ANNUAL RESEARCH DAY PROGRAM
DEPARTMENT OF PATHOLOGY AND LABORATORY
MEDICINE
UNIVERSITY OF OTTAWA
APRIL 29th, 2009
ROOM 2021
ROGER GUINDON HALL
HEALTH SCIENCES BUILDING
8:55
WELCOME
9:00-9:15
PEDIATRIC MALIGNANT PERIPHERAL NERVE
SHEATH TUMOUR OF THE RADIAL NERVE –
CASE REPORT AND REVIEW OF THE
LITERATURE.
B.M Purgina2, Dr. TA Flood2, Dr. J. Michaud2, Dr.
MF Shamji1, Dr. E. Ventureyra1,3.
1Division of Neurosurgery, The Ottawa Hospital,
Ottawa, Ontario. 2Department of Anatomical
Pathology, The Ottawa Hospital, Ottawa, Ontario.
3Division of Neurology, Children’s Hospital of
Eastern Ontario, Ottawa, Ontario.
9:15-9:30
EXPRESSION OF TISSUE
TRANSGLUTAMINASE IN FORMALIN-FIXED,
PARAFFIN-EMBEDDED TISSUE IS IT USEFUL
IN THE DIAGNOSIS OF CELIAC DISEASE?
I Teo, H Marginean and EC Marginean.
Department of Pathology and Laboratory
Medicine, University of Ottawa, Ottawa, Ontario,
Canada.
9:30-9:45
RENAL CELL CARCINOMA WITH HYBRID
FEATURES OF CONVENTIONAL AND
CHROMOPHIL CYTOMORPHOLOGY: A
FLUORESCENT IN SITU HYBRIDIZATION
STUDY.
H. Faraji, Susan J. Robertson, MD, Eric C.
Belanger, MD, Kien T. Mai, MD. Department of
Pathology and Laboratory Medicine, The Ottawa
Hospital and University of Ottawa, Ontario,
Canada.
1
9:45-10:00
LUPUS MILIIARIS DISSEMINATUS FACIEI OF
THE EYELIDS: REPORT OF TWO CASES
W. Liao1,2, S. Brownstein1,2, D.R. Jordan1, S.
Gilberg1, S.S. Jolly1,2, R. Prokopetz2. 1University of
Ottawa Eye Institute, Ottawa, ON, Canada;
2Department
of Pathology and Laboratory
Medicine, University of Ottawa, Ottawa, ON,
Canada.
10:00-10:15
COMPARATIVE IMMUNOHISTOCHEMICAL
STUDY OF SEROUS AND MUCINOUS CYSTIC
NEOPLASMS OF THE PANCREAS: SIMILAR
STROMA PHENOTYPE SUGGESTING A
POSSIBLE HISTOPATHOGENIC
RELATIONSHIP
A.D Edgecombe 1, BN Nguyen1, MM Gomes1, J
Côté2, KT Mai1.
1Pathology and Laboratory Medicine, The Ottawa
Hospital, Ottawa, Ontario, Canada and
2Pathology, Saint-Luc Hospital, CHUM, Montreal,
Quebec, Canada
10:15-10:30
UNUSUAL PRESENTATION OF A COMMON
INFECTIOUS DISEASE IN THE BREAST
T. Jayasinghe, PGY2 Resident Anatomical
Pathology
Department of Pathology and Laboratory
Medicine, The Ottawa Hospital, Ottawa, Ontario,
Canada
10:30-10:45
INVESTIGATION OF CADHERIN AND CATENIN
EXPRESSION
IN
INVASIVE
DUCTAL
CARCINOMA OF THE BREAST VIA TISSUE
MICROARRAY
I Teo, L Pelletier and S Islam
Department of Pathology and Laboratory
Medicine, University of Ottawa, Ottawa, Ontario,
Canada.
10:45-11:00
BREAK
2
11:00-11:15
LETHAL RUPTURE OF A TRAUMATIC
ANEURYSM OF THE POSTERIOR INFERIOR
CEREBELLAR ARTERY A CASE REPORT AND
REVIEW OF THE LITERATURE.
B.M Purgina1, Dr. C. Milroy1,2, and Dr. G.
Jansen1.
1The Ottawa Hospital, Department of Anatomical
Pathology, Ottawa, ON and 2Eastern Ontario
Regional Forensic Pathology Unit, Ottawa, ON.
11:15-11:30
SPONTANEOUS PNEUMOTHORAX AND LUNG
CARCINOMA: SHOULD ONE CONSIDER
SYNCHRONOUS MALIGNANT PLEURAL
MESOTHELIOMA?
T.A .Flood Sekhon HS, Seely J, Shamji F and
Gomes MM. Department of Pathology and
Laboratory Medicine, The Ottawa Hospital and
University of Ottawa, Ontario, Canada.
11:30-11:45
UNUSUAL ADENOCARCINOMA WITH
FEATURES SUGGESTIVE OF MESONEPHRIC
ADENOCARCINOMA OF THE PROSTATE
H. Faraji, Susan J Robertson, Eric Belanger, Kien
T Mai,. Division of Anatomical Pathology,
Department of Laboratory Medicine, Hospital and
Department of Pathology and Laboratory
Medicine, University of Ottawa, Ottawa, Ontario,
Canada
11:45-12:00
ATYPICAL SMALL ACINAR PROLIFERATION
WITH
AND
WITHOUT
ASSOCIATED
PROSTATIC ADENOCARCINOMA
T.A. Flood, Hamid Faraji, Susan J. Robertson,
Eric Belanger, Kien T. Mai.
Department of Pathology and Laboratory
Medicine, The Ottawa Hospital and University of
Ottawa, Ottawa, Ontario, Canada
12:00-1:15
LUNCH AND POSTER VIEWING
(ATRIUM 2ND FLOOR, FACULTY OF MEDICINE)
3
1:15-2:15
GUEST SPEAKER
Dr. LUAN TRUONG
RENAL TUBULAR CELL APOPTOSIS IN
TUBULOINTERSTIAL RENAL
Pathologist and Director of Nephropathology, The
Methodist Hospital, Houston, Texas
2:15-2:30
RESPIRATORY SUNCYTIAL VIRUS (RSV)
DETECTION IN CLINICAL SPECIMENS USING
A NANOLITER REAL TIME PCR RESPIRATORY
PATHOGEN PANEL
R. Slinger, F. Chan, D. Goldfarb, N. Barrowman, I.
Moldovan, H. Ji, J. Brooks
1Children's Hospital of Eastern Ontario, 2University
of Ottawa, Ottawa, ON, CANADA, 3National HIV
& Retrovirology Laboratories, Public Health
Agency of Canada.
2:30-2:45
UNUSUAL HISTOPATHOLOGICAL PATTERN
OF A NEPHROGENIC ADENOMA IN A
URETHRAL DIVERTICULUM
A.D Edgecombe, M Lamba, KT Mai, V Acharya.
Department of Pathology and Laboratory
Medicine, The Ottawa Hospital, Ottawa, Ontario,
Canada
2:45-3:00
PROSTATIC ADENOCARCINOMA AND
STATUS OF RESECTION MARGIN OF
RADICAL PROSTATECTOMY ASSOCIATED
WITH CORE BIOPSIES WITH ATYPICAL
SMALL ACINAR PROLIFERATION OR MINIMAL
CANCER
T.A Flood, BN Nguyen, EC Marginean, BM
Purgina, KT Mai. The Ottawa Hospital, Ottawa,
ON, Canada; The University of Ottawa, Ottawa,
ON, Canada
3:00-3:15
BREAK (ATRIUM)
4
3:15-3:30
A RETROSPECTIVE REVIEW OF OCTAPLEX
UTILIZATION AT THE OTTAWA HOSPITAL
M. Wozniak and J. Bormanis.
Pathology and Laboratory Medicine, The Ottawa
Hospital, Ottawa, Ontario, K1H 8L6
3:30-3:45
IMMUNOHISTOCHEMICAL
AND
IN
SITU
HYBRIDIZATION STUDIES OF MULTILOCULAR
CYSTIC RENAL CELL CARCINOMA
Bibianna M. Purgina MD, Trevor A. Flood MD,
Eric C. Belanger MD FRCPC, Kien T. Mai MD
FRCPC.
Division of Anatomical Pathology, Department of
Laboratory Medicine, The Ottawa Hospital and
Department of Pathology and Laboratory
Medicine, University of Ottawa, Ontario, Canada.
3:45-4:00
FLUORESCENT IN SITU HYBRIDIZATION OF
NON-PAPILLARY ONCOCYTIC/EOSINOPHILIC
RENAL CELL CARCINOMA
Itrat Ahmed, MD, Susan J Robertson, MD, Eric
Belanger, MD, Kien T. Mai, MD
Division of Anatomical Pathology, Department of
Laboratory Medicine, Hospital and Department of
Pathology and Laboratory Medicine, University of
Ottawa, Ottawa, Ontario, Canada
4:00-4:15
ANNOUNCEMENT OF PRIZE WINNERS AND
CONCLUSION








Nadia Mickhael 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
Best Poster Presentation by a Resident
2nd Best Poster Presentation by a Resident
Dr. M. Orizaga Award for Best Teacher
5
POSTERS
1.
ROLE OF p300 IN REGULATION OF Myf5 GENE
EXPRESSION
Tanja Francetic and Qiao Li
Department of Pathology and Laboratory Medicine, Department
of Cellular and Molecular Medicine, Faculty of Medicine,
University of Ottawa, Ontario, Canada.
2.
ROLE OF THE RETINOID X RECEPTOES IN SKELETAL
MUSCLE DIFFERENTIATION
Melanie Le May, Tanja Francetic, Qiao Li
Department of Pathology, Department of Cellular and Molecular
Medicine, Faculty of Medicine, University of Ottawa.
3.
ROLE OF THE 26S PROTEASOME IN THE EXPRESSION OF
RETINOIC ACID INDUCED GENES
Aliaa Higazi, Mahmoud abed and Qiao Li
Department of Pathology and Laboratory Medicine, Department
of Cellular and Molecular Medicine, Faculty of Medicine, Ottawa
University, Ottawa, Ontario, K1H 8M5, Canada.
4.
INVOLVEMENT OF PML BODIES IN CBP DEGRADATION
VIA PROTEASOME PATHWAY
Jonathan St-Germain, Jihong Chen and Qiao Li
Department of Pathology and Laboratory Medicine, Faculty
Medicine, University of Ottawa, Ottawa, Ontario, Canada
5.
EFFECTS OF P300 HAT ACTIVITY ON SKELETAL MUSCLE
DIFFERENTIATION
Sourianna Awada (Honours student), Supervisor: Qiao Li
Department of Pathology and Laboratory Medicine, Faculty of
Medicine, University of Ottawa
6.
SODIUM TRANSPORT INTO THE CENTRAL NERVOUS
SYSTEM AND SALT SENSITIVE HYPERTENSION
Md Shahrier Amin, Frans H H Leenen
University of Ottawa Heart Institute, Ottawa, ON, Canada
6
7.
EXPRESSION PROFILE OF P16 (INK 4A) and MIB1 (KI-67) IN
HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESION
(HSIL) AND IMMATURE SQUAMOUS METAPLASIA (ISM) OF
THE UTERINE CERVIX
Md Shahrier Amin, MD, PhD candidate; Mary Senterman, MD,
FRCSC, FRCPC and Shahidul Islam, MD, PhD, FCAP
Division of Anatomical Pathology, The Ottawa Hospital, Eastern
Ontario Regional Laboratory Association (EORLA), The
Department of Pathology and Laboratory Medicine, The
University of Ottawa, Ontario, Canada.
8.
MALE BREAST CARCINOMA: PROGNOSTIC MARKERS,
AGE AS A VARIABLE?
M. Marinescu, S.J. Robertson. Department of Pathology,
University of Ottawa; Department of Pathology and Laboratory
Medicine, The Ottawa Hospital, Ottawa, Ontario.
9.
PRIMARY MELANOMA OF THE LUNG: A CASE REPORT
AND REVIEW OF THE LITERATURE
M. Marinescu1, M. Gomes1, F.M. Shamji2, J.M. Seely3, H.
Sekhon1.
1Department of Pathology, 2Department of Thoracic Surgery,
3Department of Radiology, University of Ottawa , The Ottawa
Hospital, Ottawa, Ontario.
10.
UROTHELIAL
CARCINOMA
ASSOCIATED
WITH
CLINICALLY DIAGNOSED PROSTATIC ADENOCARCINOMA
TA Flood, B Nguyen, EC Marginean, BM Purgina, KT Mai. The
University of Ottawa, Ottawa, ON, Canada; The Ottawa
Hospital, Ottawa, ON, Canada
11.
RING CHROMOSOME 7 AND TRISOMY 8 IN A PEDIATRIC
CASE OF HEPATOSPLENIC T-CELL LYMPHOMA
M. Wozniak, L. Sinclair-Bourque, M. Lamba, K. Mandel, F.
Alseraye, E. McCready
Pathology and Laboratory Medicine, The Ottawa Hospital,
Ottawa, Ontario, K1H8L6
Cytogenetics Laboratory, Children’s Hospital of Eastern Ontario,
Ottawa, Ontario, K1H8L1
12.
LUPUS MILIIARIS DISSEMINATUS FACIEI OF THE
EYELIDS: REPORT OF TWO CASES
W. Liao1,2, S.S. Jolly1,2, S. Brownstein1,2, D.R. Jordan1, S.
Gilberg1, , R. Prokopetz2. 1University of Ottawa Eye Institute,
Ottawa, ON, Canada; 2Department of Pathology and Laboratory
Medicine, University of Ottawa, Ottawa, ON, Canada.
7
13.
IMMUNOHISTOCHEMICAL STUDY OF MULTILOCULAR CYSTIC
RENAL CELL CARCINOMA
BM Purgina MD, TA Flood MD, BN Nguyen MD FRCPC, EC
Marginean MD FRCPC and KT Mai MD FRCPC.
Department of Pathology and Laboratory Medicine, University of
Ottawa, Ottawa, Ontario, Canada.
14.
IMMUCYTOCHEMICAL
STUDY
OF
THE
URINE
CYTOLOGICAL PREPARATIONS OF THE SECONDARY
PROSTATIC ADENOCARCINOMA OF THE URINARY
BLADDER
IT Ahmed1, HQ Al-Moghrabi1, S Islam1, EC Marginean1 and
KT Mai1. 1Department of Laboratory Medicine, The Ottawa
Hospital, Department of Pathology and Laboratory Medicine,
The University of Ottawa, Ottawa, Ontario, Canada.
15.
CLINICAL AND LABORATORY PROFILE COMPARISON OF
T(15;17) POSITIVE AND T(15;17) NEGATIVE ACUTE
PROMYELOCYTIC LEUKEMIA
Zhaodong Xu, 1 David Conrad, 2 Mitchell Sabloff, 2 Ruth
Padmore 1
1Department of Laboratory Medicine and Pathology, Division of
Hematology and Transfusion Medicine, 2Division of Clinical
Hematology, Ottawa Hospital, Ottawa
16.
VALIDATION OF ORTHO NEW FORMULATION 0.8%
SURGISCREEN SCREENING CELLS.
D. Neurath, M. Pilon, M. Tokessy Transfusion Medicine, The
Ottawa Hospital
Ottawa, ON, Canada
17.
BLOOD
TRANSFUSION
IN
BONE
MARROW
TRANSPLANTATION.
D. Neurath, A.Alsughayir, M. Tokessy, A. Giulivi,
Transfusion Medicine, The Ottawa Hospital, Ottawa, ON
Canada
18.
IMPLENMENTATION
OF
APHERESIS
PLATELET
UTILIZATION
TOOL
TO
IMPROVE
INVENTORY
MANAGEMENT
D. Neurath, M. Tokessy, A. Alsughayir, A. Giulivi
Transfusion Medicine, The Ottawa Hospital, Ottawa, ON
Canada
8
WELCOME
9
PEDIATRIC MALIGNANT PERIPHERAL NERVE SHEATH TUMOUR OF
THE RADIAL NERVE – CASE REPORT AND REVIEW OF THE
LITERATURE.
Dr. BM Purgina2, Dr. TA Flood2, Dr. J. Michaud2, Dr. MF Shamji1, Dr. E.
Ventureyra1,3.
1Division
of Neurosurgery, The Ottawa Hospital, Ottawa, Ontario.
of Anatomical Pathology, The Ottawa Hospital, Ottawa,
Ontario. 3Division of Neurology, Children’s Hospital of Eastern Ontario,
Ottawa, Ontario.
2Department
Malignant peripheral nerve sheath tumours (MPNST) are a group of
malignant tumours that arise from cells that are differentiating or have
differentiated toward those of the peripheral nerve sheath. They are
extremely uncommon in the pediatric population and children appear to
have a worse prognosis with a median survival of less than 2 years. We
report a highly unusual case of a nine-year-old girl with a past medical
history significant for Prader-Willi syndrome, vesiculoureteral reflux, and
chronic pyelonephritis and a biopsy that demonstrated MPNST of the left
radial nerve. She underwent local excision and no adjuvant therapy and
exhibits long-term survival. She has been followed for the last 22 years
and has no evidence of local recurrence or metastatic disease. The
original
biopsy
and
excision
material
was
reviewed
and
immunohistochemical studies were performed. Microscopic examination
reveals similar histologic features in both the biopsy and the excised
specimen. Foci of typical appearing schwannoma are intermixed among
larger areas with atypical epithelioid and spindle cells, mitotically active
areas including atypical forms, large areas of necrosis, hemorrhage, and
cyst formation. The tumour does not penetrate through the perineural
capsule. The lesion demonstrated strong reactivity for S100, vimentin, and
focal reactivity for GFAP. The lesion was also reactive for PGP9.5, which
has been reported to be a sensitive marker for MPNST. The Ki-67 index is
estimated to be up to 5% in the most active areas, which also favours the
diagnosis of MPNST. There was an absence of reactivity for HMB-45. The
original diagnosis of epithelioid MPNST was confirmed. The significant
heterogeneity in the biological aggressiveness of MPNSTs requires further
investigation into features prognosticating favourable postoperative course.
Reporting histological characteristics and immunophenotype of cases with
either early demise or long-term survival may help identify such features.
10
EXPRESSION OF TISSUE TRANSGLUTAMINASE IN FORMALINFIXED, PARAFFIN-EMBEDDED TISSUE IS IT USEFUL IN THE
DIAGNOSIS OF CELIAC DISEASE?
I Teo, H Marginean and EC Marginean.
Department of Pathology and Laboratory Medicine, University of Ottawa,
Ottawa, Ontario, Canada.
Introduction: Celiac disease, also known as celiac sprue, or glutensensitive enteropathy, affects one in 100 to 300 people. Current diagnostic
algorithms rely on a combination of findings, including the presence of
tissue transglutaminase (TTG) in the serum and confirmed by a small
intestinal biopsy. Research on tissue transglutaminase expression in
formalin-fixed paraffin-embedded tissue has yielded equivocal results thus
far, with few studies in the literature.
Materials and Methods: The files of the Department of Anatomic Pathology
at the Ottawa Hospital were searched for duodenal biopsies between
2007-2009. One hundred five cases were selected, and were divided into
the following groups: normal controls (30 cases), duodenitis (22 cases),
celiac disease (46 cases), and treated celiac disease (7 cases). The
hematoxylin and eosin slides were first reviewed and a modified Marsh
score was assigned according to current criteria, and then
immunohistochemistry was performed on all cases with antisera for CD3,
CD4, CD8, and TTG. For CD3, CD4 and CD8, T-lymphocyte counts were
recorded per one hundred enterocytes. For TTG, the degree of positivity
within the surface and crypt epithelium was recorded and intensity was
scored as 1+, 2+ and 3+. Both investigators assessed the specimens
separately and were blinded to the initial diagnosis made upon the biopsy.
Results: TTG stains in the subepithelial lamina propria, and demonstrates
variable staining within the surface enterocytes. TTG staining was variable,
with normal biopsies staining from 0-3+ in intensity; duodenitis biopsies
ranging from 1+ to 3+; celiac disease from 0 to 3+; and treated celiac
disease 0 to 2+. Statistical analysis shows that the Marsh score correlates
with the intensity of TTG staining of surface enterocytes. However, the
addition of TTG to Marsh scoring, CD3 and CD8 immunohistochemical
staining shows a statistically significant improvement in diagnosis.
Conclusions: As an adjunct to histologic features, CD3 and CD8, TTG is
most useful in the diagnosis of celiac disease which is graded Marsh 2 and
3. However, in biopsies in the Marsh 1 category (which are the most
nonspecific for celiac disease), TTG does not contribute significantly to the
diagnosis of celiac disease. These findings are in concordance with other
reports in the literature. This immunostain should be validated in larger
studies before adding it to current clinical practice.
11
A RETROSPECTIVE REVIEW OF OCTAPLEX UTILIZATION AT THE
OTTAWA HOSPITAL
M. Wozniak and J. Bormanis
Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa,
Ontario, K1H 8L6
Introduction: Frozen plasma has been the standard of therapy in Canada
for urgent reversal of anticoagulant effect from vitamin K antagonists.
Prothrombin Complex Concentrates are plasma derived blood products
that contain concentrated amounts of the four vitamin K dependent
coagulation factors (II, VII, IX, and X). They are a safer, more effective
alternative to frozen plasma by producing faster results with minimal
infusion volumes and better overall outcome. Octaplex, a four factor
prothrombin complex concentrate, has recently been approved for use in
Canada.
Methods: The main objective of this chart review is to investigate the
overall efficacy of Octaplex in oral anticoagulation reversal and bleeding
control in patients at The Ottawa Hospital. Areas of focus include
determining the efficacy of our current dosing protocol by monitoring final
INR values, looking at efficiency and timing of administration, and overall
achievement of hemostasis and survival. Furthermore, we plan to estimate
the extent to which frozen plasma use for the replacement of vitamin K
dependent factors has decreased since Octaplex has become available.
Results: This research is currently ongoing and completion is expected by
May 2009. So far 200 patients have received a standardized dose of
Octaplex based on the current protocol at the Ottawa Hospital since
September 2008. It is reasonable to expect that most, if not all, patients
achieved an INR value <1.5 based on this standard dose. It is more
unlikely however that all patients achieved complete hemostasis, moreover
received the therapy in an efficient time-frame. We do not expect to see
any significant side effects.
Conclusion: It is established that Octaplex is an effective therapy for
immediate reversal of vitamin K antagonists. It is important to establish the
efficacy of our current dosing protocol for this product and the overall
appropriateness and effectiveness of its use at the Ottawa Hospital.
12
LUPUS MILIIARIS DISSEMINATUS FACIEI OF THE EYELIDS: REPORT
OF TWO CASES
W. Liao1,2, S. Brownstein1,2, D.R. Jordan1, S. Gilberg1, S.S. Jolly1,2, R.
Prokopetz2. 1University of Ottawa Eye Institute, Ottawa, ON, Canada;
2Department of Pathology and Laboratory Medicine, University of Ottawa,
Ottawa, ON, Canada.
Purpose: To present 2 cases of lupus miliaris disseminatus faciei (LMDF),
an asymptomatic chronic papular eruption affecting the central area of the
face, especially the eyelids.1,2 Except for the description by Duke-Elder3 in
1974, to our knowledge, this condition has not been reported previously in
the ophthalmic literature.
Methods: Biopsy specimens from two women with LMDF affecting their
eyelids and periorbital areas were processed for pathological studies.
Results:
Histopathological examination disclosed 3 subepithelial
granulomas showing a zonal pattern. Two granulomas had a central area
of caseation necrosis and one had a central abscess. Special stains
revealed no evidence of microorganisms. All 3 lesions contained inflamed
hair follicles within the granulomatous inflammation and one lesion had hair
follicles continuous with the central necrosis. One patient was treated with
minocycline with gradual resolution of her papules.
Conclusions: Lupus miliaris disseminatus faciei may be a diagnostic
dilemma for both the ophthalmologist and pathologist as illustrated in both
of our patients. Our findings are consistent with the hypothesis that the
granulomas develop in response to damaged and inflamed pilosebaceous
apparatuses.
13
COMPARATIVE IMMUNOHISTOCHEMICAL STUDY OF SEROUS AND
MUCINOUS CYSTIC NEOPLASMS OF THE PANCREAS: SIMILAR
STROMA
PHENOTYPE
SUGGESTING
A
POSSIBLE
HISTOPATHOGENIC RELATIONSHIP
AD Edgecombe 1, BN Nguyen1, MM Gomes1, J Côté2, KT Mai1.
1Pathology
and Laboratory Medicine, The Ottawa Hospital, Ottawa,
Ontario, Canada and 2Pathology, Saint-Luc Hospital, CHUM, Montreal,
Quebec, Canada.
Background: Serous and mucinous cystic neoplasms (SCNs/MCNs) are
the most common true cystic neoplasms of the pancreas. They both occur
more frequently in females. Although SCN’s malignant potential is remote,
MCNs can demonstrate aggressive behaviour. They both boast a more
favourable clinical outcome than ductal adenocarcinomas. The aims of this
study were: 1) To characterize the stroma of SCNs and 2) To investigate
the possibility of a similar role of the stroma in the histogenesis of SCNs
and MCNs.
Design: 12 SCNs and 5 MCNs were analyzed immunohistochemically
using the following antisera: vimentin, CD10, inhibin, PR and ER. Normal
pancreatic tissue (17 cases) and sections of ductal adenocarcinomas of
the pancreas (3 cases) were used as controls.
Results: The age of the patients ranged from 45 to 80 years old (mean
63.8) for SCNs and 32 to 63 years old (mean 50) for MCNs. 8/12 patients
with SCNs and all 5 patients with MCNs were female. For SCNs, the
stroma was sclerotic, pauci-cellular and showed focal but moderate to
strong reactivity for PR, whereas immunostaining for ER was negative.
Inhibin and CD10 were expressed in 2 cases. For MCNs, the stroma was
more cellular with focal ovarian-like features and showed a larger number
of PR positive cells as well as expression of ER and inhibin (focal).
Vimentin was expressed in all stromal cells.
Conclusion: Both SCNs and MCNs contain similar PR positive stromal
cells. We postulate that the pauci-cellularity of the SCN stroma is possibly
a secondary change, as often seen in large MCNs. The predominant
occurrence in females and the presence of PR in both groups of tumours
raises the question of a similar stromal component, hence similar stromainduced pathogenesis with divergent epithelial differentiation.
14
UNUSUAL PRESENTATION OF A COMMON INFECTIOUS DISEASE IN
THE BREAST
Thamara Jayasinghe, PGY2 Resident Anatomical Pathology
DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE, THE
OTTAWA HOSPITAL-GENERAL CAMPUS, OTTAWA, ONTARIO
Primary tuberculosis in the breast is an extremely rare condition, affecting
women of reproductive age group. This condition is often misdiagnosed, as
the clinical features and radiological findings are non specific and can
mimic other mammary lesions, including carcinoma. Demonstration of the
causative organism by special stains and by culture is often negative due
to the paucibacillary nature of mammary tuberculosis. Fine needle
aspiration cytology is an important diagnostic tool. The presence of
epithelioid granulomata with caseous necrosis on histology is sufficient for
diagnosis even in the absence of demonstrable mycobacterial organisms.
It is important to be aware of this condition as a complete cure can be
achieved with antituberculous therapy along with surgical intervention
when necessary
15
INVESTIGATION OF CADHERIN AND CATENIN EXPRESSION IN
INVASIVE DUCTAL CARCINOMA OF THE BREAST VIA TISSUE
MICROARRAY
I Teo, L Pelletier and S Islam
Introduction: The relationship between intercellular adhesion molecules
and clinicohistopathologic features of the breast carcinomas is
controversial. Some studies have shown significant associations between
expression of adhesion proteins and parameters, such as tumour size,
grade, hormone status and lymph node status. Only E-cadherin has been
extensively studied to date, leaving unprobed 89 other members of the
cadherin family. By constructing tissue microarrays (TMAs), we can
explore the relationship between cadherin and catenin expression and
breast cancer. To maximize immunohistochemical resources and minimize
tissue use, the tissue microarray technique will be employed.
Materials and Methods: One hundred cases of tumour resections for
infiltrating ductal carcinoma (not otherwise specified) were drawn from the
records of the Department of Anatomic Pathology between 2006 and 2007.
Tumour characteristics and patient demographics were recorded. The
tumour slides were reviewed to ensure adequacy of material, and the
microarrays were constructed using one 2mm core taken from the
resection specimen. Along with a routine H&E stain, immunohistochemical
stains for E-cadherin, N-cadherin and beta-catenin were performed. The
microarray slides were reviewed independently, and membranous intensity
was graded as follows: 0 for no staining; 1 for weak staining; 2 for
moderate staining and 3 for strong staining. Results were then correlated
with nodal status and presence of lymphovascular invasion.
Results: Of the one hundred cases, eleven cases had indeterminate nodal
status (NX), and were excluded from analysis. There was no statistical
correlation between E-cadherin or beta-catenin expression and nodal
status. Lack of N-cadherin expression was associated with a positive nodal
status (Fisher's exact test, P = 0.0496). None of the immunohistochemical
stains showed any correlation with lymphovascular invasion.
Conclusions: E-cadherin and beta-catenin expression are not associated
with nodal metastases. While promising, the relationship between Ncadherin expression and nodal metastases should be validated in a larger
prospective study.
16
BREAK
17
LETHAL RUPTURE OF A TRAUMATIC ANEURYSM OF THE
POSTERIOR INFERIOR CEREBELLAR ARTERY A CASE REPORT
AND REVIEW OF THE LITERATURE.
Dr. BM Purgina1, Dr. C. Milroy1,2, and Dr. G. Jansen1.
1The
Ottawa Hospital, Department of Anatomical Pathology, Ottawa, ON
and 2Eastern Ontario Regional Forensic Pathology Unit, Ottawa, ON.
Subarachnoid haemorrhage (SAH) secondary to closed head injury is
rarely associated with traumatic aneurysms of the posterior circulation. We
report a case of ruptured posterior inferior cerebellar artery (PICA)
aneurysms following closed head injury without penetrating injuries or skull
fractures. A 22 year-old man was involved in an altercation and was struck
at least once to the head. He collapsed immediately and was unconscious
and was brought to hospital. Diagnostic imaging demonstrated an evolving
traumatic aneurysm in the left PICA. The aneurysm ruptured on Day 9 on
hospital admission, causing severe SAH and intraventricular hemorrhage
and patient was pronounced brain dead on Day 12. Autopsy was
performed, and the presence of a traumatic aneurysm was confirmed
grossly and histologically. To our knowledge, only a handful of cases of
traumatic aneurysms located at the PICA have been reported. Our case is
unique since we will present diagnostic imaging demonstrating the
evolution of the aneurysm in hospital.
18
SPONTANEOUS PNEUMOTHORAX AND LUNG CARCINOMA:
SHOULD ONE CONSIDER SYNCHRONOUS MALIGNANT PLEURAL
MESOTHELIOMA?
Flood TA, Sekhon HS, Seely J, Shamji F and Gomes MM
ABSTRACT:
We describe the clinical and pathological findings of a 68-year-old smoker
with previous asbestos exposure who presented with spontaneous
hydropneumothorax and was diagnosed with synchronous undifferentiated
lung carcinoma and incidental malignant pleural mesothelioma. The
synchronous occurrence of these two neoplasms is an extremely rare
event with fewer than twenty reported cases in the English literature. The
accurate diagnosis of synchronous tumors can be extremely challenging
and the identification of a concomitant mesothelioma in our case was not
made until an extensive immunohistochemical analysis was done on the
resection specimen. Spontaneous pneumothorax occurs much more
commonly in patients with malignant mesothelioma than with primary lung
carcinomas. Consequently, although synchronous pleural mesotheliomas
and lung carcinomas are infrequent, this diagnosis should be considered
when a patient with a lung mass and a history of asbestos exposure
presents with spontaneous pneumothorax and pleural thickening on
imaging. Identification of synchronous tumors is of critical importance for
determining the patient’s stage and management, and can have significant
medicolegal implications should the patient seek compensation.
19
UNUSUAL ADENOCARCINOMA WITH FEATURES SUGGESTIVE OF
MESONEPHRIC ADENOCARCINOMA OF THE PROSTATE
Hamidrea Faraji, Susan J Robertson, Eric Belanger, Kien T Mai,. Division
of Anatomical Pathology, Department of Laboratory Medicine, Hospital and
Department of Pathology and Laboratory Medicine, University of Ottawa,
Ottawa, Ontario, Canada
Abstract
Mesonephric carcinoma (MCA) is rare and has been often described in
female lower genital tract and urinary bladder and very occasionally in
male urinary bladder. We reported the first case of MCA.
The patient was 81 year-old and presented with lower urinary tract
symptoms. The serum PSA was up to 9/uL. CT scan revealed lesions in
the pelvic bones consistent with metastatic disease.
Microscopic
examination of the TURP specimen showed a papillary adenocarcinoma
accounting for 70% % of tissue. The adenocarcinoma displayed tubulopapillary with snout formation from the luminal cells and tubular structures
in retiform architecture. The carcinoma cells showed marked cytologic
atpia. Basal cells were occasionally present. Three foci of atypical
adenomatous hyperplasia were also seen. There was no high grade PIN.
Immunohistochemically, the tumor showed positive reactivity for
cytokeratin AE1/3, EMA, PAX2 and CD10 and negative reactivity for PSA,
vimentin, ER PR, AR, CK7 CK20 and neuroedocrine markers.
In conclusion, the adenocarcinoma likely represents the MCA and mimics
prostatic ductal adenocarcinoma. Recognition of the highly unusual
histopathological pattern of MCA is important in the diagnosis of the entity
in the surgical prostatic specimens.
20
ATYPICAL SMALL ACINAR PROLIFERATION WITH AND WITHOUT
ASSOCIATED PROSTATIC ADENOCARCINOMA
Trevor A. Flood, Hamid Faraji, Susan J. Robertson, Eric Belanger, Kien T.
Mai.
Department of Pathology and Laboratory Medicine, The Ottawa Hospital
and University of Ottawa, Ottawa, Ontario, Canada
Background: Atypical small acinar proliferation (ASAP) in prostatic biopsy
cores is associated with a high rate of detection of prostatic
adenocarcinoma (PCA) on repeat biopsy. The principal aim of this study
was to characterize ASAP with and without associated prostatic
adenocarcinoma in radical prostatectomy specimens.
Materials and Patients: Cases presenting ASAP on 5 transrectal
ultrasound-guided biopsy cores with their corresponding hemiprostate
resected by radical prostatectomy (RP) were retrieved from our institution.
Cases were divided into groups of hemiprostates with PCA (Group 1) or
without PCA (Group 2) in the RP specimens.
Results: There were a total of 32 cases with 24 and 8 cases belonging to
Groups 1 and 2 respectively. Nine cases were associated with clinically
significant PCA in the same hemiprostate. Most PCA occurred in patients
with cores having ASAP from the mid and apical portions of the prostate.
All ASAP associated with 1-3 isolated acini without basal cells but with
frequent nucleoli larger than 0.5 microns or with high grade prostatic
intraepithelial neoplasm (HGPIN) involving small ducts or acini were
associated with PCA. Other criteria that were not specifically associated
with malignancy included blue-tinged luminal secretions, dark cytoplasm,
positive AMACR reactivity (features more often observed in Group 1), and
small acini without basal cells but with infrequent nucleoli (feature more
often observed in Group 2).
Conclusions: The presence of prominent nucleoli in a large proportion of
luminal cells of small acini is a highly specific marker of PCA in the
prostate.
21
LUNCH AND
POSTER
VIEWING
(ATRIUM 2ND FLOOR, FACULTY OF
MEDICINE)
22
GUEST SPEAKER
DR. Luan Truong
RENAL TUBULAR CELL APOPTOSIS
IN TUBULOINTERSTIAL RENAL
23
RESPIRATORY SUNCYTIAL VIRUS (RSV) DETECTION IN CLINICAL
SPECIMENS USING A NANOLITER REAL TIME PCR RESPIRATORY
PATHOGEN PANEL
R. Slinger, F. Chan, D. Goldfarb, N. Barrowman, I. Moldovan, H. Ji, J.
Brooks
1Children's
Hospital of Eastern Ontario, 2University of Ottawa, Ottawa, ON,
CANADA, 3National HIV & Retrovirology Laboratories, Public Health
Agency of Canada.
Background: A novel microfluidic molecular diagnostic platform from
BioTrove™ Inc., bases upon performance of several thousand individual
33 nanoliter real-time PCR reactions at the same time may allow for both
detection and quantitation of multiple infectious disease agents. Since
detection of viral pathogens in human clinical specimens has not
previously been described, we investigated whether respiratory viral
infections could be diagnosed with nanoliter PCR.
Methods: A prototype respiratory panel containing primers for respiratory
pathogens, including respiratory syncytial virus (RSV), influenza viruses,
and coronaviruses, was designed. RSV detection accuracy was used as
the initial main outcome measure since a large number of RSV-positive
nasopharyngeal aspirates (NPA) were available for study. Real-time PCR
was performed on OpenArray™ plates in an NT thermocycler with SYBR
Green detection and melting curve analysis.
Results: One hundred eighty-eight NPA specimens collected during 20072008 RSV season at a children’s hospital were studied, with 88 of these
RSV-positive by the reference method of immunofluorescent antibody
assay and viral culture. Three of these 88 showed non-specific
fluorescence by nanoliter PCR and were considered indeterminate. Of the
remaining 85 specimens, 81 were nanoliter PCR-positive, for a sensitivity
of 95.3% (88.5-98.2). PCR specificity was 100% (96.3-100). In addition,
multiple other respiratory viruses were detected with the panel including
influenza viruses, rhinoviruses, and the human coronaviruses.
Conclusions: This study demonstrates that an important respiratory virus,
RSV, can be detected in clinical samples with high sensitivity and
specificity using the BioTrove™ nanoliter volume real-time PCR platform.
As well, simultaneous detection of multiple human respiratory pathogens
appears feasible. The ability to quantify viral pathogen load is noteworthy,
since quantitation is not possible with many multi-target diagnostic
platforms, and will allow us to determine if higher respiratory viral loads
correlate with increased disease severity.
24
UNUSUAL HISTOPATHOLOGICAL PATTERN OF A NEPHROGENIC
ADENOMA IN A URETHRAL DIVERTICULUM
AD Edgecombe, M Lamba, KT Mai, V Acharya. Department of Pathology
and Laboratory Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada
Background: Nephrogenic adenoma (NA) is a rare benign lesion which
develops from implantation of renal tubular cells in the lower urinary tract. It
mostly occurs in the bladder but is also seen in the urethra, ureter and
renal pelvis. Urinary tract injury predisposes to NA. The significance of NA
is its potential confusion with adenocarcinoma.
Design: We present a case of a 39 year old female who presented with
dysuria, dyspareunia, urinary incontinence and an intermittent anterior
vaginal wall cystic mass. She was diagnosed with a urethral diverticulum
and a diverticulectomy was performed.
Results: A multifocal NA displaying tubular, papillary and cystic growth
patterns was identified within the urethral diverticulum. NA infiltrated the
anterior vaginal wall mucosa. The cells lining tubules and papillae were
flattened to cuboidal with some showing a hobnail pattern. Most cells had
an eosinophilic cytoplasm but in a minority, the cytoplasm was clear.
Atypia was present but thought to be reactive in nature due to the
significant acute and chronic inflammation. Mitotic activity was absent. The
cells were positive for cytokeratin CK7 and negative for CK20, CD10,
monoclonal CEA and MIB1. Focal positivity of RCC and CK5/6 was noted.
Discussion: This NA had several unusual features. The multifocal,
infiltrative pattern in this case was worrisome. However, the benign cellular
appearance and immunohistochemical findings support a diagnosis of NA
over its primary differential diagnosis of clear cell adenocarcinoma.
25
PROSTATIC ADENOCARCINOMA AND STATUS OF RESECTION
MARGIN OF RADICAL PROSTATECTOMY ASSOCIATED WITH CORE
BIOPSIES WITH ATYPICAL SMALL ACINAR PROLIFERATION OR
MINIMAL CANCER
TA Flood, BN Nguyen, EC Marginean, BM Purgina, KT Mai. The Ottawa
Hospital, Ottawa, ON, Canada; The University of Ottawa, Ottawa, ON,
Canada
Background: The finding of atypical small acinar proliferation (ASAP) in
prostate biopsy cores has been previously investigated with repeat
biopsies that show a rate of prostatic adenocarcinoma (PAC) ranging from
15 to 40%. The relationship between cancers missed on biopsy and cores
positive for ASAP, minimal cancer, and absence of PAC has not been
examined. In this study we use a model of hemiprostates corresponding to
5 cores associated with no cancer, ASAP, and minute cancers.
Design: The PAC biopsy negative hemiprostates of radical prostatectomy
(RPs) specimens with biopsy proven contralateral PAC were examined.
PAC negative hemiprostates with biopsy cores corresponding to minute
cancers (group 1), ASAP (group 2) and no cancer (group 3) were obtained
retrospectively from 2002 to 2008 from our institution. Groups 2 and 3 were
subdivided into 2a/3a and 2b/3b for hemiprostates with or without PAC
respectively.
Results: The interval from biopsy to RP ranged from 1 to 8 months. Of 637
total RPs, there were 31, 14, 18, 86 and 75 hemiprostates that fulfilled the
criteria for groups 1, 2a, 2b, 3a and 3b respectively. There was a higher
rate of PAC, including clinically significant PAC, in the hemiprostates
associated with ASAP compared to non-ASAP hemiprostates. However,
this difference was not statistically significant. Positive resection margins
were observed in 2 cases. The biopsies for these 2 cases had
demonstrated minute cancer and negative for cancer.
Conclusions: ASAP in needle core biopsy appears to be associated with
an increased rate of PAC, however this increase was not statistically
significant in the current study. There was no difference in the surgical
resection margin status of RPs performed soon after an ASAP positive
biopsy or following a delay of up to eight months. Furthermore, biopsies
with ASAP were not associated with a higher rate of positive margins when
compared to biopsies with minute cancer or negative for cancer.
26
BREAK
(ATRIUM)
27
RENAL CELL CARCINOMA WITH HYBRID FEATURES OF
CONVENTIONAL AND CHROMOPHIL CYTOMORPHOLOGY: A
FLUORESCENT IN SITU HYBRIDIZATION STUDY.
Hamidreza Faraji, MD, Susan J. Robertson, MD, Eric C. Belanger, MD,
Kien T. Mai, MD. Department of Pathology and Laboratory Medicine,
The Ottawa Hospital and University of Ottawa, Ontario, Canada.
Background: We performed fluorescent in situ hybridization (FISH) to
investigate the numeric change of chromosomes 7, 17 and Y and loss of
chromosome 3p of “chromophil renal cell carcinomas (RCC) with extensive
clear cell changes (CCC)”. This subtype of RCC often pose differential
diagnostic problem between chromophil RCC and clear cell RCC (CRCC)
Method: Consecutive cases of RCC over a 12-year period were reviewed
to identify “chromophil RCC with extensive CCC”. Immunostaining for
cytokeratin 7 and AMACR and FISH for chromosomes 7, 17 and Y were
applied.
Results: Of the total of 521 RCC retrieved, there were 49 RCC having
chromophil or papillary features that could be grouped into: a) group 1 (12
cases), typical CRCC with focal areas of papillary formation; b) group 2 (28
cases), focal typical chromophil RCC having papillary architecture with
extensive CCC; c) group 3 (9 cases) RCC with an admixture of
eosinophilic /clear cytoplasm and solid/ papillary architecture. Group 1
showed negative immunoreactivity for CK7 and AMACR and absence of
numeric chromosomal gain or loss. Group 2 and 3 showed variable
reactivity for CK7 and AMACR. 25 tumors in the group 2 and 5 in the group
3 showed trisomies of chromosomes 7 and /or 17 with or without loss of
chromosome Y.
Conclusions: Light microscopic examination correctly classified RCC in a
majority of RCC with typical morphology. Chromophil RCC may show
phenotypical CCC mimicking CRCC. In a small number of cases with
mixed histopathological features, FSH is helpful in the sub-typing the RCC
#
CRCC,
papillar
y
15
PRCC
CCC
27
RCC,
mixed
26
Total
68
Table 1 Pathological and Clinical Data of Study Cases
Sarcomatous
Size
Grade Stage
VI
LN
DM
change
0.5-14
6.37.
4
2.6-6.6
4.62.
0
2-14
6.86.8
DOD
2-4
(3.2)
1-4
(3.05)
14(9)
0
7
3[1]
9
1-3
(2.6)
1-3
(2.3)
3(2)
3
2
2[2]
2
2-4
(3.10)
1-4
(3.10)
7(3)
1
5
7[3]
6
24(14)
4
14
12[6]
17
VI: venous invasion, ():Renal Vein Invasion)
LN: lymph node metastasis, DM: distant metastasis, DOD: dead if disease
[ ]: focal sarcomatous change
VI difference between CRCC and mixed, and between CRCC and PRCC with CCC were
statistically significant, p<0.05
28
IMMUNOHISTOCHEMICAL AND IN SITU HYBRIDIZATION STUDIES OF
MULTILOCULAR CYSTIC RENAL CELL CARCINOMA
Bibianna M. Purgina MD, Trevor A. Flood MD, Eric C. Belanger MD
FRCPC, Kien T. Mai MD FRCPC.
Division of Anatomical Pathology, Department of Laboratory Medicine, The
Ottawa Hospital and Department of Pathology and Laboratory Medicine,
University of Ottawa, Ontario, Canada.
Objective: Multilocular cystic clear cell renal cell carcinoma (MCCRCC) is
a distinct subtype of renal cell carcinoma (RCC).
The
immunohistochemical properties and the molecular changes of MCCRCC
have not been studied.
Materials and Methods:
21 MCCRCC and RCC with extensive
multilocular areas were retrieved from the files at our institution. All cases
were submitted for immunohistochemical and FISH studies. Five alveolar
clear cell RCC (CRCC) measuring less than 2 cm in diameter and two
cystic nephromas (CN) with focal clear epithelial cells were used as control
Results:
MCRCC were associated with female:male ratio of 1:4.
Immunostaining for CK7 showed extensive reactivity in 3 tumors (group 1),
focal immunostaining in 7 tumors (group 2) and negative in 11 cases
(group 3). In group 1, the MCCRCC were predominantly cystic, with minor
solid component. The tumor had focal areas of chromophil cells. The
intercystic septa was relatively cellular and showed positive reactivity for
PR in a large number of cells. FISH demonstrated the absence of loss of
3p25/3p14. Group 3 showed solid areas of clear cells. The tumor cells
showed positive reactivity for RCC and CD10, and the intercystic stroma
was sclerotic and showed negative reactivity for PR. The tumor was
associated with loss of 3p25/3p14 loci in all cases. Group 2 had
intermediate histologic and immunhistopathological features of the other
two groups and loss of 3p25/3p14. Immunostaining for CRCC and CN
showed CK7-RCC+/CD10+/PR- and CK7+/focal CD+/focal RCC+/PR+ for
CRCC and CN as previously described in literature. Focal areas with clear
cells in CN showed weak CK7+. No loss of 3p25/3p14 in CN
Conclusions : Some MCRCC contained areas simulating CN. We
propose that there is at least a subset of MCRCC that develop from CN.
The difference in gender ratio between MCRCC and CN may be due to the
fact that CRCC tend to develop more often in CN in male patients.
29
FLUORESCENT IN SITU HYBRIDIZATION OF NON-PAPILLARY
ONCOCYTIC/EOSINOPHILIC RENAL CELL CARCINOMA
Itrat Ahmed, MD, Susan J Robertson, MD, Eric Belanger, MD, Kien T.
Mai, MD
Division of Anatomical Pathology, Department of Laboratory Medicine,
Hospital and Department of Pathology and Laboratory Medicine, University
of Ottawa, Ottawa, Ontario, Canada
Aims: Chromophil (papillary) renal cell carcinoma (PRCC) and clear cell
renal cell carcinoma (CRCC) can display extensive areas with
oncocytic/eosinophilic changes and may be associated with either minimal
or no papillary architecture. These oncocytic/eosinophilic and solid RCC
(OSRCC) often mimic renal oncocytoma (RO). We investigated numeric
changes of chromosomes 7,17 and Y and loss of the small arm of
chromosome 3 in the above-mentioned oncocytic RCC by using the FISH
technique.
Materials and Methods: Archival cases of oncocytic RCC previously
screened by immunohistochemical study to exclude RO and chromophobe
RCC and RCC with immunohistochemical properties of RO were submitted
for study.
Results: There were a total 9 cases.
The tumors displayed an
immunoprofile of CRCC or chromophil RCC with RCC(+) and PR(-) and
variable reactivity for CK7 and AMACR in 7 cases. In addition there were
two cases previously reported as malignant RO due to cytological atypia
and lymph node metastasis in one case. FISH study showed trisomies
7/17 with or without loss of Y in five tumors. Loss of loci 3p25 and 3p14
was identified in another 2cases. The remaining 2 tumors with features of
RO showed no evidence of numeric changes for chromosomes 7, 17 and
Y or loss of loci 3p25 or 3p14
Conclusions: In this setting of study, FISH for chromosomes 7, 17 and Y
lend more support for the role of immunostaining in distinguishing RO and
chromophobe RCC from the non-chromophobe RCC.
FISH for
chromosomes 7,17, Y and loci 3p25 and 3p14, and not immunostaining for
AMCR and CK7 is helpful in distinguishing CRCC from chromophil RCC
30
AWARDS TO
BE
ANNOUNCED
31
POSTERS
32
ROLE OF p300 IN REGULATION OF Myf5 GENE EXPRESSION
Tanja Francetic and Qiao Li
Department of Pathology and Laboratory Medicine, Department of Cellular
and Molecular Medicine, Faculty of Medicine, University of Ottawa,
Ontario, Canada.
The differentiation of skeletal muscle cells during embryogenesis is driven
by highly complex interplay of transcriptional regulators. The key players in
this process belong to MyoD family of transcription factors. Myf5 and MyoD
are the early transcription factors which are the first to induce expression of
skeletal muscle specific genes. The study of regulation of these two factors
is of great importance to understanding the process of skeletal muscle
differentiation. Histone acetyltransferase (HAT) activity of p300 is one of
the factors known to be necessary for expression of both Myf5 and MyoD.
However, the specific target of p300 HAT at this stage of differentiation is
not known. In order to elucidate the mechanism by which p300 regulates
Myf5 expression we have inhibited the HAT activity of p300 by curcumin.
We found that decrease in p300 HAT activity had limited effect on Myf5
protein levels in cells induced to differentiate to skeletal muscle. However,
we observed a decrease of Myf5 mRNA levels. We will next determine the
occupancy of p300 at Myf5 promoter. Further more we will examine the
role of p300 in chromatin remodelling and its function as a co-activator at
the Myf5 promoter. With this research we aim to increase our
understanding of transcriptional regulation in the early stages of skeletal
muscle differentiation.
33
ROLE OF THE RETINOID X RECEPTOES IN SKELETAL MUSCLE
DIFFERENTIATION
Melanie Le May, Tanja Francetic, Qiao Li
Department of Pathology, Department of Cellular and Molecular Medicine,
Faculty of Medicine, University of Ottawa.
Retinoids are powerful regulators of cell growth and differentiation.
Retinoic acid (RA) is a retinoid which exerts its pleiotropic effects primarily
through the action of two families of ligand-inducible transcriptional factors,
the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). When
RA binds, the transcription co-activator p300 is recruited. Interestingly, a
growing body of evidence indicates that the acetyltransferase function of
p300 is able to act on proteins other than histones, such as transcription
factors. The formation of myoblasts from myogenic precursor cells and
their successive differentiation into muscle cells involves four master
transcriptional regulators: Myf5, MyoD, myogenin, and Mrf4. The activity of
p300 is responsible for the activation of MyoD and Myf5 and embryonic
stem cells lacking p300 or its acetyltransferase activity are strongly
impaired in their ability to activate these transcription factors during skeletal
myogenesis. Preliminary results from our lab show that treatment of cells
with the aromatic retinoid TTNPB which is a synthetic RAR specific
retinoid, does not induce muscle differentiation while the natural all-trans
retinoic acid (ATRA) does. Since ATRA can be metabolized into 9-cis RA
which binds the RXRs, the RXRs are implicated in this process. While
both RA and TTNPB to some extent maintain levels of p300 inside the cell,
only ATRA is capable of sustained maintenance of p300 to day nine of
differentiation. Furthermore, Myf5 is independent of RA signaling as its
level of expression did not change with different treatment concentrations.
It is possible that RA is targeting other factors in the signaling cascade,
perhaps through its ability to maintain levels of p300. Activation of
RAR/RXR heterodimers could be the mechanism by which the RA induced
skeletal muscle differentiation response is strengthened. Our goal is to
elucidate the molecular mechanism behind the RA induced increase in
skeletal muscle differentiation and to study the interaction of p300 and the
master regulator MyoD.
34
ROLE OF THE 26S PROTEASOME IN THE EXPRESSION OF RETINOIC
ACID INDUCED GENES
Aliaa Higazi, Mahmoud abed and Qiao Li
Department of Pathology and Laboratory Medicine, Department of Cellular
and Molecular Medicine, Faculty of Medicine, Ottawa University, Ottawa,
Ontario, K1H 8M5, Canada.
Retinoic acid (RA) is the most potent derivative of vitamin A. It is involved
in various cellular processes such as development and differentiation. The
physiological effects of RA are mediated through retinoic acid receptors
(RAR) and retinoid X receptors (RXR) which are transcription factors that
require the function of coactivators and corepressors. It has been reported
that the activity of the 26S proteasome is essential for retinoid receptors
mediated transactivation. However, the mechanism by which the 26S
proteasome affects RAR-mediated gene expression remains elusive. Here,
we examined the occupancy of RAR promoters with RAR/RXR by
chromatin immunoprecipitation (ChIP) assay as well as the binding of
endogenous
retinoid
receptors
to
the
coactivators
by
coimmunoprecipitation. We demonstrated that both promoter occupancy
and coactivators binding to retinoid receptors require the 26S proteasome
function. Thus, the 26S proteasome appears to function as a crucial factor
regulating the formation of protein complex that binds to the promoter of
RA induced genes. Hopefully, this study will help to fully understand the
molecular bases underlying the role of the 26S proteasome in modulating
RA responsive genes.
35
INVOLVEMENT OF PML BODIES IN CBP DEGRADATION VIA
PROTEASOME PATHWAY
Jonathan St-Germain, Jihong Chen and Qiao Li
Department of Pathology and Laboratory Medicine, Faculty of Medicine,
University of Ottawa, Ottawa, Ontario, Canada
Transcriptional coactivator CBP is involved in the regulation of various
biological processes including cellular differentiation, proliferation and
survival. The function of CBP is critical for proper embryonic development
and is relevant in cancer biology. Although much is known about the
functional roles of CBP in these cellular processes, fewer studies have
assessed what in turn regulates CBP activity per se. It has been reported
that CBP colocalize with PML bodies which are nuclear structures
disrupted in acute promyelocytic leukemia. However, the biological
relevance of CBP localization to PML nuclear bodies is still unclear. We
demonstrate, in this study, that histone deacetylase inhibitor valproic acid,
a therapeutically relevant compound used for the treatment of epilepsy,
modulates CBP activity. Valproic acid reduces the steady-state level of
CBP by inducing CBP degradation through the ubiquitin-proteasome
pathway, while increasing colocalization of CBP with ubiquitin nuclear
speckles and with PML nuclear bodies. Our results suggest that PML
nuclear bodies are nuclear sites involved in the ubiquitin-dependent
degradation of CBP, which provides novel insights in the regulation of CBP
function and highlights the relevance of CBP localization to PML nuclear
bodies.
36
EFFECTS OF P300
DIFFERENTIATION
HAT
ACTIVITY
ON
SKELETAL
MUSCLE
Name: Sourianna Awada (Honours student)
Supervisor: Qiao Li
Department of Pathology and Laboratory Medicine, Faculty of Medicine,
University of Ottawa
Abstract:
Histone acetylation is one of the processes that makes DNA accessible for
the transcriptional machinery, and subsequently increases levels of gene
expression. Chromatin remodelling occurs through two major enzymatic
activities, ATP-dependent remodelling complexes and histone
acetyltransferase activity (HATs). The transcriptional co-regulators
p300/CBP possess this HAT activity, and their prime target is the Nterminal tails of the core histones H2A, H2B, H3, and H4. p300 HAT
activity specifically has been shown to be required for the expression of the
primary myogenic regulatory factors (MRFs) MyoD and Myf5 during
skeletal muscle differentiation1. However, the mechanism of action of
p300 activity in regulating primary MRF expression during skeletal
myogenesis has yet to be elucidated. Once these mechanisms are fully
understood in this type of system and eventually translated into stem cells,
therapies and treatments can be developed for an array of degenerative
muscle diseases. We are studying the role of p300 HAT activity in skeletal
muscle differentiation using curcumin to inhibit this activity. Here we have
found that curcumin inhibits skeletal muscle differentiation. We also show
that curcumin inhibits histone acetylation during the early stages of
aggregation, however it does not affect Myf5 protein expression.
37
SODIUM TRANSPORT INTO THE CENTRAL NERVOUS SYSTEM AND
SALT SENSITIVE HYPERTENSION
Md Shahrier Amin, Frans H H Leenen
University of Ottawa Heart Institute, Ottawa, ON, Canada
Both Na+-K+-ATPase and benzamil sensitive Na channels, possibly ENaC,
contribute to increases in [Na+] in the CSF in Dahl S (DS) rats on high Na
diet. All three subunits of ENaC are expressed in the choroid plexus (CP).
To elucidate their role in Na+ transport by the CP we studied ENaC protein
localization by electron microscopy (EM) and Na+ transport by assessing
uptake of 22Na and sodium green fluorescence in the CP.
Lateral ventricle CPs were removed from 5-6 weeks old, male Wistar, Dahl
R (DR) and DS rats on regular (0.3%) or high (8.0%) Na diet for 7 days.
The effects of benzamil (10-8 M), ouabain (10-3 M) or both (n=6-8 per
group) were evaluated by studying uptake of 22Na by the CP after 30 sec
incubation in aCSF versus aCSF+drug. Fluorescence emission of sodium
green was assessed to evaluate changes in intracellular [Na].
Comparisons were done pair-wise between the LV CPs from the same rat.
By EM, all three ENaC subunits were present in the CP of Wistar, DR and
DS. In individual cells, ~10-15% of labeled subunits were in the microvilli,
~70-80% in the cytoplasm and ~5% on the basolateral membrane.
In Wistar rats on regular Na diet, benzamil decreased uptake of 22Na (as
cpm/100 µg) by the CP ~20% (Ctrl 700±35, Benz 570±38; p=0.01).
Ouabain increased uptake ~40% (Ctrl 590±69, Oua 780±60; p=0.0005)
and blocked the effect of benzamil (Ctrl 585±41, Benz+Oua 539±45;
p=0.35). Similar effects were observed on sodium green fluorescence.
Uptake of 22Na was lower (p=0.0001) in DS (419±28) than DR (552±23) or
Wistar (595±30) on regular diet. High Na diet for 7 days decreased
(p=0.04) uptake in DR (473±28) but not Wistar (572±41) or Dahl S
(413±39). The effect (percent change vs control) of ouabain was
attenuated (p=0.04) with high Na diet in both Wistar (RS 41±7%, HS
22±7%) and DR (RS 38±16%, HS 16±7%) but not in Dahl S (RS 43±18%,
HS 64±20%). High salt did not have a significant effect on the benzamil
sensitive uptake in any strain (Wistar: RS -21±4%, HS -19±5%; DR: RS 25±8%, HS -28±10%; DS: RS -29±10%, HS -26±7%).
The results suggest that 1) ENaC mediated Na+ transport is significant in
CP and dependent on Na+-K+-ATPase activity, 2) 22Na uptake is lower in
DS than DR or Wistar rats, 3) high Na diet attenuates 22Na uptake in DR
but not in Wistar or DS, 4) high Na diet inhibits Na+-K+-ATPase activity in
salt resistant strains but not in salt sensitive strains. These variances might
contribute to increases in CSF [Na+] and thereby neuronal response in
Dahl S on high salt diet. The results provide novel insights into the central
mechanisms of salt sensitive hypertension.
38
Percent change in
22
Na uptake by the CP
p<0.05
63.94
65.00
45.00
42.75
40.54
37.86
21.97
25.00
15.51
5.00
lS
-18.71
D
-28.15
ah
ar
-21.16
is
t
-24.49
W
-35.00
lR
-15.00
D
ah
Percent change from the control CP
85.00
-55.00
-75.00
Ouabain Reg Salt
Benzamil Reg Salt
39
Ouabain High salt
Benzamil High salt
-29.54
-26.20
EXPRESSION PROFILE OF P16 (INK 4A) AND MIB1 (KI-67) IN HIGH
GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL) AND
IMMATURE SQUAMOUS METAPLASIA (ISM) OF THE UTERINE
CERVIX
MS Amin, MD, PhD candidate and S Islam, MD, PhD, FCAP
Division of Anatomical Pathology, The Ottawa Hospital, Eastern Ontario
Regional Laboratory Association (EORLA), The Department of Pathology
and Laboratory Medicine, The University of Ottawa, Ontario, Canada.
ABSTRACT
Background: Recognition of HSIL from ISM can be a very difficult task,
particularly in those cases with "borderline" morphologic features. The p16
gene product inhibits progression of the cell cycle. Integration of the HRHPV DNA into the genome however activates a positive feedback loop that
paradoxically elevates p16 proteins in cervical dysplasia and carcinoma.
MIB1 (Ki-67) is expressed in the nucleus of cells that are no longer in G0
phase of the cell cycle.
Objective: The purpose of the current study was to examine p16 and
MIB1 expression profile and cellular localization in HSIL and ISM of the
uterine cervix.
Methods: Immunohistochemistry was done with commercially available
monoclonal antibodies against p16 and MIB1 on 150 cases of HSIL and
150 cases of ISM. Reactivity to p16 was scored as negative (no
immunoreactivity), focal positive (<5% of cells) and diffuse positive (>90%
of cells). MIB1 expression was assessed in the basal, parabasal and
intermediate keratinocytes. Intensity of staining was graded as weak,
intermediate or strong. Localization was categorized as cytoplasmic,
nuclear or combined. Assessment of immunostains was confirmed with 2
independent pathologists.
Results: All 150 (100%) cases of HSIL showed diffuse and strong nuclear
and cytoplasmic staining of p16. In all HSIL, MIB1 expression was strong
with nuclear staining seen in basal, parabasal and intermediate cells. In 30
(20%) cases of ISM, p16 immunostain was focally positive with weak
nuclear staining. Additional 15 (10%) cases showed a weak cytoplasmic
p16 staining. All 150 (100%) cases of ISM showed strong nuclear staining
for MIB1 in the basal keratinocytes.
Conclusion: Diffuse and strong nuclear and cytoplasmic p16 expression
in combination with strong MIB1 nuclear expression in basal, parabasal
and intermediate cells favor
HSIL over IMS.
40
MALE BREAST CARCINOMA: PROGNOSTIC MARKERS, AGE AS A
VARIABLE?
M. Marinescu, S.J. Robertson. Department of Pathology, University of
Ottawa; Department of Pathology and Laboratory Medicine, The Ottawa
Hospital, Ottawa, Ontario.
Background and Objective: Male breast carcinoma (MBC) is rare (<1%),
and although the literature suggests that the majority of cases are ER
positive, there is no consensus with respect to AR receptor status
(Contractor, et al., 2008). Also there is no agreement re prognostic
implication of AR in MBC. As there is some suggestion, at least in women,
that AR may mediate the antineoplastic action of Medroxyprogesterone in
breast cancer (Riva et al., 2005) the presence of AR in MBC may also be
of interest from a therapeutic standpoint. With respect to methodological
issues there is not even a consensus as to the usual AR status of adjacent
non-neoplastic breast tissue in males and indeed this is often not reported
in the literature. For these reasons, a review of AR, ER, PR, and HER2/neu status in MBC was undertaken. These were correlated with age,
grade and node status.
Method: All MBC diagnosed between January 2003 and February 2009
were reviewed (n=22). ER, PR, AR were assessed by IHC. Her-2neu
status was assessed by IHC or FISH (n=13). Adjacent normal tissue,
where available, was also assessed for ER, PR and AR status.
Results: The age distribution of MBC in our series showed a bimodal peak
but, unlike female breast cancer, there was no difference in the ER, PR,
AR or Her-2/neu status in the older or younger MBC. This does not support
a theory of a different AR related etiology (Toro et al., 1998) in these age
groups. In contrast to Pich et al. (1999) who describe uniform weak
positive staining, our series showed a range of AR positivity in nonneoplastic breast from negative to strong. This suggests AR status of nonneoplastic breast should not be completely excluded as a factor in MBC
pathogenesis. In our series there was no correlation between any of the
markers tested and the standard prognostic factors (grade, node status or
stage).
41
PRIMARY MELANOMA OF THE LUNG: A CASE REPORT AND
REVIEW OF THE LITERATURE
M. Marinescu1, M. Gomes1, F.M. Shamji2, J.M. Seely3, H. Sekhon1.
1Department of Pathology, 2Department of Thoracic Surgery, 3Department
of Radiology, University of Ottawa , The Ottawa Hospital, Ottawa, Ontario.
Primary malignant melanoma (MM) of the lung is one of the rarest types of
melanoma (< 1%) with approximately fifty five cases reported in the
literature, but when strict criteria for diagnosis are applied are even less
cases. We report a case of 74-year-old man who was found to have an
incidental 3 cm solitary mass in the lower lobe of the right lung during
investigations to rule out pulmonary embolism. The histopathological and
IHC (Melan-A, HMB45) findings of the biopsy and resection specimens
were consistent with spindle cell MM, with invasion of bronchial epithelium.
Interestingly, S-100 stain was essentially negative. All eight lymph nodes
recovered were negative for malignancy.
The uninvolved lung
parenchyma showed diffuse interstitial fibrosis. The patient was extensively
evaluated, clinically and by the best available imaging technique, to
exclude metastasis from an occult primary MM, before considering the
diagnosis of primary MM of the lung. He underwent right lower lobe
lobectomy and at nine months postoperative follow-up there was no
evidence of recurrence or metastasis. Previously reported cases were
reviewed with respect to clinical, histopathological features and diagnosis
criteria for primary MM of the lung and our case fulfills the recommended
criteria. Although melanoma arising in the lung as a primary tumour
remains controversial, this case supports the likelihood of the scenario.
The oncogenesis of primary MM of the lung is still unclear, because of the
absence of melanocytes in lower respiratory tract. Therefore, the
hypotheses of development of primary pulmonary MM are of academic
interest and will be further discussed.
42
UROTHELIAL CARCINOMA ASSOCIATED
DIAGNOSED PROSTATIC ADENOCARCINOMA
WITH
CLINICALLY
TA Flood, B Nguyen, EC Marginean, BM Purgina, KT Mai. The University
of Ottawa, Ottawa, ON, Canada; The Ottawa Hospital, Ottawa, ON,
Canada
Background: Prostatic adenocarcinoma (PAC) and urothelial bladder
carcinoma (UC) are the two most common malignancies of the lower
urinary tract in males. There is an elevated incidence of incidental PAC in
patients with UC who undergo cystoprostatectomy. An increased incidence
of UC is also observed in patients diagnosed with PAC. The aims of this
study were 1) to validate the association between these two groups of
tumors and 2) to further characterize the relationship of UC with PAC, with
regards to their clinical impact (incidental versus clinically symptomatic
PAC) in a population living in a Canadian city.
Design: All cases of UC and PAC between 2002 and 2008 were retrieved
from the archives of our institution and retrospectively analyzed.
Results: There were a total of 790 patients with biopsies positive for UC (n
= 670) or who underwent cystoprostatectomy for invasive UC (n = 120).
The UC was of low grade (LGUC) in 408 of the cases and high grade
(HGUC) in 382 of the cases. Of the 120 cystoprostatectomies for UC, 78
(65%) had incidental findings of PAC of which 50 were clinically
insignificant and 28 were clinically significant. A total of 2568 patients were
diagnosed with PAC over the six year period. Twenty-one (0.8%) of these
patients (ages: 76+/- 8) had both high grade/advanced stage PAC and UC.
Categorization of the twenty-one UC cases included 16 non-invasive
LGUCs, 3 non-invasive HGUCs, and 2 superficially invasive HGUCs. In
addition, three patients had concurrent UC and secondary PAC invading
into the urinary bladder. All UC cases occurred within 6 years prior to or 12 years following the diagnosis of PAC.
Conclusions: Cystoprostatectomy for the management of invasive UC
was associated with incidental PAC in 65% of cases, although the majority
of these PACs were clinically insignificant. Conversely, a subset of patients
underwent further investigations for symptomatic high grade or clinically
detectable PAC. These patients were more likely to be diagnosed with
incidental UC, typically of low grade.
43
RING CHROMOSOME 7 AND TRISOMY 8 IN A PEDIATRIC CASE OF
HEPATOSPLENIC T-CELL LYMPHOMA
M. Wozniak, L. Sinclair-Bourque, M. Lamba, K. Mandel, F. Alseraye, E.
McCready
Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, Ontario,
K1H8L6
Cytogenetics Laboratory, Children’s Hospital of Eastern Ontario, Ottawa,
Ontario, K1H8L1
Background: Hepatosplenic T-cell lymphoma is a rare, aggressive
disease predominantly affecting young adult males. It is an extranodal
lymphoma derived from mature cytotoxic T-cells, usually of γδ T-cell
receptor type. The disease mainly infiltrates the spleen and liver in an
intrasinusoidal pattern, but similar involvement of the bone marrow is also
common. Isochromosome 7q is the primary, non-random cytogenetic
abnormality seen in this disorder with trisomy 8 being the next most
common.
Some suggest that in combination these aberrations are
pathognomonic for this disease. At present there is still debate as to
whether the amplification of 7q or the loss of 7p is more pathologically
important.
Design: A 15 year old previously healthy boy presented with a 3
history of intermittent fevers, decreased appetite, and night sweats.
bone marrow examination he was diagnosed with Hepatosplenic
Lymphoma and underwent chemotherapy treatment. A repeat
marrow examination post-treatment revealed no sign of malignancy.
currently undergoing allogeneic bone marrow transplantation.
week
After
T-cell
bone
He is
Results: The patient presented with moderate anemia, thrombocytopenia,
and mild-moderate hepatosplenomegaly. His bone marrow aspirate
revealed an abnormal monomorphic population of large cells with irregular
nuclei and abundant pale blue cytoplasm. Flow cytometry of these cells
showed a CD3+ γδ T-cell population coexpressing CD2 and CD7 but
negative for CD4 and CD8. T-cell receptor rearrangement studies were
positive for clonality. The karyotype of the malignant cells included a ring
chromosome 7 and trisomy 8. Fluorescence in situ hybridization analysis
with chromosome 7 probes showed amplification of a 7q31 sequence. The
presence of 7p material is currently being investigated.
Conclusion: Hepatosplenic T-cell lymphoma is an aggressive disease
mostly seen in young adult males. The primary cytogenetic aberration
associated with this disease is isochromosome 7q resulting in amplification
of 7q and loss of 7p. It is still unknown whether the gain of 7q or the loss
of 7p contributes to the pathogenesis. Ring chromosome 7 is a rare
finding in this disorder with only two other cases reported in the literature.
As with our patient, both cases report amplification of a 7q31 sequence in
combination with trisomy 8. Interestingly, each case reported full or partial
preservation of 7p material supporting the hypothesis that 7q amplification
is more significant. Certainly our case would support this hypothesis as
well, however we cannot be fully certain until the analysis of 7p material is
completed.
44
LUPUS MILIIARIS DISSEMINATUS FACIEI OF THE EYELIDS: REPORT
OF TWO CASES
W. Liao1,2, S. Brownstein1,2, D.R. Jordan1, S. Gilberg1, S.S. Jolly1,2, R.
Prokopetz2. 1University of Ottawa Eye Institute, Ottawa, ON, Canada;
2Department of Pathology and Laboratory Medicine, University of Ottawa,
Ottawa, ON, Canada.
Purpose: To present 2 cases of lupus miliaris disseminatus faciei (LMDF),
an asymptomatic chronic papular eruption affecting the central area of the
face, especially the eyelids.1,2 Except for the description by Duke-Elder3 in
1974, to our knowledge, this condition has not been reported previously in
the ophthalmic literature.
Methods: Biopsy specimens from two women with LMDF affecting their
eyelids and periorbital areas were processed for pathological studies.
Results:
Histopathological examination disclosed 3 subepithelial
granulomas showing a zonal pattern. Two granulomas had a central area
of caseation necrosis and one had a central abscess. Special stains
revealed no evidence of microorganisms. All 3 lesions contained inflamed
hair follicles within the granulomatous inflammation and one lesion had hair
follicles continuous with the central necrosis. One patient was treated with
minocycline with gradual resolution of her papules.
Conclusions: Lupus miliaris disseminatus faciei may be a diagnostic
dilemma for both the ophthalmologist and pathologist as illustrated in both
of our patients. Our findings are consistent with the hypothesis that the
granulomas develop in response to damaged and inflamed pilosebaceous
apparatuses.
45
IMMUNOHISTOCHEMICAL STUDY
RENAL CELL CARCINOMA.
OF
MULTILOCULAR
CYSTIC
BM Purgina MD, TA Flood MD, BN Nguyen MD FRCPC, EC Marginean
MD FRCPC and KT Mai MD FRCPC.
Department of Pathology and Laboratory Medicine, University of Ottawa,
Ottawa, Ontario, Canada.
Background: Multilocular cystic clear cell renal cell carcinoma (MCCRCC)
is a distinct subtype of renal cell carcinoma (RCC). The
immunohistchemical properties of MCCRCC have not been studied.
Design: 21 MCCRCC were retrieved from the files at our institution. All
cases were submitted for immunohistochemical studies. Five alveolar clear
cell RCC (CRCC) measuring less than 2 cm in diameter and two cystic
nephromas (CN) with focal clear epithelial cells were used as control.
Results: MCRCC were associated with female:male ratio of 1:4. The
patient ages or tumor sizes ranged from 45 to 75 years (648) and 2.5 8
(42.5). Immunostaining for CK7 showed extensive reactivity in 3 tumors
(group 1), focal immunostaining in 7 tumors (group 2) and negative in 11
cases (group 3). In group 1, the MCCRCC were predominantly cystic, with
minor solid component. The tumor had focal areas of chromophil cells and
displayed negative reactivity for RCC and weak reactivity for CD10. The
intercystic septae were relatively cellular and showed positive reactivity for
PR in a large number of cells. Group 3 showed large solid areas of clear
cells. The tumor cells showed positive reactivity for RCC and CD10, and
the intercystic stroma was sclerotic and showed negative reactivity for PR.
Group 2 had intermediate histologic and immunhistopathological features
of the other two groups. Immunostaining for CRCC and CN showed CK7RCC+/CD10+/PR- and CK7+/focal CD+/focal RCC+/PR+ for CRCC and
CN as previously described in literature. Focal areas with clear cells in CN
showed weak CK7+.
Conclusions: Some MCRCC contained areas simulating CN. We propose
that there is at least a subset of MCRCC that develop from CN. The
difference in gender ratio between MCRCC and CN may be due to the fact
that CRCC tend to develop more often in CN in male patients.
46
IMMUCYTOCHEMICAL STUDY OF THE URINE CYTOLOGICAL
PREPARATIONS
OF
THE
SECONDARY
PROSTATIC
ADENOCARCINOMA OF THE URINARY BLADDER
IT Ahmed1, HQ Al-Moghrabi1, S Islam1, EC Marginean1 and KT Mai1.
1Department of Laboratory Medicine, The Ottawa Hospital, Department of
Pathology and Laboratory Medicine, The University of Ottawa, Ottawa,
Ontario, Canada.
Background: Involvement of the urinary bladder by prostatic
adenocarcinoma (PAC) occasionally occurs and is usually associated with
high grade and high stage PAC. In this study, we analyzed urine
cytological findings in patients with secondary involvement of the urinary
bladder by PAC with the help of the immunocytochemistry.
Design: Urine specimens from 15 patients with history of PAC with
suspected secondary involvement of the urinary bladder and adequate
urine cytospin specimens were included in the study group. The cases
were divided into two groups: 1) prospective study group: 3 cases and 2)
retrospective study group: 12 cases which were retrieved from the
Cytopathological files. The urine cytology specimens (cytospins) from all
the cases in the study group were submitted for PSA
immunocytochemistry. Additional immunostaining for cytokeratin 7
(CK7)/HMW CK was performed if PSA immunoreactivity was negative.
Result: All cytospin smears showed atypical cells characterized by large
round and uniform nuclei with prominent nucleoli and dense cytoplasm.
They were present as single cells or in cell groups simulating urothelial
carcinoma. The diagnosis of PAC was made if the atypical cells were
either immunoreactive for PSA or nonreactive for CK7/HMW CK. The
urothelial cells were either PSA- or CK7/HMW CK+. The immunostaning
supported the PAC diagnosis in all 3 cases in the prospective and 2 cases
in the retrospective groups. The remaining 10 cases in the retrospective
group were diagnosed as negative: 3, atypia: 5 urothelial carcinoma: 2.
The positive diagnosis for PAC was based on the PSA immunoreactivity or
nonreactivity to CK7/HMW CK and the cytological atypia.
Conclusion: Immunostaining for PSA and CK/7HMW CK performed on
cytospins of urine specimens of patients with prior history of high grade
and/or stage of PAC is helpful to make the positive diagnosis of bladder
involvement of PAC.
47
CLINICAL AND LABORATORY PROFILE COMPARISON OF T(15;17)
POSITIVE AND T(15;17) NEGATIVE ACUTE PROMYELOCYTIC
LEUKEMIA
Zhaodong Xu, 1 David Conrad, 2 Mitchell Sabloff, 2 Ruth Padmore 1
1Department
of Laboratory Medicine and Pathology, Division of
Hematology and Transfusion Medicine, 2Division of Clinical Hematology,
Ottawa Hospital, Ottawa
Acute promyelocytic leukemia (APL) is a subtype (M3) of acute myeloid
leukemia with severe bleeding tendency, characterized by the t(15;17) or
PML-RARalpha fusion protein. Combined chemotherapy and all-trans
retinoic acid (ATRA) treatment significantly improve the complete
remission (CR) rate up to 95% and 5 year disease free survival to 74%.
Nevertheless, in a minority group of APL diagnosed by morphology, flow
cytometry and expert opinions, t(15;17) or PML-RARalpha fusion protein
cannot be demonstrated and the clinical, prognostic information on this
group of APL is limited. To characterize the t(15;17) negative APL, we
investigated the clinical, immunological and molecular profile of this group
and compared it with the t(15;17) positive APL group. In the study, we
reviewed 242 leukemia cases which occurred in the past 10 years at the
Ottawa Hospital. 44 cases were diagnosed as APL by morphology, flow
cytometry and or cytogenetics/PCR. Of 44 APL cases, 28 cases were
t(15;17) positive APL, 16 cases were t(15;17) negative APL. By
categorizing APL cases into t(15;17) positive or t(15;17) negative group,
we compared the clinical features, laboratories features, flow cytometry,
morphology, cytogenetics/PCR, treatment, overall survival, disease free
survival, and relapse free survival between the groups. The study results
showed that t(15;17) positive APL had a better prognosis than t(15;17)
negative APL, suggesting that t(15;17) negative APL group might be either
variant APL or other subgroup of AML (non-M3). PML immunofluorescence
study to further characterize and diagnose t(15;17) negative APL is
pending.
48
VALIDATION OF ORTHO NEW FORMULATION 0.8% SURGISCREEN
SCREENING CELLS.
D. Neurath, M. Pilon, M. Tokessy Transfusion Medicine, The Ottawa
Hospital
Ottawa, ON, Canada
Introduction: Ortho surgiscreen 0.8% cells suspension released initially in
2002 had problems with detecting some weakly reactive antibodies.
Following the release of the new formulation surgiscreen in 2007 we
prepared a plan for validation before placing these cells into routine testing.
Method: Validation of new formulated Ortho 0.8% surgiscreen was
performed to ensure
the required sensitivity and specificity. Two
validations were performed: Validation #1. New formulation surgiscreen
0.8% cell suspension was compared with the in house prepared 0.8% cell
suspension of 3-5% surgiscreen. Antibody screen testing was done in
parallel using the ProVue instrument. Antibody screen positive samples
were tested for antibody present. Additional frozen samples with known
weak antibodies were also retested using the new cell formulation, to
validate the increased sensitivity for weakly reactive antibodies. Validation
#2. New formulation Ortho 0.8% surgiscreen antibody screen on ProVue
instrument was compared to the PEG antibody screen tube test. Antibody
screen positive samples were tested by both method for antibody present.
Results: Validation #1. A total of 242 routine patient samples submitted for
Type and screen had been tested by in house prepared 0.8% cell
suspension and new formulation 0.8% surgiscreen. Parallel testing was
performed once a week for entire shelf life of the new formulation. Five
discrepancies were found. New formulation detected 3 antibodies (anti-M,K,-Kpa) missed by the in house cell screening and missed one low incident
antibody (anti-__). In addition, 34 frozen samples with known weakly
reactive antibodies were retested and all had the same antibodies
detected. Seven of these known antibodies were re-tested on the last day
of the new formulation dating with same results; all antibodies were
detected. Validation #2. A total of 200 samples were tested with Gel
ProVue using the new 0.8% surgiscreen formulation and by the PEG tube
test. There was one discrepancy in this comparison. Anti-Sda was missed
by the Gel ProVue but detected by the PEG antibody test. Discussion:
Validation of the new 0.8% cell formulation surgiscreen was successful. In
total, almost 500 samples tested in duplicate to assess the new cell
sensitivity and specificity. New cells have a good sensitivity to detect
clinically significant antibody including the weakly reactive ones. No
nonspecific reactivity has been seen. Conclusion: New formulation
surgiscreen performed with good sensitivity and specificity while tested in
comparison to a same or equally sensitive technique. This sensitivity was
retained for duration of the cells shelf life. We were satisfied with the
validation outcome and started these cells routinely.
49
BLOOD TRANSFUSION IN BONE MARROW TRANSPLANTATION.
A.Alsughayir, D. Neurath, M. Tokessy, A. Giulivi,
Transfusion Medicine, The Ottawa Hospital, Ottawa, ON Canada
Introduction: Blood transfusion support is an integral part of the
management of patients with hematological malignancies and plays an
even greater role in bone marrow transplantation (BMT), both allogeneic
and autologous. The Ottawa Hospital Bone Marrow Transplant Program is
a very busy regional program that works closely with the Transfusion
Medicine (TM) laboratory to achieve the best possible transfusion support
for their patients. Methods: The transfusion occurrences for 2007 were
reviewed on all BMT patients. Patients’ data were extracted from the BMT
data registry and separated into allogeneic and autologous groups. The
information included patient age, gender, diagnosis, recipient versus donor
blood group, conditioning regimen and the bone marrow/stem cell source.
The transfusion history was extracted from the laboratory information
system and sorted into two groups: transfusions during 1-30 days and 31100 days post transplant. The retrieved data included all blood
components transfused with a special focus on red cells and platelets.
Results: In 2007, a total of 116 patients underwent bone marrow
transplantation, 39 allogeneic and 77 autologous. The most common
conditions for allogeneic transplants were Acute Myelogenous Leukemia
16/39, Myelodysplastic Syndrome 9/30 and Non-Hodgkins Lymphoma
5/39. During the period of 1-30 days post transplant patients were
transfused on average with 6.3 red cells ranging between 0-16 units.
During the same period they received an average of 7.2 apheresis
platelets ranging between 0-38 units. Two patients did not receive any
blood components. A total of 246 red cells and 281 apheresis platelets
were utilized for these patients. During the period of 31 to 100 days post
transplant 62 % of patients did not require any transfusions; only 10
patients required red cells with an average of 10 units (2-21) and 12
patients received an average of 6 platelets (1-13). The 77 autologous
transplant patients during the period of 1-30 days post transplant were
transfused with a total of 244 red cells, 151 random platelet pools (each
pool consists of 5 random donor platelets) and 182 apheresis platelets. An
average of 3.1 (0-17) units of red cells and 4.3 (0-16) platelets (either
random pool or apheresis) were transfused. No red cell transfusions were
required for 14/77 patients and 2 patients did not require any transfusions
during this time period. During the period of 31-100 days post transplant
only 10 patients required transfusion support. Conclusion: The bone
marrow transplant patients require extensive blood transfusion support.
Transfusion Medicine laboratories play a pivotal role in their post transplant
management. Special attention is given to maintaining a sufficient
inventory of specialized blood components of specific blood groups,
irradiated red cells and apheresis platelets. Due to the ongoing changes of
the patients’ clinical situation detailed daily monitoring is required to
provide effective and timely blood transfusions.
50
IMPLENMENTATION OF APHERESIS PLATELET UTILIZATION TOOL
TO IMPROVE INVENTORY MANAGEMENT
M. Tokessy, D. Neurath, A. Alsughayir, A. Giulivi
Transfusion Medicine, The Ottawa Hospital, Ottawa, ON Canada
Introduction: In our three site tertiary care institution one site is involved in
BMT transplantation where the majority of our single donor apheresis
platelets (SDP) are transfused. Platelets with an already short shelf life of 5
days, are received by the hospital Transfusion Medicine (TM) often on day
2-3 from the Canadian Blood Services (CBS). The difficulty in monitoring
and eliminating the platelet wastage is a known problem faced by TM.
Canadian data shows 20% for platelet outdating nationally.
Method: To achieve an improvement in SDP utilization with a goal to
reduce the outdating to < 10% we implemented a new approach in platelet
ordering which involves patient need monitoring and redistribution between
patients if the requirement changes. Patients’ list for platelets required is
established weekly for the following week, based on the patients’ clinical
situation, and submitted to the CBS to plan their collection. Patients are
monitored on on-going basis, daily, and any changes are relayed to CBS to
adjust the collection requirements. Results: Prior to the implementation of
this new approach, the estimated requirement for SDP was submitted
directly by the BMT service to CBS bypassing the TM, often not knowing
that patient still has platelets on hand and additional platelets were
ordered. Prior to the implementation, at least 16%, total of 146 SDP were
outdating in 2006. Each month we have seen a significant decrease in
outdating, averaging at 4.0 % (0%-9.2%), after one year post
implementation. In 2007 we received 1827 SDP units from the CBS,
transfused 1662 and outdated only 73 units.
Discussion: Platelet outdating is an universal problem in most institutions.
With short shelf life and patients requirements constantly changing, it is
difficult to manage the platelet inventory, ensuring sufficient inventory but
at the same time not exceeding that it may lead to outdating. By
establishing very strict, meticulous assessment of daily patients’
requirements, monitoring the patients’ platelet counts vs. platelet
transfusion needs, the estimated platelet requirement is much closer to
reality. Platelets are no longer dedicated to a patient but transfused to
patient with a most current need. The new ordering, releasing and
redistribution approach proved very successful in our institution. Our
platelet outdating decreased from16% in 2006 to 4% in 2007. The total
number of platelets received from CBS has decreased with actual higher
number of SDP units transfused. Conclusion: Improving the platelet
utilization and reducing or completely eliminating the apheresis platelet
outdating requires special attention with well defined process and
dedicated staff.
51