF
reviewed, only 21 included all mandatory information and a complete
clinical history. Fifteen requisitions did not include any clinical information.
Of those that included information, 38 described the lesion being sampled,
30 provided a previous pathological diagnosis, 13 included a clinical
question, and 16 proposed a clinical diagnosis. In 18 cases the history was
incomplete; 2 were incorrect.
Conclusions: Very few laboratory requisitions are submitted complete.
Collaborating with our clinical colleagues, we have drafted a new
requisition which will make it easier to communicate critical information
including time in formalin and key aspects of the clinical history.
MAPPING OF UROTHELIAL CARCINOMA IN RADICAL CYSTECTOMY
SPECIMENS
Kien T Mai, Muhanad Hassan,Trevor Flood, Eric C Belanger
Department of Anatomical Pathology,
The Ottawa Hospital and Ottawa University, Ottawa, Ontario, Canada
Introduction
Topographic study of urothelial carcinoma (UC) has not been well studied.
Materials and Methods
Consecutive specimens of radical cystectomy (RC) for UC without preoperative treatment with chemo or radiotherapy were prospectively
selected for study. At least four horizontal rings of the urinary bladder with
at least two rings through the main lesion were entirely submitted with
additional sections. Tumor size, multifocality were determined by the
cystoscopic, imaging and pathological findings.
Results
Consecutive 50 RC specimens (male: n=39, muscle invasive UC: n= 31)
were studied. UC were associated with secondary urothelial neoplastic
lesions in 94% including contralateral involvement in 6% and extensive
UIN in 28%. Distal and ipsilateral ureteral, contra-lateral ureteral and
prostatic involvements occurred in 16, 6 and 12% of cases respectively
and were accompanied by involvement of the trigone. In a 90% of cases
with multifocality, satellite neoplastic lesions tended to decrease in size as
they were distant from the main lesion
Conclusions:
The sampling in this study was relatively limited but non-random. UC was
unifocal in only 6% and extensive in 28% of cases. The topographic
distribution of neoplastic urothelial lesion appears to be random as seen in
field effect in a smaller proportion of foci than non-random distribution. The
majority of secondary multiple neoplastic foci were in the vicinity of the
main lesion, a phenomenon suggestive of soil-seeding.
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