canadian laboratory medicine congress

ARTICLE IN PRESS

0344-0338/$ - se

doi:10.1016/j.pr

Pathology – Research and Practice 204 (2008) 27–76

www.elsevier.de/prp

CONGRES CANADIEN DE MEDICINE DE LABORATOIRE

CANADIAN LABORATORY MEDICINE CONGRESS

ASSOCIATION OF PATHOLOGISTS

ASSOCIATION CANADIENNE DES PATHOLOGISTES

ABSTRACTS – RESUMES

JUNE 9–13, 2007

58TH ANNUAL MEETING

TORONTO, ONTARIO

9–13 JUIN 2007

58EASSEMBLEE ANNUELLE

TORONTO (ONTARIO)

PLATFORM PRESENTATIONS

O101

AN AUDIT OF THE SCREENING HISTORIES OF

WOMEN WITH CERVICAL CANCER

Maire A. Duggana,b MD, FRCPC, Jill G. Nationb MD,FRCSC, P. Ghatageb MD, FRCSC, June Bergmanc

MD, Aref Tabarsia MD, FRCPC, Penny Brahserd PhD

aDepartments of Pathology and Laboratory Medicine,bObstetrics and Gynecology,cFamily MedicinedCommunity Health Sciences,

University of Calgary, Calgary Alberta, T2N2Y9 Canada

e front matter

p.2007.10.001

Objectives: To audit the Pap test screening histories ofwomen residing in the Calgary Health Region (CHR)diagnosed with carcinoma of the uterine cervix in the6 year period 1996–2001 in order to identify deficienciesin the screening pathway.Materials: Eligible women were identified from thecancer registry along with their tumor type and date ofdiagnosis. For the 3 years prior to their diagnosis date,cancer care and colposcopy charts were reviewed fordata on investigation and treatment and the laboratoryinformation system was searched for results of all Paptests and cervical biopsies.Results: Out of 247 eligible women, 182 (74%) hadsquamous cell carcinoma, 54 (22%) adenocarcinoma

www.elsevier.de/prp

dx.doi.org/10.1016/j.prp.2007.10.001

ARTICLE IN PRESSAbstracts / Pathology – Research and Practice 204 (2008) 27–7628

and 11 (4%) adenosquamous cell carcinoma. A screen-ing Pap test (n ¼ 213) was identified for 152 (62%)women, 81 (33%) had no Pap test history and in 14(5%) a test was performed outside of the 3-year interval.Most (112, 74%) had 1Pap test, but 23 (15%) had 2, 13(9%) had 3 and 4 (2%) had 4. The mean (median)interval between the most abnormal Pap test per womanand cancer diagnosis date was 131 (47) days. The Paptests were negative in 7%; unsatisfactory in 2 (1%) andNILM in 9 (6%) women. The test was abnormal in27%; ASCUS in 16 (11%), AGUS in 21 (14%) andLSIL in 3 (2%). The test was positive in 66%; HSIL in72 (47%) and malignant in 29 (19%).Conclusions: In the period 1996–2001, 38% of cervicalcancer screening failures in the CHR were attributableto remote or nonparticipation in Pap test screening anda further 7–27% were attributed to under diagnosis ofthe neoplasm by the Pap test.

O102

MMP2, MT1-MMP AND TIMP2 IN OVARIAN

CANCER—A TISSUE ARRAY STUDY

D. Trudela, I. Popaa, I. Bairatib, F. Harelb, B. Tetua,b

aDepartment of PathologybCancer Research Center,

Centre Hospitalier Universitaire de Quebec, l’Hotel-Dieu

de Quebec and Laval University, Quebec, Canada

Background: Ovarian cancer is the second most frequentgynecologic cancer. Ovarian cancer leads to a highmortality rate. Matrix metallo-proteinases such asMMP2 and MT1-MMP are involved in the progressionof many cancer types, including ovarian cancer. TIMP2,which serves either as an activator or as an inhibitor ofMMP2 is also linked to cancer progression.Design: We tested the immunohistochemical expressionof MMP2, MT1-MMP and TIMP2 in 136 cases of serouspapillary ovarian tumors organised in three tissue arrayblocks, following the usual avidin–biotin technique.Clinical response to chemotherapy was assessed afterthe completion of treatment. The w2 test was used inorder to search for correlation between marker intensityand clinical response. Landmark analysis was used toexamine the progression-free survival (PFS) of patientswho had a complete response to chemotherapy. Hazardratios (HRs) and 95% confidence intervals (CIS) werecalculated using the multivariate Cox regression analysisadjusted for stage, grade, and chemotherapy regimen.Results: Most significant results were obtained withMT1-MMP (multivariate analyses). In the subgroup ofpatients who expressed MT1-MMP (93 patients,71.0%), 61 patients experienced complete response(HR ¼ 2.67, 95% CI [1.12; 6.37], p ¼ 0.03). After

complete response to chemotherapy, MT1-MMP stain-ing was associated with a 0.55-fold decreased risk ofrecurrence (95% CI [0.3; 0.998], p ¼ 0.049). Overall,MT1-MMP expression was associated with a longerPFS (HR ¼ 0.59, 95% CI [0.37; 0.92], p ¼ 0.02).Conclusion: MT1-MMP overexpression may be asso-ciated with a better response to chemotherapy and to alonger PFS after complete response to chemotherapy.

O103

EXPRESSION OF HMGB1 mRNA/PROTEIN IN

HUMAN LUNG ADENOCARCINOMA AND

SQUAMOUS CELL CARCINOMA

R. Hea, R. Gheorgheb, Y. Niub, T. Cuttsa, G. Qingb

aHealth Canada/Department of Medical Microbiology,bDepartment of Pathology,

University of Manitoba, Canada

Objective of the study: Recently a gene named High-Mobility-Group 1 (HMGB1) has been found to playimportant roles in cancer development, invasion, andmetastasis in a variety of malignant tumors. Never-theless, there is scarce information about HMGB1expression in lung cancer. The objective of this studyis to investigate HMGB1 mRNA and protein levels inlung tissues of patients with lung adenocarcinoma andsquamous cell carcinoma. We also studied whethersmoking contributes to the development of lung cancerby stimulating HMGB1 production.Methods: Human lung tumour tissue samples wereobtained from the Department of Pathology, Universityof Manitoba. Protein expression levels of HMGB1 weredetermined by immunohistochemistry (IHC) scoring, whichwas measured by estimating the signal intensity from 0 to 3depending on the proportion of epithelial cells showing apositive signal (0–100%). The mRNA levels of HMGB1were measured by real-time RT-PCR using the same groupof patient samples. Nicotine induced HMGB1 proteinexpression in Vero cells was investigated by Western blot.Data and results obtained: Nicotine dramatically stimulatesthe expression of HMGB1 protein in Vero cells. HMGB1mRNA expression is markedly increased in lung adeno-carcinoma and squamous cell carcinoma when comparedwith normal lung tissue. Furthermore, HMGB1 mRNAlevels in squamous cell carcinoma are much higher thanthose in adenocarcinoma. Similar results were obtainedfrom HMGB1 protein expression analysis, the expressionlevels of HMGB1 protein in both squamous cellcarcinoma and adenocarcinoma were found to besignificantly higher than that of the normal tissue.Conclusion: Elevated HMGB1 mRNA/protein expres-sion may play important roles in the development of lungcancer. Smoking may contribute to the development oflung cancer by stimulating HMGB1 expression.

ARTICLE IN PRESSAbstracts / Pathology – Research and Practice 204 (2008) 27–76 29

O104

BARRETT’S ESOPHAGUS AND CARDIC

INTESTINAL METAPLASIA: TWO CONDITIONS

IN THE SAME SPECTRUM?

N. Whitea, M. Gabrilb, M. Mathewsc, F. Kamela,J. Fardyd, J. Dorea, G.M. Yousefe

aBasic Medical Sciences, Memorial University,

St. John’s, NL,bDiscipline of Pathology, Eastern Health, St. John’s, NL,cDivision of Community Health, Memorial University,

St. John’s, NL,dDepartment of Medicine, Eastern Health, St. John’s, NL,eDepartment of Pathology, St. Michael’s Hospital,

Toronto, Canada

Barrett’s esophagus (BE) is an acquired condition inwhich the squamous epithelium at the distal esophagusis replaced by intestinal epithelium with goblet cells.Intestinal metaplasia of the gastric cardia (CIM) ishistologically similar to BE, but with no endoscopicabnormalities. A characteristic pattern for CK7/CK20immunostaining has been reported in BE. This studyaims to compare BE and CIM in different character-istics including CK7/CK20 pattern, PAS/Alcian Bluestaining, prevalence of H. pylori, and history of acidreflux. CK7/20 staining pattern in BE had a sensitivityof 100%, compared with 62% in CIM. Specificity was95% in BE vs. 70% in CIM. In all false positive cases ofBE except one, BE was documented histologically in aprevious or a follow-up biopsy, or by PAS/AB stain.Patients with BE showed a statistically significant higherincidence of reflux compared to CIM (p ¼ 0.004). Therewere no statistically significant differences between BEand CIM regarding H. pylori infection, type ofmetaplasia present (complete vs. incomplete). Thesensitivity of the CK7/20 pattern reached 93% in thesubgroup of CIM with history of acid reflux. Out of 26cases of CIM where follow-up endoscopy was available,4 cases progressed to BE in 2 years, and one patientdeveloped dysplasia. All 4 cases showed a BE pattern ofCK7/20 staining and all were negative for H. pylori

infection. We hypothesize that CIM comprises aheterogeneous population of two subgroups; thosewho have acid reflux and can be identified by CK7/20pattern, and should be followed up on a regular basis,and those with H. pylori infection. Larger scale studiesare needed to confirm these findings.

O105

RESUSCITATION-RELATED INJURIES IN

INFANTS AND CHILDREN

E.W. Matshesa, E.O. Lewb

aDepartment of Pathology, University of Calgary, AB,

CanadabMiami-Dade County Medical Examiner Department,

Miami, FL, USA

Objectives: To determine if resuscitative efforts: (1) causeorofacial or upper airway injuries; (2) cause hollow orsolid thoracoabdominal viscera injuries; (3) cause ribfractures; (4) by non-medically trained individuals leadto more severe injuries than resuscitation by medicalpersonnel.Methods: Ten-year (1994–2003) retrospective case re-view of all pediatric deaths investigated by the Miami-Dade County Medical Examiner Department.Results: All children dying of atraumatic causes, with orwithout resuscitative efforts (n ¼ 546) were initiallyincluded. Of these, 382 had a history of cardiopulmonaryresuscitation; 248 had CPR provided by trained indivi-duals only; 133 had CPR provided by both trained anduntrained individuals; 1 had CPR provided by untrainedindividuals only. There was no overlap between these 3distinct groups. Twenty-two findings potentially attribu-table to CPR were identified in 19 cases: 15 cases withorofacial injuries compatible with attempted endotra-cheal intubation; 4 cases with focal pulmonary parench-ymal hemorrhage; 1 case with prominent anteriormediastinal emphysema; and 2 cases with anterior chestabrasions. There were no significant solid or hollowthoracoabdominal organ injuries. There were no ribfractures. The estimated risk of injury subsequent toresuscitation was not statistically different betweenchildren receiving CPR from trained individuals, andchildren receiving CPR from both trained and untrainedindividuals. No injuries were identified in the 164atraumatic children who died without resuscitation.Conclusion: In infants and young children, resuscitativeefforts: (1) infrequently cause orofacial and upperairway injuries; (2) do not cause significant hollow orsolid thoracoabdominal visceral injuries; (3) do notcause rib fractures; (4) undertaken by non-medicallytrained individuals are not more likely to cause injury.


O106

EXPRESSION OF EPIDERMAL GROWTH

FACTOR RECEPTOR, VASCULAR ENDOTHELIAL

GROWTH FACTOR RECEPTOR AND BAD IN

NON-SMALL CELL LUNG CANCER

Sen Rong Yana, Zhaolin Xua, Drew Bethuneb,Neale Ridgwayc

aDepartments of Pathology,bThoracic Surgery,cQueen Elizabeth II Health Sciences Centre and Atlantic

Research Centre, Dalhousie University, Halifax, NS, Canada

Background: Growth factor receptors (e.g., EGFR andVEGFR) and intracellular molecules (e.g., BAD)regulate and control cellular proliferation and survival.This study was aimed to investigate the expression ofthese molecules in non-small cell lung cancer (NSCLC)and their relationship with classification and biologicalbehaviors.Methods: Tissue microarray of 51 NSCLC was immuno-stained for EGFR, VEGFR, BAD and phospho-BAD.The results were correlated with classification, gradingand staging.Results: Overexpression of EGFR and VEGFR wasobserved in 10 of 51 (20%) and 14 of 51 (27%) cases,respectively. VEGFR was expressed by SCC (7/16,44%) and adenocarcinoma (7/26, 27%) cases, but notby large cell carcinoma (LCC) (0/8, 0%). Loss of BADexpression was observed in 22 of 51 (43%) NSCLC.Loss of BAD was more frequently detected in SCC(10/16, 63%) and LCC (5/8, 63%), but less frequently inadenocarcinomas (7/26, 27%, po0.05). Overexpressionof phospho-BAD was observed in 25 of 51 (49%)NSCLC; including 13/26 (50%) adenocarcinomas, 8/16(50%) SCC and 4/8 (50%) LCC. Expressions of EGFR,VEGFR, BAD and phosphor-BAD were not statisti-cally correlated with gender, tumor cell differentiation,or pathological aggressiveness (measured by pleuralinvasion, vascular invasion, lymph node metastaticstatus, intrapulmonary and brain metastasis).Conclusions: SCC was more likely, and LCC was leastlikely to overexpress VEGFR. Loss of BAD expressionwas observed in SCC and LCC. Thus, there molecules maybe potential targets for cancer therapy. However, expres-sion of EGFR, VEGFR, BAD and phospho-BAD did notsignificantly correlate with aggressiveness of NSCLC.

O107

IMMUNOHISTOCHEMICAL PROFILE OF

SMALL BOWEL ADENOCARCINOMAS

C. Rowsella,b, C.J. Streutkera,b

aDepartment of Pathology and Laboratory Medicine,

St. Michael’s HospitalbDepartment of Pathology, Sunnybrook Health Sciences

Centre, University of Toronto, Toronto

Hypothesis: Primary non-ampullary adenocarcinomasof the small intestine are extremely rare but are slightlymore common in patients with small bowel Crohn’sdisease. Immunohistochemistry for cytokeratins 7 and20 have been utilized to identify potential primary sitesfor metastatic tumors. Studies on primary small bowelcarcinomas are few and generally have reported uniformpositivity for cytokeratin 7, with a lower percentage ofcytokeratin 20 positivity. We report the results ofimmunohistochemistry of a group of 4 small boweladenocarcinomas, 3 of which arose in patients withlong-standing Crohn’s disease.Methods: Pathology records were searched for cases ofprimary small bowel adenocarcinoma. Four cases wereidentified; 3 cases occurred in patients with Crohn’sdisease of420 years duration. Three cases were resectedwhile one case was biopsied as it was consideredunresectable. A representative block was chosen andimmunohistochemistry for cytokeratins 7 and 20 as wellas p53 and EGFR was performed. The slides werescored as negative or staining weakly, moderately orstrongly with each antibody.Results:

Patient
Cytokeratin
7

Cytokeratin

20

p53
EGFR
1
Moderate Strong Moderate Negative
2
Negative Moderate Moderate Weak
3
Weak and
focal

Negative
Strong Weak
4
Negative Strong Negative Unavailable
Conclusions: Our results differ from previously pub-lished reports of 100% of small bowel carcinomasstaining with cytokeratin 7 antibodies; only 50% of our4 cases stained with this antibody and in 1 case thestaining was weak and focal. Cytokeratin 20 positivityhas been reported in up to 69% of cases in the literature;75% of our cases were positive. Three of our 4 cases(75%) were positive for p53, and 2 were weakly positivefor EGFR. This study expands our knowledge of thevariable staining patterns in small bowel adenocarcino-mas, which may be of use in identification of the originof metastatic tumors of unknown origin.


O108

SEGMENTS OF DNA COPY NUMBER

PREFERENTIALLY ALTERED IN INVASIVE

BREAST CANCER

V.V. Iakovleva,b, N.C. Arnesona, C. Wanga, S.J. Donea,c

aOntario Cancer Institute/Princess Margaret Hospital,

University Health NetworkbCIHR Molecular Oncologic Pathology fellowship programcDepartments of Laboratory Medicine and Pathobiology

and Medical Biophysics, University of Toronto, Toronto,

Ontario, Canada

Invasion is the most important step in breast cancerprogression. Identification of the genes involved in thisprocess will reveal important therapeutic targets as wellas diagnostic markers. We performed array comparativegenomic hybridization (aCGH) to compare regions ofaltered DNA copy number in DCIS and invasive breastcancer cells. Sections of archival formalin-fixed paraffin-embedded tissue of 22 cases of breast carcinoma weresubjected to microdissection, whole genome amplifica-tion and aCGH. Fifteen cases had invasive carcinomawith areas of DCIS and the remaining 7 samples hadDCIS only without evidence of invasion at the time ofresection. Amplified DNA from these samples andpooled control DNA from normal lymph nodeswas hybridized to human cDNA arrays containing19,000 spots (Clinical Genomics Centre, UniversityHealth Network). The data were centered, normalizedand formatted for the ‘‘DNAcopy’’ package (byE. Venkatraman & A. Olshen) for ‘‘R’’ (www.r-project.org). Altered chromosome segments were identified withthe circular binary segmentation algorithm whichcalculates median value within a DNA segment.Self-hybridization experiments were used to define thesignificance thresholds for the degree of segmentdeviation from the baseline and the segment length.Common regions of frequent DNA copy gains or losseswere identified and compared between the groups.Regions of gain specific for invasive tumors were foundon 1p, 3p, 8q, 11p, 18q and Xp chromosome arms withsegments of loss on 3q, 12q, 16p and Xq. Published geneexpression array data and analysis of function of thegenes located within the altered segments were used toselect candidate genes for PCR validation. The selectedcandidate genes are likely to include those important forbreast cancer cells to invade.

O109

THYROID FINE NEEDLE ASPIRATION BIOPSY

REPORTING

Laurette Geldenhuys

Dalhousie University and QE II Health Sciences Centre

Department of Pathology, Canada

Objective: In order to increase the consistency of thyroidfine needle aspiration biopsy reporting, the QE IIcytopathology laboratory introduced a reporting tem-plate, and after 5 months, assessed the impact of thetemplate on reporting.Method: A thyroid fine needle aspiration biopsy report-ing template was developed and introduced at the QE IIcytopathology laboratory. Reports 5 months beforeintroduction of the template, and 5 months after werereviewed and compared in order to assess the impact ofthe template. Clinicians, cytopathologists and cytotech-nologists were requested to report on their satisfactionwith reports.Results: Non-diagnostic reports decreased significantlyfrom 29% to 18%. The diagnosis of a hyperplasticnodule increased from 18% to 38%. Overall, terminol-ogy was more consistent and accurate. Clinicians,cytopathologists and cytotechnologists expressed satis-faction with reports.Conclusion: A reporting template increases the quality ofthyroid fine needle aspiration biopsy reporting.

http://www.r-project.org

http://www.r-project.org


O110

DIAGNOSTIC PITFALLS OF ALVEOLAR

RHABDOMYOSARCOMA INVOLVING LYMPH

NODES AT THE TIME OF DIAGNOSIS

Arredondo Jorge L., Alowami Salem, Ross Cathy,Sur Monalisa

Department of Pathology, Henderson General Hospital,

McMaster University, Canada

It is very rare for sarcomas to present initially as alymph node or bone marrow metastasis. One suchexception is alveolar rhabdomyosarcoma (ARM).Objective: To highlight 3 cases of ARM with the unusualinitial presentation involving lymph nodes that maymimic a high-grade lymphoma both clinically andhistologically. Role of morphology, immunohistochem-istry, and molecular studies are discussed.Methods: Retrospective search of 20 years identified 3cases. The clinical, radiology and pathology informationof each case was obtained and reviewed, including routineH&E stains, immunohistochemistry, flow cytometry,electron microscopy and genetic results where available.Results: 3 male cases (2, 10, and 18 years of age),presented with lymph node involvement in the sub-mandibular, right cervical and left groin regions,respectively. The predominant pattern was solid withsinusoidal invasion. Two cases had starry sky pattern,and all cases showed capsule, sub-capsular sinus, andperi-nodal soft tissue infiltration. The cells were positivefor vimentin, desmin, myogenin, Myo-D1, CD56 andnegative for CD45 (LCA), CD20, CD3, S100, epithelialmarkers, CD34, CD10, TdT and myeloperoxidase. Onecase was positive for translocation t(2;13).Conclusions: The presence of small blue tumoral cellsmake the diagnosis problematic in most patients.Architectural patterns and tumor cell cytology requireto be recognized specifically in the solid variant of ARMthat may not have an alveolar component. Immunohis-tochemistry, electron microscopy and molecular geneticsare recommended to help determine the correct diag-nosis with its significant clinical impact because thetreatment and clinical prognosis are different.

O111

MULTICENTRIC SQUAMOUS INTRAEPITHELIAL

NEOPLASIA AND INVASIVE CARCINOMA OF

THE FEMALE LOWER ANOGENITAL TRACT

A. Mojtahedzadeh, L. Elit, K. Ceballos, A. Zaidi,S. Sawar, D. Daya, A. Lytwyn

Departments of Pathology and Molecular Medicine, and

Obstetrics and Gynecology, Division of Gynecological

Oncology, McMaster University, Canada

Objectives: Carcinomas and preneoplastic epitheliallesions of the lower female anogenital tract are causedby human papillomavirus (HPV). The cervix is the mostcommon site of lesion development, however, somepatients also develop either synchronous or metachro-nous lesions in the vagina, vulva or anus.The purpose of our study was to identify patients seen atHamilton Health Sciences Centre with multicentricanogenital disease of the female genital tract, describethe demographic and clinical characteristic of thisdisease and to establish a database for further molecularinvestigations.Methods: We searched the pathology computerizeddatabase at Hamilton Health Sciences from 1987 to2005 for women with squamous intraepithelial neoplasiaand invasive cancer involving at least 2 anogenital sites:cervix, vagina, vulva, or anus. Clinical and demographicdata were abstracted from the clinical charts. Cases wereconsidered as having multicentric disease and not simplycontiguous spread if the lesions were geographically ortemporally separate, for example, if cervix and vulvawere involved, or if occurrence of lesions in differentsites was more than 12 months apart.Results: Search of the pathology database yielded 81women with lesions originating from at least 2anogenital sites. Fifty one of these women met ourdefinition of multicentric disease and they form ourstudy group. Median age at first clinic visit was 38 years(range 19–69 years). Forty five (88%) were ever-smokers. Four were immunosuppressed secondary torenal/lung transplant, systemic lupus erythematosis, andinflammatory bowel disease. HIV status was notavailable. Patients sustained new or recurrent lesionsover a median of 6 years (range 1–31 years). Vulvarlesions were present in 50 women (98%), cervical in 48(94%), vaginal in 21 (41%), and anal in 3 (6%) women.Thirty one (61%) women had 2 site involvement, 20(39%) had lesions in 3 anogenital sites. In 29 (57%)women, high-grade lesions (including 3 invasive cancers)were present in all involved sites, and 4 (8%) women hadonly low grade intraepithelial neoplasia. In the remain-der, both low- and high- grade lesions were present,including 5 invasive cancers.Conclusions: A history of current or ever smoking wasfrequent in women with multicentric anogenital neopla-sia. Lesions occurred over a substantial number ofyears. These cases provide a database for molecularinvestigations including human papillomavirus typing,determination of DNA integration sites, and identifica-tion of genetic polymorphisms.


O112

PREDICTING POSSIBLE ZONISAMIDE

HYPERSENSITIVITY SYNDROME IN THE

GERIATRIC POPULATION

Manuela Neumana,b, Neal Shearc, Izabella Malkiewicza,Amy Leea,b, Lawrence Cohend

aIn Vitro Drug Safety and Biotechnology Laboratory,

MaRS Discovery CentrebDepartment of Pharmacology and Institute of Drug

Research, University of TorontocDrug Safety Clinic, Division of Dermatology, anddDivision of Gastroenterology, Sunnybrook Sciences

Centre, Toronto, Ontario, Canada

The antiepileptic drug, zonisamide (ZNS) contains asulpha moiety, making the drug a candidate to trigger ahypersensitivity reaction (HSR). The study examinedwhether there is a ZNS cross-reactivity with otheranticonvulsants and/or with sulphonamide and if thisHSR may be predicted using the lymphocyte toxicityassay (LTA). The LTA was previously validated inpatients who received sulphamethoxazole (SMX),carbamazepine (CBZ), phenytoin (PHY), and phenobar-bital (PB). Elderly patients with previously clinicalHSR to SMX (10 patients) or CBZ, PHY, PB (10patients) participated in the study. In vitro LTA-SMX,LTA- anticonvulsants, and LTA-ZNS from 20 patientsthat previously presented a clinical manifestation toone of the drugs and had an LTA positive to the specificdrug were compared to 20 individuals that received thesame drugs without presenting the clinical reaction.In vitro results correlated with clinical diagnoses.T-tests indicated statistical significance (po0.0001) be-tween control and hypersensitive patients. One patientwho had a severe clinical manifestation of SMX-HSRtested positive to SMX and ZNS. In conclusion, use ofthe LTA to predict a possible ZNS reaction isrecommended for SMX-sensitive individuals when pre-scribed ZNS.

HEMATOPATHOLOGY

PLATFORM PRESENTATIONS

O151

PRIMARYANAPLASTICLARGECELLLYMPHOMA

OF THE BREAST ARISING IN RECONSTRUCTION

MAMMOPLASTY CAPSULE OF SALINE-FILLED

BREAST IMPLANT AFTER RADICAL

MASTECTOMY FOR BREAST CANCER:

AN UNUSUAL CASE PRESENTATION

M. Bisharaa,b, M. Sur, C. Rossa,b

aMcMaster University, Hamilton, Ontario,bDepartment of Pathology and Molecular Medicine,

Henderson General Hospital, Hamilton, Ontario, Canada

Primary non-Hodgkin lymphoma (NHL) of the breastrepresents 0.04–0.5% of malignant lesions of the breastand accounts for 1.7–2.2% of extra-nodal NHL. Mostprimary cases are of B-cell phenotype and only rare casesare of T-cell phenotype. Anaplastic large cell lymphoma(ALCL) is a rare T-cell lymphoma typically seen inchildren and young adults with the breast being one of theleast common locations. There are a total of 8 cases ofprimary ALCL of the breast described in the literature.Five of these cases occurred in proximity to breastimplants, 3 in relation to silicone breast implant and 2 inrelation to saline-filled breast implant with 2 cases havingprevious history of breast cancer treated surgically withoutadjuvant chemotherapy or radiotherapy. Secondary he-matological malignancies after breast cancer chemother-apy have been reported in literature. However, in contrastto acute myeloid leukemia (AML), the association betweenlymphoma and administration of chemotherapy has neverbeen clearly demonstrated.In this report, we present a case of primary ALCL of thebreast arising in reconstruction mamoplasty capsule ofsaline-filled breast implant after radical mastectomy forinfiltrating ductal carcinoma followed by postoperativechemotherapy 12 years ago.Histologic sections of the capsule were examined andappropriate panel of Immunostains were performed.Molecular analysis for B- and T-cell gene rearrangementwas also performed by PCR.Based on histology and ancillary tests performed, adiagnosis of primary ALK negative ALCL of T-cellphenotype was made.In conclusion, we are reporting a case of primary ALK-negative ALCL of the breast. This is the first case ofprimary ALCL of the breast occurring in proximity tosaline-filled breast implant following chemotherapy forbreast cancer. Based on morphology, the differentialdiagnosis includes sarcomatoid/anaplastic carcinoma, ma-lignant melanoma, pleomorphic sarcoma, nos and hema-tological neoplasms such as Hodgkin’s lymphoma and therare ALCL. So an appropriate panel of immunostainsshould be performed to avoid misdiagnosis.It is still unclear whether chemotherapy and breastimplantation increases risk of secondary hematologicalmalignancies significantly. However, it is important tobe aware of these complications and need for carefulpathologic examination of tissue removed for implant-related complications to make the correct diagnosis forfurther patient management and treatment.


O152

PLASMACYTOID DIFFERENTIATION

IN CHRONIC LYMPHOCYTIC LEUKEMIA

E. Torlakovica, C. Fibichb, S. Angela, M. Voraliab,J. DeCoteaua

aDepartment of Pathology, Royal University Hospital,bUniversity of Saskatchewan, and Saskatoon Regional

Cancer Centre, Saskatoon, SK, Canada

Chronic lymphocytic leukemia (CLL) is a commonneoplasm of mature B-cells. While plasmacytoid differ-entiation may be seen in various B-cell lymphomas, it isexceedingly rare in CLL and thus its biologic back-ground and clinical significance are not known. We herepresent 4 patients with evidence of terminal B-celldifferentiation in CLL in a form of cytoplasmicimmunoglobulin expression as well as plasmacytoidmorphology of the cells. Patients’ age was 46, 53, 66 and70 years. In all 4 patients, lymphocytosis was apresenting feature and flow cytometric immunopheno-typing revealed typical CLL profile: CD19+, CD20+,CD5+, CD23+, and CD10�. FMC7 was negative in 3and positive in 1 patient. Immunohistochemically, noexpression of cyclin D1 was found. MUM1 andmonotypic cytoplasmic immunoglobulin were uniformlyfound. The percent of cells with Ki-67 expression washigher in plasmacytoid cells than in non-plasmacytoidcells (when the latter were present). Plasmacytoiddifferentiation was predominately diffuse in 2 patients,and focal in 2. Three patients had CLL with plasmacy-toid differentiation at presentation and 1 patientdiagnosed with CLL 4 years ago, developed plasmacy-toid differentiation only recently. One patient hadsynchronous diffuse large B-cell lymphoma in the bonemarrow only, 1 patient had synchronous classicalHodgkin lymphoma, and 1 patient had synchronousfollicular lymphoma confirmed by molecular, morpho-logic, and immunohistochemical findings. One patienthad large proliferation centers. While our series is small,it appears that the presence of plasmacytoid differentia-tion in CLL may indicate a more aggressive andbiologically more complex variant of this low gradelymphoproliferative disorder.

O153

PRIMARYNON-HODGKIN’S LYMPHOMAARISING

IN AN OVARIAN MATURE CYSTIC TERATOMA

R. Behjati, D. LeBrun, T. Childs, P. Farmer

Department of Pathology and Molecular Medicine, Kingston

General Hospital and Queen’s University, Kingston, Ontario,

Canada

Malignant transformation within a mature cysticteratoma is a rare but well-documented phenomenonand in 80% of cases is found to be a squamous cellcarcinoma. A short list of other tumor types has beendescribed but, to the best of our knowledge, this is onlythe second-published report of a non-Hodgkin’s lym-phoma arising within a mature cystic teratoma. Thepatient was a healthy 59 year old woman who was foundto have, as an incidental finding on abdominal ultra-sound, a 7� 5.5� 4.5 cm right-sided persistent complexadnexal mass. She underwent a total hysterectomy andbilateral salpingo-oophorectomy which confirmed thepresence of a unilateral ovarian tumour. Gross andmicroscopic examination of the tumour revealed amature cystic teratoma. In addition, however, therewas a prominent sheet-like infiltrate of lymphoid cells inseveral sections directly beneath several of the epithelial-lined spaces. The lymphoid cells were heterogeneous andcomprised of small, round, mature-appearing forms,small forms with irregular nuclei, and larger forms withimmunoblast and centrablast-type nuclei as well asoccasional plasma cells. Numerous sections revealedthat this abnormal proliferation of lymphoid cells wasconfined entirely within the teratoma. Immunohisto-chemistry was performed and showed the followingresults in the cells of interest: CD20+; CD3�; CD5�;CD23�; CD10�; CD43+; cyclin D1�; BCL6�; andBCL2+. Extensive invasion of epithelial structuresby the lymphoid cells was highlighted by cytokeratinAE1/AE3 staining. Taken together, the morphology andthe immunophenotype would be consistent with amarginal zone lymphoma. Further confirmation of theneoplastic nature of this process was achieved with aPCR test, which revealed B-cell monoclonality.


O154

ALGORITHM USE IN DIAGNOSIS OF

HEPARIN-INDUCED THROMBOCYTOPENIA

(HIT), AN UPDATE

E.R. McBride, I. Sadek, A. Shawwa

Department of Pathology, Dalhousie University, Halifax,

Canada

Introduction: HIT is a potentially life-threateningcomplication of heparin use. It is a clinicopathologicentity with no consensus regarding the best methods ofdiagnosis. Laboratory evaluation using the most specifictests is currently available in specialized centers. Aclinical scoring system has been described (The 4T’s)with varying reports of negative and positive predictivevalues (NPV, PPV). We evaluate a diagnostic algorithmcombining a screening assay with this clinical scoringsystem in the diagnosis of HIT.Methods: We reviewed all samples received for HITtesting between September 2003 and December 2006.Screening tests were performed on 455 samples of whichclinical scores were available in 410 (90%). Confirma-

tory testing (serotonin release assay) was available in188 cases. The screening assay was a commercial (GTI-Genetic Testing Institute) PF4/polyanion enzyme im-munoassay (EIA) and results were negative for opticaldensity (OD) o0.4, positive for OD 41.0 and incon-clusive if 0.4XODp1.0. In our algorithm, low orintermediate pre-test probability (PTP) coupled withnegative screen excluded HIT, and high PTP withpositive EIA confirmed HIT. All other combinationswere considered non-diagnostic and sent to a referencelaboratory for confirmatory testing.Results: Screening EIA was inconclusive in 10.1% ofsamples however, 64% of samples had diagnostic resultswithout further testing. Combining low or intermediateclinical score had a 70.3% NPV for HIT, whichincreased to 97.4% when associated with a negativeEIA. A high clinical score alone provided a PPV of11.5%, but this increased to 100% when coupled with apositive EIA.Conclusions: Our data support the use of a diagnosticalgorithm for the diagnosis of heparin-induced throm-bocytopenia.


POSTER PRESENTATIONS

P201

KIMURA’S DISEASE IN A CAUCASIAN PATIENT

I. Ahmed, M. Lamba, B. Burns

Department of Pathology and Laboratory Medicine, Ottawa

Hospital, 501 Smyth Road, Ottawa, Ontario, Canada

Background: Kimura’s disease (KD) is a chronic inflam-matory disease of unknown etiology, common in Asians,but rare in Caucasians. It generally presents as subcuta-neous nodules in the head and neck region, with associatedlymphadenopathy. It is recognized as a separate entityfrom angiolymphoid hyperplasia with eosinophilia.Design: We report an unusual case of KD in the elbowof a 37 year Caucasian male, clinically mimicking aneoplasm. Morphologic examination, immunohisto-chemistry and molecular studies were performed onthe excised lump.Results: The initial core biopsy was suggestive ofangiolymphoid hyperplasia with eosinophilia. However,the lumpectomy specimen revealed the characteristictriad features of KD (florid reactive hyperplasia, corticaland paracortical eosinophilia and cortical and para-cortical hypervascularity). Evidence of peripheral eosi-nophilia was also noted. The renal functions wasnormal. Minimal axillary lymphadenopathy was con-firmed by CTscan. Immunohistochemical stains (CD20,CD3 and BCL2) confirmed reactive lymphoid follicles.The lesion was present at excision margin.The elbow mass recurred and was excised 6 months afterthe initial surgery. The histology re-confirmed KD. TCR(beta, gamma and delta) gene rearrangement studies onboth the initial and recurrent mass were non-clonal.Conclusion: The rare KD needs to be differentiated fromangiolymphoid hyperplasia with eosinophilia. Clinically,KD patients should be followed up for recurrence andpossible renal involvement.

P202

IDENTIFICATION AND CHARACTERIZATION

OF PROTEINS INTERACTING WITH THE

TUMOR SUPPRESSOR PROTEIN, p16

E. Akbaria, L. Allanb, D.J. Demetrickc

aDepartment of Undergraduate Medical Education,bDepartment of Medical Biochemistry,cDepartments of Pathology, Oncology and Medical

Biochemistry, Faculty of Medicine,

University of Calgary, Alberta, Canada

Introduction: p16 is a member of cyclin-dependentkinase inhibitors (INK4), a group of proteins that areinvolved in the G1/S transition of the cell cycle. The 4members of the INK4 family (p15, p16, p18, and p19)are biochemically indistinguishable in their ability tobind CDK4/CDK6, and cause pRb-dependent cell cyclearrest in G1. Interestingly, only p15 and p16 are knowntumor suppressors that are often deregulated orinactivated in many cancers. The p16 gene is locatedin chromosome 9p21, a region that is linked to familialmelanoma. Molecular analyses of melanoma in situ andof squamous cell carcinoma (SCC) in situ, show that lossof p16 plays a critical role in carcinogenesis. In addition,p16 expression in primary malignant melanoma hasbeen associated with prognosis and lymph node status.We hypothesize that p16 has distinct and specificfunctions from those of p18 and p19, in addition tocell cycle arrest in G1. These functions are likelymediated through the interactions of p16 with itsspecific binding partners.Materials and methods: A mammary tissue cDNAlibrary was screened using a yeast two-hybrid systemfor detecting specific binding partners of full-length p16.Identified interactions are currently being confirmed inan in vivo expression system using co-immunoprecipita-tion technique.Results and conclusions: Over 40 possible p16 bindingpartners were identified in our initial screening. Im-portin 4 and transcription factor AP-2g were chosen forfurther investigation based on the biological likelihoodof their interaction with p16. Such proteins may conferspecific function to certain INK4 proteins and not toothers. If true, this finding would help to explain howthe deregulation of this particular INK4 protein, p16,leads to cancer development.


P203

COMPARISON OF THE IMMUNOPHENOTYPE

OF ENDOMETRIOID AND SEROUS

COMPONENTS OF MIXED ENDOMETRIAL

ADENOCARCINOMA

Raeda Albannaia, Abdulmohsen Alkushib,C. Blake Gilksc

aDepartment of Pathology, Vancouver General Hospital

and University of British Columbia, Vancouver BC,

Canada,bDepartment of Pathology, King Fahad National Guard

Hospital, Riyadh, Saudi Arabia,cGenetic Pathology Evaluation Centre of the Prostate

Research Centre and Department of Pathology, Vancou-

ver General Hospital and University of British Columbia,

Vancouver BC, Canadac

Background: Mixed endometrial adenocarcinoma is atumor with two or more cell types present with eachcomprising at least 10% of the tumor. Mixed adeno-carcinoma account for approximately 10% of cases ofendometrial adenocarcinoma.Objective: To determine whether there are consistentdifferences in immunostaining between the endome-trioid and serous components of mixed endometrialadenocarcinoma.Methods: Ten cases of mixed endometrial adenocarci-noma with endometrioid and serous components werestained for p16, ER, PR, p53, and MIB-1.Results: p16 and p53 staining (distribution and intensity)were the same in the endometrial and the serouscomponent in 6 and 7 cases, respectively and strongerin the serous component in 3 cases. ER and PR stainswere identical in the endometrioid and serous compo-nent in 6 cases, and stronger in the endometrioidcomponent in 4 (ER) and 3 (PR) cases. MIB-1 stainingshowed higher proliferative indices in the serouscomponent in 7 of 10 cases and similar proliferation inthe endometrioid and serous components in 3 cases.Three of 10 cases showed more than two differences inimmune staining in the endometrioid versus serouscomponents, based on p16, ER, PR and p53 staining.Conclusion: The immunophenotype of endometrioid andserous components of mixed endometrial adenocarcino-ma are similar in most cases, with the notable exceptionof high-proliferative index being characteristic of theserous component. This suggests that the serouscomponent arises through progression from the endo-metrioid component.

P204

COLLISION TUMOR: CLEAR CELL

ODONTOGENIC CARCINOMA AND SQUAMOUS

CELL CARCINOMA

Sadeq Al-Dandana, Richard Nasonb, Carla Pennera

aDepartment of Pathology, Health Sciences Center,

University of Manitoba, 820 Sherbrook Street, MS 471,

Thorlakson Building, Winnipeg, Manitoba, Canada,

R3A 1R9bDepartment of Surgery, Health Sciences Center, Uni-

versity of Manitoba, 820 Sherbrook Street, GF547,

Winnipeg, Manitoba, Canada, R3A 1R9

Neoplasms with predominant clear cell population inthe head and neck region are rare and represent adiagnostic challenge. Most of these neoplasms are ofepithelial origin; however, mesenchymal and melanocy-tic lesions can include clear cells. In addition, metastatictumors have to be also considered and they must beexcluded before a diagnosis of primary odontogenictumor is made. A 51-year-old man presented to hisdentist with a painful non-healing oral ulcer in his leftlower jaw of about 4 months’ duration. Oral examina-tion revealed an ulcer in the area of left lower canine.The CT-scan of the head and neck showed a solitarylytic focus in the left mandibular alveolus. The patientthen underwent segmental mandibulectomy of thetumour, left neck dissection and reconstruction withreconstruction plate and fibular flap. Microscopicexamination revealed an infiltrative neoplasm consistingof solid sheets and nests of tumour cells separated bymature fibrous connective tissue septa. Areas of tumournecrosis were focally noted. Tumour cells are polygonaland have distinct outlines and clear cytoplasm. Thetumour invaded the underlying bone and muscles of thefloor of the mouth and collided with an invasivesquamous cell carcinoma arising from the overlyingoral squamous mucosa. Special studies showed diastase-digestable PAS granules that are negative for mucinstain (mucicarmine). Immunohistochemical stainingshowed positivity for CK (AE1/AE3), CK-19, Cam5.2, EMA, CK-7, and high-molecular-weight cytoker-atin. We present a case of clear cell odontogeniccarcinoma in connection with squamous cell carcinoma,a combination of entities that has not been reportedbefore in the English literature.


P205

A RARE ENTITY: ACTH PRODUCING LUNG

CARCINOID

S. Almarzooqi, R. Fraser

Department of Pathology, McGill University Health

Centre, Montreal, Quebec

Cushing syndrome is a rare manifestation of pulmonarycarcinoid tumor. We present 2 cases of this association.The first is that of a 24-year-old man who presented witha one year history of increasing weight, hypertensionand aggressiveness. CT of the chest revealed a 1.2 cmnodule found to be a typical carcinoid tumor followinglobectomy. The second case is that of a 21-year-old manwho presented in 1999 to a psychiatric institute for anattempted suicide. CT of the chest revealed a lungnodule measuring 1.8 cm. A left upper lobectomyspecimen revealed a typical carcinoid with metastasesto two peribronchial lymph nodes. In 2003, he hadrecurrence of Cushing syndrome associated with metas-tases to the ipsilateral hilar lymph nodes. Completionpneumonectomy and mediastinal lymphadenectomywere performed followed by chemotherapy and radia-tion to the medistinum. He remains free of disease.Cushing syndrome associated with pulmonary carcinoidtumor typically has a prolonged period of symptoma-tology before diagnosis. Tumors are usually small andoften not evident on standard radiographs. The majorityare classified as typical carcinoid tumors. Despite this, asignificant number behave in a more aggressive fashionthan non-ACTH secreting carcinoid tumors. Lymphnode metastases are present in about 30–55% ofreported cases and a recurrence rate of 18% has beenreported in some series. The basis for this behavior isunknown.

P206

DIFFUSE LARGE B-CELL LYMPHOMA WITH

PLASMACYTOID FEATURES ARISING IN AN

ILEOSTOMY

Arredondo Jorge L, Alowami Salem, Sur Monalisa,Cathy Ross

Department of Pathology and Molecular Medicine,

Henderson General Hospital, McMaster University,

Canada

Small bowel rarely develops a malignant tumor. Theileostomy is an unusual site for lymphomas, with only 3previous cases reported. Our case, A 70-year-old manwith past history of Crohn’s disease underwent totalcolectomy with an ileostomy and with stable disease for15 years. A 15 cm mass at the ileostomy site wasidentified. Biopsy demonstrated a diffuse large celllymphoma.Objectives: To report a case of lymphoma involving alongstanding ileostomy. Morphology, cell marker pro-file and DNA analysis are reported as well as theaggressive nature of this lesion.Methods: Tissue slides, immunohistochemistry stains,genetic studies and patient chart were ordered andreviewed. Pathology reports for the last 20 years yieldedno similar cases.Results: The tumor was of the large B cells with someplasmacytoid features including Russell bodies. Thetumor infiltrates diffusely the ileostomy tissue withextensive ulceration and skin involvement. Immunohis-tochemistry markers were positive for: CD45 (LCA),CD20, CD79a, CD138 (focal), Bcl-2, IgM, Kappa, Ki67(90%), and P53. PCR for B cell immunoglobulin heavychain DNA gene rearrangement was positive confirmingthe monoclonal B cell lineage.Conclusions: Our report corresponds to an unusualprimary non-Hodgkin large B cell lymphoma arising ina longstanding ileostomy site with aggressive and fatalclinical outcome. Although rare, awareness of this lesionis important for early identification and distinction fromother non-neoplastic ulcerative lesions that can involveileostomy sites. Early detection may lead to betteroutcome based on timely intervention and therapy.


P207

CONTRIBUTIONS OF MOLECULAR BIOLOGY

AND URINE CYTOLOGY TO THE DIAGNOSIS

OF BK POLYOMA VIRUS NEPHROPATHY IN

RENAL TRANSPLANT PATIENTS

S.J. Bauer, G. Johnson, R. Devlin, V. Bell, G. Gardiner,S. Jothy

Department of Laboratory Medicine, St. Michael’s

Hospital and University of Toronto, Toronto, Ontario,

Canada M5B 1W8

BK virus can become activated and cause nephropathyafter kidney transplantation. The clinical goal is todetect and treat patients early enough to limit theamount of damage to the transplanted kidney. The aimof our study was to compare the relative contribution ofmolecular and morphological approaches in the diag-nosis of BK-virus associated nephropathy.Thirty seven plasma specimens from 28 renal transplantpatients were tested by PCR for the presence of a BKgenomic sequence, a test which has the advantage ofgiving technically unambiguous results. The results werecompared with 56 urine cytology specimens obtainedfrom the same patients, searching for decoy cells.Ten urine specimens from 8 patients had a positive urinecytology and 1 of these 10 had a positive BK plasmatest. Twenty eight out of the 56 urine specimens (50%)were reported as indeterminate. The plasma of 7patients was positive by PCR. One out 7 of thesepatients had a positive urine cytology, the other 6 werereported as having an indeterminate or negativecytology.We conclude that molecular testing of viremia for thedocumentation of BK virus replication in renal trans-plant patients is more specific than the demonstration ofdecoy cells in urine cytology specimens. Urine cytologyfor decoy cells leads to a large number of indeterminateand false positive results.

P208

DISTINCT ONCOCYTIC RENAL CELL

CARCINOMA WITH IMMUNOHISTOCHEMICAL

PROPERTIES OF RENAL ONCOCYTOMA

Cyrille Bicamumpaka, MD, PhD, Kien T. Mai, MD,FRCPC, Akram Elkaleini, MD, Susan J. Robertson,MD, FRCPC, Esmeralda C. Marginean, MD, Eric C.Belanger, MD, FRCPC

Division of Anatomical Pathology, Department of La-

boratory Medicine, The Ottawa Hospital, and Depart-

ment of Pathology and Laboratory Medicine, University

of Ottawa, Ottawa, Ontario, Canada

Renal oncocytoma (RO) is a characteristic benign renaltumor. The existence of malignant RO is controversial,and anecdotal, partly due to a lack of specific markersfor RO. With recent advances in immunohistochemis-try, RO can be distinguished from other renal neoplasmswith routine stains and characteristic immunoprofile ofCD117+, Renal Cell Antigen negative and vimentinnegative. In our laboratory it was found the RO werealso reactive for progesterone receptor. We report 2cases of renal neoplasms with oncocytic cytoplasm,numerous intra-cytoplasmic vacuoles, uniform round tooval hyperchromatic nuclei with remarkably thicknuclear membranes and prominent nucleoli. The tumorcells were closely packed and disposed in an alveolarpattern. The neoplastic cells were diffusely reactive forCD117, cytokeratin AE1/AE3 and progesterone recep-tor, and focally for CD10. The cells were non-reactivefor renal cell carcinoma antigen, vimentin, CK7, S100,racemase, as well as neuroendocrine markers. Due to theremarkable cytological atypia, lymph node metastasisand similar immunological features of RO, the tumorlikely represents a distinct subtype of RCC related toRO, which has not been previously described.


P209

12-O-TETRADECANOYLPHORBOL-13-ACETATE

(TPA) AND CALCIUM IONOPHORE A23187

STIMULATE CEACAM1 EXPRESSION AND

EFFECT THE INVASIVENESS OF PLACENTAL

CELLS

J. Briesea,d, T. Heilmanna, C.M. Bambergera,C. Wagenerb, P. Nollaub, T. Loningc, S.L. Asad,S. Ezzate, A.M. Bambergera

aSection on Endocrinology and Metabolism of Ageing,bDepartment of Clinical Chemistry,cDepartment of Pathology,

University Clinic Hamburg-Eppendorf, Hamburg,

Germany,dDepartment of Laboratory Medicine and Pathobiology,

University of Toronto,eThe Freeman Centre for Endocrine Oncology, Mount

Sinai Hospital, Toronto, Canada

Human embryo implantation is a complex process,requiring synchronous development of a receptive endo-metrium and an activated blastocyst. CEACAM1, whichis expressed in the extravillous trophoblast (EVT) of theplacenta and increases invasiveness of EVT hybridomacells after transfection with CEACAM1, may also play arole in endometrial/trophoblast interactions. The mechan-isms for the implantation and the role of hormones for theexpression of CEACAM1 in the utero-placental system arenot fully understood. In the present study we investigatedthe potential role of TPA and A23187 for CEACAM1expression and the effect on the invasiveness of placentalhybridoma cells using WB, luciferase and invasion assays.Treatment with TPA and A23187 resulted in strong re-expression of CEACAM1 in trophoblast cells at theprotein level. Addition of MPA to TPA and A23187reversed this stimulation. Luciferase-reporter assays withCEACAM1 promoter constructs demonstrated that there-expression of CEACAM1 is regulated at the transcrip-tional level. Double antigen labelling demonstrated acolocalization of AP-1 transcription factors and CEA-CAM1 in the EVT of the human placenta. In addition, weshow that TPA and A23187 enhanced the invasiveness ofEVT hybridoma cells, which was inhibited through MPAand blocked by monoclonal antibody against CEACAM1.This is the first report demonstrating that activators of AP-1 are able to specifically induce the expression ofCEACAM1 in human placental cells and also could beresponsible for increasing invasiveness in these cells.

P210

OSTEOPONTIN (OPN) IS EXPRESSED IN

HUMAN ADRENAL AND ENHANCES WITH ITS

RECEPTOR INTEGRIN b3 THE INVASION OF

NCI259R CELL LINE

J. Briesea,b, J. Niemanna, A.M. Bambergera, W. Liub,S.L. Asab, S. Ezzatc, C.M. Bambergera

aSection on Endocrinology and Metabolism of Ageing,

University Clinic Hamburg-Eppendorf, Hamburg, Germany,bDepartment of Laboratory Medicine and Pathobiology,

University of Toronto,cThe Freeman Centre for Endocrine Oncology, Mount

Sinai Hospital, Toronto, Canada

OPN is a glycoprotein of the extracellular matrix andinteracts with its receptor integrin b3, which wepreviously found to be expressed in the utero-placentalsystem, and which were shown to contribute totumorigenesis in several types of cancers. Recently,expression profiling of adrenal neoplasms revealed OPNmRNA to be expressed in these tumors. IHC withspecific anti-OPN and anti-integrin b3 antibodies wereperformed in normal adrenal tissue as well as in benignand malignant adrenocortical tumors. In addition, westudied OPN and integrin b3 protein expression usingWestern blot analysis. Invasion assays were used tostudy the functional role of OPN in regulating tumorcell invasion. In the normal human adrenal gland, OPNand its receptor integrin b3 were found to be expressedstrictly in the cortex, with the staining intensityincreasing in a centripetal fashion. Expression of OPNand integrin b3 was more heterogenous in adrenocor-tical adenomas and carcinomas with staining intensitybeing more accentuated in single tumor cells or nests.These results were confirmed by Western blot analysis.OPN protein expression could also be found in thehuman adrenocortical cell line NCI259R. Treatment ofthese cells with human OPN increased invasivenessdramatically; this increase was partially reversed bytransfection of the cells with with integrin b3, support-ing the idea that OPN acts to facilitate tumor develop-ment and metastases. In this study we show for the firsttime, that OPN protein is expressed in the humanadrenal gland. Furthermore, we demonstrate that OPNexpression is strictly confined to the cortex, making it,thus, a potential diagnostic marker to distinguishbetween adrenal cortex and medulla.


P211

MALIGNANT MELANOMA OF THE GALLBLAD-

DER: PRIMARY VERSUS METASTATIC? CASE

REPORT AND REVIEW OF THE LITERATURE

M.C. Castonguaya, N.G. Chana, J.A. Gomez-Lemusa,M.G. Josepha, W.J. Wallb, C.A. McLeana

a Department of Pathology,bDepartment of Surgery, London Health Sciences

Center, London, Ontario, Canada, N6A 5A5

Background: Gallbladder melanoma (GBM) is a rareclinical entity. Both primary and metastatic GBM aredocumented in the medical literature, although theexistence of primary GBM is still contested. Histologicalcriteria have been introduced for the diagnosis ofprimary gallbladder melanoma, but are deemed inaccu-rate by some authors.Case Report: We describe a case of a 45 year-old manwho presented with biliary colic. Abdominal ultrasoundand CT examinations revealed a large gallbladder mass,and he underwent a radical cholecystectomy thatincluded removal of the common bile duct and resectionof the liver fossa. The gallbladder was enlarged; themucosa contained multiple brown/black polypoidbroad-based lesions. Histological examination revealedmultiple foci of malignant melanoma confined to thelamina propria, with no lymphovascular invasion orlymph node metastases. The neoplastic cells werepositive for S-100, Melan-A, and HMB-45.Review of a recently excised abdominal skin lesionshowed a completely regressed melanocytic lesion.Physical examination revealed no other skin/mucosallesions, lymphadenopathy, or evidence of metastasis.CT scanning of the head, thorax, and abdomen werenegative.Conclusion: We report this case to emphasize thatmelanoma can occur in the gallbladder and should beconsidered in the differential diagnosis of gallbladdermass lesions. Meticulous clinical and radiologicalinvestigations are needed to delineate primary versusmetastatic GBM. Our case may represent a primaryGBM; however, metastasis from a completely regressedcutaneous melanoma cannot be excluded.

P212

A PATHOLOGICAL STUDY OF SURGICALLY

EXCISED MITRAL VAVLES

G.J.R. Charrois, J.H. Ma, B.K. Chiu

Department of Laboratory Medicine & Pathology,

University of Alberta, Edmonton, Alberta, Canada

Background: The relative frequency of pathologiesidentified in surgically excised mitral valves (MV) hasshown substantial change over time. Post-inflammatorychanges of rheumatic etiology represented the mostcommon functional and morphologic lesions seen in thepast. The objective of our study was to examine thefunctional and pathologic correlations of 1000 surgicallyexcised MV.Design: The pathology of surgically excised MV from atertiary center was reviewed for a 10 year-period. Datawere collected from the Capital Health’s pathologydatabase and electronic health record (Co-path andnetCARE).Results: Among 1037 surgically excised MV (meanage ¼ 61.0, F:M ¼ 1:1.06), mitral regurgitation (MR)with myxomatous/fibromyxoid changes (n ¼ 687,66.2%) was seen most commonly. These changes wereassociated with valve prolapse (n ¼ 107, 10.3%), leftventricular (LV) dysfunction and/or coronary arterydisease (n ¼ 165, 15.9%). This was followed by fibro-calcific changes with mitral stenosis (MS) (n ¼ 213,20.5%) and combined MS/MR (n ¼ 127, 12.2%), whichwere often associated with chronic rheumatic etiology(n ¼ 218, 27.1%) and annular calcification (n ¼ 43,4.1%). Infective endocarditis was seen in 59MV(5.7%). Concomitantly resected pathologic tissues in-cluded aortic valves (AV) (n ¼ 219, 21.1%), septalmyomectomies (n ¼ 47, 4.5%), which were commonlyassociated with calcific aortic stenosis (CAS).Discussions and conclusions: The associations of athero-sclerosis, CAS and cardiovascular mortality and co-morbidities have been extensively studied. Our studyconfirms the temporal changes of MV pathologies frompost-inflammatory changes to myxomatous/fibromyx-oid changes in recent years. That MV dysfunction isnot an isolated disease, increasingly seen in associationswith atherosclerosis-associated diseases (CAD, CAS),LV dysfunction, and concomitant-resected patho-logic tissues, has significant clinical and therapeuticimplications.


P213

MULTICENTRICITY OF PULMONARY

INFLAMMATORY MYOFIBROBLASTIC

TUMORS

I. Chebib, S.J. Urbanski

Department of Pathology and Laboratory Medicine,

University of Calgary and Calgary Laboratory Services,

Calgary, Alberta, Canada T2N 2T9

Background: Inflammatory myofibroblastic tumors(IMT) are infrequent in the adult population. Lungsare affected most commonly among older patients.Occasionally, pulmonary IMTs may be multicentricwhich creates additional diagnostic and managementdilemmas.Design: We conducted a retrospective analysis of alllesions resected in our institution between September1999 and September 2006 with a diagnosis of IMT.Clinical and radiologic data have also been reviewed.Result: Six pulmonary IMTs were seen in patients over theage of 18, 3 of which were multicentric (two females aged37 and 61 and one 36 year-old male). The male patientpresented with a 7 cm mass involving the right middle andupper lobe associated with a small satellite nodules on theright and a 3mm nodule in the LUL. The main tumor wassampled by core biopsy that was interpreted as suggestiveof IMT. Incisional biopsy followed that was interpreted asIMT. The 37-year-old female presented with multiplebilateral pulmonary nodules (presented following full-termdelivery). The largest was 3.5 cm. Incisional biopsy of oneshowed IMT. The patient was treated with steroids thatresulted in diminution of the lesions. The 61-year-oldfemale had multiple LUL nodules the largest of which was2.2 cm with possible left hilar involvement. Core biopsyshowed IMT.Conclusion: These cases illustrate diagnostic difficultiesof pulmonary IMT. Two of the patients had bilaterallesions raising suspicion of malignancy. Interpretationof core biopsies requires caution because of a danger ofsampling error. Pulmonary IMT may be locally invasiveor may recur.

P214

COMPOSITE PARAGANGLIOMA-

GANGLIONEUROMA OF THE URINARY

BLADDER: A RARE NEOPLASM PRESENTING

WITH LABILE BLOOD PRESSURE DURING

TUMOUR RESECTION

C-H. Chena, A.H. Boaga, D.T. Beikob, D.R. Siemensb,A. Froesec, P.A. IsotaloaaDepartment of Pathology and Molecular Medicine,bDepartment of Urology,cDepartment of Anesthesiology,

Kingston General Hospital, Queen’s University, Kingston,

Ontario, Canada

Paragangliomas of the urinary bladder are extra-adrenalpheochromocytomas that account for less than 0.1% ofall bladder neoplasms. These tumors commonly presentwith hematuria, although symptoms related to catecho-lamine release (headache, tremor, palpitations, syncope)can occur in more than 50% of patients. Due to theirrarity in this anatomic location and frequent involve-ment of muscularis propria, primary paragangliomas ofthe urinary bladder are often misdiagnosed as invasiveurothelial carcinomas. We describe a 64-year-old manwith well-controlled systemic arterial hypertension andtype-II diabetes mellitus who was found to have asolitary bladder neck mass during cystoscopic investiga-tion for gross hematuria. The patient developedbradycardia and severely labile blood pressure duringtransurethral resection of the tumour. The neoplasmwas composed of large, mitotically quiescent, polygonalcells with abundant granular cytoplasm that werearranged in a characteristic Zellballen growth patterncharacteristic of paraganglioma. In addition, the tumourcontained a component of ganglioneuroma consisting ofmature ganglion and spindle cells that merged with theparaganglioma component. The polygonal neoplasticcells were strongly immunoreactive for chromograninand synaptophysin and were negative for keratin stains.The ganglion and sustentacular cells were immunoreac-tive for S-100 protein. The patient was diagnosed with aprimary bladder composite paraganglioma–ganglio-neuroma and underwent a partial cystectomy. Thepatient is well a year following partial cystectomy andhas no evidence of tumour recurrence or metastaticdisease. This case highlights an uncommon differentialin the diagnosis of bladder cancer with unique patho-physiologic effects.


P215

MICROARRAY IDENTIFIES POTENTIAL

MOLECULES THAT CONTRIBUTE TO THE

RESISTANCE OF HPV-16 INFECTED

LARYNGEAL CANCER CELLS TO ANTI-TUMOR

TREATMENT

G.G. Chena, A.C. Vlantisa, Wei-Wei Liub, B.C.S. LeungLeunga, M.C.F. Tongb, Z.M. Guo, C.A. van Hasselta

aDepartment of Surgery, Prince of Wales Hospital, The

Chinese University of Hong Kong, Shatin, N.T. Hong Kong,bCancer Center of Sun Yat-sen University, Guangzhou,

China

Objectives: Our previous study has shown that laryngealcancer cells infected with E6 and/or E7 of HPV16 areresistant to cell death stimulation, which may cause theresistance of cancer cells to anti-tumor treatment. Inorder to identify the molecules that are targeted by E6 orE7, we use cDNA microarray to screen potentialmolecule targets.Methods: We stably transfected laryngeal cancer cellsUMSCC12 with E6 and E7, respectively to establish twocell lines that expressed E6 and E7. cDNA microarraywas used to explore the target molecules between thecells with E6 and E7 and those without.Results: E6/E7-expressing cells were significantly resis-tant to cell death stimuli. Six genes were up-regulated atleast 20 folds in the cells with E6/E7. The increasedgenes were DAF, GRO2, PTPLA, S100A4, SDF2L1,and RAB22. Most of these genes participate in the cellproliferation and growth. Some of these up-regulatedgenes, for example, DAF, also increased in laryngealcancer tissues positive for HPV16. We found that 6other genes were down-regulated at least 20 folds in thecells with E6/E7. These down-regulated genes includedGPX, KRT, KLK10, TACSTD1, ASC, and CD9. Incontrast to the up-regulated genes, genes that are down-regulated by E6 and E7 are more likely to promote celldeath such as ASC and KLK10.Conclusion: Laryngeal cancer cells with E6/E7 of HPV-16 are resistant to cell death stimuli and the resistancemay be associated with several genes that are regulatedby E6/E7 of HPV16.

P216

CATEGORIZATION OF RIB FRACTURES IDEN-

TIFIED AT PAEDIATRIC AUTOPSIES: A RETRO-

SPECTIVE 8 YEAR REVIEW

J.A. Reyesa, G.R. Somersa,b, G.P. Taylora,b,D.A. Chiassona,b

aPaediatric Forensic Pathology Unit, Department of

Paediatric Laboratory Medicine, The Hospital for Sick

ChildrenbDepartment of Pathobiology and Laboratory Medicine,

University of Toronto, Ontario, Canada

Fractures are a common sequelae of childhood injury,but there is scant information in the pathologicliterature regarding the patterns of fracture andcorrelation with the underlying cause. Of particularconcern for the pathologist is how to distinguishfractures due to non-accidental injury (NAI) from thosedue to accidental injury (AI) and natural disease. Theobjectives of this study were to catalogue the number,distribution and age of rib fractures in a series ofpaediatric autopsies, and to determine whether there is acorrelation between rib fracture pattern and the under-lying cause. Post mortem files held in the Department ofPaediatric Laboratory Medicine at the Hospital for SickChildren over an 8-year period (1998–2005) werereviewed for the number, type and distribution of ribfractures, and the cause and manner of death wererecorded. Rib fractures were identified in 40 of 1915 postmortems (2%). Seventeen decedents were female and 23were male. The age range was 1 month to 15 years(mean, 2 years). Fractures in 19 decedents were attrib-uted to AI, including motor vehicle accidents (n ¼ 10)and cardiopulmonary resuscitation (n ¼ 3), and 9 wereattributed to NAI. Natural disease was the underlyingcause in 3 patients, and in 9 patients the fractures wereunexplained. AI fractures were acute in 17 decedentsand remote in 2; multiple rib fractures were present in14. NAI fractures were remote in 8 of 9 decedents, andall had fractures involving multiple sites. Thus, althoughthe presence of multiple and/or remote rib fractures ishighly suggestive of NAI, natural disease or AI cannotbe completely excluded. These findings highlight theneed for thorough clinicopathological correlation ininterpreting the significance of rib fractures identified atpaediatric autopsies.


P217

TISSUE MICROARRAYS ARE EQUIVALENT TO

WHOLE SECTIONS FOR CLINICAL ASSESSMENT

OF BREAST CANCER BIOMARKERS

C.T. Chunga, C.B. Gilksb, M.M. Hayesc, C.C. Ruttanb,K. Gelmond, D. Banerjeec, D.G. Huntsmanb

aDepartment of Laboratory Medicine and Pathobiology,

University of Toronto, Toronto ONbGenetic Pathology Evaluation Centre of the Prostate

Research Centre and Department of Pathology, Vancouver

General Hospital, Vancouver BC,b,cDepartment of Pathology,dDepartments of Medical Oncology and Breast Tumor

Group, British Columbia Cancer Agency, Vancouver BC,

Canada

Context: The proven benefits of trastuzumab foradjuvant chemotherapy has intensified the need formore cost effective and accurate approaches to breastcancer biomarker studies. Tissue microarrays (TMAs)are increasingly used for cancer biomarker research,providing equivalent or superior results to whole sectiondata.Objective: To compare the results of a blinded prospec-tive comparison of whole section and TMA-basedassessment of ER and Her-2 in breast cancer samples.Design: TMAs were constructed using triplicate 0.6mmcores from 523 breast cancer cases including 48 corebiopsies. Sections were stained for ER and Her-2 at twolaboratories using different automated stainers. TMAand whole section results were compared using Kappastatistics. Fluorescence in situ hybridization for Her-2amplification or overexpression was performed on allTMAs and on whole sections with an indeterminatescore (+2) on Her-2 staining.Results: TMA-yielded data from all but 1 case. For ER(523 cases), TMA produced 6 whereas whole sectionsproduced 11 false negative results (97% concordance).For Her-2 (416 cases), TMA produced 7 whereas wholesections produced 9 false negative results (96% con-cordance).Conclusion: Our study indicates that the application ofTMAs in the routine clinical assessment of breast cancerbiomarkers can achieve results of comparable quality towhole sections at a greatly reduced cost. Broaderapplication of a TMA-based system for the assessmentof breast cancer biomarkers would allow the implemen-tation of a rigorous quality assurance program, andfacilitate the seamless integration of novel biomarkersinto routine practice.

P218

COLORECTAL CARCINOMA IN INFLAMMATORY

BOWEL DISEASE: OBSERVATIONS FROM A

DETAILED PATHOLOGIC ASSESSMENT AND

MAPPING OF DYSPLASIA AND CARCINOMA IN

A CROHN’S COLITIS CASE

L. Dahla, D.J. Hurlbuta, D. Dextera, W. Depewb

aDepartments of Pathology and Molecular Medicine,bMedicine (Gastroenterology),

Queen’s University, Kingston, Ontario, Canada

Surveillance for colorectal cancer (CRC) in patients withinflammatory bowel disease (IBD) requires an under-standing of the endoscopic–pathologic features ofIBD-associated neoplasia. We present findings from adetailed pathologic assessment and mapping of dyspla-sia and carcinoma in a Crohn’s colitis (CC) resectionspecimen that illustrate the pathology and relateddiagnostic challenges of IBD-associated CRC.Study case and design: Colonoscopy in a 42-year-oldman with CC for 17 years showed a pancolitis with areasof dysplasia and one biopsy with adenocarcinoma. Totalproctocolectomy was performed. After routine pathol-ogy sectioning revealed 4 separate adenocarcinomas andmultiple areas of dysplasia, the entire specimen wassectioned at 4mm intervals and blocked for histology.Mucosal appearance of each block was assessed using adissecting microscope. Histological assessment includedsemi-quantitative acute and chronic inflammation scor-ing, presence and severity of dysplasia and presence andcharacteristics of CRC. Detailed inflammation, dyspla-sia and carcinoma maps of the entire protocolectomyspecimen were prepared.Results: Pathological assessment showed a chronicpancolitis with multifocal dysplasia and 6 synchronousadenocarcinomas of variable grade, size and extent ofspread. Neoplasia maps showed carcinomas developedin regions of dysplasia. No tumour presented as adiscrete mass lesion. Low magnification tumour-relatedmucosal characteristics did not distinguish areas ofcarcinoma from the background chronic colitis. Wallthickening and intramural mucin were gross findingsthat correlated with carcinoma.Conclusion: Synchronous carcinoma formation, tumourprogression from dysplasia, and poor cancer detectionby endoscopy and low-magnification mucosal examina-tion are clinically relevant features of IBD-associatedCRC illustrated by the neoplasia mapping in this IBDcase study.


P219

PRIMARY GASTROINTESTINAL STROMAL

TUMOUR OF THE PROSTATE

B.C. Dicksona, A.F. Pollettb, J.D. Honeyc, J. Srigleyd,J.W. Jucoa

aDivision of Pathology, St. Michael’s Hospital,bDepartment of Pathology and Laboratory Medicine,

Mount Sinai Hospital,cDepartment of Urology, St. Michael’s Hospital; University

of Toronto, Ontario,dDepartment of Laboratory Medicine, The Credit Valley

Hospital, Department of Pathology and Molecular

Medicine, McMaster University, Ontario, Canada

Recent studies have identified the presence of theinterstitial cell of Cajal (ICC) in locations outside thegastrointestinal tract, including the prostate and blad-der. Indeed, there are 2 recent case reports of agastrointestinal stromal tumour (GIST) arising fromthe prostate. Here we document the third-known GISTarising de novo from the prostate. A 72-year-old malewith a history of BPH was referred to our institution forretropubic prostatectomy after twice previously under-going transurethral resection of the prostate (TURP). ACT scan of the abdomen revealed an enlarged prostate,but no other intra-abdominal pathology. Ultrasoundconfirmed an enlarged cystic prostate. Histologicexamination of the resected gland revealed sheets ofplump spindle cells effacing the normal prostatic tissue.The cytoplasm was eosinophilic with focal stromalhyalinization. The nuclei were fusiform with very raremitotic activity. Imunohistochemistry revealed intenseexpression of CD34 and CD117; there was focalexpression of alpha smooth muscle actin and CD99; itwas negative for S100, keratin, and desmin. Molecularanalysis confirmed there to be a mutation (deletion) inexon 11 of the KIT gene. Until recently GISTs werethought to be neoplasms of strictly gastrointestinalorigin. Our case further confirms that, despite itsmisnomer, these tumors can arise outside the gastro-intestinal tract, presumably from extra-gastointestinalICC cells.

P220

IMMUNOHISTOCHEMICAL COMPARISON OF

ENDOCERVICAL ADENOCARCINOMAS AND

ENDOMETRIOID CARCINOMAS

B. Djordjevica, E. Demellawy, W. Chapman

Department of Pathology, University Health Network,

University of Toronto, Toronto, Ontario, Canada

Objective: Distinguishing endometrial and endocervicaladenocarcinomas on biopsy specimens may be difficult.The objective of this project was to study the expressionof two cell cycle regulating proteins, retinoblastoma(Rb) and cyclin D1, in cervical vs. endometrialcarcinomas, and to determine whether these markerscan help differentiate between the two tumor types.Methods: Immunohistochemistry was performed onblocks containing tumor from 48 cases of invasive orin-situ cervical and 48 cases of endometrial adenocarci-noma. The markers assessed were cyclin D1 and Rb,along with the more traditional markers used for thedistinction of cervical and endometrial primaries: CEA,vimentin, ER and PR. The cut-off for positive cases was45% for CEA and vimentin (membranous), 410% forER and PR (nuclear), 410% for cyclin D1 (nuclear)and 475% for Rb (nuclear).Results: The percentage of positive cases for endocervi-cal vs. endometrial carcinomas was 82% vs. 6% forCEA, 13% vs. 69% for vimentin, 52% vs. 90% for ER,23% vs. 73% for PR, 17% vs. 98% for Rb and 29% vs.90% for cyclin D1. The patterns of Rb and cyclin D1expression were markedly different; Rb was eitherdiffusely positive or downregulated. In contrast, cyclinD1 was either diffusely positive or completely absent.Conclusions: Cyclin D1 and Rb expression may be usefulin distinguishing endocervical vs. endometrial carcino-mas in difficult cases. Both Rb and cyclin D1 arepreferentially expressed in endometrial carcinomas in adiffuse pattern. In cervical carcinomas, however, Rbexpression is downregulated , whereas cyclin D1 tends tobe completely absent. The patterns observed with theseproteins are substantially more distinct than those withthe traditional markers such as ER, PR, vimentin andCEA.


P221

AN AUDIT OF THE SCREENING HISTORIES OF

WOMEN WITH CERVICAL CANCER: A REVIEW

OF THE SCREENING PAP TESTS

Maire A. Duggana,b, MD, FRCPC, Jill G. Nationb,MD, FRCSC, Prafull Ghatageb, MD FRCSC, JuneBergmanc, MD, Aref Tabarsia, MD, FRCPC, PennyBrahserd, PhD

aDepartments of Pathology and Laboratory Medicine,bDepartments of Obstetrics and Gynecology,cDepartment of Family Medicine,dDepartment of Community Health Sciences, University

of Calgary, Calgary, Alberta, Canada T2N 2Y9

Objectives: To review the screening Pap tests of womendiagnosed with carcinoma of the uterine cervix residingin the Calgary Health Region (CHR) in the 6-yearperiod 1996–2001 in order to assess the accuracy of thelaboratory interpretation of the tests.Materials: All Pap tests on 152 women with carcinomaand performed within 3 years of their cancer diagnosiswere identified from a search of the laboratoryinformation system and a review of their cancer careand colposcopy charts. All available tests plus an equalnumber of unrelated Pap tests were rescreened by 1technologist and reviewed by 1 pathologist.Results: From 210Pap tests, 122 (58%) pertaining to118 (78%) women were available for review. Theoriginal (99% satisfactory and 1% unsatisfactory) andreview (100% satisfactory) assessments of adequacywere essentially the same. The original results were 3(2.5%) negative (1 unsatisfactory and 2 NILM) 41(34%) atypical (23 ASCUS, 15 AGUS, and 3 LSIL) and78 (64%) positive (59 HSIL and 19 malignant). Thereview results were 2 (2%) negative (2 NILM), 46 (38%)atypical (25 ASCUS, 16 AGUS, and 5 LSIL), and 74(61%) positive (34 HSIL and 40 malignant). Thesensitivities for a diagnosis of malignancy with a falsenegative defined either as negative/unsatisfactory ornegative/unsatisfactory/atypical were almost the same;98 and 64%, respectively, for the original and 98 and61% for the review interpretations.Conclusions: Laboratory error in the screening andinterpretation of Pap tests was not a factor in the underdiagnosis of cervical carcinoma in the CHR.

P222

PROSPECTIVE TIMELINE STUDY OF IMPACT

OF CLINICAL PRACTICE GUIDELINE OF SENTI-

NEL LYMPH NODE FOR MELANOMA

L.J. Elavathil, Monalisa Sur, Anbreen Zaidi, SalemAlowami

Department of Anatomical Pathology, Henderson Gen-

eral Hospital, McMaster University, Hamilton, Ontario,

Canada

Objective: Prospective impact analysis of the pathologistand pathology assistant workload associated withsentinel lymph node (SLN) protocol for melanoma.Materials and methods: The standard SLN protocolincluded serially sectioning the lymph node in 2.0mmthickness and submitting for processing was performedon 31 prospective consecutive cases. After the review ofthe initial H & E slide, if the SLN was negative, 3additional levels, S100, and HMB45 were done on allSLN blocks. Timelines for pathology assistant and thepathologist were captured. This time also included thegrossing and reporting of the entire case, i.e. includingthe wider excisional specimens.Results: All cases except one had wider excision donealong with SLN. The number of SLN of this case seriesvaried from 1 to 4. The blocks and slides for entire case,respectively are: 639 (Median 21; Range 4–37) and 1507(Median 43; Range 18–108). The blocks and slides forsentinel lymph nodes respectively are: 128 (Median 3;range 2–12) and 1024 (Median 24; Range 16–96). Thetotal time spent by Pathology assistant (grossing):1309min (Median 43; Range 13–75min) and bypathologist: 2105min (Median 70, Range 20–140min).Conclusion: Our study effectively determined the impactof the SLN protocol on pathologist assistant/patholo-gist workload. We recommend doing impact analysis onsuch clinical/surgical practice guidelines affecting theanatomical pathology workload.


P223

A COLLISION TUMOR: DEDIFFERENTIATED

LIPOSARCOMA WITH METASTATIC BREAST

ADENOCARCINOMA. A CASE REPORT

Akram Elkeilani, MD, E. Celia Marginean, MD, FRCPC


Division of Anatomical pathology, University of Ottawa,

the Ottawa Hospital, Ottawa, ON, Canada

Background: The term ‘‘collision tumor’’ represents theproximal coexistence of two histologically distinct andindependent tumors. Collision tumors can occur withinthe same organ, in adjacent organs, or as a metastaticphenomenon. We describe a patient with metastaticbreast adenocarcinoma to a recurrent dedifferentiatedmediastinal liposarcoma. To the best of our knowledge,this is the first well-documented example of such acomplex tumor.Case report: A 56-year-old woman admitted to theOttawa hospital on January 2006, for management ofmediastinal mass discovered on radiological investiga-tion. The patient had a history of retroperitonealwell-differentiated liposarcoma for 10 years, and inflam-matory carcinoma of right breast for 6 years. Sheunderwent surgical exploration with resection of thetumor mass. Grossly, a lobulated tissue measuring 15 cmin greatest dimension, and covered with thin, tan fibro-membranous sheath. Histologic examination showed acollision tumor composed of two distinct, well demarcatedcomponents: a sarcomatous component and an epithelialcomponent. Immunohistochemical analysis confirmed thebreast origin of the epithelial component, which stainedwith CK7, CEA, ER, but failed to stain with TTF1,CA125, and WT1. The biphasic nature of the tumor wasclearly emphasized by negative staining of the mesench-ymal component to the above-mentioned markers.Conclusion: Several hypotheses have been suggested asmechanisms for collision tumors. The mechanism ofcollision in this reported case is probably due toalteration of the microenvironment by the previousradiotherapy treatment of liposarcoma, but we can’tentirely exclude the possibility of accidental meeting ofthe two tumors.

P224

CUTANEOUS AND SUBCUTANEOUS LEIOMYO-

SARCOMA: A CLINICOPATHOLOGIC REVIEW

C.T. Fautha, A. Bruecksa, W. Templeb,L.M. DiFrancescoa

aDepartment of Pathology and Laboratory Medicine,bDepartment of General Surgery,

University of Calgary, Calgary, Alberta, Canada

Cutaneous and subcutaneous leiomyosarcomas are raresoft tissue malignancies, accounting for only 1–2% of allsoft tissue sarcomas. They have been associated withtrauma or irradiation, and can present as a painful mass.The prognosis is generally better than their soft tissuecounterparts. There are few recent large case series; thelargest study (80 cases) was over 20 years ago. Wereviewed 27 cases diagnosed at Calgary LaboratoryServices between 1990 and 2006. Clinical informationincluding: presentation, site, size, treatment, and out-come, was obtained. Pathology was reviewed to assesstumor depth and grade, necrosis, and mitotic rate.Immunohistochemical stains for vimentin, actin, des-min, caldesmon, and CD117 were also evaluated. Therewere 14 males and 13 females, with a mean age of 59years. The most common presenting complaint was asoft tissue ‘‘lump’’. Two tumors were confined to thedermis, and 15 extended into subcutaneous tissue. Ninetumors were low grade (Grade I), while 16 were highgrade (Grade II-III). Smooth muscle markers werepositive in most cases, with actin most consistently so.CD117 was not positive in any cases. Changes of noteincluded epidermal hyperplasia and sclerotic collagenbands. Five cases showed a trend towards increasingatypia with the depth of the lesion, with two misdiag-nosed as benign on superficial biopsy. Most patientswere disease free following wide excision. Five patients,developed metastases, and three died of their disease.Poor outcome was associated with size 4 2 cm, highgrade, and depth of the lesion, as previously reported.Features that may aid in the differential diagnosisinclude epidermal hyperplasia, thickened collagenbands, and lack of CD117 staining. It is importantrecognize that superficial biopsies may be undergradedor misdiagnosed as benign, leading to inappropriate ordelayed treatment.


P225

THYROID CANCER PROTEOME ANALYSIS BY

TANDEM MASS SPECTROMETRY

S.E. Fischera, V. Kulasingamb, E.P. Diamandisb,S. Ezzata, S.L. Asaa

aApplied Molecular Oncology Division, University Health

Network,bDepartment of Biochemistry, University of Toronto,

Toronto, Ontario

Thyroid cancer makes up more than 90% of allendocrine cancers. We hypothesize that tumor cellssecrete fingerprint proteins that may allow early cancerdetection and sub-classification, and may predict tumorbehavior and treatment response. The aim of this studyis to identify differentially secreted and membrane-bound proteins in the conditioned media (CM)of human thyroid cancer cell lines using extensivefractionation by liquid chromatography (LC), and massspectrometry (MS). TPC-1, MRO and ARO, humanthyroid cancer cell lines, were incubated in serum-freemedium. The conditioned medium (CM) was processedby dialysis, lyophilization, and trypsin digestion. Thetrypsin-digested sample was fractionated by strongcation exchange LC. The eluted peptides were analyzedby tandem MS. The resulting mass spectra weresearched using two search engines: MASCOT andglobal proteome machine (GPM). We identified 319,258 and 182 proteins in the CM of TPC-1, MRO andARO cells, respectively. A total of 80 proteins werecommon to all three cell lines. TPC-1, MRO and AROdifferentially expressed 188, 84 and 25 proteins,respectively. Secreted, membrane and cytoplasmic pro-teins were mostly detected in TPC-1 cells (59%). MROcells CM contained predominantly nuclear, cytoplasmicand membrane proteins (51%). The predominantsubcellular localization of proteins in ARO cells wascytoplasmic and nuclear, cytoplasmic exclusive andsecreted (48%). The identified peptides included cellsurface receptors and adhesion molecules to growthfactors that may be implicated in growth and invasion.Further studies are under way to validate the mostpromising candidates as thyroid cancer biomarkers. Theuse of MS combined with extensive fractionation by LCis a useful tool for cancer biomarker discovery byresolving a major part of the cell proteome.

P226

PATHOLOGY EDUCATION IN A MULTI-SITE

URBAN/RURAL DISTRIBUTED CURRICULUM

J.C. Forda, K.E. Pinderb, W.K. Ovalleb, C.H. Lic

aDepartments of Pathology & Laboratory Medicine,bDepartments of Cellular & Physiological Sciences,cDepartment of Medicine,

University of British Columbia, Vancouver, BC, Canada

In order to address concerns about physician shortagesin rural areas of British Columbia, the University of BC,Faculty of Medicine began distributing its undergradu-ate medical curriculum across multiple campuses(Vancouver, Victoria, and Prince George, BC) in 2005.Several medical schools across Canada and othercountries have begun similar distribution planning.Given Pathology’s central role in the undergraduatemedical curriculum, the question ‘‘how and why doesone distribute pathology education to rural sites?’’deserves special consideration.The experience of UBC points to three specificchallenges in developing a distributed pathology curri-culum: (1) recruitment of pathologists to teach;(2) implementation of high-quality technologies tofacilitate distribution; and (3) creation of an electronicpathology learning centre.Recruitment of pathologist educators proved challengingdue to comparatively limited staffing levels in thepreviously non-academic sites (Victoria and PrinceGeorge), and meeting the academic burden necessitatedextraordinary commitments from individual pathologistsespecially in the smallest centre. Technological needs weremet by a state-of-the-art videolink system allowingsimultaneous interactive didactic sessions across all 3sites, and by the use of a digital ‘‘virtual slide’’ systemsuccessfully implemented first by the Division of Anat-omy. A real and virtual pathology learning centre, stillunder development, will permit students during theirclerkships to benefit from a clinically oriented and self-directed pathology curriculum.Pathology education continues to be a vital part of adistributed undergraduate medical program, and stu-dent surveys demonstrate the value of the technologieswe have used. Distribution of pathology educationrequires considerable financial and infrastructure invest-ment, and commitment from pathologists and adminis-trators, to be implemented successfully.


P227

ESTROGEN RECEPTOR (ER) POSITIVE

CARCINOMA EX PLEOMORPHIC ADENOMA

(CXPA) OF MINOR SALIVARY GLAND

METASTATIC TO BREAST, MIMICKING A

PRIMARY MAMMARY TUMOR

L. Fu, A. Omeroglu


Center, Montreal, Quebec, Canada

Carcinoma ex Pleomorphic Adenoma (CXPA) is a rare,aggressive salivary gland malignancy and is defined asthe malignant transformation of a pre-existing pleo-morphic adenoma. We report the case of a 53-year-oldwoman presenting with a 2 cm breast mass and historyof a malignant minor salivary gland tumor excised 2years before. Histologically, the breast mass showed acribriform architecture resembling ductal carcinomain-situ or a cribriform mammary carcinoma. Thesalivary gland tumor, originally thought to be apolymorphous low grade adenocarcinoma (PLGA),had foci identifiable as pleomorphic adenoma (PA)and was reclassified as a CXPA. The carcinomatouscomponent of CXPA showed cribriform areas with fociof comedo necrosis consistent with an intermediate tohigh grade adenocarcinoma, NOS type. Based ondetailed immunohistochemical and morphological stu-dies, the breast tumor was confirmed to be a metastasisfrom the CXPA. Interestingly, the salivary gland tumorstained positively for ER, rendering the diagnosis moredifficult. To the best of our knowledge, metastasis ofminor salivary gland CXPA to the breast and ERpositivity in CXPA have not been previously reported.

P228

SYNCHRONOUS PULMONARY CARCINOMA

AND PLEURAL MESOTHLIOMA: A REPORT OF

TWO CASES

L. Fu, D. Dion, R.S. Fraser



Synchronous presentation of pulmonary carcinoma andpleural mesothelioma is rare. Since its first description in1980, only 17 cases have been reported, including threeidentified in a retrospective study of 16,000 cases ofpleuropulmonary tumors (0.019%) in 2006. We report 2cases of this unusual combination. The first is that of a66-year-old woman who had a 3.2 cm mass in theright upper lobe unassociated with other radiologicabnormality. Resection showed the mass to be poorlydifferentiated adenocarcinoma; a well differentiatedepithelioid mesothelioma was also identified in thevisceral pleura of the lobectomy specimen and inbiopsies of the right parietal pleura. The second casewas that of a 78-year-old man with a 3.0 cm mass in theleft upper lobe and a right pleural effusion. Biopsies ofthe lung mass and right pleura showed non-small cellcarcinoma and epithelioid mesothelioma, respectively.The fact that we saw these 2 cases over a relatively shorttime suggests that the incidence of the combination maybe higher than reported. It is possible that such under-reporting may be related to an assumption that, in thepresence of a documented primary lung carcinoma, apleural lesion is metastatic and thus is not sampled forhistologic examination. Although rare, the presence ofthese 2 neoplasms should be considered when there is anunusual localization of tumor (such as an apparentlyisolated mass in one lung and pleural effusion/thicken-ing on the opposite side), particularly if there is evidenceor a history of asbestos exposure.


P229

SALIVARY DUCT CARCINOMA PRESENTED BY

VAGINAL METASTASIS

Manal Y. Gabril, George M. Yousef

Discipline of Pathology, Eastern Health, St. John’s,

Canada

Department of Pathology, St. Michael’s Hospital,

Toronto, Canada

Vaginal cancer represents about 1–2% of the genitaltract malignancies. Most cases represent metastasis fromcervix, endometrium or colon. Salivary duct carcinoma(SDC) is a highly aggressive tumor that most ofteninvolves the parotid gland. On presentation, SDC ismetastasized to regional lymph nodes in about 40% ofcases. We present a case of a woman presented by avaginal mass and bleeding. CT scan revealed a lobulatedmass in the pelvis extending to the proximal vagina.Subsequent physical examination revealed a small rightparotid mass that was unnoticed by the patient.Microscopic examination showed an infiltrating poorlydifferentiated carcinoma with various histologic pat-terns. The majority of the tumor was characteristicallyformed of circumscribed nodules of tumor cells forminglarge duct-like structures with comedonecrosis resem-bling intraductal carcinoma of the breast. Other areasshowed cribriform and solid patterns in a scleroticstroma. Immunohistochemistry was positive for CK7,GCDFP-15, ER, p53 and moderately positive for PSAand negative for AR, PR, CK20, and Her2/neu. Thisimmunopattern is consistent with primary salivary ductcarcinoma of the parotid gland.To our knowledge this is the first-reported case ofvaginal metastasis from salivary duct carcinoma. Small-sized primaries might be ignored by the patient, speciallyin the older age group, probably due to lack ofmanifesting symptoms like pain and bleeding. Somecancers, like SDC, have various histologic patterns indifferent areas of the tumor. Careful examinations ofmultiple sections, in addition to an immunohistochem-ical panel, and histologic comparison of all lesions arekeys to a correct diagnosis.

P230

FIBRILLARY GLOMERULONEPHRITIS

RESULTING IN DIFFUSE PROLIFERATIVE

GLOMERULONEPHRITIS WITH AN IGG kMONOCLONAL GAMMOPATHY

V. Bhan, L. Geldenhuys, N.S. FINKLE

Departments of Medicine and Pathology, Dalhousie

University, Canada

Introduction: Fibrillary glomerulonephritis (FGN) is anuncommon glomerular disease characterized by deposi-tion of randomly arranged Congo negative fibrils in theglomerular mesangium and basement membrane. Theglomerular deposits usually contain polyclonal IgG.FGN differs from immunotactoid glomerulopathy (IT)by having smaller fibrils and a lower incidence of serumor urinary monoclonal gammopathy, lymphoprolifera-tive disorders and hypocomplimentemia.Case: This report describes an atypical case of FGNresulting in diffuse proliferative glomerulonephritis(DPGN) with fibrillary deposition of an IgG l mono-clone associated with IgG lmonoclonal gammopathy ofundetermined significance (MGUS).Clinical and laboratory findings: A 63-year-old femalepresented with microscopic hematuria and proteinuriaof 4.67 g/day following a 2-month history of fatigue,edema and new onset hypertension. Serum proteinelectrophoresis showed an IgG l monoclonal protein.Urine immunofixation showed an IgG l monoclonalprotein with free l light chains. Bone marrow biopsyshowed normal trilineage hematopoiesis with 5%plasma cells.Pathologic findings: A renal biopsy showed diffuseglobal endocapillary and mesangial proliferation. Con-go red staining was negative. Immunofluorescenceshowed peripheral and mesangial granular positivityfor IgG, C3 and l. Electron microscopy showedprominent subendothelial and intracapillary depositsof regularly arranged fibrils, 10 nm in diameter, with abanded pattern.Course: She was treated with a combination ofprednisone and cyclophosphamide.Conclusion: This case is unusual, since there have beenonly rare case reports of FGN associated with MGUS,and also only rare case reports of FGN associated with amonoclone containing a l light chain.


P231

THE ROLE OF HEDGEHOG PATHWAY IN LUNG

CANCER

I.P. Gialmanidisa, S.G. Amanetopouloua, J. Varakisa,H. Koureab, H. Papadakia

aDepartment of Anatomy, School of Medicine, University

of Patras, 26500 Rio Patras, Greece,bDepartment of Pathology, University Hospital of Patras

26500 Rio Patras, Greece

The Hedgehog (Hh)-signaling pathway is crucial fornormal development and patterning of numerous hu-man organs. Aberrant activation of the Hh pathway inadult tissues is associated with the development ofdifferent types of cancer. The aim of this study was todetermine the expression pattern of Hh-signalingmolecules in lung cancer. Eighty four (n ¼ 84) lungcancers with adjacent normal tissue were immuno-histochemically analyzed with anti-Shh, anti-Patched1(Ptch-1) and anti-Gli-1 antibodies on paraffin tissuesections. Histologic types were 22 squamous cellcarcinomas, 17 large cell carcinomas, 3 alveolarcarcinomas, 3 adenosquamous carcinomas, 4 small celllung carcinomas and 35 adenocarcinomas. All the Hh-signaling molecules that examined were aberrantlyexpressed in lung tumors (78.6% activation of the Hhpathway) compared with normal lung parenchyma(p ¼ 0.033). Activation of the Hh pathway was sig-nificantly correlated: (a) With gender as it was mainlyactivated in men compared to women (p ¼ 0.018). (b)With high histologic grade (p ¼ 0.013). (c) Withhistologic type since it was more frequently activatedin squamous cell carcinomas (p ¼ 0.021). These resultsstrongly suggest an increased activation state of Hh-signaling pathway in lung carcinogenesis that can beconsidered as a potential therapeutic target for lungneoplasms.

P232

CAUSES OF EARLY POST-OPERATIVE DEATH

FOLLOWING CORONARY ARTERY BYPASS

GRAFTING

A. Grin, K.S. Cunningham, J. Butany

University Health Network, Toronto General Hospital,

Toronto, Ontario, Canada

Coronary artery bypass grafting (CABG) is a commontreatment for ischemic heart disease. Surgical techniquehas greatly evolved since its introduction in the late1960s. Although multiple studies have looked at causesof death post-CABG, few have re-examined the topic inrecent years in light of improved surgical technique. Theaim of this study was to determine the causes of earlypost-operative death following coronary artery bypassgrafting.Design: Retrospective review of autopsy files from2003–2006 for cases of death within 30 days followingCABG. Patients with prior cardiac surgery wereexcluded from the study. Cause of death was determinedthrough review of clinical data along with gross andmicroscopic autopsy findings.Results: Twenty cases met inclusion criteria: 13 withCABG only and 7 with CABG and concomitant cardiacprocedures. The average post-operative survival was7.85 days. Myocardial infarction (MI) was determinedto be the cause of death in 85% (17/20) of cases and65% (11/17) of these occurred peri-operatively. Grosslyunidentified thrombosis and coronary artery dissectionwere observed microscopically in 53% and 35% of MIcases, respectively. The majority of dissections (4 of 6)involved the left-sided circulation. Concomitant surgicalprocedures contributed to MI in 2 cases: one at amyomectomy site and another showed thrombosis anddissection at the coronary endarterectomy site. Otherfindings contributing to death not appreciated grosslyincluded myocarditis and amyloidosis. In 2 cases thecause of death was determined to be non-cardiac innature: bronchopneumonia with sepsis in one anddisseminated intravascular coagulation in another.Conclusions: (1) Myocardial infarction is the leadingcause of early death post-CABG. (2) Most of theinfarcts in this series occurred peri-operatively. (3) Inour institution, coronary artery dissection involving oradjacent to the distal anastomosis is a significantcontributing factor in both early and late MIs (whichwas not appreciated grossly). (4) Microscopic examina-tion is essential in determining cause of death post-CABG.


P233

THE SUCCESS OF CORE BIOPIES IN THE

DIAGNOSIS OF SUSPECTED LYMPHOMA AT

OUR INSTITUTION

A.R. Haig, R. Rizkalla

Department of Pathology, London Health Sciences

Centre & University of Western Ontario, London,

N6A 5A5 Ontario, Canada

Purpose: The number of image-guided core biopsies, todiagnose lymphoproliferative disorders, has been sig-nificantly increasing at our institution. The less invasive,cost-effective procedure is used by radiologists, as wellas surgeons, and seems to replace many excisionalbiopsies. The aim of this study was to evaluate ourdiagnostic success with core biopsies taken for lympha-denopathy with suspected lymphoma.Materials and methods: A retrospective review of 78 corebiopsies, taken for lymphadenopathy with suspectedlymphoma, was conducted for the years 2005 and 2006.The histologic subtypes, subsequent pathology reports,number of tissue cores, and the availability of flowcytometry results were evaluated.Results: Out of 78 cases a definitive diagnosis was madein 63 cases (81%), including 47 lymphoproliferativedisorders and 16 non-hematological metastasis/benignlesions. Staging or therapy was often initiated based onthe diagnosis from the core biopsy. Of the non-diagnostic cases, 11 were indeterminate/inadequate and4 could not rule out the diagnosis of a lymphoproli-ferative disorder. Three tissue cores were found to be anadequate number. The most frequent diagnosis wasdiffuse large B cell lymphoma, followed by follicularlymphoma. Flow cytometry proved to be a valuableadjunctive test, minimizing the tissue required forimmunohistochemical markers.Conclusions: At our institution core biopsies have beensuccessful in the primary diagnosis of lymphoma. Threetissue cores appear to be an adequate number fordiagnosis, and flow cytometry analysis is recommendedto facilitate diagnosis. Further studies are needed tocompare the diagnoses with clinical follow-up and theInternational Prognostic Index.

P234

DIFFUSE SEGMENTAL LIPOMATOSIS OF THE

SMALL BOWEL

C.J. Howletta, A. Cherney, M. Brackstoneb,D.K. Drimana,b

aDepartment of Pathology,bDepartment of General Surgery,

London Health Sciences Centre and University of

Western Ontario, London, Ontario, Canada

Benign tumors of the small bowel are uncommon.Lipomas are the most common type, with a reportedincidence ranging from 0.04% to 5.8% in autopsy caseseries. Small intestinal lipomatosis is rarer still, withapproximately 25 cases reported since 1903. There arevarying definitions of lipomatosis, with reported casesranging from a few lipomas to intense segmentallipomatosis, where the affected region of small bowelis carpeted with tumors.We describe a case of diffuse segmental lipomatosis inan 81-year-old man with no significant medical history,who presented with small bowel obstruction that did notresolve with conservative management. A laparotomywas performed, at which time a segment of small bowelfrom mid jejunum to distal ileum showed massivedilatation as well as significant mesenteric fatty deposits.This segment was resected and a primary anastomosiswas performed. The post-operative course was unevent-ful. Pathological examination of the resection specimenrevealed a 230 cm segment of small bowel withnumerous (4100) well-defined, soft yellow polypoidlesions measuring 1–6 cm in greatest dimension carpet-ing the proximal 150 cm. A cluster of the lesions wasinfarcted. There were multiple-associated diverticula.Histologically the lesions were submucosal and com-posed of mature adipose tissue. The overlying mucosawas flattened, showed goblet cell depletion and in-creased intraepithelial lymphocytes.Small bowel lipomatosis is a rare benign condition thattypically presents with small bowel obstruction, some-times secondary to intussusception or volvulus. Com-mon associations include diverticulosis, as seen in thepresent case, as well as malabsorption secondary tobacterial overgrowth. There are no known associatedsyndromes.


P235

BETA-THALASSEMIA INTERMEDIA WITH

MARKED HISTOCYTIC INFILTRATION BY

PSEUDO-GAUCHER CELLS IN THE BONE

MARROW: A CASE REPORT

H. Huwait, R.P. Michel

Department of Pathology, McGill University and McGill

University Health Center, Montreal, QC, Canada

Gaucher like-cells have been described in the bonemarrow in various hematological disorders includingneoplastic, such as chronic myelogenous leukemia, acutelymphoblastic leukemia, and Hodgkin lymphoma, andnon-neoplastic, such as thalassemia major and idio-pathic thrombocytopenic purpura. Pseudo-Gauchercells have also been identified at extramedullary sites,including soft tissue and lung, in connection withneoplastic, infectious and inflammatory disorders.We report a case of b-thalassemia intermedia withautoimmune hemolytic anemia after blood transfusionin a 24-year-old Italian male in whom bone marrowbiopsy revealed marked infiltration by histiocyticGaucher-like cells. The patient had no evidence ofinherited Gaucher disease. These cells were large withabundant eosinophilic and PAS positive cytoplasm.Immunohistochemistry showed they were positive forCD68, negative for keratins, myeloperoxidase, hemo-globin A, S100 protein and CD10; Ziehl–Neelsen stainand Gram stains were also negative. After ruling outseveral other differential diagnostic possibilities, weconcluded that these cells in the bone marrow were theresult of a reaction to severe hemolysis.The histological, ultrastructural features and pathogen-esis of these pseudo-Gaucher cells are described. Inaddition, we review the literature and discuss thedifferential diagnostic approach to histiocytic lesionsof the bone marrow.

P236

A METHOD OF ASSESSMENT OF SAMPLING

ERROR IN BIOLOGICAL TISSUES

V.V. Iakovleva,b, Andrew Morrisonb, Richard Hillb,David Hedleyb

aOntario Cancer Institute/Princess Margaret Hospital,

Toronto, ON, CanadabCIHR Molecular Oncologic Pathology Fellowship

Program

Intratumoral heterogeneity causes sampling error in themeasurement of biomarkers and morphological struc-tures used in diagnosis and research. In our previouswork the sampling error did not allow accuratecategorization of438% of tumors as hypoxic/normoxicusing carbonic Anhydrase IX (CAIX) immunostaining.Variance component analysis showed that the size oftissue section was the major factor affecting theaccuracy of measurement within a biopsy. Using thesampling theory of Gy and our data we hypothesizedthat sampling error is dependent on the size of thebiopsy and the marker-rich-poor foci within it. Math-ematical equations predicting maximum and minimumvalues for a given biopsy size were developed:

DsMax ¼ sr (sr–st)/S,DsMin ¼ sp (st–sp)/S,

where DsMax is deviation toward the maximum value;DsMin the minimal value for a given biopsy size S; sr —size of subject-rich regions; sp—size of subject-poorregions; sr—density within subject-rich regions; sp—density (concentration) within subject-poor regions;st—subject density within total tumor, organ or tissuetype. The equations were tested on 138 images of CAIXstaining to predict a range of values in relation to biopsysize by a novel method based on progressive sampling. Itwas found that sampling error is dependent on the sizeof the biopsy, size of the marker-rich-poor foci within itand also marker density within the foci. The methodmay be useful in the development of biopsy sizeadequacy criteria for diagnostic and research purposes.


P237

CD138 EXPRESSIONS IN MERKEL CELL

CARCINOMA: A POTENTIAL DIAGNOSTIC

PITFALL WITH CD138 POSITIVE

HEMATOLOGICAL MALIGNANCIES

Dina El Demellawy, Prashant Jani

Northern Ontario School of Medicine, West Campus,

Thunder Bay Regional Health Sciences Centre (TBRHSC),

Thunder Bay, Ontario, Canada

Background: Merkel cell carcinoma is a neuroendocrinecarcinoma of the skin that overlaps morphologicallywith hematological malignancies having blastic mor-phology. The consistent expression of CD 56 has beendocumented in Merkel cell carcinoma. Recent report hasfound TdT expression in a subset of cases. The currentstudy assesses MCC expression for CD138.Method: Ten cases with the diagnosis of Merkel cellcarcinoma were retrieved retrospectively from theTBRHSC archives, from the period of 2000 to 2007.For all cases, review of the clinical and pathological datawas performed. In addition, immunohistochemicalstaining using antibodies against CD138, CK20, CK7,EMA, TdT, Bcl 2, CD 45, CD20 Synaptophysin andCD56 was assessed.Results: CD138 has been consistently expressed (90%)in all cases of Merkel cell carcinoma.

Marker
CD138 TdT
CK7

CD 45

CD 20

CD56

Bcl2

EMA

CK20
Synaptophysin
Expression
Membranous None Cytoplasmic Cytoplasmic Cytoplasmic
Interpretation
Positive Negative Positive Positive Positive
% of cases
90 0 100 100 80
Conclusion: CD138 is documented as a consistentmarker of plasma cells and their originating tumorsincluding plasmablastic myeloma. Though CD138 isconsistent, it is non-specific for plasma cells, beingexpressed in the majority of Merkel cell carcinoma.Other markers as CD56, EMA and Bcl2 are expressed ina subset of myeloma and almost all Merkle cellcarcinoma. Plasmablastic lymphomas are also CD138positive. On dealing with CD138 positive tumorsshowing blastic morphology, a panel of immunohisto-chemical markers including hematological, neuroendo-crine markers and CK20 is recommended todifferentiate blastic hematological malignancies fromMerkle cell carcinomas. To the best of our knowledgethis is the first study to report CD138 expression inMerkle cell carcinoma and highlights the potentialdiagnostic pitfall.

P238

SYNCHRONOUS ADRENOCORTICAL AND

RENAL CELL CARCINOMAS: CASE REPORT

AND BREIF LITERATURE REVIEW

Dina El Demellawy, MD, PhD, FRCPC, Prashant Jani,MD, FRCPC


Northern Ontario School of Medicine, Thunder Bay

Regional Health Sciences Centre, Thunder Bay, Ontario,

Canada

Synchronous composite tumors though described areuncommon. We report a case of adrenocortical andrenal cell carcinomas occurring synchronously in a 53year-old male. Clinical findings were diagnostic ofpheochromocytoma and partial nephrectomy and adre-nectomy were performed. Pathological examination ofthe tumors including a panel of immunohistochemicalstains revealed synchronous adrenocortical and renalcell carcinomas. Cases of metastatic renal cell carcinomato ipsilateral or contralateral adrenal glands have beenreported. A single case of synchronous renal cellcarcinoma and adrenocortical adenoma has beenreported. To our knowledge this is the first time thatsynchronous occurrence of these two malignant pro-cesses is described. In this case it is important to excludewhether these tumors represent metastases or twosynchronous tumors as it has implications on thepatient’s management and prognosis. Clinical andpathological clues are discussed in detail to achieve thediagnosis.


P239

VALUE OF CD138 IN NORMAL AND

PATHOLOGIC ENDOMETRIUM

P. Jani, D. El Demellawy

Northern Ontario School of Medicine, Thunder Bay,

Ontario, Canada

Background: CD138 is a marker of plasma cells that hasrecently been documented to be expressed in carcinomaslike renal cell and hepatocellular carcinomas.Design: A total of 35 cases of benign endometrium(5 proliferative, 5 secretory, 5 chronic endometritis and 5atrophic), endometrial hyperplasia (5 cases withoutatypia and 5 cases with atypia) and endometrialcarcinoma (5 cases) were reviewed for their clinicopath-logic findings and stained for CD138.Results: A consistent pattern of membranous staining ofsurface epithelium was seen in all cases. Proliferativeendometrium showed focal and weak membranousstaining of the glandular epithelium. Secretory endome-trium showed focal but strong staining of the glandularepithelium. Areas with tubal metaplasia showed strongstaining. Atrophic endometrium didn’t stain for CD138.Endometrial hyperplasia showed strong and diffusestaining in atypical glands. Endometrial carcinomashowed diffuse and strong staining. In all the cases,there was no staining in the endometrial stroma. Caseswith chronic endometeritis stained only plasma cells.Conclusion: CD138 strongly stains surface endometrialglandular epithelium in secretory phase, with tubalmetaplasia, atypical hyperplasia and carcinoma. Inac-tive and proliferative endometrium show absent andweak, focal staining, respectively. The diagnosis ofchronic endometritis should be made if incidentalstaining of plasma cells is noted. Endometrial carcinomashould be included in the differential diagnosis ofcarcinomas expressing CD138.

No.
Age
group

Pathology
CD138
staining

intensity

CD138 staining

pattern

5
25–38 yrs Proliferative Weak, Focal Membranous
Foci of Tubal

metaplasia

Strong, diffuse
Membranous
5
52–68 yrs Atrophic Absent NA
5
25–38 yrs Secretory Strong, focal Membranous
10
32–45 yrs Endometrial
hyperplasia

(simple and

complex, with and

without atypia)

Diffuse

staining.

Strong at the

site of atypical

glands

Membranous

5
42–59 yrs Endometrial
carcinoma

Diffuse and

strong

Membranous

5
25–35 yrs Chronic
endometeritis

Staining of

glands and

plasma cell

Membranous

staining in both

the glands and

plasma cells

P240

EXPRESSION OF EGFR, AKT, BAD, VEGFR AND

SV40 IN MALIGNANT MESOTHELIOMA:

A TISSUE MICRO ARRAY STUDY

Namrata Junejaa, Zhaolin Xua, Wojceich Morzykib,Drew Bethunec, Gordon Youngd

aDepartments of Pathology,bMedical Oncology,cThoracic Surgery, anddInternal Medicine, Queen Elizabeth II Health Sciences

Centre, Halifax, Nova Scotia, Canada

Background: Malignant Mesothelioma (MM) is a fataltumor of increasing incidence usually associated withasbestos exposure. However, little is known about itsmolecular pathogenesis. In this study, we evaluated theprotein expression of EGFR and its downstreamsignaling molecules as well as VEGFR and SV40 inMM and correlated the findings with histopathologicalparameters.Design: Tissue micro array blocks were constructedusing representative formalin-fixed paraffin embeddedtissue from 62 MM patients. The sections wereimmunostained to evaluate the expression of EGFR,Phospho-EGFR, AKT, BAD, Phospho-BAD, VEGFRand SV40. A scoring protocol was used to standardizethe interpretation of the immunostains.Results: Of the 62 MM cases, 58 (94%) were pleural and4 (6%) peritoneal. The histological subtype wasepithelioid in 42 (68%); sarcomatoid in 12 (19%) andbiphasic in 8 (13%) cases. EGFR expression was seen in44 (71%) cases, Phospho-EGFR in 6 (10%), AKT in 36(58%), BAD in 33 (53%), Phospho-BAD in 31 (50%),SV40 and VEGF in 14 cases (22%) each. Coexpressionof EGFR with BAD and AKT was seen in 30 cases each(48%); with Phospho-BAD in 27 cases (43%) and withVEGF and SV40 in 13 cases each (21%).Conclusion: EGFR expression was identified in asignificant proportion of MM cases, particularly theEpithelioid and Biphasic subtypes (po0.05). There wasa significant coexpression of EGFR with VEGF, SV40,BAD, Phospho-BAD and AKT (po0.05). The expres-sion of BAD and Phospho-BAD was significantly lowerin Sarcomatoid MM than the Epithelioid and BiphasicMM subtypes (po0.05). There was no statisticaldifference in the expression of SV40, VEGF and AKTamong the subtypes of MM. These over expressedproteins in Malignant Mesothelioma may be targets forselective therapies in the future.


P241

ADVANCING THE PATIENT SAFETY AGENDA IN

PATHOLOGY AND LABORATORY MEDICINE:

THE DISTANCE COVERED

J. Kalraa, A. Mullab

aDepartments of Pathology and bGeneral Surgery,

College of Medicine, University of Saskatchewan and

Royal University Hospital, Saskatoon, Saskatchewan,

Canada

Medical errors and patient safety form one of the salientissues in health care today. The profession of laboratorymedicine continues to strive towards achieving optimaland safer care for patients in a proactive manner. Theprevention of errors in laboratory medicine requirescontinuing efforts directed at all levels to make thesystem safer. We present a series of risk managementinitiatives that have showed immense promise towardsour continuing commitment in improving quality andenhancing patient safety. We began by conducting a riskmanagement audit to classify the various quality issuesand errors in laboratory practice. The results suggestedthat the majority of risk events occur in the pre-analytical phases of testing. The next step was introduc-tion of an educational program aimed at all sectors ofthe laboratory professionals to imbibe a culture ofsafety. This was mostly accomplished through a formatof case discussion and synopsis of the critical incidents.This was followed with adopting a ‘no-fault’ model thatencourages voluntary anonymous error reporting of allcritical incidents occurring in the laboratory testingprocess. The educational program has been integratedinto the ‘no-fault’ model. The model emphasizesevaluation of the critical incidents through a root causeanalysis approach and an internal audit of the riskissues. Simultaneously with the implementation of the‘no-fault’ model, we also introduced quality carerounds. This initiative provided a forum for discussionand evaluation of medical errors in a guilt-free andsecure environment. In conclusion, it is emphasized thattremendous opportunities exist for improvement inpatient safety and error reporting. In laboratorymedicine, the key to creating a culture of safety isorganizational commitment to implementation of newerevidence-based strategies in error reduction.

P242

DEDIFFERENTIATED LIPOSARCOMA WITH

RHABDOMYOSARCOMATOUS COMPONENT—

A CASE REPORT WITH NOVEL MORPHOLOGY

H. Kaur, B.M. Wehrli


Centre and University of Western Ontario, London, ON,

Canada

Dedifferentiated liposarcomas with rhabdomyosarco-matous differentiation are rare with only 10 casesreported in the literature. These cases have shown apredilection for males, retroperitoneal location, and atendency to arise ab initio. The rhabdomyosarcomatouscomponent would all be classified as pleomorphic. Wereport a dedifferentiated liposarcoma with a rhabdo-myosarcomatous component that resembles the embry-onal subtype of rhabdomyosarcoma.A 54 year-old male presented with symptoms relating toa mesenteric mass. The resected tumor weighed 5.3 kgand had a yellow cut surface with extensive areasof necrosis. Histologically, it was a dedifferentiatedliposarcoma with two components. The first componentshowed features of low-grade liposarcoma with variablysized adipocytes, lipoblasts, and increased fibrous septawith atypical stromal cells. The second componentconsisted of solid sheets of small blue round cells withlimited cytoplasm and that stained positively for desminand myogenin. These tumour cells failed to stain forother markers utilized to distinguish small blue roundcell tumors (CD99, muscle specific actin, neuron specificenolase, CD10, Bcl6, Bcl2, CD5 and CD20).This case documents a unique morphologic appearanceof dedifferentiated liposarcomas with rhabdomyosarco-matous component.


P243

PHLEBOTOMY MAY REDUCE IRON OVERLOAD

AND PREVENT PROGRESSION OF LIVER

INJURY IN JUVENILE HAEMOCHROMATOSIS:

A CASE REPORT

H. Kaura, P.C. Adamsb, S. Chakrabartia

aDepartment of Pathology,bDepartment of Medicine, University of Western Ontario,

London, ON, Canada

Juvenile hemochromatosis, an autosomal recessive ironoverload disorder of the 2nd to 3rd decade causescardiomyopathy, hypogonadism and arthritis, even-tually leading to cirrhosis, heart failure and fatalarrhythmias. Recently, a specific mutation (G320V) ofthe hemojuvelin gene on chromosome 1q21 was foundin two-third of cases. Here, we report an interesting casedemonstrating prevention of liver injury in juvenilehaemochromatosis.A 26-year-old man with known G320V mutationpresented with shortness of breath, impotence, arthro-pathy and skin pigmentation in 1994. Investigationsrevealed iron overload with a ferritin of 8472 mg/L andabnormal liver function tests. The initial liver biopsyshowed cirrhosis and iron overload with an ironconcentration of 884 mmol/G dry weight (referencerange: 0–36) and a hepatic iron index of 34. He wastreated by weekly phlebotomies for 2 years andintermittent phlebotomies for another 2 years. A repeatliver biopsy in 1996 showed moderate to marked portalfibrosis and normal iron concentration. His recentbiopsy in 2007 shows features of chronic hepatic venousoutflow obstruction with fibrous septa and earlycirrhosis, focal bile ductular proliferation, withoutany evidence of lobular inflammation or hepatocytenecrosis. In spite of not having any phlebotomies for6–7 years, he didn’t demonstrate signs of iron re-accumulation. He has normal liver function tests,normal iron stores and a ferritin of 33 mg/L. However,he underwent cardiac transplantation for congestiveheart failure.This case demonstrates that reduction in systemic ironoverload by phlebotomy may prevent progressive liverinjury in juvenile hemochromatosis. However, tissuedamage may continue to progress in other organs. Theexact reason(s) is/are not clear. It is, however, possiblethat reduced iron may lead to diminished oxidativestress and free radical injury, preventing progressivetissue damage in an organ with high regenerativecapacity.

P244

RARE COMPLICATIONS OF VENTRICULAR

ASSIST DEVICES

C. Keprona, J. Butanyb

aDepartment of Laboratory Medicine and Pathobiology,

University of Toronto,bDepartment of Pathology, University Health Network,

Toronto, Ontario, Canada

Congestive heart failure is a leading cause of morbidityand mortality in Canada, and for end-stage disease,heart transplant has been the only means of improvingquality of life and survival. Chronic donor shortagesand unsuitability of many patients for transplant havemeant that few benefit from this treatment, and mucheffort has gone into developing alternatives. Since 1994ventricular assist devices (VADs) have been approvedfor use as bridge-to-transplant therapy (BTT), andrecent trials have shown that in patients ineligible fortransplant, VADs improve both survival and quality oflife. Serious adverse events post-VAD implantationoccur in as many as 67% of patients and includebleeding, sepsis, right heart failure, acquired aortic valve(AV) disease, and renal dysfunction. Here, we report 2cases of unusual VAD complications; one with a deviceused as BTT, the other is a device intended asdestination therapy (DT). A 57 year-old male diagnosedwith dilated cardiomyopathy received a VAD as BTTand simultaneous AV replacement with a porcinebioprosthesis. Thirty-nine days later, he went on toorthotopic heart transplant. Examination of the ex-planted heart revealed significant changes to theprosthetic AV with pannus formation covering theentire flow surface, including the orifice. A 61 year-oldmale with ischemic cardiomyopathy and aneurysms ofthe left ventricular wall and interventricular septumreceived a VAD as DT. Eleven days later he experiencedmultiple episodes of arrhythmia, deteriorated medicallyand died. At autopsy, a significant ventricular septaldefect was identified, corresponding to the edge of theVAD inflow cannula. In this report, the commonadverse events following VAD implantation are re-viewed and these two unusual complications arediscussed. We conclude that as there is still much to belearned about the short and long-term effects of VADtherapy, thorough gross examination of explantedspecimens or examination of the heart and device atautopsy is essential in all cases involving VADs.


P245

THE ROLE OF INTRAOPERATIVE CONSULTA-

TION (IOC) IN PANCREATIC TUMOR SURGERY:

A 15-YEAR-WORTH EXPERIENCE

M.A. Khalifaa, C.H. Rowsella, D. El Demellawya,V. Maksymova, A. Plotkina, C. Lawb, S. Hannab

aDepartment of Pathology,bDepartment of Surgical Oncology,

University of Toronto, Canada

Objective: Surgical decisions for pancreatic tumors areincreasingly dependant on the clinical impression andthe results of imaging procedures with a diminishingneed for preoperative biopsies. This work summarizesour experience at a tertiary care teaching hospital.Method: Surgical pathology database and medicalrecords were searched. Only the data related to surgeriesperformed for tumors in the pancreas were collected.The subgroup of patients who had IOC requested wasfurther analyzed.Results: Surgery was performed on a total of 183 patientswith pancreatic tumors, of which IOC was requested in 141cases. Surgeries included 37 distal pancreatectomies, 4 totalpancreatectomies, 65 pancreatico-duodenectomies and 35bypass procedures. The status of the margin was requestedin 91 cases, assessment of extra pancreatic spread in 62 caseswhile a diagnosis was requested in only 37 cases. Followingthe IOC, the initially planned surgery proceeded with nochange in 104 cases (73.8%), was modified in 2 cases (1.4%)and was terminated in the remaining 35 cases (24.8%)where only a bypass procedure was performed. To securecomplete excision, surgical margins were revised in 6 caseswith a positive pancreatic margin and 2 with a positiveuncinate process margin. In 3 other cases, a positiveuncinate process margin could not be revised for technicalreasons. These 3 cases had recurrences in 1–6 months anddied of their disease in 11–12 months.Conclusions: In our hospital, the most common indica-tion for which an IOC is requested is the status of themargins while an intraoperative diagnosis is an unlikelyrequest. Pathologists, as intraoperative consultants playa critical role in detecting positive surgical margins andconfirming extra pancreatic spread.

P246

THE ROLE OF INTRAOPERATIVE CONSULTA-

TION (IOC) IN WHIPPLE PROCEDURE FOR

AMPULLARY/DUODENAL TUMORS: A 15-YEAR

WORTH EXPERIENCE

M.A. Khalifaa, D. El Demellawya, C.H. Rowsella,V. Maksymova, A. Plotkina, C. Lawb, S. Hannab

aDepartment of Pathology,bDepartment of Surgical Oncology,

University of Toronto

Objective: The purpose and accuracy of IOC in Whippleprocedure for ampullary/duodenal A/D tumors has notbeen documented. The aim of this work is to summarizeour experience at a tertiary care teaching hospital.Method: Surgical pathology database and medicalrecords were searched for all cases with A/D tumors.Only the data related to Whipple procedure performedfor these tumors were collected.Results: 143 Whipple specimens were identified, ofwhich 42 were performed for A/D tumors. IOC wasrequested in 41 cases. A preoperative tissue diagnosiswas available in 21 cases (51.2%). This series included28 patients (68.3%) with ampullary adenocarcinoma, 3(7.3%) with ampullary adenoma, 8 (19.5%) withduodenal adenocarcinoma, 1 (2.4%) with duodenaladenoma, and 1 (2.4%) with ampullary carcinoid. Thestatus of the margin was requested in 38 cases,assessment of metastatic spread in 16 cases while aprimary diagnosis was requested in only 2 cases.Following the IOC, the planned surgery proceeded withno change in 39 cases (95.1%) and was terminatedbecause of established metastases in 2 cases (4.9%). TheIOC was concordant with the final diagnosis in 39 cases(95.1%) and discordant in 2 cases (4.9%). A falsepositive IOC was given in 1 case with a liver lesion andone false negative diagnostic consultation occurred witha duodenal biopsy at the time of the Whipple. In bothcases, surgeons followed their clinical impression andthe preoperative imaging results.Conclusions: In our hospital, the most common indica-tion of an IOC is assessment of the status of themargins, which is confidently and accurately achieved.IOC errors are mostly encountered during assessment ofmetastatic spread or obtaining a primary diagnosis.With uncertain findings, adequate communication withthe surgeon and correlation with preoperative images isessential.


P247

SOLID ONCOCYTIC PAPILLARY RENAL CELL

CARCINOMA: A RENAL CELL CARCINOMA

THAT MIMICS RENAL ONCOCYTOMA

Derek M. Kohler, MD, Kien T. Mai, MD, FRCPC,Susan J. Robertson, MD, FRCPC, Eric C. Belanger,MD, FRCPC, E. Celia Marginean, MD, FRCPC,FACP

Division of Anatomical Pathology, Department of

Laboratory Medicine, The Ottawa Hospital, and Depart-

ment of Pathology and Laboratory Medicine, University

of Ottawa, Ottawa, Ontario, Canada

Objectives: A solid variant of papillary renal cellcarcinoma (RCC) has been recognized and is associatedwith similar cytogenetic alterations as those of the usualpapillary RCC (PRCC). In this study, cases of solidoncocytic PRCC that mimic renal oncocytoma (RO) arereported.Materials and methods: Anatomical pathology files ofthe Ottawa Hospital were reviewed to identify cases ofoncocytic renal cell neoplasm (ORCN) with featuresposing a differential diagnostic problem with RO,oncocytic PRCC, eosinophilic (granular) clear cellRCC (CRCC), and oncocytic chromophobe RCC.Studied cases were submitted for CD117, PR, AMACR,RCC, Vimentin, CD10, and CK7 immunostaining.Results: Thirty-eight RO, 15 oncocytic PRCC, 10eosinophilic CRCC, 10 oncocytic chromophobe RCC,and 11 ORCN were identified. The 11 ORCN consistedof circumscribed or encapsulated tumors with solid anddiffuse growth pattern. Tubular structures were in 7 andnon-tubular structures in 4 ORCN, and occasionalpapillae were in 4 ORCN. For immunostaining of the 11ORCN, 6 tumors displayed CD117+/PR+ (featuresshared by RO) and 5 tumors displayed CD117�/PR�(features shared by PRCC). The CD117�/PR� ORCNalso displayed AMACR+, RCC+, VIM+, CD10+,and mostly focal reactivity for CK7. None of the ORCNcases had features of eosinophilic CRCC. The 5 ORCNcases with immunohistochemical features of PRCC hadsizes ranging from 1 to 6 cm, patient ages ranging from52 to 67 years, and male : female ratio of 5:1. Twopatients developed metastases, and 1 patient died ofdisease.Conclusions: The solid oncocytic variant of PRCC is arare type of RCC having similar immunohistochemicalproperties to the common type of PRCC. Awareness ofthis entity may be helpful when diagnosing oncocyticrenal cell neoplasms.

P248

MALIGNANT FIBROUS HISTIOCYTOMA OF THE

LIVER: CLINICOPATHOLOGIC STUDY OF 10

CASES AND REVIEW OF THE LITERATURE

Yunru Li, Elaheh Akbari, Zu-Hua Gao


University of Calgary and Calgary Laboratory Services,

Calgary, AB, Canada

Background: malignant fibrous histiocytoma (MFH), acommon soft tissue tumor, rarely occurs in the liver.There is incomplete understanding of its etiology,pathogenesis, histological spectrum and clinical beha-vior.Methods: we studied the clinicopathologic and immu-nohistochemical features of 10 cases of liver MFHobtained from Foothills Medical center, Tom BakerCancer Center and Cross Cancer Institute in theprovince of Alberta, Canada.Results: The patients were 5 men, 5 women, age range33–80 years. Clinical presentation included abdominalpain or discomfort (7 cases), back pain (1 case) andincidental finding (2 cases). CT and ultrasound revealeda heterogeneous low-density lesion within the liverparenchyma in 6 cases. Grossly, the tumor size ranged5–20 cm. In 3 cases, the tumor invaded into adjacenttissue (lung and diaphragm). In 4 cases, tumor involvedother organs (retroperitonum, pancreas and spleen).Microscopically, the tumor was composed of hapha-zardly arranged fibroblast-like spindle cells with variabledegrees of nuclear pleomorphism and mitosis. Sevencases showed hemorrhage and necrosis; 4 cases showedinflammatory cell infiltration and none of the casesshowed lymphvascular space or perineural invasion.Immunohistochemically, the tumor cells stained positivefor vimentin, CD68, lysosome and factor 13a. Thetumor cells were negative for epithelial markers (cyto-keratin, EMA), lymphocytic markers (CD45), dendriticcell markers (CD21) and markers of specific mesench-ymal differentiation such as smooth muscle, neural,endothelium, etc. Seven patients died of tumor within 1year. One patient died 4 years after diagnosis due torecurrent tumor. One patient is alive with tumor (follow-up periodo1 year).Conclusion: Combined study of the current 10 cases andreview of a total of 27 reported cases in the Englishliterature indicate that liver MFH is a distinct entitywith unique clinicopathologic characteristics.


P249

HAIRY CELL LEUKEMIA OCCURING WITH

CHRONIC LYMPHOCYTIC LEUKEMIA. A TREA-

TABLE CLONE, IMPORTANT TO RECOGNIZE

N. Nasseria, H. Feilottera, T. Baetzb, D.A. Rapsona

aDepartment of Pathology and Molecular Medicine,bDepartment of Medicine, Queen’s University, Kingston,

Ontario, Canada

Biclonal B cell lymphoproliferative disorders have beenreported to occur in 4.6% of leukemic chroniclymphoproliferative disorders, and include rare casesof chronic lymphocytic leukemia (CLL) and hairy cellleukemia (HCL). We report a unique case of a 78 year-old man, who presented with cervical lymphadenopathy.Biopsy results revealed small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), and immu-nophenotyping on peripheral blood detected a CD5,CD23+ clonal B cell population characteristic forB-CLL. Watchful waiting was instituted. Two yearslater, the patient felt fatigued and unwell. Physicalexamination revealed splenomegaly and was otherwiseunremarkable. Peripheral blood film showed a secondneoplastic lymphoid population of hairy cells. Immu-nophenotyping confirmed the presence of the HCLclone, positive for CD19/CD20/CD11c/CD25/CD103,with the same sIg light chain idiotype. Molecular studiesshowed detectable single clonal populations by PCR andSouthern blot for the immunoglobulin heavy chain butalso for the T cell receptor, suggesting a possible clonalproliferation of early hematopoietic origin. The patientwas treated with Cladribine for HCL with good clinicalresult. The favorable response of HCL to therapydemonstrates the importance of recognizing the possi-bility of multiple concurrent clonal proliferations.

P250

PRIMARY BURKITT’S LYMPHOMA INVOLVING

THE APPENDIX AND MIMICKING ACUTE

APPENDICITIS

C. Luedtke, B. Taylor, K. Rizkalla


Centre, University of Western Ontario, London, Ontario,

Canada

Purpose: Burkitt’s lymphoma uncommonly presentsitself in the region of ileocecal valve and involves theappendix. We document a case of a 75 year-old malewho developed Burkitt’s lymphoma and presentedclinically and radiologically as an acute appendicitis.Case report: Twenty months prior to bowel resection,this patient had had right lower quadrant pain. Imaging(CT scan) demonstrated a fluid-filled abscess which wasconsidered to be missed and ruptured appendicitis.Drainage catheter was inserted. The symptoms relievedand the patient remained well, with the exception ofsome urinary tract symptoms. Twenty months later, thepatient presented to an emergency room with recurrentright lower quadrant pain. An ultrasound showedcomplex appearing mass with a differential of inflam-matory and neoplastic processes. Due to the intractablepain, right hemicolectomy was performed.Gross examination showed an inflammatory like masswith purulent exudate on the serosal surface of theileocecal region. The appendix could not be identifiedgrossly due to a mass lesion in the area, extending to thebase of the cecum and ileocecal valve.Microscopy revealed Burkitt’s lymphoma with classicimmunophenotypic and cytogenetics characteristics;regional lymph nodes were free of malignancy andstaging bone marrow biopsy was positive.Conclusion: This is a rare clinical presentation ofBurkitt’s lymphoma, simulating acute appendicitis.Frequent imaging might have been helpful to detectmalignancy, if the inflammatory like mass persisted.


P251

HIGH-GRADE FRONTAL LOBE MIXED GLIOMA

ARISING ON THE BACKGROUND OF A BILAT-

ERAL LOW-GRADE THALAMIC ASTROCYTOMA:

MALIGNANT TRANSFORMATION VS. FIELD

EFFECT

M. Manducha, P. Isotaloa, P. Ellisb, J.P. Rossitera

aDepartment of Pathology and Molecular Medicine andbDivision of Neurosurgery, Queen’s University, Kingston,

Ontario, Canada

Primary thalamic gliomas include a rare subtype knownas bilateral thalamic glioma. This occurs as relativelysymmetric bilateral thalamic masses, typically present-ing with behavioural changes and cognitive deteriora-tion. We report the case of a 64 year-old female withsevere mental retardation who had a bilateral low-gradethalamic glioma and a high-grade right frontal lobeglioma. This patient presented with non-lateralizingneurologic features including bilateral lower extremityweakness and intermittent paralysis. Computed tomo-graphy (CT) revealed a large right thalamic mass thatremained unchanged until approximately 2 years laterwhen CT and magnetic resonance imaging (MRI)showed a probable left thalamic glioma as well as anadditional ring-enhancing cystic right frontal lobe mass.The patient died shortly after a prolonged generalizedseizure. Postmortem examination established the pre-sence of bilateral thalamic low-grade (WHO grade II)fibrillary astrocytoma and a right frontal lobe high-grade (WHO grade IV) mixed glioma (oligoastrocyto-ma). The high-grade glioma may represent a malignanttransformation of the low-grade bilateral thalamicglioma or alternatively may reflect a de novo lesion dueto a ‘field effect’. To the best of our knowledge, this isthe first report of a high-grade mixed glioma arising on abackground of low-grade bilateral thalamic glioma.

P252

CONGENITAL INTRA-CRANIAL GLIAL

TUMORS: A REPORT OF TWO CASES

Meliti A., Provias J.

Department of Pathology & Molecular Medicine,

Hamilton Regional Laboratory Medicine Program,

McMaster University

Introduction: Congenital intra-cranial tumors are quiterare, and account for approximately 0.5–1.5% of allpediatric brain tumors. Amongst the congenital intra-cranial tumours, glial tumours represent a relativelyuncommon subtype, less frequently encountered, thanthe more common teratomas and primitive neuroecto-dermal type tumours.Case report: We report 2 cases of congenital cerebralhemispheric gliomas. The first presented neonatally withthe development of fairly sudden onset of severe emesisat 7 months. She was the product of a normal, full-termpregnancy. Radiologic imaging at the time of presenta-tion showed marked hydrocephalus with a large,centrally located, non-homogeneous mass, partly fillingthe lateral and 3rd ventricles. The 2nd case presented in

utero, a baby girl born at 35-week gestation. Prenatalultrasound at approximately 19 weeks was interpretedas normal. Subsequent prenatal neuroimaging showedmarked abnormalities of the cerebral hemispheres withlarge cystic spaces and a probable tumourous mass. Thepostmortem exam showed a large cerebral hemispherictumour with marked distortion of the normal anatomy.Results: Histologically, both cases were glial astrocyticneoplasms, the first largely intraventricular with high-grade features, conforming however only partially to anadult glioblastoma multiforme, and demonstratingpredominantly intraventricular growth. The second casealso showed glial astrocytic features with gemistocyticqualities with marked discordance amongst histologicgrading parameters.Conclusion: Both cases emphasize the relatively uniquefeatures of these rare congenital glial neoplasms thattend not to conform to adult and pediatric concepts ofgliomas and may not follow traditional WHO gradingparameters. Future studies may discern these to have afundamentally different molecular basis.


P253

PEDIATRIC PRIMARY INTRACRANIAL NEO-

PLASMS: HAMILTON. REGIONAL EXPERIENCE

OVER THE LAST 20-YEARS

A. Meliti, J. Provias



McMaster University

Objectives: We conducted a comparative and analyticalretrospective study of primary intracranial tumors inchildren less than 18 years of age, diagnosed in ourdepartment over the last 20 years, with regards to theirgender distribution, age-related location and histo-pathologic diagnosis. In addition, we specifically ana-lyzed the subgroup of intracranial tumors affectingchildren who are 4-years of age or younger.Patients and methods: We analyzed the data compiledfrom 160 children, with CNS tumors operated on andhistologically diagnosed at HHSC between 1986 and2006. The pathologic specimens in the study includedboth biopsies and autopsies. We excluded vascular,lymphoid and hematopoietic diseases and metastatictumors. We followed the criteria of the World HealthOrganization (WHO) classification of central nervoussystem (CNS) tumors.Results: We found that 35.6% of CNS tumors werelocated in the supratentorial region, 64.4% of CNStumors were located in the Infratentorial region. Themale to female ratio is 1.1:1. The most commonhistologic entities in our study were pilocytic astro-cytoma 43.1% followed by medulloblastoma 22.5%.Pilocytic astrocytoma predominates both in supraten-torial as well as infratentorial regions, 45.6% and 41.7%respectively, followed by craniopharyngioma 12.3% inthe supratentorial region and medulloblastoma 34.9%in the infratentorial region. The total number of thechildren who were 0–4 years of age was 33; in thissubgroup we found that the male to female ratio is 1.2:1,and the most common tumor was pilocytic astrocytoma45.5%, followed by medulloblastoma 21.2%. Further-more, Pilocytic astrocytoma was more prevalent in theinfratentorial region 56%, followed by medulloblasto-ma, which accounts for 25% of tumors involving theinfratentorial region. Glioblastoma multiforme andprimitive neuroectodermal tumors equally affect thesupratentorial region 25%.Conclusion: The age and sex distribution of the subjects,the histologic entities and the location of tumors in ourstudy were compared with those of the previouslypublished North American series. Analysis of datacompiled from our series shows more or less the sameepidemiological figures as the previously publishedseries.

P254

EXTRAUTERINE MULLERIAN ADENOSARCOMA

ARISING IN PERITONEAL ENDOMETRIOSIS

A. Misir, A. Daya, M. Sur


McMaster University, Hamilton, Ontario, Canada

Mullerian adenosarcoma is a neoplasm composed ofbenign mullerian epithelium and sarcomatous stroma. Ittypically occurs in the endometrium of postmenopausalwomen and less frequently in the extrauterine genitaltract. Rare cases of extrauterine adenosarcoma occur-ring in the context of endometriosis have been reported.We report a case of a nulliparous 53 year-old womantreated for endometriosis by partial and subsequentcompletion hysterectomy with bilateral salping-oophor-ectomy 17 and 14 years previously, respectively. Shesubsequently underwent surgical resection of a largeabdominal mass detected on CT. The mass containedmultiple foci of hemorrhage and necrosis. Microscopi-cally, areas of benign appearing glands surrounded byan overgrowth of stroma showing periglandular con-densation were present. The stromal cells were atypicalwith mitotic figures. There was a background ofischemic necrosis and hemorrhage. There was peritonealendometriosis in the background. Similar findings werenoted on transmural sections of resected bowel wall. Thepatient was subsequently treated with chemotherapy.One year after surgery, she presented with obstructiverenal insufficiency, hydronephrosis, and E. coli septice-mia. Despite ICU management, she died after 1 week.Examination at the time of resection revealed extra-uterine mullerian adenosarcoma in a background ofperitoneal endometriosis. This entity affects middle-aged women and is reported to have arisen inrectovaginal septum, vagina, peritoneum and bladder.It is an aggressive tumour with treatment that involvessurgical resection as well as chemotherapy with orwithout radiation. This is only the second case, to ourknowledge, in which this lesion has arisen fromperitoneal endometriosis, and the first such case havingarisen subsequent to TAH-BSO after many years.Though relatively rare, extrauterine mullerian adeno-sarcoma should be considered in the differentialdiagnosis of a patient with a history of endometriosispresenting with a new pelvic tumour.


P255

SOLITARY FIBROUS TUMOR OF THE URINARY

BLADDER. A CASE REPORT AND REVIEW OF

THE LITERATURE

J. Moreno, S. Salama

Department of Anatomical Pathology, HRLMP,

St. Joseph Healthcare Site, McMaster University

Objective: We present a case of solitary fibrous tumor(SFT) of the bladder.Case report: 36 year-old female patient presented withabnormal periods for several months. A pelvic U/Sshowed a small mass in the posterior aspect of thebladder. She had no history of gross hematuria orurologic complaints. The mass was resected transureth-rally. Histologically, the tumor was composed of aproliferation of small oval to slightly spindled cells. Insome areas the cells were arranged in sheets withsclerotic and vacuolated myxoid stroma. The nucleiwere uniform without significant atypia or mitoticactivity. Immunohistochemical analysis showed strongexpression to CD34 and vimentin, with less strongimmunoreactivity to smooth muscle actin. There was noexpression to Cytokeratins, Desmin, HHF35, CD31,S100, CD117 or P504S.Discussion: Distinguishing SFTs from other spindle cellprocesses can be difficult due to its varying lightmicroscopic appearance, which mimicks other entities.The histopathlologic differential diagnosis can includeboth benign and malignant tumors such as nephogenicmetaplasia, hemangiopericytoma, leiomyoma, schwan-noma, gastrointestinal stromal tumor, fibrosarcoma,leiomyosarcoma, carcinosarcoma, malignant fibroushistiocytoma, as well as benign and malignant nervesheath tumors. SFT invariably expresses CD34, withrecent descriptions of expression of Bcl2, type II insulin-like growth factor and CD99. Entities that commonlyenter the differential diagnosis are uniformly CD34negative. The main differential diagnosis in the presenceof such panel would be hemangiopericytoma. This isalso a rare tumor, which presents richer vascularizationand tends to exhibit a less prominent reactivity to CD34.

P256

IMMUNOHISTOCHEMICAL PROFILE OF

MENINGIOMAS REVISITED

Mothafar Fatmaa,b, J. Proviasa,b

aHamilton Regional Laboratory Program,bDepartment of Pathology and Molecular Medicine

Hamilton General Hospital, McMaster University,

Hamilton, Ontario, Canada

Objective: The aim of the study is to evaluate theimmunoprofile of various morphological subtypes andgrades of meningiomas with special emphasis onE-Cadherin, CD99, Bcl-2 and CD10 expression todifferentiate meningioma from other primary meningealor metastatic lesions.Material and methods: Forty five cases of meningiomasof various subtypes and grades were reviewed andreclassified according to WHO classification. Of the 45cases examined 33 were of grade I, 7 of grade II and 5 ofgrade III. All cases were immunostained for C-Kit,E-Cadherin, Calretinin, carcino-embryonic antigen,epithelial membrane antigen (EMA), S-100 protein,CD56, Ki67, estrogen and progesterone receptor pro-teins, Bcl-2, CD99, CD10 and panel of low and highmolecular weight keratins. The immunoreactivity wasevaluated on a quantitative scale of 0–3.Results: Forty-four cases were positive (in variableintensities) for E-Cadherin, EMA and CD99. Thirtyfive were immunoreactive for Bcl-2 and 10 for C-Kit andCalretinin. CD10 positivity was observed in 23 cases.The Bcl-2 was present in 6/12 (50%) grade II/III tumorsand in 29/33 (87%) cases of grade I.Conclusion: The immunohistochemical findings did notshow correlation between the immune profile and themorphological subtypes and grades of meningiomas.Contrary to the previously reported the absence ofE-Cadherin in malignant meningiomas; our studyshowed variable expression of this marker, includingthe high-grade lesions. A few reports have suggested theuse of CD99 to differentiate meningeal hemangioper-icytoma from meningioma but the current study showedexpression of CD99 in the majority of the tumors. Thefindings also suggest a trend toward the absence of Bcl-2in high-grade meningiomas and that CD 10 cannot beused to differentiate meningioma from a metastaticlesion.


P257

UVEAL METASTASIS FROM PULMONARY

LARGE CELL NEUROENDOCINE CARCINOMA:

A CASE REPORT

B. Moussaa, L. Allenb, P. Hooperb, S. Chakrabartia

aDepartments of Pathology andbOphthalmology, The University of Western Ontario,

London, ON, Canada

Intraocular tissues may be involved by various metastatictumors, most commonly originating from the breast, lung,and gastrointestinal tract. Ocular metastasis may occa-sionally be the initial manifestation of the disease. In suchcases, the primary lesions are discovered only afterenucleation of the eye. The posterior choroid is the mostcommon site for these metastases. Here we present a rarecase of choroidal metastasis. A 77 year-old male presentedwith myesthenia-like symptoms along with progressive lossof vision in the left eye. B-scan showed a large choroidalmass. Further examination revealed that the patient haslung and mediastinal lesions. Clinical differential diagnosisincluded primary lung tumour with ocular metastasis orvice versa. The eye was enucleated. Histopathologicalexamination revealed a 6� 2mm malignant tumourlocated in the posterior choroid and composed of largecells with moderate cytoplasm and prominent nucleoli.The tumour demonstrated prominent blood vessels androsette-like areas. The tumour cells stained positively forsynaptophysin, chromogranin, TTF-1, and CAM5.2 (peri-nuclear), and stained negatively for melanoma markers(S-100, melan A and HMB45). The tumour cells show aKi-67 index of 50% and a mitotic activity of 4/hpf. Thelung tumour was also diagnosed as large cell neuroendo-crine carcinoma by cytology. Metastases to the eye andorbit develop in approximately 0.7 to 21% of patients withpulmonary malignancies. The majority of such tumors areof epithelial type. Among the neuroendocrine tumors,endobronchial carcinoids are known to produce uvealmetastases. There are no known reports of uvealmetastasis from a pulmonary large cell neuroendocrinecarcinoma in the literature. Generally, the development ofocular metastases is a bad prognostic sign. Treatmentregimens depend on the number, size and extent of thechoroidal tumors, the visual status of the affected andunaffected eye, age and general health of the patient.

P258

VITREOUS HUMOR BIOCHEMISTRY: RESOLVING

THE CONTROVERSIES IN FORENSIC

PATHOLOGY

A. Mullaa, J. Kalrab

aDepartment of Pathology andbGeneral Surgery, Royal University Hospital, Saskatoon,

Saskatchewan, Canada

Vitreous humor is considered to have high utility incertain forensic pathology applications like prediction ofpost-mortem interval (PMI). However, the use ofvitreous humor biochemistry has been controversial inview of the reported between-eye differences in the samepair of eyes. We have previously reported that nosignificant between-eye differences existed for variousvitreous biochemical constituents at identical post-mortem interval (PMI). The objective of the presentstudy was to evaluate the utility of vitreous biochemistryin PMI estimation and formulate vitreous biochemistrybased formulae to aid PMI estimations. Vitreous humorsamples were collected through a scleral puncture from atotal of 61 subjects (Female, 22; Male, 39; Age, 16–95years) with precisely documented time of death (PMIrange, 4.5–84.3 h; Mean PMI7SD, 27.9716.5). Rightand left eye vitreous humor samples were collectedseparately and the mean values were used for statisticalanalyses. The vitreous humor was analyzed for sodium,potassium, chloride, calcium, magnesium, urea, creati-nine, glucose and lactate on an LX-20 Analyzer(Beckman-Coulter) and hypoxanthine, xanthine wereanalyzed using a colorimetric method. There was asignificant correlation between vitreous potassium(po0.0001), hypoxanthine, (po0.0001), xanthine(po0.0001), lactate (po0.0001), calcium (po0.01) andPMI. The resulting formulae, derived from the linearregression equation, for PMI estimation were: forpotassium (6.41 (K+)–46.25), hypoxanthine (0.32(Hypoxanthine)–60.94), xanthine (0.14 (Xanthine)–50.08),lactate (5.21 (Lactate)–27.69) and calcium (200(Ca2+)–380.4). These results underline a useful role forvitreous potassium, hypoxanthine, xanthine, lactate andcalcium in PMI estimation. The proposed formulae forestimating PMI may be used in conjunction to enhancePMI estimations by narrowing the error margin.


P259

DANON’S DISEASE—A RARE CAUSE OF

HYPERTROPHIC CARDIOMYOPATHY

Vidhya Naira,b,c,d, MBBS, MD, Jagdish Butanya,b,c,d,MBBS, MS, FRCPC

aDepartment of Pathology,bToronto General Hospital/University Health Network

andcDepartment of Laboratory Medicine and Pathobiology,dUniversity of Toronto, Toronto, ON, Canada

In 1981, Danon and colleagues reported the case of 2young boys with a clinical triad of cardiomyopathy,mental retardation and myopathy.1 Skeletal musclebiopsies showed vacuolar alterations reminiscent of typeII glycogenosis. No acid alpha-glucosidase defect wasdetected. Since then few cases have been reported inliterature and have been referred to as ‘glycogen storagedisease without acid maltase deficiency’. This disease iscaused by the primary deficiency of lysosome-associatedmembrane protein-2(LAMP-2).Clinical features: We present a rare and interesting caseof an 18 year-old boy who presented with congestiveheart failure and hypertrophic cardiomyopathy. Oninvestigation, he had a strong family history ofhypertrophic cardiomyopathy. The initial clinical pre-sentation was that of proximal muscle weakness.Following this he developed with AV blocks andmultiple episodes of congestive cardiac failure. Thepatient died suddenly, before heart transplantationcould be performed. An autopsy revealed features ofcardiac failure and the heart showed biventricularhypertrophy and dilation. Ultrastructural examinationshowed numerous autophagic vacuoles in the cardiacmuscle fibers and large areas of myocardial fibrosis.Autophagic vacuoles were also noted in other organs.All these findings were consistent with a diagnosis ofDanon’s disease. Disease usually affects males, and theusual clinical presentation is with the clinical triad ofcardiomyopathy, mental retardation and skeletal myo-pathy. Death often occurs in the second decade.3 Ourpatient presented with cardiac failure due to hyper-trophic cardiomyopathy and features of skeletal myo-pathy. Death occurred in the second decade. At autopsythe ultrastructural examination revealed autophagicvacuoles in cardiac muscle and multiple other organs,consistent with a diagnoses of Danon’s disease.

P260

A 15 YEAR REVIEW OF PLEOMORPHIC LIPOMA

AND IMMUNOHISTOCHEMICAL COMPARISON

WITH LIPOSARCOMA

C. Naugler, A.K. Guha, S.K. Murray

QE II HSC and Dalhousie University, Halifax, NS,

Canada

Introduction: Pleomorphic lipoma (PL), a rare benignvariant of lipoma, may have overlapping features withliposarcoma (LS). The objectives were to review andcontrast PL with LS.Methods: The files of the QEII HSC were searched[1991–2006] for PL, LS, and lipoma. All cases of PL anda sample (n ¼ 6) of LS were retrieved. The sex, age,tumor site, and histologic features were recorded. Usingimmunohistochemistry (IHC), selected blocks werestained for: vimentin, CD34, CD10 and cyclin D1.Results: No. Cases: lipoma 5039, PL 6 (including 3outside referrals) and LS 69. PL comprised 0.12%(6/5039,) of lipomas. Mean age: PL 59.9, LS 50. M:Fratio: PL 4:3, LS 1:2. Proportion on the neck, back, orshoulders: PL 33%, LS 0. IHC positivity: vimentin [3/3PL, 6/6 LS], cyclin D1 [3/3 PL, 6/6 LS], CD10 [3/3 PL,5/6 LS], and CD34 [6/6 PL, 4/6 LS {pos (3 welldifferentiated, 1 myxoid); neg (1 pleom., 1 myxoid)}].Conclusions: The prevalence of PL [referral pop.�1.8� 106] was similar to that previously reported.The M:F ratio was lower than that generally cited (4:1),and a minority of PL cases (33%) occurred in typicalreported sites. PL and LS were not statistically differentimmunohistochemically; however lack of CD34 mayfavor LS over PL. Careful case interpretation is requiredto exclude CD34 vascular and background staining.


P261

EXPRESSION OF ENDOTHELIN-1 IN THE

VESSELS OF PANCREAS OF NEWBORNS AND

FETUSES FROM MOTHERS WITH IDA OF

DIFFERENT DEGREE OF SEVERITY

O. Polyakova

Department General and Clinic Pathology, School of

Fundamental Medicine, V.N. Karazin Kharkiv National

University, Kharkiv, Ukraine

Recently in a list of extragenital violations for thepregnant women top position has been occupied by IronDeficiency Anemia (IDA). Multiple researches showthat IDA is influencing not just a health of a mother, butalso health of a fetus. Formed by IDA chronicfetoplacental insufficiency and chronic hypoxia of afetus, produce the delay of fetus’ intrauterine develop-ment.The goal of current research was to investigate themorphological features of vessels of pancreas stroma ofnewborns and fetuses from mothers with IDA ofdifferent degree of severity.Research was based on the study of observations ofautopsy of the fetuses, which were lost in gestational age30 weeks and more, and also of newborns from motherswith IDA. The following control groups were formeddepending on the degree of severity of maternal anemia:I–the fetuses and newborns from the mothers with theIDA of 1st degree of severity (27 cases of observations);II–fetuses and newborns from the mothers with IDA of2nd degree of severity (21 cases of observations);III–fetuses and newborns from the mothers with IDAof 3rd degree of severity (17 cases). The group ofcomparison was formed by the fetuses and the new-borns, worn-out in the conditions of physiological flowof pregnancy, but lost as a result of acute violation ofuteroplacental and umbilical cord hemodynamics (23cases).Research was conducted in accordance with principlesof Helsinki declaration. Serial cuts in thick 4–5� 10�6

were made from the pieces of pancreas parenchyma,taken from tail part, after the spiriting wiring andparaffin inundation.Immunohistochemical research was conducted on par-affin’s cuts, 5–6microns thick, by indirect method of

Coons implementing Brosman methodics (1979). En-dothelin-1 producing cells were highlighted by MCAb toendothelin-1 (Novocastra Laboratories Ltd. UK).F(ab)-2 (the fragments of rabbit antibodies againstmouse immunoglobulins, marked by FITC) was used asa luminescent marker. Preparations were studied withluminescent microscope ML-2 using variety of colorfilters. The light intensity was determined by micro-fluorimeter and expressed in relative units, derived fromthe power flow of the measuring device, indicated inmicroamperes (A� 10�6).As a result of the current research (from the point of theendothelial cover of pancreas vessels) there was indi-cated a reliable increase of intensity of light in exposedpreparations, treated MCAb to endothelin-1, along withthe growth of severity degree of maternal IDA (Fig. 1).The coefficient of correlation between those indexes wasdefined equal 0.72.

Fig. 1. Intensity of light in endotheliocytes, expressing superficial

receptors to endothelin-1 in the pancreas microcirculation of explored

fetuses and newborns (in A� 10�6).

There is also to be noticed, that at many pathologicalstates the increase of content of endothelin-1 in vessel’sendothelium microcirculation. Similar picture is usuallyinterpreted as a sign of dysfunction of endothelium.Thus the research studied the phenomenon of dysfunc-tion of endothelium of pancreas of fetus in prenatalperiod under the influence of the maternal IDA.


P262

INTRAVASCULAR TUMOR EMBOLI MASQUER-

ADING AS THROMBOTIC THROMBOCYTOPE-

NIC PURPURA (TTP)

B. Purgina, M. Lamba, G. Jansen, J.P. Veinot


University of Ottawa, Ottawa Hospital, Ottawa, Ontario,

Canada

Background: The diagnosis of TTP may be difficult asother disorders causing microangiopathic hemolyticanemia (MAHA) and thrombocytopenia may not beapparent. Several cases of TTP secondary to dissemi-nated adenocarcinoma have been described. The me-chanism is likely due to tumor emboli causingendothelial damage with platelet aggregation. MAHAresults from mechanical fragmentation of red blood cellsas they travel through damaged microvasculature.Design: A 72-year-old woman with a recent diagnosis ofbreast carcinoma, pre-treatment, presented with acuteneurological symptoms, renal failure, acute myocardialinfarction and fever. Bloodwork revealed anemia,thrombocytopenia, and schistocytes on blood smear.Idiopathic TTP was diagnosed and urgent plasmapher-esis begun. She had rapid multisystem failure andexpired 2 days after admission. Complete autopsy wasdone.Results: Autopsy demonstrated an 8 cm infiltratingducal breast carcinoma with no solid organ metastases,and a patent cardiac foramen ovale. Tumor emboli insmall arteries and arterioles were numerous in the lung,heart, and brain, with multiple ischemic and hemor-rhagic infarcts in the latter 2 organs. The embolic tumorcells were positive for BRST2, keratin AE1.3 and CK7and negative for CK20, LCA, ER and PR.Discussion: The embolic tumor cells were consistent withbreast carcinoma origin. As these tumor emboli were ageneralized phenomenon, the clinical picture of TTPresulted. Although TTP and urgent plasmapheresis mustbe considered in patients with MAHA and thrombocy-topenia, the possibility of a disseminated malignancyshould be considered. The diagnosis of disseminatedmalignancy excludes the diagnosis of TTP and thisshould not be considered as ‘‘cancer-associated TTP’’.Although multiple etiologies may contribute to a TTPlike syndrome, disseminated malignancy is pathologi-cally and clinically distinct entity.

P263

BILATERAL LOW MALIGNANT POTENTIAL

SEROUS FALLOPIAN TUBE TUMOR PRESENT-

ING AS HYDROSALPINX ON ONE SIDE AND

HEMATOSALPINX ON THE OTHER. A CASE

REPORT

Kurosh Rahimi, MD, MSC, Jocelyne Arseneau, MD,Amira Mehio, MD



Serous tumor of fallopian tube with low malignantpotential (STLMP) is a recently defined entity. To ourknowledge, there are 7 cases reported in Englishliterature. The patients are approximately 10–20 yearsyounger than those with Fallopian Tube Carcinoma(FTC). Here we present a 72-years-old woman G1 p0 A1who was admitted with bilateral cystic fallopian tubeswith intracystic solid lesions, suspicious uterus andcervical lesion, which were discovered during themetastatic workup for bilateral breast carcinoma bypelvic ultrasound and CT scan. The left side fallopiantube was dilated and cystic mainly on the fimbrial endmeasuring 14 cm with smooth serosal surface. The cystconsisted of a clear serous fluid and a fragile papillarystructure that protruded into and partially filled thefallopian tube. The right fallopian tube was grosslysimilar to the left but was smaller and filled with aserosanguinous fluid. Histopathological evaluation re-vealed multiple finely arborizing papillary structureswith a densely collagenized fibrovascular core, coveredby single serous type low cuboidal to columnarepithelium. In medium to high magnification, the cellsdisplayed mild atypia, infrequent mitosis forming adelicate tuft or hobnail pattern, without invasion of thefallopian tube stroma. Each cell had an eosinophiliccytoplasm with a round to oval nucleus and finechromatin. The left fallopian tube revealed the samepathological features.Conclusion: Our patient was unique due to her age, thepresence of bilateral FT lesions, and the presence oftumor implant in the cervix. Recognition of histologicfeatures of this tumor during intra-operative consulta-tions is imperative since most of the patients who havebeen diagnosed so far with this tumor during were in thefertile age.


P264

IMMUNOHISTOCHEMICAL STUDY OF AREAS

OF CLEAR CYTOPLASMIC CHANGE IN PAPIL-

LARY RENAL CELL CARCINOMA—AN AID IN

DISTINGUISHING PAPILLARY RENAL CELL

CARCINOMA WITH CLEAR CYTOPLASMIC

CHANGES FROM CLEAR CELL RENAL CELL

CARCINOMA

Nicolas L.D. Roustan Delatour, MD, Kien T. Mai,MD, FRCPC, Derek Kohler, MD, Manisha Lamba,MD, FRCP, John P. Veinot, MD, FRCPC

Department of Pathology and Laboratory Medicine, The

Ottawa Hospital and University of Ottawa, Ontario,

Canada

Background: Clear cell renal cell carcinoma (CRCC) andpapillary renal cell carcinoma (PRCC) occasionally posea difficult problem of classification. CRCC may beassociated with areas of papillary architecture and areaswith eosinophilic (chromophil) cytoplasm, such as seenin PRCC. Similarly, PRCC may show areas with clearcytoplasmic changes (CCC), within the papillae and/orin solid areas adjacent to the papillae. In this study, weinvestigate the immunohistochemical properties of 40cases of RCC with clear cells, including PRCC withsmall areas of CCC, PRCC with large areas of CCC,and CRCC.Materials and method: Consecutive cases of total orpartial nephrectomy for CRCC and PRCC with CCCwere retrieved from the Anatomical pathology files.Study cases were divided into: Group 1: PRCC withsmall areas of CCC (16 cases). CCC was defined as thepresence of solid areas of clear cells adjacent to PRCCand/or as the presence of clear cells within the papillaeof PRCC; Group 2: PRCC with large areas of CCC (4cases); and Group 3: CRCC (20 cases). The tumors werestained for CK7, CD10, RCC and AMACR.Results: All clear cell areas in Groups 1 and 2 showednegative or weak focal reactivity for CD10 and RCC,whereas all CRCC, regardless of size, showed moderateto strong reactivity for these two immunomarkers. Incontrast, immunostaining for CK7 and AMACR wassimilar in the clear cell areas of Groups 1 and 2 andCRCC.Conclusions: Areas of CCC associated with PRCC maymimic CRCC with routine stains, but the two lesions areimmunohistochemically distinct by using immunostain-ing for RCC and CD10.

P265

IMPROVED LYMPH NODE RETRIEVAL IN

WHIPPLE SPECIMENS AS A RESULT OF

IMPLEMENTATION OF A NEW UNCINATE

MARGIN PROTOCOL

C. Rowsella, S. Hannab, E. Hsieha, C. Lawb,M. Khalifaa

aDepartment of Anatomic Pathology,bDepartment of Surgical Oncology, Sunnybrook Health

Sciences Centre, University of Toronto, Toronto, Canada

Background: Lymph node status is an importantprognostic factor in pancreatic and peri-ampullaryadenocarcinoma. We recently changed our protocolfor assessment of the uncinate margin of Whipplespecimens at our institution and noted that lymphnodes were often present in the radially sectioneduncinate margin. The aim of this work is to determinewhether our new uncinate margin protocol had animpact on the assessment of lymph node status.Design: Cases of Whipple resections performed at ourinstitution during the years 2004–2006 were reviewed.Prior to 2005, the uncinate margin was assessed using anen face technique. In 2005, we adopted a new protocolwhereby the uncinate margin was painted, sectioned in aperpendicular fashion, and entirely submitted. Caseswere divided into 2 groups, those that were handledaccording to the former protocol, and those handledaccording to the new protocol. The number of lymphnodes found in uncinate margin sections were assessed,as well as the overall number of nodes found in thespecimen.Result: 16 cases during the study period were handledaccording to the en face protocol, and 20 were handledaccording to the new protocol. In the en face group, 2nodes were found in the uncinate margin (0.1 nodes percase), while in the radial group, 36 nodes (1.8 nodes percase) were identified in the uncinate margin sections(po0.05). No positive lymph nodes were found in the en

face sections, but 8 cases in the radial group had positivenodes in the uncinate margin sections. In 2 of these casesthe positive lymph node was the only lymph node withmetastasis. Overall lymph node retrieval was 15.5 lymphnodes per case in the en face group, and 20 nodes percase in the radial group (po0.05).Conclusion: Since our change in protocol, our lymphnode retrieval rate in Whipple specimens has increasedby approximately 4 lymph nodes per case. This may bedue to additional nodes found in serial sections of theuncinate margin or due to increased attentiveness in thehandling of Whipple specimens. In 2 cases, nodes foundin the radial sections of the uncinate margin played arole in the final N stage.


P266

ENDOMETRIAL CARCINOMA IN BOTH HORNS

OF A BICORNUATE UTERUS

A.A. Samania, O. Boutross-Tadrossa

McMaster University Medical Center, Department of

Pathology, Room 2N10, 1200 Main St. West, Hamilton,

Canada

Congenital anomalies of the uterus are called mulleriananomalies and included hypoplastic, aplastic, unicornu-ate, didelphys, bicornuate, and septate uterus. Theincidence of these anomalies is 4–5% in the generalpopulation. The endometrial cancer is the fourth mostcommon primary site of cancer among women andaccounts for 5.6% of all cancers. Risk factors for uterinecancer are obesity, diabetes, hypertension, infertility/nulliparity, late menopause, unopposed estrogen ther-apy, a history of atypical endometrial hyperplasia andbreast cancer,and a family history of breast cancer andendometrial cancer.Herein, we report on a 56-year-old woman with theendometrioid adenocarcinoma of the endometriumarising in both horns of her bicornuate bicollis uterus.To the best of our knowledge, this is the first report inthe literature for the involvement of both horns.The patient presented with 4 years history of dysfunc-tional uterine bleeding (DUB). She is gravida 2, para 2and all were cesarian section deliveries. She has a historyof hypertension, hyperlipidemia, silent MI (age 53) andGlucose intolerance. Her pap smear done at age of 49showed atypical glandular cells of undetermined sig-nificance. This was followed (in the same year) with anendometrial biopsy from both horns which showed thefocal tubal metaplasia and some gland crowding andbranching in both horns. However, the latest endome-trial biopsies from both horns at age of 56 revealedendometrial carcinoma of both horns. This was followedby total abdominal hysterectomy and bilateral salphin-gooophorectomy. The microscopic examination ofspecimens showed the FIGO I endometrioid adenocar-cinoma for both horns with 5% of myometriuminvasion for both sides and no lymphovascular invasion.The cervicies, fallopian tubes and ovaries were negativefor malignancy.

P267

GIANT ONCOCYTOMA OF THE KIDNEY IN A

CHILD: A CASE REPORT AND REVIEW OF THE

LITERATURE

A.W. Schall, J.G. Gartner

Department of Pathology, Health Sciences Centre,

University of Manitoba, Winnipeg, Manitoba, Canada

Oncocytomas represent approximately 7% of all adultrenal tumors. Only 4 cases of renal oncocytomas havebeen described in children.We describe a tumor which was an incidental finding ina 13-year-old girl. On further questioning the patientreported having noticed a lump four years earlier, whichsuggests a slow growing neoplasm. Gross examinationof the nephrectomy specimen revealed a 20� 18� 15 cmwell-circumscribed encapsulated light brown tumorfirmly attached to the kidney. Prominent vessels werenoted within the centre of the tumor. Histologicexamination showed uniform polygonal cells withabundant clear to eosinophilic finely stippled cytoplasm.The cells had round nuclei with prominent nucleoli.There was extensive tumor necrosis with occasionalcalcifications. No capsular or lymphovascular invasionwas identified.We present the differential diagnosis, immunohisto-chemical profile, and electron microscopic findings ofthis giant oncocytoma. This oncocytoma appears to bethe third largest ever described in the English literature,and the largest ever reported in a child.


P268

PRIMARY CARDIAC DIFFUSE LARGE B-CELL

LYMPHOMA: AN UNUSUAL CAUSE OF SUPER-

IOR VENA CAVA SYNDROME

A.J. Schella, A. Johrib, D. Lebruna, K. Harrisona, H.Feilottera, R. Nolanc, G. Ropchand, A.J. Sanfilippob,P.A. Isotaloa

aDepartments of Pathology and Molecular Medicine,bDepartment of Cardiology,cDepartment of Radiology,dDepartments of Cardiothoracic Surgery,

Queen’s University, Kingston, Ontario, Canada

The majority of cardiac atrial neoplasms representbenign myxomas. Rarely, malignant cardiac neoplasmsare encountered and can include primary cardiacneoplasms, as well as secondary tumors involving theheart. As many cardiac neoplasms lack pathognomonicclinical features, histopathologic diagnosis is crucial forthe appropriate classification and treatment of theseneoplasms. A 60-year-old man presented with superiorvena cava (SVC) syndrome and CT scan revealed aninfiltrative mass of the right atrium that nearly filled theatrial chamber and partially occluded SVC flow. Allother cardiac structures were uninvolved. There was noevidence of metastatic disease. Urgent surgical resectionrevealed a 5.5� 4.5� 4.5-cm soft mass that had thegross appearance of ‘‘fish flesh’’. Histologic examinationrevealed complete replacement of the atrial wall bydiffuse sheets of pleomorphic lymphoid cells withoccasional smaller plasmacytoid cells. The predominantlymphoid population was immunoreactive for CD45,CD20, CD79a, BCL-2, BCL-6, Ki-67 (approximately,75%), CD10, and p53. The neoplastic cells alsodemonstrated light chain-restricted expression of IgMlambda. A diagnosis of primary cardiac diffuse large B-cell lymphoma with plasmacytoid differentiation wasestablished and was supported by cytogenetic studiesdemonstrating the presence of a t(14;18)(q32;q21)translocation. FISH revealed no evidence of a C-MYCtranslocation. Postoperatively, the patient underwent 6cycles of rituximab and CHOP chemotherapy andcurrently demonstrates no evidence of residual disease8 months following surgery. Primary cardiac lympho-mas are extranodal lymphomas that should be distin-guished from primary cardiac sarcomas and fromcardiac involvement by disseminated non-Hodgkinlymphoma as significant therapeutic and prognosticdifferences exist between neoplasms.

P269

ROLE OF N-CADHERIN IN PANCREATIC

ENDOCRINE TUMORS

S. Serra, S.L. Asa, R. Chetty

University Health Network and Toronto Medical

Laboratories, Toronto, Ontario, Canada

N-cadherin is frequently up-regulated in cancer and, inepithelial cells induces changes in morphology to afibroblastic phenotype, rendering the cells more motileand invasive. However, in some cancers N-cadherin maybehave as a tumor suppressor. The aim of this study wasto evaluate the role of N-cadherin in tumor progressionin fifty pancreatic endocrine tumors (PETs) using atissue microarray (TMA). The mitotic count, expressedper 50 HPF, and MIB-1 index of the tumor wereassessed. All the TMA blocks were stained with anextensive panel of endocrine markers as well as withspecific antisera to N-cadherin. Twenty four were malepatients and 26 female, ranging in age from 23 to 80years (mean 49.8 years). The tumors ranged in size from0.8–8.7 cm with a mean size of 3.6 cm. Nineteen PETswere localized to the pancreas and 3 extended only intosurrounding peripancreatic adipose tissue, 12 showedlymphovascular involvement, 10 had lymph nodeinvolvement and 6 had hepatic metastases. In normalislets, N-cadherin was negative or weakly expressed. InPETs, N-cadherin showed mainly cytoplasmic immu-noreactivity of variable intensity in 33 cases (66%).N-cadherin was positive 13 PETs localized to thepancreas: 4 showed diffuse cytoplasmic positive, and 9showed a focal dot-like staining pattern in the cyto-plasm. Of the 3 locally invasive tumors, 2 (66%) showeda focal dot-like cytoplasmic stain and 1 was negative.Ten PETs (83%) with lymphovascular invasion showedcytoplasmic positivity, 4 diffusely, 6 focally with a dot-like pattern. Four out of 10 PETs (40%) with lymphnode involvement showed cytoplasmic positivity, 3diffusely and 1 focally with a dot-like pattern. Five of6 cases (83%) with liver involvement showed cytoplas-mic positivity, 2 diffusely and 3 focally with a dot-likepattern. N-cadherin does not appear to play a clear keyrole in progression of PETs. It is overexpressed in 66%of all the cases studied. However, there is not significantdifference in expression among the different pathologi-cal groups.


P270

THE NCIC CTG TUMOUR/TISSUE/DATA REPO-

SITORY, A CANADIAN RESOURCE: HOW HAVE

WE BEEN DOING?

Y. Markovich, S. Virk, M. Tsao, L. Shepherd


NCIC CTG, Queen’s University, Kingston, Ontario,

Canada K7L 2V7

Background: The NCIC Clinical Trials Group (NCICCTG) has maintained a Tumour/Tissue/Data Bank(TTDR) since 1997. We have been collecting archival,paraffin-embedded material for a variety of Phase 3trials with the intent of creating a national resource ofwell characterized, malignant tumour tissue associatedwith an extensive, well-validated matching clinical dataset. The goal of this resource is to provide disease-specific tissue from oncology clinical trials patients toinvestigators posing specific research questions at thecellular and molecular level. Most recently, FFPE excesstumour, serum, and plasma have been collected in aprospective manner. TTDR oversight is provided byQueen’s, a Correlative Science/Tumour Biology Com-mittee with membership from the pathology communityacross Canada, and the NCIC CTG. All patients signwritten informed consent; a specific database has beendeveloped to log, catalogue, and track requests, receipts,and dispersals; a website has been developed with anapplication process; and all requests for access tomaterial must meet defined criteria and are reviewedfor scientific validity. A TMA facility and digitalscanning have increased the scope and accessibility ofsamples to investigators.Results: More than 5000 patient blocks/slides of FFPEtissue and 410,000 serum/plasma samples have beencollected. In most studies, patient consent to collectionis 490%, and compliance with requests for material is480%. There have been 420 requests to access tissue.Numerous publications have resulted, including 4NEJM articles published in the last 2 years. The TTDRis a member of the CIHR funded Canadian TumourRepository Network, and the US NCI Group BankingCommittee.Conclusion: Clinical trial patient material arguably is aplatinum level resource and accounts for o5% ofoncology patients seen. In spite of considerable success,institutional and provincial jurisdictions, Ethics Boards,competition, funding, and academic commitment fromCanadian pathologists remain a challenge.

P271

IMPLEMENTATION IMPACT ANALYSIS OF THE

CELLAVISION DM96 AUTOMATED DIGITAL

IMAGE DIFFERENTIAL ANALYSER

B.L. Sheridana, M. Lolloa, D. Hoa, E. Sampsona,S. Hubbarda, M. Urquarhtb, W.F. Brienb

aDivisions of Laboratory Hematology, St. Michael’s

HospitalbUniversity Health Network and Toronto Medical

Laboratories, Toronto, Ontario, Canada

Introduction: The purpose of our study was to validatethe CellaVision DM96 digital image capture system incomparison to a manual blood film review and to carryout timing studies of both methods to identify thelabour savings potential which could justify acquisitionof this instrument.Methods: A timing study was carried out for 3 weeks ofall technologists working at hematological morphology(at SMH) bench. The second phase of this timing studywill be carried out when the DM96 has been fullyimplemented. The validation study was performed atSMH by two technologists of varying experience. Slideswere prepared in triplicate and each technologistperformed a 200 cell manual slide review and differentialand then repeated the procedure on the DM96.Discrepant results were resolved by a third reviewer.Abnormal slides were selected from both institutions torepresent clinical challenges that would be expected inour usual workload.Results: Timing Study: Over 21 days 2300 slides, from13,190 CBC’s, were reviewed by 25 technologists, a slidereview rate of 17%. Morphological analysis took277 hours, an average of 7.23min per slide. In thevalidation study, 111 normal and 98 abnormal slideswhere tested. The largest differences noted were betweentechnologists, particularly with the identification ofvariant lymphocytes and band neutrophils.Conclusions: Our study demonstrates good cellularidentification with the DM95 and the manual technol-ogist interpretation remains the largest variable in thedifferential count. The ‘current state’ timing study hasidentified a longer than reported technologist time perslide. DM96 timing will be completed on full imple-mentation of the system.


P272

CONCORDANCE AND DISCORDANCE IN

CLINICAL AND AUTOPSY FINDINGS-

A RETROSPECTIVE ASSESSMENT

S. Suryavanshi, J.D. Gomez, J. Kalra

Department of Pathology, Royal University Hospital,

Saskatoon, Saskatchewan, Canada

Autopsy has been used as the ‘‘Gold Standard’’ andregarded as the quality criterion for determining thecause of death. Autopsy has also played a major role incontributing to clinical knowledge, medical education,and quality assurance program. The purpose of thisstudy was to determine the rate of concordance anddiscordance between clinical diagnoses and postmortemfindings in patients admitted to various hospitals ofSaskatoon Health Region. We also studied the impactof diagnostic modalities on the rate of concordance anddiscordance. All adult in-patient autopsy charts for theperiod from January 1, 2002 to December 31, 2004 werereviewed, retrospectively. Data collection includeddemographics for all patients, length of hospital stay,employed diagnostic imaging studies, clinical diagnosesand autopsy findings. A total of 3416 in-patient deathswere registered during the study period. Autopsies wereperformed on 206 of the deceased resulting in anautopsy rate of 6%. In accordance with selectioncriteria, 158 cases were included for this study. Themean age of subjects was 66.6715.2 years with a rangeof 16–94 years. The study group constituted of 92 males(58.2%) and 66 females (41.8%) with an average lengthof stay at the hospital of 12.9710.9 days. Theconcordance and discordance rate between clinical andautopsy findings was 75.3% and 20.9%, respectively,and 3.8% of cases were indecisive. The impact ofdiagnostic modalities, where used, was shown to bediagnostic in 12–14% of cases. Our preliminary studydata are comparable with the reported findings in theliterature. These results suggest that despite of thetechnical advances in medical and diagnostic modalities,there still persists a significant discordance in clinicaland autopsy diagnoses. We encourage residents andphysicians to continue considering autopsy as animportant tool that extends our understanding ofdisease processes.

P273

LEUKEMIC PHASE OF MANTLE CELL LYMPHO-

MA WITH CENTRAL NERVOUS SYSTEM INVOL-

VEMENT. CASE REPORT AND REVIEW OF

LITERATURE

S. Tauqir, C. Ross, M. Sur



McMaster University

Introduction: Non-Hodgkin’s Lymphoma (NHL) repre-sents approximately 4% of all cancer diagnoses and isthe seventh most common cancer. Mantle Cell Lym-phoma (MCL) represents 2–10% of all NHLs. MCL isderived from a subset of naive pre-germinal center cellslocalized in primary follicles or in the mantle region ofsecondary follicles. Most cases of MCL are associatedwith chromosome translocation t(11;14)(q13;q32). MCLis associated with a poor prognosis and it remainsincurable with current chemotherapeutic approaches.Despite response rates of 50–70% with many regimens,the disease typically progresses after chemotherapy. Themedian survival time is approximately 3 years (range,2–5 y); the 10-year survival rate is only 5–10%.Objectives: Leukemic phase of MCL is quite rare andpresents with anemia and leukocytosis in the peripheralblood, involvement of liver, spleen, bone marrow, andlymph nodes. This is the case of MCL presenting in theleukemic phase with Intracranial Hemorrhage. Two casesof MCL with leukemic phase without CNS involvementand one case with CNS involvement without leukemicphase have been reported in literature previously.Methods: Autopsy was performed after consent. Histo-logical sections were submitted from different organsand immunohistochemistry was performed using theLabeled StreptAvidin Biotin (LSAB) method using apanel of antibodies including LCA, CD20, CD79A,CD5, CD10, BCL2, CD23, CD43, BCL6 and Cyclin D1.Tissue was submitted for t(11; 14) using PCR technique.Results: MCL was diagnosed the liver, spleen, lymphnodes, bone marrow and peripheral blood showingsmall lymphocytes having the same morphology as thoseseen in the other organs, consistent with the leukemicphase of MCL. These cells were also seen in multiplesmall aggregates in the CNS.Conclusions: MCL can have rare presentation inleukemic phase with diffuse CNS involvement wherethe presentation of the MCL in leukemic phase wasshown with the widespread intracerebral hemorrhagewith widespread intracerebral hemorrhage. Two cases ofMCL with leukemic phase without CNS involvementhave been reported in the literature previously.


P274

IMMUNOHISTOCHEMICAL EVIDENCE OF

ENDOMETRIAL STROMAL ALTERATION IN

DYSFUNCTIONAL BLEEDING

I. Teob, MD, H. Al-Maghrabib, MD, M. Lambaa, MD,FRCPC, J.P. Veinota, MD, FRCPC, K.T. Maia, MD,FRCPC

aDepartment of Laboratory Medicine, The Ottawa

HospitalbDepartment of Pathology and Laboratory Medicine,

University of Ottawa, Ottawa, Ontario, Canada

Aims: It is commonly believed that dysfunctionalbleeding (DUB) is caused by ovulation disordersresulting in hormonal disturbances, which in turn leadto disturbed angiogenesis. The role of endometrialstromal cells (ESC) in DUB is neither well understoodnor emphasized in the assessment of endometrialbiopsies. In normal premenopausal endometrium, cal-retinin reactivity is limited to the functionalis layer (FL).The FL displays zonal reactivity ranging from super-ficial zone of the FL in the early proliferative phase tofull-thickness in the secretory phase. In the menstrualperiod, ESC display negative or focal reactivity.Throughout all phases, CD34 is limited in the basalislayer (BL).Materials and methods: Immunostains for calretinin andCD34 were performed on 50 endometrial specimensfrom women with DUB.Results: Regardless of hormone exposure or histologicappearance, ESC from women with DUB often showedweaker calretinin reactivity than in normal endome-trium, with focal to extensive loss of reactivity in the FL.In all cases with DUB, CD34 reactivity appeared toextend from the BL into the FL and was seen in areaswith or without calretinin reactivity. In superficialsecretory endometrium, endometrial glands surroundedby calretinin- or CD34+ stroma tended to be asyn-chronic as compared with adjacent glands.Conclusions: The altered calretinin and CD34 stromalreactivity suggests an expansion of the BL-type stromainto the FL, generating a ‘‘disordered endometrialstroma.’’

P275

PROGESTERONE RECEPTOR REACTIVITY IN

RENAL ONCOCYTOMA AND CHROMOPHOBE

RENAL CELL CARCINOMA

K.T. Maia, MD, FRCPC, I. Teob, MD, N. RoustanDelatourb, MD, S.J. Robertsona, MD, FRCPC, E.C.Margineana,b, MD, FRCPC FACP

aDivision of Anatomical Pathology, Department of

Laboratory Medicine, The Ottawa Hospital, Ottawa,

Ontario,bDepartment of Pathology and Laboratory Medicine,

University of Ottawa, Ottawa, Ontario, Canada

Aims: Estrogen (ER) and progesterone receptors (PR)display less than 1% positive reactivity in renal cellcarcinoma (RCC). ER and PR reactivity in renaloncocytoma (RO) and chromophobe RCC (CHRCC)has not been investigated. We study the ER and PRimmunohistochemical staining as potential diagnosticmarkers for RO and CHRCC.Materials and methods: 38 RO, 25 CHRCC (10oncocytic CHRCC and 15 typical CHRCC), 20 OPRCCand 10 eosinophilic (granular) clear cell RCC werestained for ER, PR, CD117 and RCC.Results: All RO and eosinophilic variants of CHRCC,including cases with sarcomatoid changes, displayedmoderately positive nuclear reactivity for PR. Thenuclear reactivity ranged from 90% to 60% in RO,and from 70% to occasional cells in eosinophilicvariants of CHRCC. In CHRCC, tumour cells witheosinophilic cytoplasm had more diffuse reactivity,whereas cells with vacuolated cytoplasm, sarcomatoidchanges and non-oncocytic CHRCC had more focalreactivity. Typical CHRCC were not reactive for PR.CD117 reactivity tended to be stronger in the typicalCHRCC than eosinophilic CHRCC. No tumors reactedwith ER.Conclusions: PR is a highly sensitive and specific makerfor RO and oncocytic CHRCC. Therefore, PR can beused in combination with CD117 and RCC in thedifferential diagnosis of RO and eosinophilic variant ofCHRCC with other oncocytic types of RCC.


P276

BUILDING CANADIAN IMMUNOHISTOCHEMIS-

TRY QUALITY CONTROL (CIQC)

S. Bahzada, B. Gilksb, S. Klassenb, E. Torlakovica

aDepartments of Pathology and Laboratory Medicine,

Royal University Hospital, University of Saskatchewan,

Saskatoon, SKbVancouver General Hospital, The University of British

Columbia, Vancouver, BC

Immunohistochemistry is an integral part of anatomicpathology and hematopathology practice and its out-come is the basis of an expanding number of diagnosesand also treatment choices. Despite its wide and routineclinical use, its standardization still lags behind.External quality control/assurance allows comparisonof performance and results, serves as an early warningsystem for problems, identifies systematic kit problems,provides objective evidence of laboratory quality, servesas an indicator of where to direct improvement efforts,and identifies training needs. No such national programis established in Canada so far. Fifteen Canadianclinical immunohistochemistry laboratories were invitedto stain tissue microarrays (TMA) slides that contained76 tissue cores to represent lesions with variousexpressions of tested epitopes. Selected were tests thatare in daily use for evaluation of undifferentatiatedtumors: pancytokeratin, low-molecular-weight cytoker-atin (LMWCK), vimentin, S-100, and HMB-45. Inappropriate setting, these markers enable distinctionbetween carcinoma, melanoma, and sarcoma. The stainswere scored on the scale of 0 to 3+ with separate scoresfor pathological or predominant cell population asappropriate and background non-specific staining.Pancytokeratin staining produced from 0% to 30%false negative rate, with similarly significant differencesbetween the laboratories also for LMWCK, vimentin,and S-100. While most laboratories employed similardetection methods, the differences appeared to besecondary to variations in antigen retrieval proceduresor dilution of the primary antibodies. The results are inmore detail posted for viewing and virtual microscopy atwww.ciqc.ca. We conclude that Canadian clinicalimmunohistochemistry laboratories produce variableresults even with most commonly used test and that anexternal QC programs would probably help to achievestandardization in immunohistochemistry.

P277

CYCLOPHILIN C-ASSOCIATED PROTEIN

(CyCAP) NULL MICE: A MODEL OF

EXPERIMENTAL MUCOSAL HYPERPLASIA

OF THE COLON

C. Wanga, E. Torlakovica, Vicki Keelerb, T. Benerjeea,S. Laferte, PhDb

aDepartment of Pathology, Royal University HospitalbDepartment of Biochemistry, University of Saskatch-

ewan, Saskatoon, Canada

The discovery of a ‘‘serrated neoplasia pathway’’ hasshifted the attention from classical adenomas toserrated/hyperplastic mucosa as the significant precur-sor of colorectal carcinoma. In mice, hyperplasia of thecolonic mucosa is a regular phenomenon after achallenge with colonic carcinogens. CyCAP, murineorthologue of the tumour-associated antigen 90K(TAA90K)/Mac-2 BP, is a widely expressed secretedglycoprotein that modulates the host response tobacterial endotoxin.Wild-type (WT) and CyCAP-knock out (KO) mice weretreated by azoxymethane (AZ). Five animals wereincluded in each group (WT, WT+AZ, KO, KO+AZ).The number and the size of colonic tumors wasrecorded/The crypt depth was measured in at least 60perfectly oriented crypts per animal and the number ofcolonocytes was counted in the same number of crypts.KO+AZ animals had more mucosal hyperplasia thanWT+AZ animals (p ¼ 0.005, Independent SampleT-test). In both groups, the crypt depth (r ¼ 0.723,p ¼ 0.018, Spearman Correlation) and colonocyte num-ber (r ¼ 0.863, p ¼ 0.001, Spearman Correlation) werepositively associated with total numbers of tumors andtotal tumour size. KO mice had larger numbers oftumors (p ¼ 0.003, linear regression) and overall largertumour mass (p ¼ 0.016, Linear Regression). In fact,KO mice spontaneously developed colonic mucosalhyperplasia early in life (po0.0001, Independent SampleT-test).KO mice represent the first model of spontaneouscolonic mucosal hyperplasia and highlight the potentialrole of CyCAP as a tumour suppressor during earlystages of colonic carcinogenesis. Studies of KO miceshould provide novel insights about the possiblefunction of TAA90K in early stages of colon carcino-genesis.

http://www.ciqc.ca


P278

JUXTAGLOMERULAR CELL TUMOUR: A CASE

REPORT AND REVIEW OF THE LITERATURE

E. Tugaleva, K. Rizkalla, B. Wehrli, D.W. Malott,M. Moussa, N.G. Chan

Department of Pathology, London Health Sciences Center

and University of Western Ontario, London, ON, Canada

Background: Juxtaglomerular cell tumour (JGCT) is a rarerenal neoplasm that is associated with severe hypertensiondue to excessive renin secretion. Less than 100 cases havebeen described in the literature, mostly in young individualswith no definite gender or racial predilection.Case history: We report a case of JGCT in a 15-year-oldgirl who presented with significant hypertension, elevationof renin and aldosterone levels, and low serum potassium.Imaging showed a complex cystic mass in the right kidney.She underwent a laparoscopic radical nephrectomy.Pathology: Surgical resection revealed a well-circum-scribed tan firm tumour, measuring 3 cm in greatestdimension. Histology demonstrated mildly atypicalround to polygonal neoplastic cells, arranged in sheets,nodules, and trabeculae with a network of delicatevessels, and a vague hemangiopericytoma-like vascularpattern. Mitoses were inconspicuous. The cells con-tained fine PAS-positive, diastase-resistant, intracyto-plasmic granules. The neoplastic cells were positive forvimentin and smooth muscle actin, and negative forcytokeratin. CD34 was also positive, and this hasrecently been reported to be a helpful marker. Ultra-structural analysis revealed the presence of rhomboid-shaped renin protogranules. The diagnosis of JGCT wasmade. The patient had an excellent post-operativerecovery with subsequent improvement in her bloodpressure and potassium levels.Conclusion: JGCT is a rare cause of secondary hyperten-sion that is curable by surgical resection. This diagnosisshould be suspected in a younger individual presented withuncontrolled hypertension and hypokalemia associatedwith a renal mass and high aldosterone-renin levels.

P279

SIGNIFICANCE OF FINDING MULTINUCLEATED

GIANT CELLS IN CYTOLOGY

N. Ursani, V. Chen, G. Gohla, S. Salama

Department of Anatomic Pathology, St. Joseph’s Hospi-

tal, McMaster University, Hamilton, Canada

Multinucleated giant cells (MGCs) are sometimes encoun-tered in cytological smears. There is no systemic study inthe literature on MGCs in cytology. We describe threeunusual cases of MGCs in FNA biopsy observed recently

in our laboratory. We also study other cytology caseswhere MGCs are identified. We then classify MGCs intothree categories: Normal, reactive and neoplastic. Exam-ples of each type are shown. We conclude that MGCs incytological smears are a useful finding whether they are thelesional cells or accompanying cells. Their appearancemust be interpreted in the context of other cells and non-cellular elements on the cytology smear. In addition, itcannot be over-emphasized that cytological findings musttake into consideration clinical history, location of lesionand other ancillary studies before rendering a finalcytological diagnosis.

P280

COLONIC ADENOCARCINOID METASTASIZE

TO THE LIVER AS SEPARATATE ADENOCARCI-

NOMA AND ENDOCRINE TUMOR

A. Yaua,c,d, I. Dattab, E. Dixonb,c,d, Z. Gaoa,e

aDepartment of Pathology,bDepartment of Surgery,cDepartment of Oncology, University of Calgary,dTom Baker Cancer Center, Alberta Cancer BoardeCalgary Laboratory Services, Calgary, Canada

Background: The biological behaviour of the relativelyuncommon adenocarcinoid tumour of the gastrointestinaltract is yet to be elucidated. We report the case of a primarycolonic adenocarcinoid tumour, which later developedsynchronous and separate metastatic foci of its adenocar-cinomatous and endocrine tumour components.Case report: A 43-year-old woman with a history ofrecurrent lymphoma underwent an uncomplicated colonicresection for adenocarcinoma. On diagnostic imaging shewas found to have multiple liver masses and underwent a leftliver lobectomy and right liver mass resection. Thehistological examination of the resected liver specimenrevealed two morphologically distinct malignancies: anadenocarcinoma and a malignant endocrine carcinoma.Review of the previous colonic resection specimen confirmedthat the primary tumour was a mixed adenocarcinoid. Themorphology of both components found in the colonictumour matches those of the liver lesions.Discussion: To our knowledge, this is the first report in theEnglish literature of this phenomenon. This reportaddressed the following issues: (1) the malignant progres-sion of different components of a mixed tumour; (2) theimportance of identifying the minor component of a mixedtumour and to assess its metastatic potential; (3) the needto differentiate the uncommon primary endocrine tumourof the liver from a metastatic endocrine tumour; and (4)the possible mechanisms for the dissociation of the twocomponents during the metastatic process.


P281

NODULAR FASCIITIS IN THE PAROTID GLAND:

A WORRISOME CLINICAL PRESENTATION IN

AN ELDELY WOMAN

A. Yaua,c,d, I.H. Jadusinghe, T.W. Matthewsb,V. Falcka,f

aDepartment of Pathology,bDepartment of Surgery,cDepartment of Oncology, University of Calgary,dTom Baker Cancer Center, Alberta Cancer BoardeMedical Laboratory Consultants, CalgaryfCalgary Laboratory Services, Calgary

Background: Nodular fasciitis is uncommon in the headand neck. It rarely can present as a salivary gland mass;approximately 23 parotid gland cases could be found inthe literature. Their rapid growth simulates a malig-nancy, and a neoplastic diagnosis may be difficult toexclude on FNA and histology.Case report: A 76-year-old woman presented with a 2month history of a rapidly growing mass in her leftparotid gland region. FNA suggested a benign spindlecell lesion. Pain and erosion of the surface of themandible prompted a nerve sparing parotidectomy. Acircumscribed, unencapsulated myofibroblastic prolif-eration with focal areas of loose, tissue culture-likefibroblasts was resected. Immunostains supported adiagnosis of nodular fasciitis.Discussion: Rapid growth, pain, and possible bonyinvolvement are worrying clinical features. AccurateFNA assessment is important to guide optimal clinicalmanagement. While conservative excision is the mostcommon treatment, some cases have regressed withconservative management after FNA diagnosis. Thehistological differential diagnosis includes inflammatorymyofibroblastic tumour, desmoid, peripheral nerve sheathtumour and sarcoma. Recognition of the reactive nature ofthe stellate, tissue culture-like fibroblasts and the scatteredinflammatory reaction, in the face of mitotic activity isimportant to spare the patient over-treatment.

P282

PLEOMORPHIC PANCREATIC ENDOCRINE

NEOPLASM: A RARE MIMIC OF ADENOCARCI-

NOMA

A. Yaua,d,e, J. Pasiekab,e, O.P. Rorstad3,5,F.R. Sutherlandb,e, Moosa Khalila,f

aDepartment of Pathology,bDepartment of Surgery,cDepartment of Medicine,dDepartment of Oncology, University of Calgary,eTom Baker Cancer Center, Alberta Cancer BoardfCalgary Laboratory Services, Calgary, Canada

Background: Pancreatic endocrine neoplasms [PENs]confer a much better prognosis to the patient than themore common adenocarcinomas. The distinction isclinically important and usually does not pose a problemto the pathologist. However, this distinction maybecome challenging when a non-functioning tumourexhibits marked nuclear pleomorphism. We report acase of a pleomorphic PEN that was misclassified as apoorly differentiated carcinoma and is regarded, retro-spectively, as a diagnostic pitfall.Case report: A 36-year-old woman with a six-monthhistory of epigastric pain was found by imaging studiesto have a mixed solid-cystic mass in the head of thepancreas. The FNA cytology suggested an adenocarci-noma and she underwent a Whipple’s procedure.Grossly, the tumour appeared as a circumscribed‘‘cyst’’. Histologically, the ‘‘cyst’’ wall was lined byneoplastic cells that showed marked nuclear pleomorph-ism but rare mitoses. Immunohistochemistry supportedthe diagnosis of an endocrine tumour and the Ki67labelling index was low. Four years later, withoutfurther treatment, the patient remains free of disease.Discussion: Pleomorphic PENs are rare tumors withcytological features that can erroneously suggest anaggressive behaviour; still they share the same goodprognosis with classic PENs. This report addresses thefollowing points: (1) the challenge to differentiatepleomorphic PENs from other more aggressive tumors(e.g. adenocarcinoma); (2) the value of immunohisto-chemistry to differentiate these tumors; and (3) theimportance to assess the malignant potential of PENs bystrictly using the WHO criteria, which do not includenuclear atypia.

canadian laboratory medicine congress

Documents