CAP Abstracts 2006

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Pathology – Research and Practice 202 (2006) 793–834 www.elsevier.de/prp

CANADIAN ASSOCIATION OF PATHOLOGISTS ASSOCIATION CANADIENNE DES PATHOLOGISTES ABSTRACTS – RE´SUME´S JULY 15–19, 2006 57TH ANNUAL MEETING ST. JOHN’S, NEWFOUNDLAND 15–19 JUILLET 2006 57 ASSEMBLE´E ANNUELLE ST. JOHN’S, TERRE-NEUVE E

O101 STATIC TELEDERMATOPATHOLOGY FOR NON-NEOPLASTIC SKIN CONDITIONS M.J. Trotter, D.F. Barber, A.K. Bruecks, C. Ho, D.M. Sawyer, D. You Department of Pathology and Laboratory Medicine, University of Calgary, and Calgary Laboratory Services, Calgary, Alberta Static telepathology uses ‘‘store-and-forward’’ digital photomicrographs with image interpretation at a distant site. Previous studies of static teledermatopathology have not focused on the complexities of non-neoplastic skin diseases, in particular the pathology of inflammatory dermatoses. We evaluated the diagnostic accuracy of static teledermatopathology on biopsies from 50 selected cases of non-neoplastic skin conditions, including biopsies from all major inflammatory patterns doi:10.1016/j.prp.2006.08.003

(lichenoid, spongiotic, psoriasiform, granulomatous, vesiculobullous, and vasculopathic); collagen/elastic disorders, and infections. A maximum of three digital photomicrographs were acquired from each H&E stained slide by (1) a general pathologist with no subspecialty training in dermatopathology and (2) a trained dermatopathologist. All digital images and subsequently the glass slides were interpreted independently by three other dermatopathologists. Pathologists were provided with patient age and gender, specimen site, and a 2–3 word clinical description. The diagnostic concordance rate (telepathology diagnosis vs. pathologist’s glass slide diagnosis) was 89% using images acquired by a general pathologist, and 86% using images acquired by a dermatopathologist. This difference was not statistically significant. Without extensive clinical history, or access to special stains, dermatopathologists examining a single glass slide had an 87% concordance rate with the actual clinicopathologic diagnosis. We conclude that static telepathology can

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be used successfully in consultative interpretation of non-neoplastic skin disease pathology, and that photomicrographs acquired by a general pathologist with no subspecialty dermatopathology are of similar diagnostic value to those acquired by a trained dermatopathologist.

O102 QUANTITATIVE ASSESSMENT OF HETEROGENEOUSLY EXPRESSED MARKERS WITHIN HISTOLOGICAL SECTIONS V. Iakovlev, A. Morrison, M. Pintile, R. Hill, D. Hedley University Health Network, Ontario Cancer Institute/ Princess Margaret Hospital, Toronto, Ontario, Canada Immunohistochemical and immunofluorescent staining methods provide valuable information about protein expression within tissues. There is often a subjective component to assessment of immunohistochemical staining. The reproducibility of measurement is further complicated by the heterogeneous distribution of many markers. Recent advances in histological imaging equipment and the performance of personal computers provide a basis for the development of affordable and reproducible quantitative techniques. The degree of hypoxia has been shown to correlate with adverse outcome for several malignant neoplasms. This is the basis of our interest in molecular interactions within hypoxic tissue. The heterogeneous distribution of hypoxia is presents a challenge for accurate immunohistological measurement. The hypoxic state drives cells into survival pathways and ultimately leads to different expression of involved proteins in areas of different oxygenation status. Therefore the degree of expression of histological markers may be dependant on the distribution pattern of hypoxic areas. We studied the spatial distribution of a surrogate hypoxia marker Carbonic Anhydrase IX within cervical squamous cell carcinoma. Our goal was to assess if its expression correlates with direct pO2 measurements. We analyzed multiple deep sections through sets of 5 separate biopsies obtained from 10 patients with invasive cervical carcinoma (total number of sections ¼ 320). We also ran tests to measure the reproducibility of these measurements. All data were analyzed to compare variance due to the method, biopsies and patients. We found that the variance within patients has two main sources: measurement error and intratumoral heterogeneity of CAIX distribution. Multiple sampling points need to be utilized to reduce the error due to heterogeneity. Increasing biopsy size had dual positive

effect on accuracy of the measurement. It improved reproducibility of the readings taken by an operator as well as giving better representation of intratumoral heterogeneity. These data allowed us to set a threshold for biopsy size and to define a practical sampling protocol. Analyzing our analytical method, we identified that section thickness, staining and visual perception were the sources of error. These experiments suggest a general approach to the problem of sampling error when measuring tumor markers with heterogeneous distribution.

O103 PRIMARY FROZEN SECTION DIAGNOSIS BY TELEPATHOLOGY IN TORONTO: THE UNIVERSITY HEALTH NETWORK (UHN) EXPERIENCE A. Evans, D. Ghazarian, S. Croul, B. Perez-Ordonez, R. Chetty, S. Asa Department of Pathology, University Health Network, Toronto, On, Canada, M5G 2M9 Telepathology (TP) has been used for frozen section (FS) diagnosis in Europe and Scandinavia for over a decade. Its use for FS in North America has not been widely accepted due mainly to concerns over diagnostic accuracy. This study describes the early experience of a TP system used for primary FS diagnosis at a major academic health science centre. UHN comprises three sites, one of which has no on-site anatomical pathologist, but has neurosurgery (NS) and general surgery (GS) services requiring FS support. A dynamic TP system is used to transmit compressed JPEG images over our intranet at standard network speed (100 Mbs) to pathologists at the other two sites. The development phase included pathologist training with archived FS slides, dialogue with the surgeons concerning the use of TP for FS, training of pathologist assistants and histotechnologists to process the tissue and initiate the intranet connection between the robotic microscope and the FS pathologist. Due diligence prior to use for patient care included protocol review by the CMPA and medical advisory committee at UHN. Over the 16-month initial period of use, we have examined 88 specimens (66 NS and 22 GS) including tumours of the brain, spinal cord, peripheral nerves and skull as well as lymph nodes, incisional breast biopsies and peritoneal tumour implants. Resection margins from a variety of specimens have been assessed only when the surgeon defined areas of greatest concern. Turnaround times have routinely been less than 20 min. In all but one case, there has been agreement between TP FS and final diagnoses. The one discordant case was attributable to features present in the tissue examined at FS that were

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not present in the paraffin sections. Our preliminary experience shows that TP is an effective and accurate means of providing primary FS diagnoses and illustrates the importance of surgeon-pathologist communication required to implement this technology.

O104 TARGETING TUMOR-DERIVED FGFR4 (PTDFGFR4) THROUGH N-CADHERIN AS A THERAPEUTIC APPROACH TO PITUITARY TUMORS Daniel Winera,b, Lei Zhenga, Sylvia L Asaa,b, Shereen Ezzata a Endocrine Oncology Site Group, Ontario Cancer Institute, Toronto, Ontario, Canada, M5G-2M9 b Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada, M5G-2M9 Several molecular aberrations have been implicated in the pathogenesis of pituitary tumors but few have proven to be of therapeutic value. Pituitary tumorderived fibroblast growth factor receptor-4 (ptdFGFR4) is an alternatively transcribed cytoplasmic isoform lacking much of the extracellular domain. This transforming isoform recapitulates the morphologic features of human pituitary tumors in transgenic mice. To investigate the therapeutic potential of targeting ptdFGFR4, we examined the impact of FGFR4 tyrosine kinase inhibition in xenografted mice. GH4 pituitary cells expressing ptd-FGFR4 disrupt NCAM/N-cadherin interaction and result in invasive tumors in mice. Systemic treatment of mice bearing ptd-FGFR4 tumors with the FGFR-selective inhibitor PD173074 resulted in reduced tumor cell proliferation, recovery of membranous N-cadherin, less invasive growth, and a significant (50%) reduction in tumor volume. Mutation of tyrosine Y754F in ptd-FGFR4 abrogated the effect of PD-mediated inhibition. The pivotal role of Ncadherin in pituitary cell growth was demonstrated by si-RNA mediated down-regulation, which resulted in loss of beta-catenin and more invasive growth in xenografted mice. Immunohistochemical analysis of 78 surgical human pituitary specimens confirmed altered expression of N-cadherin in FGFR4-positive tumors with significantly increased cytoplasmic localization of N-cadherin associated with patchy loss of membrane staining in these areas. Primary human pituitary adenomas cells treated with PD173074 show restoration of N-cadherin to the membrane with dephosphorylation of Rb. These data highlight N-cadherin as an important mediator of ptd-FGFR4 action and as a therapeutic target to the management of inoperable pituitary tumors.

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O105 ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATH A CLINICOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY OF 18 CASES D. El Demellawy, Jagdish Butany Departments of Pathology, University of Toronto, Toronto, Canada Arrhythmogenic right ventricular cardiomyopathy/ dysplasia (ARVC) is a disease that raises many controversial issues as regards its existence, defining and diagnostic criteria, pathological spectrum of changes, and pathogenesis. A total of 18 cases of ARVC were retrospectively selected from TGH during the period of 1997–2005. These cases were diagnosed according to the criteria proposed by Lobo et al, 1997. Also, 15 non-ARVC surgical hearts from transplants were studied as controls. Cases were 11 females and 7 males, having a mean age 34.7 years (713.2). ECG showed conduction block in 8 cases, ventricular tachycardia in 6 cases and premature ventricular contractions in 4 cases. The hearts weights ranged from 300-625gm, with a mean weigh 409.6 (7188.7). Ten cases showed biventricular dilatation, 2 cases had right atrial (RA) dilatation and in 5 cases the dilatation was restricted to the right ventricle (RV) only. Twelve cases showed aneurysmal formation. In all cases, RV showed features of fibro-fatty infiltration (FFI) consistent with the fibro-fatty variant. Ten of our cases revealed a cardiomyopathic pattern and the rest had an infiltrative pattern. Mural thrombi were present in 4 cases, single fiber calcification in 5 cases and trabeculae carnae involvement by FFI in 6 cases. Immunohistochemistry showed myocarditic foci were present in 3/4 of our cases and in such cases; these foci were formed predominantly by T lymphocytes mixed with macrophages. CD 56 was found to selectively stain the intercalated discs in different parts of the heart. There was no difference in CD56 expression or morphology within the intercalated discs between cases of ARVC and controls. There was absence of co-expression of S100, or/and vimentin and desmin. PPAR gamma was not expressed. Conclusion: ARVC is a distinct disease, which in the present series showed female predominance and commonest presentation was with symptoms of congestive heart failure. The disease consistently showed RV involvement to the extent that it may suggest that transmural RV FFI is the most consistent morphological diagnostic criteria. In contrast LV morphological and septal changes, which were rather, characteristic but lacked consistency. Atrial and conduction changes were

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non-specific. The distinction between infiltrative and cardiomyopathic patterns does not show any clinical or prognostic implication. The trabeculae carnae involvement by FFI is seen in ARVD, in more than third of cases and to us it is related to the severity of ARVC and advanced stage. Single myocardial fiber calcification is seen in a subset of cases. In ARVC myocarditis is due to cell mediated immune response. Fat proliferation in ARVC is not due to trans-differentiation and not mediated through PPAR gamma. O106 COMPUTED TOMOGRAPHY (CT) STUDY OF SPHENO-OCCIPITAL SYNCHONDROSIS CLOSURE Matshes, EW, Burbridge, B, Juurlink, BH Department of Pathology & Laboratory Medicine, University of Calgary Department of Medical Imaging, University of Saskatchewan Department of Anatomy & Cell Biology, University of Saskatchewan Introduction and Objectives: The spheno-occipital synchondrosis, a plate of hyaline cartilage between adjacent centers of ossification in the basisphenoid, plays an important role in the growth of the skull base and articulating facial structures. As early observations noted apparent predictable and uniform closure (synostosis) between 18 and 23 years of age, this anatomical finding has been regarded by the forensic pathology and anthropology communities as being of some utility in separating adult from subadult cranial remains. The purpose was to study spheno-occipital synchondrosis closure in a modern population of known age and sex to determine (a) the range of fusion of this suture and (b) the possible influence, if any, of biologic sex. Materials and Methods: Data was collected from computed tomography (CT) images from the Royal University Hospital (RUH) Department of Medical Imaging, Saskatoon, Saskatchewan. Inclusion criteria were: (1) all patients undergoing CT scanning of the head at RUH; (2) patients of known age and sex; (3) adequate thin cut sections were available to allow for evaluation of the spheno-occipital synchrondrosis, or in patients where fusion has already taken place, to evaluate the region of the synostosis. The following data were recorded: (1) patient identifier; (2) age and sex; (3) identification of the synchondrosis; (4) degree of synchondrosis closure. Results: A total of 311 CT scans from 311 patients were studied. Eighty-seven of those patients were between 0 and 30 years of age. Of those older than 30 years of age (n ¼ 224), 223 had completely fused basilar sutures (99.56

percent). Partial fusion was first observed at the age of 11 years, and last observed at 26 years. The youngest individual to demonstrate a basilar synostosis was 12. The average age at which patients demonstrated partial (incomplete) basilar suture closure was 15.8 (median ¼ 15.5; standard deviation ¼ 4.14). With the exception of two individuals, all patients had completely fused sutures by the age of 19 (99.3 percent). Female patients had evidence of incomplete suture fusion by 13.3 years (standard deviation ¼ 2.42), and were completely fused by 15.9 years (standard deviation ¼ 2.48). Male patients had evidence of incomplete suture fusion by 16.6 years (standard deviation ¼ 1.95), and were completely fused by 18.1 years (standard deviation ¼ 1.46). Conclusion: The spheno-occipital synchondrosis fuses at an earlier age than stated by the classical forensic anthropology literature. Females appear to begin, and complete fusion at an earlier age than males.

O107 COMPARISON OF MICROVESSEL DENSITY BETWEEN HEPATOCELLULAR CARCINOMA ARISING FROM CIRRHOSIS AND NON-CIRRHOTIC LIVER Ivan Chebib, Taher Rad, Michelle Chow, Roland Auer, Zu-hua Gao Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta Background: Angiogenesis is essential for the growth, invasion and metastasis of tumor cells. This study compared intratumor microvessel density (MVD) and clinicopathologic features of two types of hepatocellular carcinoma (HCC): HCC arising from cirrhosis (HCC-C) and HCC arising from non-cirrhotic liver (HCC-NC). Methods: Tissue microarray composed of 20 normal livers (NL), 20 cirrhosis-only livers (CL), 20 HCC-C tumor (HCC-CT) and adjacent background cirrhotic liver (HCCCB), 20 HCC-NC tumor (HCC-NCT) and adjacent background non-cirrhotic liver (HCC-NCB) were stained immunohistochemically using antibodies against vascular endothelium antigen (CD34, CD31 and factor VIII) and analyzed using Image Pro Plus software. Results: Area of CD34 positive staining of MVD and comparison in tissue microarray NL

CL

HCC- HCC- HCC- HCC- HCC- HCCCB CT NCB NCT CT NCT

0.001 0.002 0.004 0.010 0.002 0.015 0.010 0.015 Mean MVD (mm2) P ¼ P ¼ P4 Compari- P 4 0.05 0.010 0.001 0.05 son (t-test)

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Conclusion: Although anti-CD34 staining of MVD can differentiate HCC from its background, there is no significant difference in MVD between HCC-C and HCC-NC. The survival advantage of HCC-NC over HCC-C in our group of patients seems more related to liver functional reserve rather than histopathologic features or MVD in the tumor tissue.

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O109 THE IMMUNOLOGICAL ROLE OF FIBROBLASTIC RETICULAR CELLS Robert Liwski, Tara Trenholm, Irene Sadek, Geoff Rowden and Kenneth A. West Deparments of Pathology and Medicine, Dalhousie University, Halifax, NS, B3 H 1V8

O108 RAPID AND EFFICIENT RECYCLING OF CHOLESTEROL: THE JOINT BIOLOGICAL ROLE OF C-REACTIVE PROTEIN AND SERUM AMYLOID A P.N. Manley, R. Kisilevsky Department of Pathology and Molecular Medicine, Queen’s University and Kingston General Hospital In the last 5 years 7180 papers on C-reactive protein (CRP) and 893 papers on serum amyloid A (SAA), another trace protein, have been published. Most focus on their relationship to atherosclerotic cardiovascular disease. CRP and SAA both may be predictive for death by any event but their pathogenic role in atherosclerosis remains speculative. Both of these proteins have been highly conserved for at least 500 million years, implying a critical role for them in the evolutionary survival of species. Thus far the physiological role of each remains uncertain and their joint interaction has not been explored. CRP binds phosphocholine of dying eukaryote cells and some live bacterial cell walls suggesting facilitation of phagocytosis as its role. Kisilevsky has shown that SAA markedly enhances the export of the cholesterol of phagocytosed cell membranes by delivering HDL to the macrophage and depressing acyl-CoA: cholesterol acyl tranferase (ACAT) activity while enhancing neutral cholesterol hydrolase (CEH) activity. We propose that the joint physiologic role of CRP and SAA is to facilitate the energy efficient, rapid recycling of cell membrane cholesterol and phospholipid to replace the hundreds of billions of new cells required daily during acute inflammation and also to minimize the death of foamy macrophages within inflammatory sites. Their pathogenic role in atherogenesis is likely minimal.

Objectives: Fibroblastic reticular cells (FRC) are structural cells of the lymph node (LN). While FRC are known to produce chemokines responsible for the migration of naı¨ ve T cells and DC, little is known about their interactions with these cells and their influence on DC and T cell activation. Thus, we have evaluated the interaction between DC and FRC in vivo and in vitro. Methods: Labeled DC were injected s.c. and the draining LN was stained and evaluated by confocal microscopy. Primary culture FRC were isolated from LN. DC-FRC interactions in vitro were evaluated using time lapsed photography and electron microscopy. DC survival in the presence of FRC was evaluated by FACS staining. T cell activation by DC in the presence of FRC was evaluated using CFSE and the D011.10 TCR transgenic system. Results: Quantitative analysis demonstrated that 80% of recently migrated DC made physical contact with FRC in comparison to 30% of injected T cells. In vitro, DC made stable associations with FRC. Over 12 days, less apoptosis of mature DC was observed in the presence of FRC compared to DC cultured alone. T cell proliferation was enhanced when FRC supernatant was added to DC and T cells. However, direct contact with FRC resulted in partially inhibited activation. Prolonged incubation with FRC resulted in DC that had higher expression of costimulatory and MHC class II molecules, however these cells were not able to induce T cell proliferation even in the presence of ConA. Conclusions: These results demonstrate that FRC preferentially bind and maintain contact with DC. Interactions with FRC inhibit the ability of DC to activate T cells and may generate a tolerogenic DC phenotype.

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ARRAY-COMPARATIVE GENOMIC HYBRIDIZATION (CGH) STUDY COMPARING BRONCHIOLOALVEOLAR CARCINOMA AND INVASIVE LUNG ADENOCARCINOMA S. Aviel-Ronena, B.P Coeb, W.L Lamb, M.S. Tsaoa a Department of Pathology, University Health Network, Princess Margaret Hospital, Toronto, Ontario b Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Centre, Vancouver, British Columbia

CLEAR CELL CARCINOMA OF THE LOWER GYNECOLOGIC TRACT S.K. Murray MD FRCPC, A.K. Guha MD PhD FRCPC, M. MacFarlane QEII Health Sciences Centre, Dalhousie University, Department of Pathology, Halifax, Nova Scotia, Canada

Background: Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC), has excellent prognosis and lacks stromal, vascular or pleural invasion by histological definition. However, individual pathologist’s interpretation for the presence of stromal invasion is subjective and variable. Furthermore, the invasive potential of BAC and the concept that BAC is a precursor of invasive ADC remain to be proven. Based on metaphase-CGH studies, we hypothesized that genomic profile changes may distinguish BAC from the invasive ADC, even those with prominent BAC-like growth pattern. Study Design: We sampled 7 BACs, 6 BACs with minimal invasion, 14 invasive ADCs in area of prominent BAC-like growth pattern and 4 in clearly invasive area. 8 normal lung tissues were controls. DNA was extracted from archival formalin-fixed paraffinembedded tissues and hybridized on the ‘‘27 K’’ SMRT (Sub Megabase Resolution Tiling set) array CGH. Data analysis by multiple computational software tools followed. Results: There is no clear genomic distinction between BACs and minimally invasive BACs, both showed lowlevel gene copy gains. However, they are distinguished from invasive ADCs by lower number of chromosomal changes and less variability. In invasive ADCs with prominent BAC growth pattern, progression of genomic instability was noted between BAC and invasive areas. Novel candidate marker genes are identified for distinction of BAC from invasive ADC with prominent BAC pattern. Conclusions: Consistent with their less aggressive clinical behavior, BAC and minimally invasive BAC demonstrate genomic profiles that are distinct and less complex than invasive ADC. (Dr. Aviel-Ronen is a Fellow of the cihr training program for clinician scientists in molecular oncologic pathology).

Objective: Mullerian clear cell carcinoma (CCC) of the lower gynecologic tract (LGT — cervix and vagina) is a relatively rare lesion with the major historical exception being the markedly increased incidence among women exposed in-utero to diethylstilbestrol (DES). This study examines LGT-CCC in the post-DES era. Methods: The laboratory information system of the QEII Health Sciences Centre Department of Pathology was searched for the diagnosis of CCC in the anatomical sites cervix and vagina over the time period of January 1, 1992–December 31, 2005. For identified cases clinical and pathological data were collected via review of the pathology reports, histological slides, and clinical charts. Results: Number of patients identified ¼ 12, mean age ¼ 51[18–84], 6(50%) pre-menopause mean age ¼ 33[18–47], 6(50%) post-menopause mean age 69[55–84], tumor location[cervix (8,66.7%), vagina (1,8.3%), cervix+vagina (3, 25%)], anatomical anomalies[2(16.7%)-1. duplicate uterus and cervix, septate vagina (18y.o.), 2. uterine cavity septum+fundal cleft (26y.o.)], Histological architecture[tubulopapillary(4,33.3%), solid(4,33.3%), tubular(3,25%2/3 microcystic),tubular+solid(1,8.3%),], Other histological features [oxyphilic(3,25%), mucin(4,33.3%), hyaline globules(2,16.7%), cystic-atrophic(2,16.7%), necrosis (5,41.7%), hobnail nuclei(4,33.3%), hyalinized stroma(2,16.7%), marked nuclear pleomorphism(2,16.7%), mixed tumor(1,8.3%-serous carcinoma), vaginal adenosis(1,8.3%),endometriosis(0)]. Over the 15 year study period the case occurrence averaged 0.8/year from a referral population of approx. 1
106. Conclusion: Although research on LGT-CCC has diminished greatly in the post-DES era this study identified the persistence of a bimodal age distribution for this tumor and a continued association with uterine anomalies in the young (m ¼ 22years) pre-menopausal patient with LGT-CCC. The notable association of ovarian CCC with endometriosis was not found for LGT-CCC.

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O112 CYTOMEGALOVIRUS (CMV) AS CO-EXISTING PATHOLOGY M.P. Duprea, S.A.C. Medlicottb, A.J. Urbanskia Department of Anatomical Pathology, aFoothills Medical Centre b Peter Lougheed Centre, University of Calgary Background: CMV infections may pose a difficult problem among immunosuppressed patients. Clinicopathologic aspects of CMV infections among immunosuppressed patients and those with inflammatory bowel disease (IBD) have been reported but only a few studies report CMV in patients with no evident immunosuppression. The presence of two co-existing pathologic processes in a single biopsy may represent a remarkable diagnostic challenge. Methods: We retrospectively identified colonic biopsies (January 2003 – August 2005) where CMV was detected with another pathologic process. H&E sections along with immunohistochemical stains for CMV were per-

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formed and reviewed. Clinical information was available for all cases. Results: Twelve colonic biopsies in which CMV was detected along with another pathologic process were identified. Six cases represented IBD, 2 graft Versus host disease (GvHD), 2 post bone marrow transplant (BMT) induction related changes without GvHD, 1 ischemic colitis and 1 seen within a tubular adenoma. Immunohistochemical stains confirmed presence of CMV. Conclusions: CMV inclusions can be seen in colonic biopsies as an incidental finding in apparently immunocompetent patients as shown in our material by the detection of CMV in a sporadic adenoma and in ischemic colitis. Are these CMV inclusions indicative of CMV colitis or dormant CMV infection? Detailed clinical history, exact date of transplant and multi-organ features of GvHD is essential for interpretation of colonic biopsies from BMT patients. Based on this study, it appears that CMV is detected with similar frequency in the transplant patient population as in the IBD population and the number of CMV inclusions does not predict the clinical significance to mandate treatment of CMV.

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HEMATOPATHOLOGY PLATFORM Presentations: 13:30-14:30

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DEVELOPMENT OF A DIAGNOSTIC TEST FOR THE JAK2 (V617F) MUTATION IN CHRONIC MYELOPROLIFERATIVE DISEASE—THE MANITOBA EXPERIENCE Camelia Stefanovicia,b, Ingo Schroedtera, Debra Glenn-Molinaa, Gaynor Williamsa,b a Health Sciences Centre, bUniversity of Manitoba, 820 Sherbrook St., Winnipeg, MB R3A 1R9

MANTLE CELL LYMPHOMA WITH MONOCLONAL PLASMA CELLS C.T-S. Chung, S. Kamel-Reid, K. Chun, D. Bailey Department of Pathology, University Health Network Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario

The chronic myeloproliferative diseases (CMPDs) are a heterogeneous group of disorders occurring at the level of a multipotential stem cell. This results in clonal expansion characterized by increased blood cell production with normal maturation and hypersensitivity to various cytokines. The current WHO classification divides the CMPDs into t(9;22)/ BCR-ABL positive (chronic myelogenous leukemia, CML) and negative (e.g. polycythemia vera (PV), essential thrombocythemia (ET), and chronic idopathic myelofibrosis (CIMF)) types. Non-CML CMPD’s are frequently difficult to diagnose due to clinical similarities and overlap with reactive cytoses. Recently a somatic (acquired) activating mutation (1849 G4T) resulting in substitution of phenylalanine for valine at position 617 of the JAK2 protein (V617F) has been identified in a high proportion of BCR-ABL negative CMPD. We have set-up and validated an allele specific PCR approach in our laboratory for the detection of the JAK2 (V617F) mutation in peripheral blood leukocytes. Two primer sets are used to amplify normal and mutant sequences plus positive control in one reaction. Products are visualized using ethidium bromide staining after electrophoresis on acrylamide gels. Results from 62 sequential patient specimens submitted for investigation for CMPD confirmed homozygous mutant (11.3%), mutant and wild-type (30.7%) and homozygous wild-type JAK2 (58.1%). These results are correlated with clinical and available laboratory findings including morphology, cytogenetics and BCR-ABL status. Our study confirms the importance of the JAK2 (V617F) Mutation in confirmation of diagnosis in patients submitted for evaluation of CMPD. This supports the results of other studies that this acquired mutation is important in diagnosis classification and possible targeted treatment of the CMPDs.

Plasma cell differentiation may occur in many mature B-cell lymphomas and is particularly common in marginal zone lymphoma. In contrast, mantle cell lymphoma (MCL) is considered unique in that it does not appear to show plasmacytic differentiation; that is, the plasma cells that are present in MCL show polyclonal staining. We report the case of a 76 year old woman who presented with generalized lymphadenopathy and a monoclonal IgM kappa paraprotein. Excisional biopsy of a lymph node revealed a mantle cell lymphoma – with the immunophenotype SIgKappa+/ CD20+/CD5+/cyclin D1+/FMC7-/CD23-/CD10– admixed with clusters of plasma cells showing IgM kappa monoclonality and cyclin D1 negativity by immunohistochemistry. Molecular and cytogenetic studies identified the presence of BCL-1 gene rearrangement by Southern blotting and fluorescence in situ hybridization (FISH) analyses, respectively, thereby confirming the diagnosis of MCL. A staging bone marrow biopsy including examination by flow cytometry revealed a small B-cell lymphoma with a different immunophenotype: SIgKappa+/CD20+/FMC7+/ CD5-/cyclin D1-/CD23-/CD10-, and FISH analysis negative for BCL-1 translocation. This was interpreted as a low grade B-cell lymphoma showing plasma cell differentiation. The differential diagnosis in this case is between a composite lymphoma and a mantle cell lymphoma showing plasmacytic differentiation. According to the literature, there are only rare reports of composite lymphomas that include MCL as one of the components and a low grade lymphoma showing plasma cell differentiation as the other. To the best of our knowledge there are no reports documenting MCL with plasmacytic differentiation.

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POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER AND ACUTE DISSEMINATED CANDIDIASIS: NOVEL ETIOLOGIES OF ACUTE APPENDICITIS M. Duprea, SAC Medlicotta, H Coxb, I Auera, J Conlya,c a Department of Pathology and Laboratory Medicine, Peter Lougheed Center, University of Calgary b Department of General Surgery, Peter Lougheed Centre, University of Calgary c Department of Internal Medicine, Peter Lougheed Centre, University of Calgary

HEMOPHILIA A IN MULTIPLE HETEROZYGOUS FEMALES DUE TO SKEWED X-CHROMOSOME INACTIVATION Nisa K. Renaulta, Sarah Dyackb, Melanie J. Dobsonc, Teresa Costad, Wenda L. Greera a Department of Pathology, Dalhousie University (DAL), Halifax, Nova Scotia b Department of Medical Genetics, IWK Health Sciences Centre and DAL, Halifax, NS c Department of Biochemistry and Molecular Biology, DAL, Halifax, NS d Department of Medical Genetics, Hoˆpital Sainte-Justine and Universite´ de Montre´al, Montre´al, QC

Candidal overgrowth and disseminated malignancy have only rarely been implicated as causes of acute appendicitis. Herein we report two systemic diseases manifesting as appendicitis; post-transplant lymphoproliferative disorder (PTLD) and acute disseminated candidiasis (ADC) complicating acute myelogenous leukemia. Both processes had presenting symptoms and diagnostic imaging studies suspect for appendicitis. Histology revealed mucosal ulcers, one due to an Epstein-Barr virus positive diffuse large B-cell lymphoproliferation and the other with candidal overgrowth and invasion of submucosal vascular structures. Both processes had documented involvement of lymph nodes and liver and spleen respectively. PTLD and ADC are well-acknowledged pathologies of the gastrointestinal tract. However, appendiceal involvement by either process has not been documented. Multifocal visceral illnesses including fungal infection and PTLD are rare diagnostic alternatives to the more typical pathologies of typhlitis and bacterial appendicitis in those immunechallenged individuals afflicted with lymphoproliferative or hematologic neoplasms.

Hemophilia A (HA) is an X-linked recessive bleeding disorder usually only expressed in males. Cases of HA have been reported in heterozygous females with unfavorably skewed X-chromosome inactivation (XCI). A severely affected girl (FVIII: 2%) was identified with a family history of severe HA including 2 other heterozygous females with HA. The proband and 17 relatives from three generations were studied. Factor VIII activity, and X-chromosome inactivation ratio (paternal active X: maternal active X, XCIR) in females of this family revealed a linear correlation between the degree of XCI skewing and factor VIII activity in heterozygous females. A significantly high proportion of females in this family have skewed XCI (45%). Karyotype and linkage analyses are inconsistent with known causes of familial XCI skewing, suggesting that, in this family, there is a novel heritable influence over XCI which may be similar to the mouse X-controlling element (Xce).

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POSTER PRESENTATIONS Presented Monday, July 17 at 15:00–16:00 P201

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EVALUATION OF 100% RAPID RESCREENING OF GYNECOLOGICAL CYTOLOGY SPECIMENS AT OUR INSTITUTION A.R. Haig, A. Nell, P. Downing, A. Raminhos, P. Molinaro, M. M. Weir Department of Pathology, London Health Sciences Centre & University of Western Ontario, London, Ontario, N6A 5A5

SUPRATENTORIAL PRIMITIVE NEUROECTODERMAL TUMORS (STPNETS) OF THE BRAIN: A CLINICOPATHOLOGICAL REVIEW WITH IMMUNOHISTOCHEMICAL AND MOLECULAR PROFILE Aghdas Mojtahedzadeh AP resident, J. Provias, M . Sur

Purpose: The effectiveness of the 10% rescreening of gynecologic cytology samples is questionable. The purpose of this study is to evaluate the implementation of 100% rapid rescreening of gynecologic cytology specimens in our laboratory. Materials & methods: All gynecologic cytology samples from January to mid February 2006 reported as negative or unsatisfactory by the initial cytotechnologist underwent rapid rescreening by a second cytotechnologist. ThinPreps slides were screened either vertically or horizontally. Conventional smears were screened by the turret (castle) method. As much of the slide as possible was screened in one minute with particular attention given to clear areas and small cells. Results: From the 1791 samples rapid rescreened (mostly liquid based samples), 8 abnormal cases were identified: 6 cases with atypical squamous cells of undetermined significance; 1atypical squamous cells, cannot exclude high grade SIL; and 1atypical glandular cells of undetermined significance. Twelve cases of missed transformation zone (T-zone) elements and 2 cases of yeast were also identified at rapid rescreen. Differences between cytotechnologists’ reporting criteria were identified for T-zone elements in atrophic, and post-partum samples, reactive changes and unsatisfactory samples, which required standardization. Conclusions: Rapid rescreening has been valuable in the standardization of reporting T-zone, reactive changes and unsatisfactory samples in our laboratory. Few abnormal cases have been identified by rapid rescreen, and a longer evaluation period is required to assess this new method.

Background: PNETs are uncommon malignant neoplasms of the cerebral hemispheres and suprasellar region, accounting for 2.5% of childhood brain tumors and 0.46% in adults. PNETs show a proliferation of poorly differentiated neuroepithelial cells, histologically similar to infratentorial medulloblastomas. Although cytogenetic and molecular studies have identified genetic alterations in medulloblastomas, molecular investigations in stPNETs are infrequent. Design: We evaluated 4 cases of stPNETs diagnosed in our department from 2002 to 2004 with emphasis on clinicopathological features, immunohistochemical profile and prognosis. Result: M: F ratio was 2:2; mean adult age – 57.5 years; mean pediatric age – 3 years; Site distribution – Frontal – 2, Temporal – 2. Common complaints seizure and headaches. Imaging showed inhomogeneous, contrast enhancing mass with midline shift and peritumoral edema in all cases. All cases were morphologically high grade small round blue cell tumors with endovascular proliferation, high mitotic count, necrosis with true rosettes and Homer-Wright rosettes. Immunohistochemically, two cases (adult-1, pediatric-1) showed focal GFAP positivity in the neoplastic cells indicating glial differentiation. All cases showed very focal positivity for NSE and Synaptophysin and diffuse positive staining for CD99 (MIC2 gene) and CD56. CD117 (C-Kit), Cytokeratin, Neurofilament, Actin, S-100 protein, Myogenin and Vimentin were negative in all cases. N-myc amplification by PCR and C-myc rearrangnment by FISH were negative in all cases. The tumors were negative for chimeric gene product of EWS-FL1; t (11; 22) by FISH. Treatment included surgical resection + radiation to cranio- spinal axis in adults and chemotherapy + radiation in the pediatric age group. 1 adult died 3 months after treatment due to infection and septicemia and 1 child died due to disease progression and CSF metastasis 9 months ago. Conclusion: stPNETs are poorly differentiated aggressive neoplasms. Our findings showed positive staining for CD99 and CD56 by immunohistichemistry and these

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could be potentially used as specific markers in the absence of all other markers. 2 cases demonstrated focal glial differentiation which is associated with poor prognosis. Despite unremarkable genetic analysis, overall prognosis is poor, suggesting that there are additional, unknown genetic aberrations in the pathogenesis of stPNETs which could impact on therapeutic strategies and clinical outcome. P203 A BRIEF REVIEW OF MIXED EPITHELIAL AND STROMAL TUMOR OF THE KIDNEY Akram M. Elkeilania, Kien T. Maia, John P. Veinota a Department of Pathology and Laboratory Medicine, University of Ottawa, the Ottawa Hospital, Ottawa, Ont Objective: Mixed epithelial and stromal tumor (MEST) of the kidney is recently recognized as a benign renal lesion. In this study, we reviewed cases of MEST at our institution and discuss the histopathogenesis of the lesion. Materials and Methods: All renal neoplasms and cysts at our institution for a period of 10 years were retrieved for review. Cases with features of MEST were submitted for immunostaining for ER, PR, CD10, CK7, MSA and HMB45. Results: Out of 856 renal neoplasms and cysts there were 11 MEST (incidence of 1.3%) with F:M ratio of 9:2 and patient age ranged from 39 to 70 (mean: 55710). The lesions were unifocal and measured from 2.5 to 12 cm (5.473.1) in diameter. Pathologically, MEST was diagnosed as multilocular cystic nephroma. The stromal component shows at least evidence of focal mullerian differentiation with positive immunoreactivity for estrogen and progesterone receptors in all 9 female patients, and stromal positivity for CD10 was seen in 7 female patients. In two male patients the stroma was less cellular than in female patients with fewer stromal cells reactive for ER and PR. Immunoreactivity for the melanocytic marker HMB45 was identified in a single case. The epithelial component displays features of different segments of the renal tubule with positive reactivity for CD10, CK7 and show mullerian epithelium differentiation with immunoreactivity for ER, PR in three lesions. Conclusions: The mixed features of the epithelial component suggest that the neoplastic stroma encroaches the renal tubules that subsequently show proliferation with development of cysts. Furthermore the mullerian stroma likely induces the renal tubules to differentiate into mullerian epithelium. MEST represents a tumor developing from the mullerian-type stromal cells in the kidney with or without melanocytic differentiation.

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P204 PIGMENTED SQUAMOUS CELL CARCINOMA OF THE SKIN: A CASE REPORT AND LITERATURE REVIEW Alaa Samkaria, MD, Samih Salamab a Department of Anatomical Pathology, St.Joseph’s Hospital, Hamilton, Ontario, Canada b Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada Pigmented squamous cell carcinoma (PSSC) is a rare variant of squamous cell carcinoma (SCC), which contains numerous pigmented melanocytes. This type of SCC may be difficult to distinguish from pigmented basal cell carcinomas (BCC), and cutaneous melanoma, especially those associated with pseudoepitheliomatous hyperplasia. We report an 83-year-old male, presented with a pigmented lesion on his forehead, clinically diagnosed as melanoma. Histology showed keratinizing SCC with numerous pigmented cells containing melanin interspersed among the neoplastic squamous cells. These cells expressed S100 protein and HMB-45 indicating melanocytic origin.Ultrastucturally cytoplasmic melanosomes in the neoplastic epithelial cells were seen. Recent review of the literature revealed only 28 cases of PSCC in skin and mucous membranes. Long-term follow-up showed no evidence of local recurrence or metastasis after complete excision, indicating that PSCC of the skin appears to behave similarly to SCC of the usual type. A larger study comparing cases of each type that are matched for thickness of tumor, site, extent of precursor lesions, and other factors would be needed to confirm this finding.

P205 PRIMARY SMALL-CELL CARCINOMA OF THE CAECUM: A CASE REPORT AND REVIEW OF THE LITERATURE Alaa Samkari, Dina El Demellawy, Monalisa Sur Franco Denardi, Salem Alowami Department of Anatomical Pathology and Laboratory Medicine, McMaster University, Hamilton, Ontario-Canada Cecal extra pulmonary small cell carcinoma cESC is extremely rare, with only single previous report of occurrence in a child. We report a 76- year-old man admitted for evaluation of a cecal mass seen in colonoscopy. Histology revealed small cell carcinoma with classic immunohistochemical profile of those seen in the colon. Further clinical survey documented

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absence of any other masses or abnormality. To date, this is the first case of primary cESC in an adult. Awareness of the pathologist and clinician of the cecum as a potential site of cESC may help to prevent misdiagnosis as poorly differentiated adenocarcinoma. This is crucial as ESCs usually have worse prognosis.

P207 SECONDARY PROSTATIC ADENOCARCINOMA: A CYTOPATHOLOGICAL STUDY OF 50 CASES Ali H. Assiri, Kien T. Mai, Nicolas L.D. Roustan Delatour, Hatim Al-Moghrabi, John P. Veinot, Hossein M. Yazdi Department of Pathology and Laboratory Medicine, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada

P206 A RHABDOID TUMOR ON A FINE NEEDLE ASPIRATE: A CASE REPORT AND REVIEW OF THE LITERATURE Albrecht W. Schall, Guillermo Quinonez, Fatemeh Kalantarpour Deloar Hossain Department of Pathology, Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada Finding a metastatic pleomorphic anaplastic neoplasm on a fine needle aspirate is a challenging differential diagnosis. Age, sex, location, history of disease, cytologic pattern, immunostains and electron microscopic findings are all factors necessary in identifying the origin of the tumor. We report a case in which the diagnosis of a rhabdoid tumor could have been made on the fine needle aspirate by electron microscopy if such a diagnosis had been suspected in the initial differential diagnosis. An 85-year-old woman presented with an enlarged thyroid, cervical lymphadenopathy and tumor nodules in the lungs and liver on imaging. A FNA was performed which revealed single and small irregular clusters of pleomorphic malignant cells with moderateto-abundant cytoplasm, eccentric vesicular pleomorphic nuclei, occasional prominent nucleoli and rare nuclear pseudoinclusions. The eventual diagnosis of a rhabdoid tumor was made by an open biopsy. We conclude therefore that a rhabdoid tumor should be included in the differential diagnosis of any pleomorphic anaplastic neoplasm. These aggressive tumors have characteristic nuclear and cytoplasmic features and show near consistent coexpression of vimentin and epithelial markers. Immunostains are non-specific, but typical paranuclear whorls of intermediate filament are seen on electron microscopy.

Background: Positive diagnosis of metastatic prostate adenocarcinoma (PCA) can be made with examination of the cytologic specimens and immunostaining for prostate-specific antigen (PSA) and prostate acid phosphatase (PAP). Immunohistochemical markers have been known to display negative, weak or focal staining in poorly differentiated PCA and in patients with prior hormonal and/or radiation therapy. The cytopathology of metastatic PCA has not been documented in large series. Method: Fifty cases of metastatic PCA with cytological specimens consisting of 41 fine needle aspiration biopsies (FNAB), 6 pleural fluid aspirates and 3 catheterized urine samples were reviewed and correlated with the surgical specimens and the clinical charts. Immunostaining for PSA, PAP, cytokeratin AE1/3, cytokeratin 7 (CK7), cytokeratin 20 (CK20), vimentin and carcinoembryonic antigen (CEA) was done. Results: Mean patient age was 7778 years; serum PSA, 4.172.3; and primary PCA Gleason score, 8.171.5. Cytologically, the specimens consisted of overlapping cell clusters or cell sheets with uniform hyperchromatic nuclei with or without nucleoli. Twelve cases were not reactive to PSA and PAP and 44 cases displayed negative immunoreactivity to both CK7 and CK20. Carcinoid-like lesions and small cell carcinomas were seen in 4 cases and were misdiagnosed as non-prostatic origin based on the following features: negative immunoreactivity to PSA and PAP with or without positive reactivity to CEA, and different histopathological features when compared to the primary PCA. Conclusions: In addition to the frequency of high grade PCA, awareness of the negative immunoreactivity to PSA and PAP, the discrepancy in the histopathological patterns between the primary and secondary tumors, especially the frequent neuroendocrine (NE) differentiation, are helpful features for the diagnosis of metastases of prostatic origin.

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OUR EXPERIENCE WITH ENDOSCOPIC GUIDED FINE NEEDLE ASPIRATION BIOPSY A. Nella, C. M. McLachlina, N. Hussainb, M. M. Weirb a Department of Pathology, London Health Sciences Centre & University of Western Ontario, London, Ontario Canada, N6A 5A5 b Department of Internal Medicine, London Health Sciences Centre & University of Western Ontario, London, Ontario Canada, N6A 5A5

COMPLEX MUCINOUS CYSTADENOMA OF THE URACHUS A.J. Schella, C.J. Nickelb, P.A. Isotaloa a Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ont., Canada K7L 2V7 b Department of Urology, Queen’s University, Kingston, Ont., Canada K7L 2V7

Purpose: Endoscopic ultrasound guided fine needle aspiration biopsy (EUS FNAB) is valuable for diagnosis and staging of abdominal and thoracic malignancies. The purpose of this study is to evaluate our EUS FNAB cases for: 1) diagnostic yield , 2) adequacy, 3) usefulness of rapid assessment by a cytotechnologist (CT), 4) size of sampled lesion, and 5) morphologic pitfalls. Materials & Method: We retrospectively evaluated all EUS FNABs from October 2004 to December 2005 for: site of origin, diagnostic category, adequacy, rapid assessment outcome, lesion size, and morphologic pitfalls. Results: The biopsy sites for the 33 patients (38 FNABs) were: 16 pancreas, 16 lymph node, 4 liver, and 2 adrenal glands. Satisfactory FNAB diagnostic categories (35/38 cases, 92%) included: 8 negative, 1 cystic, 7 indeterminate or atypical, 4 suspicious and 15 malignant/ neoplastic. The unsatisfactory rate was 8% (3/38 cases) and did not correlate with small lesion size. Rapid assessment was performed in all but one case, with an average number of passes for adequacy of 2 (range 1–4). The average size of the lesion sampled was 3–4 cm (range 0.6–11 cm). Excision was performed in only one case (pancreatic solid pseudopapillary tumour) and correlated with the cytology diagnosis. Morphologic pitfalls were: distinction of luminal mucus from true mucin, and of normal mucosal epithelium from lesional malignant epithelium. Conclusions: EUS FNAB at our institution is used most commonly for assessment of pancreatic masses and lymph node status. The use of a CT for rapid assessment appears to be worthwhile, given our low unsatisfactory rate (8%) and high diagnostic yield (92%). Distinction of normal from lesional tissue may be a pitfall on EUS FNAB.

The urachus is an embryologic structure that extends from the umbilicus to the urinary bladder apex. The urachus involutes in adults and persists uncommonly as a patent urachus. Rarely, the urachus may be the primary site of both benign and malignant neoplasms. We describe a 70-year-old woman who presented with a supravesical soft tissue mass and no evidence of any other disease process. Surgical resection of this mass revealed a 15.5
8
8 cm complex mucinous cystadenoma that consisted of multiple, multiloculated cysts that contained abundant mucin associated with foci of calcification. The mucinous cystadenoma did not communicate directly with the urinary bladder, but was associated with an extravesical urachal remnant. The multiloculated cysts were lined by minimally atypical mucinous epithelium. No evidence of stromal invasion was identified, however, abundant pools of hypocellular mucin did dissect through perivesical soft tissue. At surgery, the patient demonstrated no evidence of pseudomyxoma peritonei. A year post-resection, the patient is well with no evidence of local tumour recurrence or metastatic disease. Mucinous urachal neoplasms require extensive tumour sampling for accurate classification, as these tumours are often associated with a malignant process. Even in the absence of malignancy, these tumours may present with aggressive clinical behaviour, including pseudomyxoma peritonei, and it may be wise to include even the most cytologically unremarkable mucinous urachal tumours as mucinous neoplasms of uncertain malignant potential. Considering the potential for malignancy, these tumours should be excised in their entirety and patients should be followed clinically post excision. The possibility of metastatic disease should also be considered and clinically excluded for all patients with mucinous tumours involving the urachus.

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P210 PRIMARY LYMPHOEPITHELIOMA-LIKE CARCINOMA OF THE SKIN A. Misira, F. Denardib, M. Surb, S. Alowamib a McMaster University, Hamilton, Ontario b Department of Pathology and Molecular Medicine, Henderson General Hospital, Hamilton, Ontario, Canada Primary lymphoepithelioma-like carcinoma of the skin is a cutaneous neoplasm with histopathologic features identical to those seen in the undifferentiated subtype of nasopharyngeal carcinoma. We report one case observed in an 83-year-old female patient, found in skin excised from the right eyebrow. The patient was otherwise well, and had no known preexisting malignancy. Histologically, the lesion was poorly circumscribed with no connection with the overlying epidermis. It was composed of irregular infiltrating nests of round to oval cells with fine vesicular chromatin, distinct nucleoli and occasional mitotic figures. There was no obvious differentiation. There was a prominent lymphoid infiltrate surrounding these tumour nests. No cytoplasmic mucin was seen with PAS/PAS-D. Immunohistochemistry revealed that the neoplastic cells were positive for the epithelial markers AE1/AE3 and EMA. They were negative for CAM5.2, CK20 and S100. They were also negative for chromogranin and synaptophysin. TDT was negative. CD3 stained the prominent component of the admixed reactive T lymphocytes surrounding this infiltrating epithelial component. The diagnosis of lymphoepithelioma-like carcinoma of the skin is based on microscopic findings and the clinical exclusion of occult malignancy. It is typically found in older adults (50-80 years of age) with no sex predilection. The differential diagnosis is extensive and would include metastatic lymphoepithelioma, Merkel’s cell carcinoma, and cutaneous lymphadenoma, among others. Surgical excision has an excellent prognosis and is the current standard of treatment.

endometrioid carcinoma that may be confused histologically with sex-cord stromal tumors. Diagnosis is aided by a relatively benign clinical history in a postmenopausal patient and immunohistochemistry staining pattern that is negative for inhibin and positive for epithelial markers such as CAM5.2. In this case report, we review the published literature and present the case of an otherwise well 57-year-old woman with a remote hysterectomy who presented to her family doctor with abdominal pain. Radiological examination demonstrated a large left ovarian mass and an omental nodule. The patient underwent bilateral oophorectomy and omentectomy. Post-surgical gross examination showed a 12.0
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9.0 cm mass in the right ovary as well as metastases to the omentum. Histological examination demonstrated glandular areas lined by non-mucin secreting columnar epithelium arranged in small tubular glands and elongated solid tubular structures. Some areas showed pseudo-papillary configuration of the glandular structures with areas of hyalinized stroma. These structures resembled sex cords and had a storiform appearance. Focally, there were areas of solid proliferation of spindle-shaped epithelial cells. Similar histology was present in the omental metastases (FIGO II b). The diagnosis of SEC was further confirmed by positive immunohistochemical staining for epithelial markers (CAM5.2, AE1AE3 and EMA) with negative staining for inhibin. The patient was subsequently treated with chemotherapy and has had no recurrence to date. SEC should be considered as an unusual variant of well-differentiated endometrioid carcinoma despite the presence of a solid, sex cord-like proliferation. It may be misdiagnosed as a sex cord stromal tumour due to its unusual morphology particularly during frozen section diagnosis. It is important to recognise and distinguish this entity from sex-cord stromal tumors as SECs tend to present at an earlier FIGO stage than sex-cord stromal tumors and also tend to have a better prognosis in higher stages of the disease. P212

P211 SERTOLIFORM ENDOMETRIOID CARCINOMAS OF THE OVARY: A POTENTIAL DIAGNOSTIC PITFALL A. Misira, S. Alowamib, M. Surb a McMaster University, Hamilton, Ontario b Department of Pathology and Molecular Medicine, Henderson General Hospital, Hamilton, Ontario, Canada Sertoliform endometrioid carcinoma (SEC) of the ovary is a relatively rare variant of a well differentiated

ENCYSTED PAPILLARY CARCINOMA OF THE BREAST: A REPORT OF TWO CASES WITH AXILLARY LYMPH NODE MICROMETASTASES A. M. Mulligan, F. P. O’Malley Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada Encysted papillary carcinoma of the breast, widely believed to represent carcinoma in situ, has rarely been reported to be associated with metastases. We present

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two cases of encysted papillary carcinoma of the breast, both of which showed micrometastatic carcinoma in axillary lymph nodes but which failed to reveal stromal invasion despite extensively sampling. Immunohistochemical staining with myoepithelial markers (p63/ SMM-HC cocktail) showed near-complete absence of a myopeithelial cell layer around the periphery of the lesions. Both tumours were large; 5.9 cm and 4 cm respectively. One case showed three separate foci of micrometastatic carcinoma in 1 of 3 sentinel lymph nodes. The second case showed micrometastases in 2 of 11 axillary lymph nodes. The metastatic foci ranged in size from 0.5 mm to 1.8 mm and were each identified on H&E examination. The significance of micrometastases in lymph nodes associated with encysted papillary carcinoma is unknown. Given the friable nature of papillary lesions, one potential explanation for these findings is that of epithelial displacement and benign transport. Another possibility is the presence of occult invasion as a result of sampling. More recently, however, the term encapsulated papillary carcinoma has been proposed to describe papillary carcinomas that are surrounded by a fibrous rim, but which show scant or absence of myoepithelial cells. These lesions may represent borderline tumours that lie between in situ papillary carcinoma and invasive carcinoma, with a low, and as yet undefined, metastatic potential. The current 2 cases offer evidence to support the use of this term for those lesions in which a sentinel lymph node biopsy may be prudent.

P213 GROUND GLASS LAFORA-LIKE INCLUSIONS IN HEPATOCYTES IN PAEDIATRIC PATIENTS – A REPORT OF TWO CASES A.M. O’Sheaa, G. Wilsonb, B. Minassianc, E. Cutzb Departments of Pathology, aMount Sinai Hospital b The Hospital for Sick Children c Division of Neurology, Department of Paediatrics and Department of Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada Ground glass inclusions in hepatocytes have been described in a number of clinical settings, most notably in Hepatitis B virus infection, but also in many other conditions including Lafora’s disease, Glycogenosis type IV and fibrinogen storage disorders. In some patients, despite extensive investigation, a precise cause for the inclusions cannot be determined. We describe two such cases seen in children and discuss possible contributing factors. Case 1 was a liver biopsy from a patient with alpha thalassaemia major who was receiving iron chelation

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therapy and case 2 was an autopsy liver sample from a patient with Trisomy 21 who had recently undergone bone marrow transplantation. Both cases showed eosinophilic, weakly PAS-D positive, intracytoplasmic inclusions in hepatocytes which were negative for Hepatitis B surface antigen. Immunohistochemically the inclusions showed positive staining with KM279, a monoclonal antibody developed against Lafora inclusions, which stains polyglucosan (Ref: Journal of Neuropathology and Experimental Neurology 1988, 47, 572–577). Ultrastructural examination revealed intracytoplasmic inclusions composed of degenerate organelles, glycogen and irregular fibrillar structures, different from classical Lafora inclusions. Genetic analysis of the Lafora disease genes was performed in case 2 and revealed no mutations. A possible explanation for the development of inclusions in both cases is a medication effect, as reported with the use of cyanamide (Ref: Histopathology 2001, 39, 60–65). Drug induced inclusions, mimicking Lafora disease, should be included in the differential diagnosis of hepatocyte ground glass inclusions.

P214 RARE HEPATIC TUMORS: A CLINICO-PATHOLOGICAL STUDY WITH LITERATURE REVIEW OF THREE CASES A. Kurian, D. Shaw, J. Radhi Department of Pathology, McMaster University, Hamilton, Ontario, Canada Background: Myelolipomas (ML) and epithelioid angiomyolipomas (eAML) are rare mesenchymal tumors. MLs are composed of a variable mixture of fat and hematopoietic elements that resemble bone marrow while eAMLs are composed of sheets of epithelioid cells with variable fatty and vascular component. Design: We retrospectively examined the files of McMaster University Medical Center, Hamilton, to look for rare or unusual hepatic tumors from 1995 to 2006 .Two cases of eAML and one case of ML were identified. Results: The first case was a 49 year old woman who presented with an enlarging mass in the right lobe of the liver. This was clinically diagnosed as hepatic adenoma. The second case was in a 39 year old woman who presented with a spontaneous hemorrhage into a hepatic mass one month post partum. Both underwent a segmental resection of the liver. On histology both cases were AMLs of the epithelioid type with a strong positivity for HMB-45 and smooth muscle actin. The second case lacked adipose tissue. The ML case was an

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incidental finding in a liver biopsy of a 75 year old male with a history of alcoholic use. The HMB-45 stain was negative in this case. Conclusions: We conclude that epithelioid AML although rare, should be considered in the differential diagnosis of a hepatic mass even in the absence of an adipose tissue component. The expression of both melanocytic and smooth muscle markers by immunohistochemistry are considered diagnostic in AML, which helps distinguish them from ML, hepatocellular carcinoma and hepatic adenoma. Small MLs and AMLs may be seen more frequently in surgical practice due to better imaging studies. The behavior of both tumor types is generally benign but exceptional instances of malignancy in AML have been documented.

ing variants in size when interpreting otherwise benign conditions, such as mediastinal lipomatosis. To our knowledge, no association between mediastinal lipomatosis and dwarfism is known, and specifically there have been no fatal cases of mediastinal lipomatosis reported in individuals with dwarfism.

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Tumours metastasizing to the heart are rare and are infrequently the object of active investigations. Most reported metastases to the heart are of epithelial origin. We report the case of a disseminated non-seminoma germ cell tumour [NSGCT] with myocardial metastases. A 24-year-old man presented with symptoms of hemoptysis, pleuritic pain, and dyspnea of 48 h duration. A large right testicle mass was found on examination and an urgent radical orchiectomy was performed. The tumour, a NSGCT, was composed of teratoma (70%), choriocarcinoma (25%), and embryonal carcinoma (5%). The baseline b-HCG was 191,760 (normal o5 IU/liter) prior to surgery. Diagnostic imaging identified disseminated metastatic disease to the lymph nodes, liver, lungs, spleen, and brain. The patient received whole brain radiotherapy and combination chemotherapy with bleomycin, etoposide, and cisplatinum with a curative intent. However, the patient deteriorated during his first cycle of chemotherapy and died of massive hemoperitoneum. The post-mortem examination confirmed that a splenic hemorrhage from metastatic rupture caused the fatal hemorrhage. Cerebral hemorrhage and hemothorax were also present. Metastatic lesions were composed solely of choriocarcinoma and stained strongly positive for b-HCG and negative for a-FP and CD30. Choriocarcinoma is prone to spontaneous hemorrhage with or without treatment. This report illustrates the aggressive biological behavior of NSGCT with choriocarcinomatous component when presenting at an advanced stage and the rare occurrence of myocardial metastases. The clinical features, diagnostic imaging, gross and microscopic findings, and immunohistochemistry characteristics are presented.

CHRONIC RESPIRATORY DISEASE DUE TO MEDIASTINAL LIPOMATOSIS IN AN INDIVIDUAL WITH DWARFISM: CASE AND AUTOPSY REPORTS A. Yaua,b, P. Alakijaa, K. Lauplanda,c, D. Zuegea a Department of Pathology,University of Calgary, AB, Canada b Department of Oncology, University of Calgary, AB, Canada c Department of Medicine, Calgary, AB, Canada Benign mediastinal tumors in adults rarely compromise respiratory function. In children, mediastinal masses are more likely to be benign but these masses may cause rapidly progressive respiratory distress or fatal respiratory failure. In adults, mediastinal masses are more likely to be malignant and secondary to metastatic disease, most commonly from thoracic or lymphopoietic malignancies. Cases of benign mediastinal masses causing progressive restrictive pulmonary disease in adults are extremely rare. We report the case and the autopsy findings of a 79-year-old man with dwarfism who died due to consequences of restrictive lung disease caused by anterior mediastinal lipomatosis. He presented with progressive dyspnea and pulmonary restriction over 5 years culminating in hypoxemic respiratory failure. This large mediastinal mass weighed 580 g; it occupied the anterior mediastinum and partially encased the oesophagus and the descending thoracic aorta. In the context of a small chest volume due to dwarfism, the mediastinal mass compromised his cardiac and pulmonary functions. This case highlights the importance of consider-

P216 TESTICULAR MIXED GERM CELL TUMOUR WITH MYOCARDIAL METASTASES A. Yaua,b, P. Alakijaa, B. Currya, T. Chenga,b, B.W. Winstona a University of Calgary, b Tom Baker Cancer Center, Calgary, AB, Canada

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P217 THE CLINICAL CONSEQUENCES OF GENE TRANSLOCATIONS IN PROSTATE CANCERS: A FLUORESCENT IN SITU HYBRIDIZATION STUDY ON TISSUE MICROARRAYS A. Rajputa, M. Millerb, A. De Lucab, J. Palmerc, N. Boydb, A. Hurtado-collc, L. Fazlic, M. Gleavec, M. Coxc, D. Huntsmana,b a Genetic Pathology Evaluation Center at Vancouver General Hospital b British Columbia Cancer Agency, Vancouver, British Columbia c Prostate Center at Vancouver General Hospital Aim: To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in prostate cancers of varying Gleason grades and to validate the clinical consequences through the study of clinically annotated prostate tissue microarrays (TMAs). Background: It has been recently reported that prostate cancers frequently over express the ETS transcription family members, ETV1 and ERG (Tomlins et al. Science 2005). Eighty percent (23/29) of such ETS over expressing prostate cancers carry a chromosomal rearrangement caused by the translocation of the 5’ end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3’ end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG. Materials and Methods: Fluorescent in situ hybridization (FISH) was performed on a clinically annotated prostate cancer TMA composed of 84 cases. The TMA contained cases of varying grades of prostate cancers and benign prostate hyperplasia (BPH) linked to outcome data. Two independent assays, a TMPRSS2 bust-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. RT-PCR confirmation of positive cases and correlations with outcome is ongoing. Results: In 60/84 cases, more than 50 epithelial nuclei gave clear FISH signals and were deemed scorable. Our analysis revealed the presence of gene rearrangements involving TMPRSS2 and ERG in 21/55 (38.2%) prostate cancers. These translocations were seen preferentially in cases with high grade prostate cancers with Gleason scores 3 (10/18, 55.6%), 4 (5/11, 45.5%) and 5 (6/16, 37.5%). None of the cases with BPH (n ¼ 5) (not significant due to small numbers) or low grade cancers with Gleason score 2 (n ¼ 10) (p ¼ 0.017) showed the presence of fusion product. These findings reaffirm the observations by Tomlins et al. that there were no rearrangements in cases of BPH. Absence of fusion product in low grade cancers is a novel finding of this study. Five other cancers showed breaks in TMPRSS2 gene by bust-apart assay but no

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fusion with ERG or ETV1 or other genes such as FLI-1 or ETS2, suggesting that other genetic partners may be involved in the rearrangements. Conclusion: TMA based FISH analysis of 84 unselected prostate cancers involving gene rearrangements of TMRSS2 with ETS transcription factors showed the fusion product in 46.7% of high grade prostate cancers. The presence of gene rearrangements occurring in prostate cancers will change the way we think about this common malignancy. In addition to being used as a diagnostic tool, these rearrangements could be used to sub classify these cancers in a clinically meaningful way. The fusion genes and their downstream targets may represent novel therapeutic targets for prostate cancers.

P218 CEREBELLAR LIPONEUROCYTOMA: CASE REPORT A. Al Habeeba, J. Proviasb a McMaster University b Hamilton General Hospital, Hamilton, Ontario, Canada 40 years old woman with a 9 months history of a diffuse headache, presented with exacerbation of her symptoms. CT scan demonstrated an ill-defined poorly enhancing cerebellar lesion which was resected. Histologically, the tumor was cellular with isomorphic round cells and round to oval nuclei. Some cells demonstrated clear cytoplasm resembling oligodendrocytes admixed with focal lipidized tumor cells. There was no mitosis, necrosis or microvascular proliferation. These tumors are believed to have a favorable prognosis.

P219 THE CANADIAN STANDARDS ASSOCIATION AND LABORATORY MEDICINE B. Fernandes Department of Laboratory Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Canada Aim: To promote quality in laboratory medicine by raising awareness of Standards. What are Standards? Standards stipulate requirements for use, safety, and/ or performance of products, processes and services. They may outline industry guidelines and good practices. What systems exist to establish standards in Canada? The Standards Council of Canada (SCC) is a crown corporation that accredits standard development

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organizations and verify that they have the resources, structures and expertise to develop trustworthy services. The SCC approves National Standards of Canada and also represents Canada in the International Standards Organization. The Canadian Standards Association (CSA) is one of four not-for-profit, nationally accredited standards development organizations in Canada. The CSA is composed of over 9000 members working in over 400 Technical Committees that are responsible for Standards Development, Registration and Certification. The CSA has published numerous standards in many areas including Public Safety, Occupational Health and Safety, Health Care, Business Management, Built Environment and Electrical/Electronics. What impact does the CSA have on the practice of Laboratory Medicine? The CSA has published many Standards that impact on different aspects of the practice of Laboratory Medicine. These include: Applications of Electricity in the Laboratory, Biological Evaluation of Medical Devices, Blood and Blood Components, Health Care Facility Engineering, Health Information Systems, Medical Laboratory Systems and Quality Management. The CSA-Z 252 Technical Committee adopted the ISO Standards 15189.2003 (Medical Laboratory- Particular Requirements for Quality and Competence). This standard (CAN/CSA-Z 15189-03) was used to develop the Ontario Laboratory Accreditation system. How can laboratory physicians participate in the Canadian Standards Association? Become knowledgeable about the standards that impact on the practice of laboratory medicine. Make key standards document (such as CAN/CSA-Z 1518903) available and accessible to all members of the laboratory staff. Participate in the public review of draft documents by offering comments on the CSA website. P220 AN IMMUNOHISTOCHEMICAL COMPARISON OF OVARIN CANCERS TESTED FOR GERMLINE BRCA1/BRCA2 MUTATIONS B. Djordjevica,d, A. Tonea,d, H. Begleya, J. Murphya, B. Rosena, J. McLaughlinb, S. Narodc, P.A. Shawa,d a University Health Network b Mount Sinai Hospital c Centre for Research in Women’s Health d Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1L5 Ovarian carcinomas in BRCA1/2 mutation carriers are predominantly serous and high grade with frequent p53 overexpression. However, distinction of mutationassociated carcinomas from non-hereditary serous carcinoma is not possible using morphologic criteria

alone. This study aims to further characterize BRCA1/2 tumors by immunohistochemical (IHC) expression of cell cycle regulators and DNA repair proteins. Tissue microarrays using triplicate 0.6 mm cores were created from paraffin blocks of 102 tumors with known germline mutation status. IHC was performed, and percentage of positive cells, staining intensity, and histoscores were determined. Differences in expression were assessed for each antibody, comparing BRCA1/2 tumors to tumors negative for mutations. All BRCA1/2 tumors (n ¼ 38) and 42 BRCA negative cases (65%) were of serous type. Positive IHC results for BRCA1/2 tumors were: p53 81%; p27 89%; BAX 70%; Bcl-2 14%; p-p53 54%; chk-2 62%; MIB1 89%. Results for p53 (p ¼ 0.0008), p27 (p ¼ 0.029) and p-p53 (po0.0001), but not BAX, Bcl-2, chk-2 or MIB1, significantly differed from the non-carrier staining patterns. The differences in p27 (p ¼ 0.017) and p-p53 (p ¼ 0.0011) remained significant when compared to only serous cancers in non-carriers. Ovarian tumors in BRCA1/2 mutation carriers are more likely to be serous, and, when compared to the non-carrier group, have significantly increased p53, p-p53 and p27 staining as assessed by immunohistochemistry. These differences cannot be entirely attributed to differing histologic types in the non-carrier group, as the increased expression of p-p53 and p27 remains significant when compared to only serous carcinomas in non-carriers. P221 THE SIGNIFICANCE OF C-KIT EXPRESSION IN PHYLLODES TUMORS B. Djordjevica, W. Hannab a Sunnybrook & Women’s College Health Sciences Centre b Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, M4N 3M5 The expression of c-kit, a protooncogene tyrosine kinase receptor (CD117), in phyllodes tumors of the breast has been the subject of recent investigations with the aim of determining the effectiveness of Imatinib mesylate (Glivec, Gleevec, ST571) as a therapeutic agent for phyllodes tumors. We examined stromal c-kit expression by immunohistochemistry in 71 fibroepithelial lesions including mastectomy and lumpectomy specimens of 27 benign, 10 borderline and 6 malignant phyllodes tumors, 6 fibroadenomas and 4 fibroadenomas with cellular stroma, and biopsy specimens of 18 fibroepithelial lesions. C-kit positivity was noted in the cytoplasm of the epithelial elements in all cases. 69 out of the 71 cases demonstrated no positivity for c-kit in the stroma. One borderline and one malignant phyllodes tumor showed faint stromal staining, but, according to

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our criteria, the staining intensity was insufficient for the cases to be interpreted as positive. Further mutational analysis of these two tumors showed them to be negative for c-kit and PDGFRA mutations. The absence of c-kit in the stromal elements suggests that c-kit does not play a role in the pathogenesis of fibroepithelial lesions including phyllodes tumors. Therefore, the newly developed tyrosine kinase inhibitors would likely not be valuable in the treatment of phyllodes tumors.

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Erdheim-Chester disease (ECD) is a rare form of nonLangerhans cell histiocytosis characterized by widespread permeation of the skeleton and viscera by lipidladen histiocytes, leading to osteosclerosis and fibrosis respectively. We report the case of a 53-year-old woman who presented with a progressively enlarging mass in her posterior right thigh. Biopsy identified lipogranulomatous inflammation and the possibility of ECD was raised. Physical examination and imaging – including MRI of the head, CT scan of the chest, abdomen and pelvis, and a bone scan – all failed to identify multi-system disease. Consequently, the patient was treated by wide surgical resection of the lesion, and the diagnosis of ECD was confirmed. To our knowledge this is the third documented case of ECD involving muscle; moreover, the localized nature of the lesion represents an extremely unusual presentation for this disease.

ANGIOMYOFIBROBLASTOMA-LIKE LESION OF THE MALE GENITAL TRACT – AN IMMUNOHISTOCHEMICAL PROFILE OF TWO CASES B. Djordjevic, T. Van der Kwast Mount Sinai Hospital, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada Angiomyofibroblastoma-like lesion of the male genital tract is a rare entity with an incompletely established immunohistochemical profile and histogenesis. We report two cases, one arising as a 7.0 cm paratesticular mass in a 25-year old patient and the other as a 2.0 cm spermatic cord mass in a 67-year old patient. Both tumors are well-circumscribed, highly vascular and have a myxo-fibrous stroma. The paratesticular mass contains a population of plasmacytoid tumor cells, whereas the spermatic cord mass exhibits infiltration by a large number of plasma cells. The paratesticular mass contains thin-walled vessels, while the spermatic cord mass contains a mixture of thin-walled vessels and vessels with perivascular hyalinization. Both lesions show tumor cells with staining for CD 34, muscle specific actin and vimentin and no staining for CD 31, factor VIII, desmin, smooth muscle actin and caldesmon. Both stain for the androgen receptor, but not for the estrogen receptor, while only the paratesticular lesion is reactive for the progesterone receptor. Both cases show an unusual cytokeratin 18 expression in the lesional endothelial and perivascular cells. The cytokeratin 18 expression is observed also in the endothelial cells of the vessels of the spermatic cord. This parallel may further corroborate the suggestion by other authors that angiomyofibrobastoma-like lesion of the male genital tract originates from the perivascular stem cell. In addition, the androgen receptor expression may represent a distinguishing feature for this lesion from its female counterpart.

ERDHEIM-CHESTER DISEASE PRESENTING AS AN INTRAMUSCULAR LIPOGRANULOMA B.C. Dicksona, J.S. Wunderb, D.J. Howartha a Department of Pathology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario b Department of Orthopaedics, Mount Sinai Hospital, University of Toronto, Toronto, Ontario

P224 THE ROLE OF EMOTIONAL INTELLIGENCE IN FORMING BOUNDARIES IN THE PATHOLOGY LABORATORY Brent K. Wilde, G. Marcoux A. Saxena Maintenance of healthy workplace boundaries is important for optimizing workplace atmosphere, productivity and morale; boundary violations, in addition to the opposite effects, may lead to disciplinary proceedings. Since Pathology is mostly a non-patient contact specialty, educational sessions involving physician–patient relationships are generally less applicable. The intricacies of the relationships within the laboratory require that this important topic not be overlooked. In the pathology laboratory, relationships are complex and power discrepancies often blurred with the changing dynamics of healthcare governance. The pathologists are accountable not only in their daily interactions but also responsible in their role as laboratory directors. Traditional boundary literature in medicine has focused on boundary maintenance and risk management, based on power discrepancies and does little to address the contextual nature. Emotional intelligence

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(EI) is a flexible intelligence that provides the abilities to identify the context and the abilities to handle the context of boundary issues. Self-awareness and awareness of others, two principles of EI, allow participants to recognize their emotions and the emotions of others as boundaries are approached or crossed. Self-regulation and relationship management, the other two principles of EI, provide the abilities to handle the recognized emotional context by which to avoid boundary violations or minimize the impact of boundary violations. Opportunities for an improvement in EI in the Pathology departments would be mutually beneficial by improving and easing relationships, allowing relationships to occur within their boundaries, and reducing harm from any boundary violations. Developing cases involving workplace boundaries issues in the administrative hierarchy, clinical service, teaching, research and education and open discussion around these is a safe and effective way of learning the required skills. Examples of both exemplary behavior and transgression of boundaries by faculty and residents should be discussed without identification of individuals. Evaluation tools for both formative and summative evaluations, in addition to testing knowledge base about boundaries, need to test actual resident behavior. P225 SOLITARY FIBROUS TUMOUR OF THE ANTERIOR MEDIASTINUM: AN UNCOMMON MEDIASTINAL NEOPLASM B.R. Gannona, K. Reidb, C.D. O’Harac, P.A. Isotaloa a Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, K7L 2V7 b Department of Surgery, Queen’s University, Kingston, Ontario, K7L 2V7 c Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada T5J 5E2 Solitary fibrous tumours (SFTs) are uncommon spindle cell neoplasms originally thought to be restricted to the pleura. Extrapleural SFTs have now been reported throughout the body and are not confined to mesothelial-lined surfaces. The identification of SFTs may be especially difficult when these neoplasms are encountered in unusual extrathoracic sites and when limited diagnostic material is available for interpretation. We describe a 62 year old woman who presented with stridor and an anterior mediastinal mass. The patient had no symptoms of myasthenia gravis. A core biopsy revealed a spindle cell proliferation that was suggestive of a SFT. At thoracotomy, a 10.5
6.5
5.5 cm, encapsulated mediastinal mass was revealed that demonstrated no cardiac or pulmonary involve-

ment. The cross-section of the tumour revealed a white, homogeneous whorled surface with no gross evidence of necrosis. Histologically, the tumour consisted of a spindle cell proliferation characterized by hypercellular and hypocellular spindle cell regions, the latter arranged haphazardly with a rich collagenous background. The periphery of the spindle cell proliferation contained hemangiopericytoma-like vessels. The neoplastic spindle cells were strongly immunoreactive for CD99, CD34, desmin, vimentin and Bcl-2 protein. The neoplastic cells were negative for MSA, SMA and S-100 protein. The differential diagnosis of mediastinal spindle cell neoplasms is extensive and includes fibromatosis, fibrosarcoma, peripheral nerve sheath tumours, thymoma and sclerosing mediastinitis. Despite their rarity in the mediastinum, SFTs can be recognized by their classic patternless morphology and immunophenotypic pattern and can be diagnosed in the absence of pleural or pericardial-based disease. P226 FIRST PRESENTATION OF CLASSIC KAPOSI’S SARCOMA IN THE GASTROINTESTINAL TRACT OF AN ELDERLY HIV-NEGATIVE INUIT MALE B. Balachandraa, E. Tunitskyb, S. Dawoodb, I. Hings Ib, V.A. Marcusa a Department of Pathology1, McGill University Health Centre, Montreal, QC, Canada b Department of Oncology, McGill University Health Centre, Montreal, QC, Canada Kaposi’s sarcoma (KS) is a multicentric low-grade vascular malignancy. In North America, it is usually seen in AIDS and solid organ transplant populations. Classic KS is a subtype that traditionally occurs in elderly HIV-negative males of Mediterranean, Eastern European, and Jewish descent. Patients with classic KS characteristically present with skin lesions in the distal extremities. Involvement of the viscera is uncommon in classic KS, but may occur in the late stages of the disease. We report the first case of classic KS presenting initially in the gastrointestinal tract of an elderly HIVnegative Inuit male. This 61 year-old man from Northern Quebec presented for investigation of a gastrointestinal bleed. Initial colonoscopy revealed a friable ulcerated lesion in the ileocecal valve. Histological examination of the lesion showed a proliferation of bland spindle cells forming interlacing fascicles, with scattered lymphocytes, neutrophils and macrophages. The differential diagnosis included ulcer bed with florid granulation tissue versus a spindle cell tumor, possibly a gastrointestinal stromal tumor. A further upper endoscopy showed a hemorrhagic polyp in the stomach. Similar to

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the ileocecal valve lesion, the gastric polyp was composed of bland spindle cells forming interlacing fascicles. In addition, the polyp showed slit-like spaces filled with red blood cells, associated with chronic inflammatory cells. Immunohistochemical study of the gastric polyp showed positive staining for vimentin, CD 34, and Human Herpes Virus 8 (HHV 8). Further staining of the initial ileocecal valve lesion with HHV 8 also showed positive nuclear staining. The histological features and positive HHV 8 staining confirmed a diagnosis of Kaposi’s sarcoma at both sites. Investigations into the immune status of the patient were undertaken, including an HIV test. All laboratory work showed an immunocompetent, HIV-negative male. Initial dermatological examination showed no skin lesions. Since the diagnosis, the patient developed additional histologically confirmed KS in the gastrointestinal tract and inguinal lymph nodes. Classic KS skin lesions were noted 20 months after the patient’s initial gastrointestinal presentation. The patient underwent chemotherapy, but the treatment was stopped due to worsening lung function. The patient is alive 30 months after initial presentation.

P227 PLASMA TRANSFUSION PRACTICE DETERMINATION USING DATABASE METHODS IN THE CAPITAL DISTRICT HEALTH AUTHORITY, NOVA SCOTIA C. K. Chenga,b, D. Tretheweya, I. Sadeka,b a Capital District Health Authority, Halifax, Nova Scotia, Department of Pathology, bDalhousie University, Halifax, Nova Scotia, Canada Background: Transfusion auditing is crucial for managing blood products in transfusion services. Both concurrent and retrospective audits require significant resources, coordinated effort and time from technologists and clinicians to gather and re-enter relevant data related to transfusion. With commonly available database software, we have developed a pilot process to retrospectively audit clinical practice in a high volume plasma transfusion service at the Capital District Health Authority, in Nova Scotia, Canada. Methods/Materials: Using Cerner Command Language query, clinical, plasma transfusion and hematological variables were extracted into database software during the period of January 7-31, 2006. Data encompassed all plasma transfusions at the Capital District Health Authority (Nova Scotia). Results: During this pilot study period, there were 199 plasma transfusion episodes, involving 62 patients, some being transfused on multiple occasions. Of these, 16/

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199(8%) were for plasmapheresis, while the majority 183/199(92%) were transfused for other indications. Of these 183 transfusion instances, there were transfusions to 56(31%) females, and 127(69%) males, having a mean age of 49.3years (16-91years). The average dose of plasma was 567 ml, or 1.2 units. Pre-transfusion coagulation studies were ordered 4.6 hours pre-transfusion, with mean INR, PT, and PTT being 2.0, 28 seconds and 40 seconds respectively. Post-transfusion studies were ordered 3.9 hours after transfusion, in 168/ 183(92%) of cases, with a mean change in INR, PT, and PTT of -0.4, -7.7 s, and -3.7 s respectively. There was a significant number of plasma transfusions, 91/183(50%) occurring in the population with INRo1.7. Conclusions: Database methods allow for efficient transfusion practice auditing. In the future, this data can be made more granular and the results can then be used to educate medical staff about optimal plasma transfusion practice. P228 SPONTANEOUS APOPTOSIS IN LARYNGEAL CARCINOMA IS INDEPENDENT OF BAK AND BAX PROTEIN EXPRESSION G.G. Chen, A.C. Vlantis, E.C.W. Chak, H.C. Liu, C.A. van Hasselt Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong The growth of neoplasia is determined by the proliferation and loss of cells. The aim of this study is to determine the frequency of apoptosis in laryngeal carcinomas and to examine its relationship to the expression of Bcl-2 family proteins, which play an important role in the growth and biologic behavior of tumors. The materials studied are 39 cases of laryngeal caner tissues. Apoptotic cells were determined by the TUNEL method. The expression of Bak, Bax and Bcl-2 was immunohistochemically examined. The relationships between apoptosis and the Bak, Bax and Bcl-2 proteins were studied. The expression of both Bak and Bax was frequently detectable in tumor tissues but the levels of both were much lower when compared with non-tumor tissues. However, the expression of Bcl-2 was not different between tumor and non-tumor tissues. The frequency of spontaneous apoptosis was lower in tumor tissues than in non-tumor tissues but it was not significantly related to any of these three protein expression. It was found that the expression of Bak was decreased in the moderately differentiated tumors compared with well differentiated ones. In contrast to Bak, the level of Bcl-2 was increased in the moderately differentiated tumors compared with well differentiated

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ones. The result is in line with the finding decreased Bak in tumor tissues and indicates that the reduction in Bak may associate with more malignant laryngeal tumors. The lack of correlations between apoptosis and the expression of Bcl-2 family proteins suggests that the spontaneous apoptosis in laryngeal carcinoma is a complicated process and that factors other than Bak, Bax and Bcl-2 should also participate it. (This study was supported by CUHK direct Grant No. 2041167). Keywords: Laryngeal cancer; Apoptosis; Bak, Bax: Differentiation P229 INVASIVE ONCOCYTIC CARCINOMA WITH HEPATOID FEATURES ARISING FROM INTRADUCTAL ONCOCYTIC PAPILLARY NEOPLASM OF PANCREAS C-H. Chena, D.J. Hurlbuta, D. Jalinkb a Department of Pathology and Molecular Medicine, Kingston General Hospital, Queen’s University, Kingston, Ontario, Canada b Division of General Surgery Kingston General Hospital, Queen’s University, Kingston, Ontario, Canada Oncocytic carcinoma is a rare variant of invasive pancreatic ductal carcinoma characterized by cells with eosinophilic cytoplasm containing abundant mitochondria. These tumours are thought to arise from intraductal oncocytic pancreatic neoplasm (IOPN). We describe a rare case of invasive oncocytic pancreatic carcinoma with hepatoid features arising from pancreatic IOPN. Clinical: A 52-year-old woman with family history of gallbladder disease was investigated for recent onset nausea and abdominal discomfort. Imaging revealed a solid and cystic lesion in the head of the pancreas without bile duct obstruction. Following EUS-FNA, a pylorus-preserving pancreatico-duodenectomy was performed. Pathology: Pre-op FNA cytology showed atypical epithelioid cells with features suspicious for acinar cell carcinoma. The resection specimen revealed a circumscribed 7.5
5
5 cm solid tumour with central necrosis in the pancreatic head and directly invading the duodenum with focal mucosal ulceration. Invasive tumour was composed of solid lobules of oncocytic cells separated by fine fibrovascular septae. Electron microscopy showed numerous mitochondria within tumour cells. Focally tumour cells demonstrated hepatoid differentiation with eosinophilic, cytoplasmic glo-

bules (D-PAS and A1AT positive) and positive immunostaining with HepPar-1 and focally CEA (pericanalicular pattern). Invasive carcinoma was in continuity with a small focus of IOPN. Grossly the IOPN had a cauliflower-like appearance, distinct from the solid growth of the invasive tumour. Discussion: Intraductal oncocytic papillary neoplasm (IOPN) is a precursor lesion for invasive oncocytic pancreatic carcinoma. Detailed sampling of the resection specimen was needed in this case to demonstrate the IOPN component, which was small. Hepatoid features have not been previously described in this rare tumour. P230 USE OF ELASTIC STAINS TO HIGHLIGHT VENOUS INVASION IN COLORECTAL CARCINOMAS C.J. Howlett, E.J. Tweedie, D.K. Driman Department of Pathology, London Health Sciences Centre and University of Western Ontario, London, Ontario, Canada Background: Large vessel (venous) invasion is an important prognostic factor in colorectal carcinoma because of the positive association with liver metastases. We have noted that use of an elastic stain can be helpful in highlighting venous invasion in sectioned colorectal carcinomas. Objective: To compare hematoxylin and eosin stained slides with Movat’s pentachrome stained slides for the diagnosis of venous invasion in colorectal carcinomas. Methods: Colorectal cancer cases reported as negative for venous invasion were selected from departmental files. The slides were reviewed; 59 tissue blocks that were either negative (n ¼ 56) or suspicious (n ¼ 3) for venous invasion were selected for Movat staining. Statistical analysis was performed with the w2 test. Results: Of the 3 cases suspicious for venous invasion, 3 were confirmed to show venous invasion using the elastic stain. Of the 56 cases considered to be negative for venous invasion, 15 showed unequivocal venous invasion using the elastic stain (po0.001). Conclusions: The detection of venous invasion is significantly aided by the use of an elastic connective tissue stain. Consideration should be given to the liberal use of such stains in cases that are suspicious or negative for large vessel (venous) invasion, given the importance of identifying this important prognostic factor.

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FIBROMYXOID SARCOMA OF THE MAXILLA – A CASE REPORT C.J. Howletta, W. R. Leeper, K. Fungb, B.M. Wehrlia a Department of Pathology, University of Western Ontario, London, Ontario, Canada b Department of Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada

COMBINED AUTOLOGOUS GRAFT-VERSUS HOST DISEASE AND VENO-OCCLUSIVE DISEASE IN THE LIVER AFTER STEM CELL TRASNPLANT: A CASE REPORT C.T. Fautha, K. Burakb, Z.H. Gaoa, E.W. Matshesa a Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada T2N 2T9 b Department of Hepatology, University of Calgary, Calgary, Alberta, Canada T2N 2T9

Background: Low-grade fibromyxoid sarcoma (LGFMS) of the head and neck is extremely uncommon, with most cases arising in the soft tissues of the neck. The spindle cells of LGFMS have a ‘‘deceptively bland’’ histology, with a whorling growth pattern in a mixed collagenous and myxoid background. Approximately 10% show areas of greater cellularity and nuclear atypia. LGFMS typically behaves in an indolent pattern but may recur or metastasize, sometimes many years after initial presentation. We describe a case of LGFMS of the maxilla in a 72 year-old woman who presented with a history of loose teeth and cheek numbness. Imaging showed an illdefined mass with extensive destruction of the maxilla, and infiltration into the hard palate and maxillary antrum. Initial biopsies showed a proliferation of spindle cells of low to moderate cellularity with minimal atypia in a background of mixed fibrous and myxoid stroma. On subsequent resection, histologic examination revealed areas of increased cellularity, atypia and mitotic activity. The patient returned eight weeks later with local recurrence and brain metastases. She died 8 months after initial diagnosis. Conclusions: LGFMS is a rare, low-grade tumour, usually with an indolent course. Although a small fraction of these tumours show intermediate grade areas, their prognostic significance is unclear. Here we present a LGFMS of the maxilla, histologically showing intermediate grade areas. This case illustrates the potential aggressiveness of these tumours, particularly in the head and neck region, and the need for primary maximal resection. The role of adjuvant treatment remains to be elucidated.

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Complications in the liver following autologous hematopoietic stem cell transplantation can present as veno-occlusive disease or graft versus host disease (GVHD). This report describes a patient with the combined pathologic processes of autologous GVHD and veno-occlusive disease. The patient is a 51 year old male involved in a clinical trial, using autologous peripheral blood stem cell transplantation following aggressive chemotherapy to treat anaplastic oligodendroglioma. At 40 days after the transplant procedure, he presented with ascites, failure to thrive, and elevated cholestatic liver enzymes. Sections of transjugular liver biopsy demonstrated two distinct processes: (1) mild portal inflammation with cholestasis and bile duct damage consistent with graft versus host disease, (2) marked central congestion, with paracentral hepatocyte dropout and pericentral inflammatory reaction. The sinusoidal endothelial cells were damaged, with some sinusoidal spaces filled with fibrin and debris from red blood cells. These changes were in keeping with venoocclusive disease. This is the first reported case with the combined pathologic processes in the liver following autologous hematopoietic stem cell transplantation. It is not only a diagnostic challenge, but also may indicate a distinct complex pathogenic process. P233 RENAL EPIDERMOID CYST, A VERY RARE ENTITY D. Diona, S. Maheshwarib, K. Sircara a Department of Pathology, Montreal General Hospital, McGill University Health Center, Montreal, Quebec, Canada H3G 1A4 b Department of Radiology, Montreal General Hospital, McGill University Health Center, Montreal, Quebec, Canada H3G 1A4 Epidermoid cyst is commonly seen in hair-bearing skin. It is also described in the palm, sole, central nervous system, spleen, and testis. Only 5 cases of renal

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epidermoid cysts have been reported in the english literature affecting patients from 4 to 74 years-old. We report a case of a 72 year-old woman with chronic end stage renal disease undergoing peritoneal dialysis. She had left recurrent pyelonephritis and left hydronephrosis documented on ultrasound. The abdominal CT scan and MRI were suspicious for underlying malignancy. A previous CT scan dating from 1998 had not shown this latter abnormality. A left nephrectomy was done in this context of recurrent pyelonephritis with non functioning and nephrosclerotic kidney. Cut section revealed a 1 cm well circumscribed lesion within the urinary collecting system filled with white soft material. Features of classic epidermoid cyst was observed by microscopy. We report here the first patient with ESRD diagnosed with a renal epidermoid cyst. P234 A CASE REPORT OF A VIABLE ABDOMINAL GESTATION D. Koutsougiannisa, R. Nataleb, L. Gienb, V. Hanb, M. M. Weira a Department of Pathology, London Health Sciences Centre & University of Western Ontario, London, Ontario, Canada N6A 5A5 b Department of Obstetrics & Gynecology, London Health Sciences Centre & University of Western Ontario, London, Ontario,Canada N6A 5A5 c Department of Neonatology, London Health Sciences Centre & University of Western Ontario, London, Ontario,Canada N6A 5A5 Introduction: Abdominal gestation is rare, representing 1% of all ectopic gestations. Early diagnosis is essential to avoid the complications of maternal hemorrhage and fetal mortality. Differentiation between primary and secondary abdominal gestation may be difficult. Purpose: We report a case of a viable initially unsuspected abdominal pregnancy diagnosed at 34 weeks, review the literature on abdominal gestation and discuss the distinction of primary from secondary abdominal gestation. Results: Clinical Findings: The patient had recurrent abdominal pain of unknown etiology, and an abdominal gestation was identified at 34 weeks by magnetic resonance imaging. Intra-operative separation of the placenta from the external uterine fundus resulted in hemorrhage requiring hysterectomy. The adnexa were left in situ. Results: Pathological Findings: The 270 g uterus had a superior fundal hemorrhagic defect, which did not communicate with the endometrial cavity. No bicornuate uterus, or other structural anomaly was seen. Microscopy showed a fundal implantation site involving

the myometrium and serosa. The membranes included omentum, and showed amnion nodosum. Discussion & Conclusions: Pre-operative diagnosis of abdominal pregnancy is difficult, and patients may present with shock and hemoperitoneum. There are few reports of viable near-term extrauterine pregnancies with successful outcome. Implantation sites reported include omentum, spleen, and pouch of Douglas. Secondary abdominal pregnancies are more frequent than primary and associated with tubal abortion, or rupture. In this case, it was not possible to determine the method of implantation due to uterine distortion and absent adnexa. P235 HANGING DEATHS IN ONTARIO: COMPARATIVE ANALYSIS E. Tugalevaa, M.J. Shkrumb, D.R. Gorassinib, B.A. McLellanc a Department of Pathology, London Health Sciences Centre b Department of Psychology, King’s College, The University of Western Ontario, London, Ontario, Canada c Office of the Chief Coroner, Toronto, Ontario, Canada The frequency of neck injuries in deaths by hanging is controversial. In the literature, the range is wide, varying from 0 to 76.6% for hyoid and laryngeal fractures. Multiple factors account for this variation. Complete neck examination and accurate recording of not only positive but also negative findings are important. The purpose of this study was to determine whether the frequency of hyoid/laryngeal injuries varied depending on the location of the autopsy i.e forensic unit, teaching or community hospital. From 755 cases of hanging deaths in Ontario during 2-year period of 1998–1999, 700 cases were studied of which 632 had a complete autopsy, and 68 were limited to external examination only. In 55 cases, no postmortem examination was conducted. Two hundred and forty cases (34.3%) were performed in forensic facilities of which 72.9% were complete autopsies, and 27.1% were external examinations, 48 cases (6.9%) – in teaching hospitals (all complete autopsies) and 412 cases (58.9%) – in community hospitals (only 3 cases were limited to external examination). The frequency of hyoid/laryngeal fractures was 7.3% (46 cases). It was distributed between forensic, teaching and community facilities as follows: 7.4%, 16.7% and 6.1%, respectively. The frequency of fractures reported in specialized forensic facilities reached 10.6% if the Forensic Pathology Unit in Toronto was excluded from analysis. The lower frequency of fractures (2.8%) registered in this unit could be explained by different

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demographics of cases that underwent complete postmortem examination. Higher frequency of fractures correlated with a higher percentage of cases in which definite comment was made upon presence or absence of specific injury and its site. P236 COMPARATIVE WORKLOAD ANALYSIS E. Ravinsky, J. Klein, H.R.Wightman, M.J. Willard, J.G. Gartner Diagnostic Services of Manitoba, 1502-155 Carlton St., Winnipeg, MB, R3C 3H8 When amalgamation of anatomic pathology sites occurs, assurance that pathologists at each site have an equitable workload is essential to a smooth transition. It is important that the sites being amalgamated have input into the evaluation process. Six Manitoba public anatomic pathology sites are being amalgamated under a single corporation, Diagnostic services of Manitoba (DSM). DSM struck a committee made up of representatives from each of the sites to produce an evaluation process that would be accepted at all sites. The evaluation is based on assigning each specimen a complexity level with a weighted figure assigned to that level. Other activities such as teaching, conferences, consults, administration, and quality assurance are also assigned figures. The figures for each site are added up and divided by the number of equivalent full time positions at that site.

P237 CHORDOMA ARISING IN A MATURE CYSTIC TERATOMA OF THE OVARY F. Las Heras, K.P.H. Pritzker, T.J. Colgan Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada Mature cystic teratoma of the ovary (MCTO) is the most common type of ovarian teratoma and also the most frequent tumor originating from germ cells. It is usually diagnosed in early adulthood and, by definition, is composed of well-differentiated tissues which originate from all three layers. Unusual types of tissues can be found in MCTO, such as kidney, adrenal and prostatic tissue. Malignant transformation is reported in less than 2% of teratomas. Squamous cell carcinoma is the most common malignancy arising in these otherwise benign tumors. We present the first case of MCTO containing a chordoma. The notochordal derivation was supported by immunohistochemical

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staining. Interphase fluorescence in situ hybridization technique (IP-FISH) showed that 19% of the nuclei of the MCTO displayed polysomy for the chromosome X. IP-FISH, performed for chromosome 7, showed mosaicism in 28% of the chordoma nuclei examined. These results are concordant with previous studies, showing chromosomal anomalies in chromosomes X and 7 in MCTO and chordomas, respectively. Keywords: Cystic teratoma of the ovary; Notochord; Chordoma; Malignant transformation; Ovarian cancer P238 ENDOSCOPIC BIOPSY DIAGNOSIS OF GASTROESOPHAGEAL JUNCTION PRIMARY HODGKIN LYMPHOMA: A CASE STUDY G.J. Hornea, S.A.C. Medlicotta, J. Lateganb, A. Mansoora, R. Laic, P. Beckb a Department of Pathology and Laboratory Medicine, University of Calgary, Calgary Alberta b Department of Internal Medicine, University of Calgary, Calgary Alberta c Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada Objective: Gastrointestinal (GI) tract is a common site of extranodal lymphoma, yet primary Hodgkin lymphoma (HL) of the stomach or esophagus is extremely rare. The diagnosis of HL on endoscopic biopsy can be challenging, and most published examples were verified only after surgical resection. We report a rare case of a gastroesophageal (GEJ) primary HL to advocate the use of immunohistochemical (IHC) markers, PAX-5 and MUM-1, in establishing this diagnosis and advocate that a mucosal biopsy diagnosis be a criterion for confirming a visceral primary origin HL. Results: On H+E sections, sheets of dyscohesive tumor cells expanded the lamina propria and submucosa and displayed a varied morphology including: bizarre multilobated nuclei and rare bilobed nuclei reminiscent of Reed-Sternberg (RS) cells. The IHC profile of these cells included strong CD30 staining and negative CD45, CD20, CD3, CD5, ALK-1 and pancytokeratin. Subsequent IHC revealed weak PAX-5 and strong MUM-1 tumor cell staining. EBV in situ hybridization was positive and flow cytometry did not identify a monoclonal B- or T-cell population. Conclusions: We report a rare case of a GEJ primary HL diagnosed with the assistance of IHC markers, PAX-5 and MUM-1. These antibodies can help delineate the pathognomonic HL RS cells, when assessing limited biopsy material. As GI lymphoid tissue is almost exclusive to the mucosa and submucosa, primary GI lymphoma should be amenable to transmucosal biopsy procedures.

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IMMUNOHISTOCHEMICAL DIFFERENCES BETWEEN HEPATOCELLULAR CARCINOMA ARISING IN CIRRHOTIC AND IN NON-CIRRHOTIC LIVER G.J. Horne, T. Rad, M. Chow, S.J. Urbanski, Z.H. Gao Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada

CHARACTERIZATION OF THE BASAL PHENOTYPE OF BREAST CANCER BY TISSUE MICROARRAYS Garcia de la Fuentea, F. Jolicoeura, A. Robidouxb, I. Gorskaa, D. Balickic, L. Gabourya a Department of Pathology and Cellular Biology, CHUM, Universite´ de Montre´al b Department of Surgery, CHUM, Universite´ de Montre´al c Department of Medicine, CHUM, Universite´ de Montre´al

Background: The major risk factor for the development of hepatocellular carcinoma (HCC) is liver cirrhosis associated with chronic HBV/HCV infections, aflatoxin B, and various metabolic disorders. However, up to 40% of HCC cases in North America arise in noncirrhotic liver, which confers a different biological behavior. It is unclear whether immunohistochemical differences can be found between HCCs arising in cirrhotic and non-cirrhotic liver. Methods: Tissue micro-array composed of 20 normal livers (NL), 20 cirrhosis-only livers (CL), 20 HCC-C tumor (HCC-CT) and adjacent background cirrhotic liver (HCC-CB), 20 HCC-NC tumor (HCC-NCT) and adjacent background non-cirrhotic liver (HCC-NCB) were stained immunohistochemically for CK7, CAM5.2, CK19, CK20, AE1:3 and CD56. Results: Intensity of staining in tissue micro-array (mean in 0-3 tiered grading system) NL

CL

HCCCB AE1:3 0.03 0.56 0.25 CK19/ 0/0.03 0.13/0.28 0.30/0.23 CK20 CK7 0.03 0.94 0.33 CD56 1.64 1.88 1.47 CAM 1.03 1.59 1.41 5.2

HCCCT 0.26 0.12/0.13

HCCNCB 0.19 0.15/0.06

HCCNCT 0.14 0/0.12

0.44 1.41 1.29

0.25 1.62 1.12

0.09 1.39 0.56

Conclusion: Statistically significant differences in CK7 and CAM5.2 profiles were found between HCC-CT and HCC-NCT, suggesting their role in differential diagnosis and pathogenesis. CD56 shows extensive staining of all liver tissues including HCC which is previously unreported.

The basal breast carcinoma, a subtype of breast cancer ignored until recently, is now a central research topic in mammary pathology. Indeed, the treatment of this particularly aggressive entity has yet to be optimized. Hypothesis: The basal breast carcinoma is still poorly defined and characterized; its definition shows discrepancies in the literature. Further studies are needed for better characterization, identification and treatment of the basal breast cancer. We also seek to evaluate its prevalence in a representative cohort of CHUM patients. Materials and methods: We have retrospectively selected cases of high grade (1 0 0) and low grade (40) breast carcinomas from the tissue bank of the CHUM. We have constructed tissue microarrays from corresponding paraffin blocks, taking 4 cores of 0.6 mm from each tumor. Tumor areas included in the tissue microarray were selected based on the immunostaining of three basal markers (CK14, CK17, a-SMA). We are now evaluating the expression of these markers, of other recognized basal phenotype markers (CK5, p63, HER1, P-cadherin), of new possible basal markers (MEK1, MEK2), and of standard breast cancer markers (ER, PR, Ki-67, HER-2) with our tissue microarrays. The results are correlated to the clinico-pathological data. Results: The staining pattern based on CK14, CK17 and a-SMA has allowed us to detect positive staining tumors for these markers (5% among low grade tumors, 25% among high grade ones). All positive tumors are hormone receptor negative, and most, but not all, are HER2 negative. The pattern of staining is heterogeneous between tumors. Discussion: The basal phenotype is a complex and heterogeneous one. The definition of the basal breast carcinoma has to reflect this reality and to include clinically relevant criteria. High output analysis techniques, like the evaluation of expression of several antibodies in tissue microarrays, seems well indicated for this purpose.

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P241 EVALUATING VITREOUS HUMOR BIOCHEMISTRY IN POST MORTEM INTERVAL ESTIMATION OF VARIOUS CAUSES OF DEATH J. Kalra, M. Qureshi, A. Mohamed, A. Mulla Department of Pathology, College of Medicine, University of Saskatchewan and Royal University Hospital, Saskatoon, Saskatchewan, S7N 0W8 Vitreous humor has been well recognized as an important investigative fluid in forensic pathology. We have previously reported that no significant between-eye differences existed for various vitreous biochemical constituents at identical postmortem interval (PMI). The objective of this study was to investigate the utility of vitreous biochemistry in estimating PMI and to evaluate its usefulness in different diagnostic subgroups of death. Vitreous humor samples were collected through a scleral puncture from 61 subjects with precisely documented time of death (PMI range, 4.5–84.3 h). Based on the specific pathological cause of death as recorded in the final autopsy report, subgroups were devised that included deaths associated with cardiovascular causes (n ¼ 21), malignancies (n ¼ 8) and acute trauma (n ¼ 7). The vitreous humor was analyzed for sodium, potassium, chloride, calcium, magnesium, urea, creatinine, glucose and lactate on an LX-20 Analyzer (Beckman-Coulter). Vitreous humor was also analyzed for hypoxanthine and xanthine using a colorimetric method. It was observed that in the overall group, a significant correlation existed between vitreous potassium (R ¼ 0.731;Po0.0001), hypoxanthine, (R ¼ 0.450; P o0.0001), xanthine (R ¼ 0.590; P o0.0001), lactate (R ¼ 0.508; P o0.0001), calcium (R ¼ 0.33; P o0.01) and PMI. In the deaths associated with cardiovascular causes, vitreous potassium, hypoxanthine, xanthine and lactate were significantly correlated with PMI. In deaths associated to malignancy, vitreous potassium and calcium were significantly correlated with PMI. In the traumatic deaths, only vitreous potassium exhibited a significant correlationship with PMI. Vitreous potassium was the only constituent that significantly correlated with PMI in all the classified subgroups. The correlationship was strongest in the traumatic deaths (R ¼ 0.956; Po0.05) as compared to other subgroups. In conclusion, the present study emphasizes a central role for vitreous potassium as a superior biochemical marker in PMI determinations for a spectrum of causes of death. The other identified biochemical markers can be useful adjuncts to potassium in certain particular subgroups of death.

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P242 MEDICAL ERRORS IN PATHOLOGY AND LABORATORY MEDICINE: POSITIVE STEPS TOWARDS ENHANCING PATIENT SAFETY J. Kalra, M. Qureshi, S. Suryavanshi, A. Mulla Department of Pathology, College of Medicine, University of Saskatchewan and Royal University Hospital, Saskatoon, Saskatchewan, S7N 0W8 The profession of pathology is continuously striving to provide quality care and prevent medical errors. This is consistent with the Institute of Medicine (IOM) report (1999) that identified the health care professionals and organizations as major motivational forces in enhancing patient safety. The prevention of errors in laboratory medicine requires continuing efforts directed at all levels to make the system safer. These initiatives must be built into processes of care to best accomplish the desired objectives. We present a series of programs and risk management initiatives employed in clinical laboratory towards enhancing quality care and patient safety. We have introduced an educational program aimed at all sectors of the laboratory professionals to imbibe in them a culture of safety. The education pertains to the basic concepts of error generation and their influence on patient care through case discussion and synopsis of the critical incidents. The implementation of the quality care grand rounds provides a forum for discussion and evaluation of medical errors in the clinical laboratory in a guilt-free and secure environment. We hope the education about these critical incidents could help in designing interventions to reduce errors and improve quality of care. We have also previously suggested and adopted a ‘no-fault’ model that encourages voluntary anonymous error reporting of all critical incidents occurring in the laboratory testing process. The educational program has been integrated into our ‘no-fault’ model that targets all laboratory personnel including technologists and residents. The model emphasizes evaluation of the critical incidents through root cause analysis and an internal audit of the risk issues. The risk management audit performed in our laboratory suggested that the majority of risk events occur in the preanalytical phases of testing. These patient safety initiatives are solidly backed by the firm support of the clinical laboratory professional gastroscopy with biopsy of ‘‘gastric polyps’’ was included in the work-up. Poorly differentiated adenocarcinoma of the lung was demonstrated in the stomach. The third is a 85 year-old male with no known history of malignancy who presented for evaluation of iron deficiency anemia by endoscopy in February 2006. Biopsies of the colonic and gastric mucosa demonstrated moderately differentiated invasive colonic adenocarcinoma and metastatic colonic adenocarcinoma, respectively. While the pathologic

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evaluation of lesions such as these may be fraught with difficulty, awareness of such uncommon metastses to the stomach is essential for accurate diagnosis and optimal patient management. P243 PLEOMORPHIC RHABDOMYOSARCOMA OF THE LARYNX J. Chau, V. Falck, Z. Gao Department of Pathology and Laboratory Medicine, Foothills Medical Centre, University of Calgary, Calgary, Alberta, T2N 2T9 Pleomorphic rhabdomyosarcoma, a common soft tissue sarcoma, is a rare tumor of the larynx. Little is known about its etiology, pathogenesis, and clinical behavior. This report describes a patient with laryngeal pleomorphic rhabdomyosarcoma with a review of the literature. The patient is a 45-year-old male who presented with painless hoarseness. Computed tomography scan of the neck showed an abnormal soft tissue density and bulk involving the left true vocal cord. Histologically the tumor consists of large, round, pleomorphic cells with abundant eosinophilic cytoplasm and large nuclei with prominent nucleoli. Electron microscopy demonstrated distinct myofibrils with zbands, confirming the skeletal muscle origin of the tumor. At follow up 1.5 years after a right hemilaryngectomy, the patient was found to have metastatic pleomorphic rhabdomyosarcoma in the upper lobe of his left lung. A wedge resection was performed which was tolerated well. Currently he has not yet shown any signs of local recurrence or clinically detectable metastasis. Analysis of this case within the context of five previously reported cases in the English literature suggests that laryngeal pleomorphic rhabdomyosarcoma represents a distinct disease entity. Though its morphology resembles corresponding soft tissue sarcomas, this disease demonstrates a comparatively less aggressive behavior. P244 UNCOMMON MUCOSAL METASTASES TO THE STOMACH: THREE CASES AND REVIEW OF THE LITERATURE J. Fesser, S. Angel, R. Chibbar, J. Torrealba, R. Kanthan Department of Pathology, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, S7N 0W8 Metastases to the stomach from an extra-gastric neoplasm are an unusual event, identified in less than

2% of cancer patients at autopsy. The stomach may be involved by hematogenous spread from a distant primary (most commonly breast, melanoma and lung), or by contiguous spread from an adjacent malignancy, as in the case of the pancreas, esophagus, and gallbladder. These latter sites may also extend to the stomach via lymphatic spread. We present three cases of secondary gastric malignancy. The first is a 19-year-old male who received a diagnosis of testicular choriocarcinoma in September 2004. One month later, due to GI bleeding, he underwent partial gastrectomy, and metastastic testicular choriocarcinoma was identified invading the gastric submucosa with extensive lymphovascular invasion. The second is a 75-year-old male, generally well, who was diagnosed with adenocarcinoma of the lung in September 2005, after a two month history of breathlessness, cough, and weight loss. As the patient concurrently complained of significant epigastric and right upper quandrant abdominal pain, gastroscopy with biopsy of ‘‘gastric polyps’’ was included in the work-up. Poorly differentiated adenocarcinoma of the lung was demonstrated in the stomach. The third is a 85 year-old male with no known history of malignancy who presented for evaluation of iron deficiency anemia by endoscopy in February 2006. Biopsies of the colonic and gastric mucosa demonstrated moderately differentiated invasive colonic adenocarcinoma and metastatic colonic adenocarcinoma, respectively. While the pathologic evaluation of lesions such as these may be fraught with difficulty, awareness of such uncommon metastses to the stomach is essential for accurate diagnosis and optimal patient management. P245 SERRATED COLORECTAL CANCER: A CLINICOPATHOLOGICAL STUDY J.R. Parfitt, D.K. Driman Department of Pathology, London Health Sciences Centre and University of Western Ontario, London, Ontario, Canada Background & Aims: A sub-group of colorectal adenocarcinomas (CRC) arise from serrated adenomas (SA), including sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA), via a serrated neoplasia pathway. This study compares clinical and pathological features of SA related CRC with CRC associated with conventional adenomas (CA). Methods: All resections of CRC with associated adenomas during 2005 were retrieved from our files. Patient demographics and tumor location were recorded. Slides were reviewed by JRP and DKD for multiple morphological features. Statistical analysis included chi-square and t-tests.

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Results: There were 84 cases of CRC with associated adenomas: 45 with CAs, 27 with SSAs and 15 with TSAs; each group had a mean age of 76 years. Compared to patients with SSA or TSA related CRC, glandular architecture (73 vs. 30%), amphophilic cytoplasm (98 vs. 67%) and oval/dense nuclei (96 vs. 33%) were commoner among those with CA related CRC (p ¼ o0.001–0.003). Compared to patients with CA related CRC, female sex (67 vs. 36%), right side location (89 vs. 51%), serration (48 vs. 9%), acini (48 vs. 4%), solid (41 vs. 4%) or squamous (15 vs. 2%) growth, signet ring cells (26 vs. 0%), heterogeneity (56 vs. 4%), round nuclei with nucleoli (74 vs. 18%), tumor infiltrating lymphocytes (TILs) (59 vs. 13%) and Crohn’s-like inflammation (CLI) (37 vs. 11%) were commoner among those with SSA related CRC (p ¼ o0.001–0.042). Patients with CA and TSA related CRC were of similar sex (64 vs. 53% male) and site (51 vs. 67% right side) distribution, but serration (80 vs. 9%), hypereosinophilic cytoplasm (13 vs. 0%), TILs (60 vs. 13%) and CLI (40 vs. 11%) (p ¼ o0.001–0.012) were commoner among those with TSA related CRC. Conclusions: SSA, TSA and CA related CRC shows clinical and pathological differences. This suggests that the serrated neoplasia pathway may give rise to distinct cancers, depending on the type of serrated polyp from which they arise.

P246 SENTINEL LYMPH NODES IN CUTANEOUS MALIGNANT MELANOMA: CLINICAL SIGNIFICANCE OF RT-PCR DETECTED MICROMETASTASES J.R. Parfitta, C. Templeb, D. Shuma, P. Ainswortha, S.C. Chakrabartia, M.G. Josepha a Departments of Pathology and b Surgery, London Health Sciences Centre, London, Ontario, Canada Background and Aims: The current approach to examining sentinel lymph nodes (SLNs) in patients with cutaneous melanoma combines hematoxylin and eosin (H&E) histology and immunohistochemistry (IHC). Real-time polymerase chain reaction (RT-PCR) is an ultrasensitive technique for detecting melanoma micrometastases (MMs). This study compares the sensitivty of these techniques and examines the recurrence impact of MMs detected by RT-PCR alone. Methods: SLNs from 38 patients with stage I or II malignant melanoma were retrieved prospectively over a 20-month period. Half of each SLN was cryopreserved and analyzed by RT-PCR for detection of tyrosinase

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cDNA; the other half was stained with H&E, immunostained with S100, HMB45, melanA and tyrosinase and examined in a blinded fashion. Patients were followed for a 5-year period to determine outcome. Statistical analysis included chi-square and t-tests. Results: SLN MMs were detected in 4 (11%) patients by H&E, 6 (16%) patients by IHC and 19 (50%) patients by RT-PCR. The sensitivities for detecting MMs were 19%, 29% and 90% for H&E, IHC and PCR respectively. Patients with MMs that were H&E or IHC+ had a higher recurrence rate than patients with MMs that were H&E & IHC-/PCR+ (50% vs. 20%; p ¼ 0.169). When patients with and without recurrence were compared, only tumor thickness correlated with melanoma recurrence (mean 4 mm vs. 1.73 mm; p ¼ 0.03). There was an equal number of patients with and without recurrence with PCR detected MMs (50% in each group). Conclusions: Use of RT-PCR for detection of MMs in SLNs of patients with malignant melanoma improves sensitivity over H&E and IHC studies. However, there is no impact of PCR detected MMs on melanoma recurrence. Tumor thickness remains the most reliable indicator of prognosis for malignant melanoma.

P247 COMPARISON OF THINPREP AND CONVENTIONAL SMEARS IN SALIVARY GLAND FINE-NEEDLE ASPIRATION BIOPSIES J.R. Parfitt, C.M. McLachlin, M.M. Weir Department of Pathology, London Health Sciences Centre and University of Western Ontario, London, Ontario, Canada Background & Aims: Liquid-based ThinPrep (TP) cytology for evaluation of non-gynecological specimens is being increasingly used. There are few studies comparing TP to conventional smears (CS) in salivary gland (SG) fine-needle aspiration biopsies (FNAB). This study compares diagnostic accuracy and morphology of TP and CS in SG FNABs. Methods: From our files, 98 satisfactory SG FNABs with both TP and CS were retrospectively reviewed. All cases had surgical resection. CS and TP slides were assessed for: cellularity, artifacts, background, stroma, architecture, fragmentation, cell size, nuclear detail and ability to make the diagnosis on each preparation. Statisical analysis included chi-square and t-tests. Results: A specific diagnosis was rendered with both TP and CS in 52%, TP only in 11%, CS only in 20% and neither preparation in 16% of cases. Cellularity was greater in CS compared to TP (p ¼ 0.001). Artifacts (crush, airdrying, obscuring blood) were more frequent

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in CS compared to TP (12%, 13% and 27% vs. 2%, 0% and 1%; p ¼ 0.006 to o0.001). While fragmentation was greater and nuclear detail was better in TP (p ¼ 0.03 to o0.001), cell size was larger in CS (p ¼ 0.002). Degenerative changes and single cells were similar with TP and CS. A specific diagnosis of pleomorphic adenoma (PA) was more frequently rendered with CS compared to TP (83% vs. 63%; p ¼ 0.045). PA stroma was more abundant and an epithelial-stromal interface (ESI) was more frequent in CS compared to TP (ESI 76% vs. 38%; p ¼ o0.001). Diagnostic accuracy and morphology for Warthin’s tumor and adenoid cystic carcinoma were comparable for TP and CS. Conclusions: There are some morphological differences between TP and CS in the evaluation of SG FNABs. CS appears to be preferable to TP in the diagnosis of PA. Overall, TP and CS appear to be complementary preparations for SG FNAB diagnosis.

well as first year pathology residents. Main structures/ cells are identified for the student on the slide and linked to a brief description on the annotations window allowing for more effective and efficient self-directed learning. There is also the option of turning on and off the annotations layers to browse the slide in a ‘‘test’’ mode. The resource is expandable both in number of tissues and the detail of each tissue. It allows the viewer to see how the same structure/cell looks like in other areas, zoom in and out and therefore realize the small variations of normal and how the same cell looks like at different powers. The resource is portable, it can be copied into electronic media to be signed out from libraries, downloaded into a laptop or images can be posted in servers for remote retrieval.

P249 P248 VIRTUAL TUTOR FOR HISTOLOGY TEACHING IN A SELF-DIRECTED LEARNING ENVIRONMENT J. Morenoa, K. Chorneykob a PGY2 Anatomical Pathology Program, McMaster University b Pathology and Molecular Medicine McMaster University, Staff Pathologist St. Joseph’s Healthcare Hamilton, Ontario Motivation: Students learning histology face some important challenges. Access to equipment needed (i.e light microscope) is limited both in the number of microscopes available as well as the timing (i.e work hours). Histology reference books describe normal structures with the help of still pictures; these usually represent typical morphologies and make it difficult to realize the small variations in normal morphology or the way structures look at different powers. Objective: Our objective was to create an accessible and portable learning resource with some of the advantages of using a light microscope (i.e. browsing and zooming capabilities) and the ability to specifically mark structures of interest while describing them. Results: A virtual histology resource was created, covering 30 organs, and 108 tissues. Slides were scanned using a ScanScope Scanner (Aperio Technologies, Inc. Vista, CA). Images were scanned at 200
or 400
power. Slides resolution range from 50.000 to 108.000 pixels per square mm. depending on the magnification used. Slides were annotated in layers including sufficient details to cover the learning needs of medical students as

CLINICAL AND PATHOLOGICAL CORRELATIONS IN MALE BREAST CANCER: AROMATASE AND HORMONE RECEPTOR EXPRESSION PROFILES VIA TISSUE MICROARRAY K.A. Dakin Hache´, P.J. Barnes, R. Dewar, S. Gray, T. Younis, D. Rayson Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada Background: Male breast cancer (MBC) is a rare entity, making up less than 1% of breast cancer cases yearly. Principles of management are derived from protocols developed for the treatment of female breast cancer (FBC). Since therapy involving tamoxifen, trastuzumab, and aromatase inhibitors offers substantial benefit in the setting of FBC, establishing their role in the treatment of MBC is of utmost importance. Tissue microarray (TMA) technology provides the opportunity to study rare conditions like MBC by using archival, paraffinembedded tissues for the evaluation of immunohistochemical (IHC) markers relevant for these therapies. Methods: Clinical data was gathered for 54 cases of MBC between 1985 and 2005. Archival tissue from 48 patients was available. Three paraffin blocks were constructed using TMA technology for 40 cases (four representative 1.0 mm cores per case). Archival blank slides were utilized for 8 cases. IHC evaluation included estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2), and intratumoral aromatase (ITA). Results: IHC results were obtained for 45 cases and demonstrated ER positivity (n ¼ 40, 89%), PR positivity (n ¼ 33, 73%), HER-2 overexpression (n ¼ 4, 10%), and strong ITA expression (n ¼ 12, 26.3%). Invasive ductal carcinoma represented 81.5% of cases overall,

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but only 67% (8/12) of cases with strong ITA expression. Overall 5-year survival was improved for patients with strong ITA expression (92% versus 49%, p ¼ 0.038). Conclusions: Improved survival in patients with strong ITA expression may be related to 4 of 12 tumors with strong ITA expression demonstrating histology typically associated with a favorable prognosis (adenoid cystic, mucinous, secretory, and invasive intracystic papillary carcinoma). The association between ITA expression and tumor histology warrants further investigation.

P250 DOES CRESCENTIC INFLAMMATION CORRELATE WITH NON-ISCHEMIC ENTEROCOLIC LYMPHOCYTIC PHLEBITIS? K.A. Guggisberga, P.L. Beckb, S.A.C. Medlicotta a Departments of Laboratory Medicine and b Internal Medicine, Peter Lougheed Centre, University of Calgary Introduction: Enterocolic lymphocytic phlebitis (ELP) is a rare, albeit well established cause of segmental ischemic enterocolitis. This artery-sparing transmural vasculitis is classically a circumferential phlebitis with perivenular lymphocyte cuffing and thrombi in the absence of systemic manifestations. Subclinical or early stage ELP is not well delineated. We sought to discern if crescentic inflammation (confined too50% of vein circumference) correlated with non-ischemic/subclinical ELP. Materials and Methods: A case of ELP was identified. 600 submucosal and subserosal veins from ischemic and intact bowel segments were assessed to discern if vascular morphology varied between intact bowel (remote from ischemic segment), shoulder bowel (viable bowel adjacent ischemic segment) and ischemic bowel (200 veins were assessed from each of the three regions). Two of the authors (KAG, SACM) analyzed the phlebitis and scored: prevalence of phlebitis lesions, phlebitis type (lymphocytic versus necrotizing) and the presence or absence of thrombi, granulomata and myointimal hyperplasia. Results: Crescentic and circumferential lymphocytic phlebitis was more common in viable bowel, mean of 84 per 200 veins, versus 11 per 200 veins in the ischemic segment (po 0.0001). There was a non-significant trend for increasing crescentic morphology between intact bowel remote from compared to adjacent the ischemic focus (35 per 200 versus 23 per 200 veins respectively). Hallmarks of ischemic bowel were necrotizing phlebitis (88 per 200 versus 0 per 400 veins in intact bowel) and thrombi formation (75 per 200 versus a mean 12 per 200

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veins in intact bowel), both reaching statistical significance (po0.0001). Conclusions: A non-significant trend exists for crescentic lymphocytic phlebitis to be more prevalent remote from ischemic bowel. ELP complicated by ischemia was associated with necrotizing thrombophlebitic lesions that were almost exclusive to the ischemic region. P251 SMOOTH MUSCLE ANTIBODY PROFILES OF COLONIC POST-TRANSPLANT SMOOTH MUSCLE NEOPLASIA AND SPORADIC LEIOMYOMATA K. Guggisberg, S. Devlin, S.A.C. Medlicott Background: Post-transplant smooth muscle neoplasia (PTSN) is an Epstein-Barr virus (EBV) latency type IIIderived proliferation affecting multiple viscera. The tumor is presumed to originate from myocytes of vasculature. Immunohistochemistry analysis of bcl-2 may help differentiate between PTSN and sporadic leiomyoma (SL), with the former tumor staining positive. We aim to test whether a battery of common smooth muscle antibodies can discriminate between PTSN and sporadic leiomyomata of the colon. Furthermore, the pattern of h-caldesmon staining has not been documented in PTSN. Design: Four PTSN lesions from one patient, procured during two separate colonoscopies and five archival sporadic leiomyomata, all from unrelated patients, were analysed with the smooth muscle antibodies: desmin, a-smooth muscle actin and h-caldesmon. The authors assessed immunohistochemical stains and scored results as positive or negative. Positive staining was further qualified as: 1+ for o30%, 2+ for 30 to 65%, 3+ for 465% neoplastic cell staining. Results:

SL Case1 SL Case 2 SL Case 3 SL Case 4 SL Case 5 PTSN Lesion1 PTSN Lesion2 PTSN Lesion3 PTSN Lesion4

h-caldesmon 3+ 3+ 3+ 3+ 3+ 3+ 3+ 3+ 3+

Desmin 3+ 3+ 3+ 3+ 3+ 1+ 2+ 1+ 1+

Actin 3+ 3+ 3+ 3+ 3+ 3+ 3+ 3+ 3+

Conclusions: Our data indicates that both PTSNs and SLs react strongly to h-caldesmon. There is diminished desmin staining of PTSNs compared to SLs. Previous

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literature has suggested that the PTSN is vascular myocyte derived. The strong h-caldesmon, weak desmin phenotype provides credence to a vascular myocyte origin for PTSN. A combination of desmin with either h-caldesmon or actin may facilitate differentiation of colonic SL and PTSN. P252 MALIGNANT PHYLLOIDES TUMOR WITH LIPOSARCOMATOUS AND MFH FEATURES IN A 17 YEARS OLD PATIENT M.D. Kurosh Rahimi, Karim Khetani McGill University, 3775 University Street, Montreal QC H3A 2B4, Canada Since its first description by Muller in 1838, behavior of Phylloides tumor has been difficult to predict based on morphology. It is most commonly categorized as benign, malignant and of borderline malignant type based on margins, degree of stromal overgrowth, mitotic activity and pleomorphism. All categories are uncommon (less than 1% of breast tumors) occurring mostly in older age group compared to Fibroadenoma. Malignant Phylloides Tumor is extremely rare in young women. We describe case of Malignant Phylloides tumor in a 17 years old female. Tumor presented as circumscribed, 7.8 cm heterogeneous mass. The cut surface showed dense fibrous, soft gelatinous and hemorrhagic areas. Microscopic examination showed obvious sarcomatous features with foci consistent with MFH and Liposcrcoma. Diagnosis was suspected on needle core biopsy of the mass. Morphological features of the tumor are described in detail along with clues to the diagnosis on core biopsy where it can be mistaken for cellular fibroadenoma, particularly in young patients.

P253 POLYOMA VIRUS INFECTION OF THE KIDNEY IN A CARDIAC TRANSPLANT RECIPIENT L. Geldenhuys, T. Hewlett, P. Acott, C. Barber, T. Hatchette, B. Kyberd Polyoma Virus reactivation in the renal allograft has been well described, but only rare case reports exist of polyoma virus reactivation in the native kidneys of patients with cardiac transplants. A 24-yr-old male post-cardiac transplant for viral myocarditis suffered multiple rejection episodes over an 18-month period requiring pulse corticosteroids and quadruple therapy with tacrolimus, rapamycin, mycophenolate and steroids. Subsequently, he presented with

nephrotic range proteinuria and then developed sub acute renal failure and anemia, and lost 40 lb in weight. A renal biopsy showed morphologic features highly suspicious for polyoma virus. Despite immunoperoxidase staining for the SV40 antigen being equivocal, electron microscopy demonstrated polyoma virus particles in many tubular cell nuclei. The presence of polyoma virus was confirmed in serum and urine with in house real-time PCR (4.9
105 and 7.5
108 copies/ ml, respectively). An additional unusual finding was immunofluorescence positivity for IgG, C3, C1q, kappa and lambda in the mesangium without electron microscopy showing any obvious electron dense deposits. The patient was treated with cidofovir and due to the development of rejection only a limited reduction in immunosuppression. However the serum viral load remained high (range ¼ 2.7
103 to 6.8
105 copies/ ml) and renal dysfunction worsened necessitating dialysis therapy. Polyoma virus infection occasionally can cause nephritis in solid organ transplant patients other than kidney recipients. The renal impairment limited cidofovir treatment with its cumulative nephrotoxicity and the cardiac status limited immunosuppression reduction leading to inadequate polyoma viral clearance and renal failure.

P254 A CASE REVIEW OF MEDICO-LEGAL AUTOPSIES AT THE KINGSTON REGIONAL FORENSIC UNIT L. Hamiltona, D. Dexterb a Queen’s Medical School, Kingston, Ontario b Dept of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario Objective: Kingston has a unique population in that there are seven penitentiaries in the region; and it is well known that there is a higher incidence of unnatural deaths in the prison population. There was no previous data available to see if this was reflected in the types of cases seen by the Kingston Regional Forensic Unit. Method: A retrospective review of all medico-legal autopsies performed at the unit in 2003 was completed. Results: There were180 medico-legal autopsy cases conducted in 2003. 73.9% were male and 26.1% female. The manners of death in these cases were: 57.2% natural, 17.8% accidental, 16.1% suicidal, 3.9% homicidal and 5.0% unclassified. There were 16 custody cases of which 37.5% were natural, 25.0% suicidal, 25.0% homicidal and 12.5% accidental. The causes of death were also analyzed with respect to all cases, gender, age and in-custody status.

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Conclusion: In general, the majority of cases were sudden natural deaths and involved males. There was a higher incidence of unnatural and violent deaths in custody cases compared to non-custody cases. Without comparison data and with a case review of only one year, it is difficult to identify any specific trends or patterns; however given Kingston’s unique population, it is suspected that there are a higher number of unnatural deaths than expected for a community its size. This study could serve as a baseline for future analysis.

P255 RECTOSIGMOID SMOOTH MUSCLE TUMOR OF UNDETRERMINED MALIGNANT POTENTIAL PRESENTING AS A LARGE PELVIC MASS IN A YOUNG WOMAN M.P. Dupre, L. Eidus, A. Yilmaz Department of Pathology, University of Calgary, Rockyview General Hospital, Calgary, Alberta Mesenchymal neoplasms, other than GISTs, are infrequent tumors of the rectosigmoid colon. With exception of leiomyomatous polyps of the muscularis mucosa, true intramural smooth muscle tumors are exceedingly rare, with only few cases reported in the literature. Previous studies suggest they tend to categorize themselves into benign and obviously malignant types. Herein we report a large rectosigmoid smooth muscle tumor, diagnosed in an 18-year-old woman presenting with abdominal pain and emesis. Computed tomography revealed an eight centimeter multicystic pelvic mass, suspicious for an ovarian neoplasm. Diagnostic laparoscopy revealed a large mass which was free of the adnexal structures but attached to the rectosigmoid colon. Surgical resection produced a large tumor in the wall of the rectosigmoid colon which ulcerated the muscosal surface secondary to polypoid tumor growth. Tumor histology revealed a cellular spindle cell neoplasm with focal cytologic atypia, hemorrhage and rare mitoses, but without tumor necrosis. Tumor cells were positive for smooth muscle markers (actin, desmin, h-caldesmon) and negative for CD117 (C-Kit) and CD34, indicating smooth muscle origin. Relatively large tumor size and cytologic atypia in the absence of tumor necrosis and increased mitotic activity place this tumor in a category of undetermined malignant potential. Although similar smooth muscle tumors have been described in both the uterus and soft tissue, as of yet they have not been reported in the

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rectosigmoid colon. Smooth muscle neoplasms should be included in the differential diagnosis of large intramural tumors at this site. Distinction from GISTs by means of appropriate immunohistochemical studies is critical since smooth muscle neoplasms have been reported to have a better prognosis than GISTs of similar size and mitotic rate. P256 NEUROENDOCRINE PANCREATIC CARCINOMA PRESENTING AS METASTATIC HEPATOID CARCINOMA M.P. Dupre, S.J. Urbanski Department of Anatomical Pathology, Foothills Medical Centre, University of Calgary Hepatoid carcinomas (HC) are very rare and may create considerable diagnostic challenges in surgical pathology. Although most HC originate in the stomach or lung, and some germ cell tumors may exhibit hepatoid differentiation, hepatoid morphology may occasionally be seen within neuroedocrine tumors (NET). Two such cases have been reported in NET of the lung, one in espophageal carcinoma of mixed histologic type and one NET of the cervix. Although there are seven reported cases of primary HC of pancreas there is no documentation of primary pancreatic neuroendocrine tumors with hepatoid morphology. HC once detected in the liver may be very difficult to distingush from primary hepatocellular carinoma as both may produce alpha-feto-protein and both may express HepPar1. We have recently seen a liver biopsy from a 54-year-old man investigated for uncontrollable nausea. He was found to have multiple space occupying lesions in the liver and alpha-fetoprotein of 2060. Liver biopsy showed a malignant tumor with distinct hepatoid morphology. The tumor was negative for alpha-fetoprotein and did not express HepPar1 but showed strong cytoplasmic CEA positivity. Because of these findings, initial impression was of a hepatocellular carcinoma, however further investigations documented uniform and strong synaptophysin positivity of all tumor cells. Subsequent CT scan demonstrated a mass in the tail of the pancreas. This case illustrates well potential pitfalls one may encounter in the interpretation of liver biopsies showing tumor with distinct hepatoid differentiation. The clinical impact of the proper diagnosis in this instance may be paramount as the patient may respond to the available pharmacological modalities.

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EXTRASKELETAL EWING’S SARCOMA/PRIMITIVE NEUROECTODERMAL TUMOUR OF THE POSTERIOR MEDIASTINUM WITH INVOLVEMENT OF THE SPINAL CANAL M. Manducha, P.A. Isotaloa, P. Ellisb, K. Reidc, D.F. Dextera a Department of Pathology and Molecular Medicine b Division of Neurosurgery c Division of Cardiothoracic Surgery, Queen’s University, Kingston, Ontario, K7L 2V7

FATAL HEMORRHAGE FROM AN AORTOGASTRIC FISTULA SECONDARY TO GASTRIC ULCERATION ASSOCIATED WITH NISSEN FUNDOPLICATION M. Manducha, J.P. Rossitera, W.T. Depewb, C.D. Mercerc, D.J. Hurlbuta a Departments of Pathology and Molecular Medicine, b Medicine (Gastroenterology) and c Surgery, Kingston General Hospital, Queen’s University, Kingston, Ontario, Canada

The Ewing’s sarcoma/primitive neuroectodermal tumour (ES/PNET) family of tumours is a group of malignant neoplasms that may present in both skeletal and extraskeletal sites. These tumours are composed of small, round, primitive cells and may be difficult to diagnose due to a lack of specific differentiation. We describe a 24-year-old woman who presented with nonspecific back pain. Magnetic resonance imaging demonstrated a dumbbell-shaped mass of the posterior mediastinum that extended into the spinal canal through the intervertebral foramina at the T3-4 level. The patient had no symptoms of spinal cord compression and no bony lesion was identified. She underwent a left posterolateral thoracotomy and a T3-5 laminectomy and subsequent chemotherapy. The resection specimen consisted of multiple soft tissue fragments, the largest measuring 5
3
3 cm. The tumour was composed of mitotically active, small round cells that contained cytoplasmic vacuoles that indented nuclei. No rosettes were identified. The neoplastic cells were strongly immunoreactive for CD99 and vimentin. There was no immunophenotypic evidence of neural differentiation and the neoplastic cells were negative for chromogranin, synaptophysin, CD31, CD34, calcitonin, desmin, lowmolecular weight cytokeratins, wide-spectrum cytokeratins, LCA, S-100 protein, and TTF-1. Cytogenetic studies confirmed a t(11;22)(q24;q12) chromosomal translocation that was also associated with trisomy of chromosome 2. Extraskeletal ES/PNETs are rare neoplasms that should be distinguished from other small round cell tumours, including neuroblastoma, rhabdomyosarcoma, desmoplastic small round cell tumour, and lymphoma using morphology and ancillary laboratory techniques.

Aortogastric fistula is a rare but life-threatening cause of upper gastrointestinal (GI) hemorrhage that usually complicates atherosclerotic or mycotic aortic aneurysm disease. We report a case of aortogastric fistula secondary to NSAID-induced gastric ulceration associated with Nissen fundoplication. Clinical: A 55-year-old man collapsed at home following an episode of massive hematemesis. He presented to hospital in hypovolemic shock. After volume resuscitation, urgent upper GI endoscopy showed fresh liquid and clotted blood in the stomach but failed to identify a specific site of hemorrhage. Visceral angiography was also unable to identify a bleeding source. The patient died from exsanguination during an emergency laparotomy. Past medical history was significant for Nissen fundoplication, performed four years prior, to treat severe reflux esophagitis refractory to medical therapy. The patient’s medications included indomethacin and morphine sulfate for chronic back pain. Autopsy Findings: Postmortem examination revealed massive upper GI tract hemorrhage from an aortogastric fistula. The fistula tract extended from the base of a deep ulcer within the gastric fundoplication pouch into the adherent descending aorta. Aorta showed only minimal atherosclerosis. There was no reflux esophagitis or Helicobacter pylori gastritis. Conclusion: Acute GI hemorrhage from an aortogastric fistula secondary to ulceration within the gastric fundoplication is a rare late complication of this antireflux surgery. NSAID use likely contributed to fistula development. Recognition of factors that predispose to gastric ulceration in the post-fundoplication patient is critical to arouse the high index of suspicion required to diagnose and manage this rare complication.

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P259 ROUTINE DERMATOPATHOLOGY USING REALTIME, DYNAMIC DIGITAL MICROSCOPY M.J. Trotter, D.F. Barber Department of Pathology and Laboratory Medicine, University of Calgary, and Calgary Laboratory Services, Calgary, Alberta Telepathology has potential applications for remote diagnosis and consultation pathology. The utility of real-time, dynamic digital microscopy in routine dermatopathology reporting has not been evaluated. In our community-based, subspecialty dermatopathology practice, we assessed 114 consecutive skin biopsy specimens using real-time, dynamic digital microscopy (DM) (Nikon Coolscope), and compared diagnoses with those rendered using the gold standard of conventional light microscopy (LM). Slide interpretation times were recorded for both DM and LM. Diagnostic categories included non-melanoma skin cancer (31%); miscellaneous benign conditions (31%); melanocytic lesions (24%); and inflammatory conditions (14%). One major diagnostic discrepancy was recorded (cutaneous lupus erythematosus misdiagnosed on DM as erythema annulare centrifigum). Twelve minor discrepancies were observed, all without clinical significance. The mean interpretation time for DM specimens was 4.01 minutes, compared to 3.01 minutes for specimens diagnosed by LM. We conclude that real-time, dynamic digital microscopy can be effectively utilized in routine dermatopathology signout. However, DM has an 11.4% discrepancy rate compared to conventional LM, and slide interpretation time is increased. Therefore, real-time, dynamic DM may be more suited to remote diagnostic dermatopathology and network consultations.

P260 MALIGNANT MESOTHELIOMA: CYTOHISTOPATHOLOGICAL AND CLINICAL CORRELATION Namrata Junejaa, Wojceich Mozyckib, Zhaolin Xua a Departments of Pathology and b Medical Oncology, QEII Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada Malignant Mesothelioma is an aggressive neoplasm that predominantly arises from the mesothelial cells of the pleura and peritoneum. Although it is rare tumor, there is a trend of increasing worldwide incidence, especially in industrialized countries. In Nova Scotia,

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101 cases were reported to the Nova Scotia Cancer Registry between 1990 and 2002. The overall incidence was 1.3 per 100,000 and 87% cases were pleural, 12% peritoneal and 1% testicular. It is more common in men than women with the ratio of 7.4: 1. Asbestos exposure was documented in 69% of the patients and 49% of the exposed patients worked in areas of prevalent shipyard industries. The median age at diagnosis was 70 in men and 64 in women. Majority of the patients were treated with palliative and supportive care and the two-year overall survival rate was 10%. Between 1995 and 2005, there were 55 cases of Malignant Mesothelioma in our files in the Department of Pathology, QE II Health Sciences Centre in Halifax. Among those, 50 patients had Malignant Pleural Mesothelioma and 5 patients, Peritoneal Malignant Mesothelioma. The histopathological evaluation revealed that 33 cases (60%) were Epithelioid variant, 11 cases (20%) Sarcomatoid, 9 cases (16.4%) Biphasic and 2 cases unspecified. Initial fluid cytology specimens were collected in 37 cases (34 cases of pleural fluid, 2 cases of peritoneal fluid, 1 case of pericardial fluid) and 11 cases had more than one cytological evaluation. The cytology was reported as negative in 14 cases, abnormal nondiagnostic in 12 cases, suggestive for malignancy in 4 cases (two cases reported as suggestive of Malignant Mesothelioma), and positive for malignancy in 7 cases (only one reported as consistent with Malignant Mesothelioma). Cell blocks were prepared in 6 cases of which 2 cases were positive for malignancy (one reported as Malignant Mesothelioma and one consistent with Adenocarcinoma), 2 cases were reported as abnormal and two cases as negative. None of the sarcomatoid mesothelioma was diagnosed as positive for malignancy from cytological specimens. Both histological and cytological evaluation of Malignant Mesothelioma can be a diagnostic challenge, especially to distinguish them from reactive mesothelial proliferation or metastatic adenocarcinoma. The above data highlights the poor correlation between cytological and histological evaluation. A more comprehensive approach is probably necessary in order to improve the accuracy in cytological diagnosis of Malignant Mesothelioma that may include adequate specimen sampling with routine preparation of cell blocks for immunohistochemistry, familiarity with cytological diagnostic criteria and correlation of clinical, radiological and cytological findings.

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HARLEQUIN ICHTHYOSIS: A CASE REPORT AND REVIEW OF THE LITERATURE N.G. Chan, T.B. Rouse, J.G. Shepherd Department of Pathology, London Health Sciences Centre and University of Western Ontario, London, ON, Canada N6A 4G5

APPENDICEAL INTUSSUCEPTION CAUSED BY CECAL ADENOCARCINOMA, REPORT OF TWO CASES N. Liaghati-Nasseri, D.F. Dexter Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada

Background: Harlequin ichthyosis (HI) is a rare, devastating congenital skin condition, usually resulting in death shortly after birth. Inheritance is believed to be autosomal recessive. The incidence is approximately 1 in 300,000 and there is no racial or gender predilection. Neonates suffer from feeding difficulties, electrolyte abnormalities, temperature dysregulation, respiratory distress, and life threatening systemic infections. Case History: We report a case of a baby boy with HI, diagnosed at the time of delivery. He was born at 34 weeks and 3 days gestational age to a 21-year-old woman in a non-consanguinous relationship. Routine prenatal ultrasounds and examinations were unremarkable. The baby was born by Caesarean section for breech presentation after spontaneous onset of labour. Apgar scores were 9 at both one and 5 min. The obvious features of HI were recognized immediately after birth. The baby’s condition was managed conservatively in hospital and he died after five days of life. Postmortem Examination: External examination revealed generalized thickening and extensive deep fissuring of the skin. The mouth was oval with everted mucosa. The eyelids were hard and stiff, resulting in ectropion. The nose and ears were deformed and replaced by intensive hyperkeratosis. There were contraction deformities of the upper and lower extremities. Microscopic examination of the skin showed massive hyperkeratosis. The lungs and spleen were mildly congested. Sections of the brain showed hypoxic injury in the calcarine cortex, hippocampus, and pontine nuclei. No other abnormalities were identified. Discussion: Recent studies have linked HI to mutations in the ABCA12 gene, resulting in abnormal desquamation, intercellular adhesion, and skin barrier function. Further studies may lead to early prenatal diagnosis of HI and a specific treatment for this devastating disease.

Appendiceal intussusception secondary to cecal adenocarcinoma has rarely been reported in the literature to date. We report two cases of appendiceal intussusception secondary to cecal adenocarcinoma. The first case is of a 75-year-old woman who presented with anemia and was subsequently diagnosed with cecal adenocarcinoma after endoscopic biopsy. The second case is of a 78-yearold man with a similar presentation and diagnosis of cecal adenocarcinoma following endoscopic biopsy. An elective right hemicolectomy was performed in both cases. On gross examination, the longitudinal cut surface revealed partial intussusception of the appendix into the cecum in both samples. These cases highlight the importance of considering adenocarcinoma as a possible cause of appendiceal intussusception.

P263 EGFR TESTING IN COLORECTAL CARCINOMA BY TISSUE MICROARRAYS N. Makretsov, D. Fontaine, A. Hyde, K. Searle, A. Sharapov, N. Curcin, A. Pirzada, B. Younghusband Department of Pathology and Laboratory Medicine, and Discipline of Genetics, Memorial University of Newfoundland, 300, PRINCE Philip Drive, A1B3V6, St.John’s, Canada Background: EGFR testing in colorectal carcinoma is proposed to be a standard practice in order to select patients for targeted therapy with anti-EGFR monoclonal antibodies. Meanwhile, there is still a controversy in the literature regarding clinical significance of EGFR in colorectal carcinoma. The aim of this study is to examine the frequency of expression of EGRF by immunohistochemistry and tissue microarrays, and to link EGFR expression with standard clinical and pathological parameters in colorectal carcinoma. Design: Population-based series of tissue microarrays containing 286 primary colorectal carcinomas from Avalon Peninsula (1997–98) were assembled (0.6 mm duplicate cores). Paraffin embedded formalin fixed tissue blocks were used. Follow-up data were available for 190 (66.4%) patients. Median follow-up time was

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7 year. EGFR expression in tumor cells was assessed by immunohistichemistry using monoclonal anti-EGFR antibody, Novocastra. Membranous staining was scored as follows: negative- no staining, score 1 o1%, score 2 41% of tumor cells positive for EGFR. The immunostaining data were linked to patient outcome and standard clinico-pathological variables (histological type, depth of invasion, lymph node status, and tumor grade); Kaplan-Meier survival analysis and non-parametric correlation tests were performed. Results: 270 (94.4%) out of 286 cases were interpretable. There was no staining in 137 (50.7%) cases; while there was a positive staining in o1% of tumor cells in 102 (37.8%), and 41% in 31 (11.5%) cases. The positive EGFR expression in colorectal carcinoma was associated with a non-significant trend to better outcome (p40.1 for overall, disease specific and disease free survival). There was no correlation between EGFR expression and tumor grade, depth of invasion, lymph node status, grade, location and histological subtype (p40.3). Conclusion: there are no significant correlations between EGFR, clinicopathological variables and clinical outcome in our population-based series of patients. This obscures the idea of selection of patients for targeted therapy with anti-EGFR monoclonal antibodies based on immunohistochemical testing. Larger patient cohorts as well as randomized clinical trials are necessary to clarify the clinical utility of EGFR in colorectal carcinoma. P264 ACINAR PATTERN OF MAMMARY PAGET’S DISEASE: A CASE REPORT R.J. Dumonta, H.G. Higginsb, P.J. Barnesa a Departments of Pathology and Laboratory Medicine and b Surgery, QEII Health Sciences Centre, and Dalhousie University, Halifax, Nova Scotia, Canada, B3H 1V8 Mammary Paget’s disease (PD) is an uncommon disorder of the nipple-areola complex and surrounding skin. It is the presenting sign in 0.5 to 4.3% of breast cancer cases, and is almost always associated with high grade in situ carcinoma or invasive carcinoma, typically of ductal origin. We report an unusual case of an acinar pattern of PD with low-grade cytological atypia in an 83-year-old female. A nipple biopsy and subsequent nipple excision were received for pathological evaluation. The nipple biopsy showed clusters of mildly atypical cells in the basal epidermis, the majority of which displayed an acinar pattern with well-defined tubules. These cells were CK7+, CEA+, ER, PR, S100, HMB45, Her2/ neu- by immunohistochemistry. The nipple excision

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showed the acinar pattern of PD with underlying invasive papillary carcinoma, grade 2 and carcinoma in situ, intermediate grade, papillary and micropapillary patterns. Most cases of mammary PD are characterized by intraepidermal spread of markedly atypical glandular cells arranged singly and in clusters. The acinar pattern of PD is extremely uncommon, and to our knowledge, has not been formally reported. The histological features and differential diagnosis are discussed. P265 COMPOSITE DIFFUSE LARGE B-CELL LYMPHOMA AND HODGKIN LYMPHOMA TRANSFORMATION OF CHRONIC LYMPHOCYTIC LEUKEMIA R.J. Dumonta, L.A. Fernandezb, R. Juskeviciusa a Departments of Pathology and Laboratory Medicine and b Medicine, QEII Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 1V8 Background: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a mature B-cell neoplasm constituting 90% of chronic lymphoid leukemias. CLL/SLL can transform into an aggressive lymphoma, a phenomenon known as Richter syndrome. Transformation to diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) occurs in 3 to 10% and 0.5% of CLL/SLL patients, respectively. We present a case of Richter syndrome with DLBCL and HL arising simultaneously in a single lymph node in a patient with CLL/SLL. Design: The lymph node biopsy was studied with H&E and immunohistochemical stains. Flow cytometric analysis and whole-section PCR were also performed. Results: A lymph node biopsy was obtained from a 52year-old male with CLL/SLL. The nodal architecture was effaced by a diffuse infiltrate of large CD20+, CD5+, CD23+/- dysplastic lymphoid cells with focal areas containing CD30+, CD15+, CD45-, EBV LMP1+ Reed-Sternberg (RS) cells in a mixed inflammatory background. Flow cytometry demonstrated a lambda monoclonal CD19+, CD20+, CD5+, CD23+, CD10B-cell population. Clonal rearrangement of the IgH gene was detected by PCR. Conclusion: DLBCL and HL composite transformation of CLL/SLL is extremely rare. This type of transformation showed a clinically aggressive course and likely represented an EBV-related process. EBV positivity in RS cells, but not in DLBCL cells, may indicate a distinct pathogenesis of HL in this clinical context. Fludarabine may also play a role in infection/reactivation of EBV leading to transformation of B-cells to a potentially more aggressive neoplasm.

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DISSECTING HEPATIC ARTERY ANEURSYM: CASE REPORT OF AN UNUSUAL CAUSE OF FATAL INTRA-ABDOMINAL HEMORRHAGE R. Behjatia, D.J. Hurlbuta, G.R. Walkerb a Department of Pathology and Molecular Medicine and b Division of General Surgery, Kingston General Hospital, Queen’s University, Kingston, Ontario

EXPRESSION OF EDB+ONCOFETAL FIBRONECTIN: A POTENTIAL MARKER OF COLONIC CARCINOGENESIS R. George, H. Farhangkhoee, S. Chakrabarti Departments of Pathology, London Health Sciences Centre & University of Western Ontario, London, Ontario, Canada, N6A 5A5

Clinical Presentation: An 80-year-old woman with a past history of invasive breast and endometrial carcinoma collapsed at home and presented to hospital with hypotension. Following aggressive volume resuscitation, abdominal CT scan showed intraperitoneal fluid localized around the liver hilum consistent with intraabdominal hemorrhage. After a period of hemodynamic stability, further episodes of hypotension indicated ongoing bleeding. The patient refused exploratory laparotomy and died one day later. Autopsy Findings: Postmortem examination showed intra-abdominal hemorrhage with recent hematoma within the porta hepatis, associated with a large lesser sac hematoma and hemoperitoneum. Bleeding appeared to originate from the liver. Sectioning the liver revealed focal aneurysmal dilatation of an intrahepatic branch of the right hepatic artery. Microscopic examination of the aneurysm showed vessel wall dissection with extensive perivascular hemorrhage. Bleeding did not involve the biliary tract. Liver was free of metastatic carcinoma; no specific etiology for aneurysm formation or dissection was identified. Discussion: Although hepatic artery aneurysms are very rare, the hepatic artery is reported to be a relatively common site for visceral arterial aneurysm formation. Sudden intra-abdominal hemorrhage with hypovolemic shock and high mortality is the usual clinical presentation, as with this case. Reported etiologies for aneurysm formation include atherosclerosis, medial cystic degeneration, fibromuscular dysplasia, trauma, infection, primary vasculitis, periarterial inflammation (secondary to cholecystitis or pancreatitis) and as an anastomotic complication after liver transplantation. Congenital origin is also hypothesized. After thorough pathologic examination, none of these etiologies can be directly implicated in the present case.

Background and Objectives: Fibronectin (FN) is an extracellular matrix glycoprotein, which plays roles in cell adhesion and migration. Oncofetal FN (OFN), containing extra domain B (EDB) fragment, is expressed in fetal tissues and some tumors. In malignancies, OFN has been associated with angiogenesis, tumor progression and metastasis. We investigated whether EDB+ OFN expression is associated with progression of colonic tumor. Methods: Paraffin sections of 31 colorectal polyps (15 adenomatous polyps with and without high-grade dysplasia (HGD), 11 invasive adenocarcinoma, 4 hyperplastic polyps and an inflammatory polyp) were used for immunostaining, with polyclonal rabbit antihuman EDB+OFN antibody. The intensity of staining was scored as: 0; 1+ (weak); 2+(moderate) and 3+ (strong). Results: No EDB+ OFN staining was found in the epithelium of normal mucosa and of inflammatory/ hyperplastic polyps. Adenomatous polyps stained 2+ or more in areas of HGD. Invasive carcinoma, showed an equal or greater intensity of staining than in HGD. Within areas of low-grade dysplasia (LGD), no staining was seen in the majority of adenomas. However, a patchy 2+ staining was noted in some cases, which interestingly, also harbored HGD. Stromal fibroblasts and endothelial cells tended to express EDB+ OFN more strongly, in areas adjacent to the invasive carcinomas, compared to other areas. Conclusion: Data from this preliminary study suggest that an augmented EDB+ OFN expression is associated with progression of LGD, in adenomatous polyps, to HGD and carcinoma. Thus OFN could potentially be used as a predictor of the adenomacarcinoma sequence.

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P268 NODULAR HYPERPLASIA OF THE BARTHOLIN’S GLAND: A REPORT OF 2 CASES AND REVIEW OF THE LITERATURE Al-Dandan Sadeq, Baker Patricia, Safneck Janice, Quinonez Guillermo University of Manitoba, Health Sciences Center, Department of Pathology, Winnipeg, Manitoba, R3A 1R9, Canada Nodular hyperplasia of the Bartholin’s gland is a rare pathologic entity. Only 18 cases have been reported in the literature. We reported 2 additional cases of nodular hyperplasia of the Bartholin’s gland with similar clinical manifestations and pathological features. Clinically there is a painful enlarging mass in the lower genital area in a middle-aged female. Physical examination shows smooth, mobile and tender lump in the genital area. Grossly, there is a rubbery and solid nodule with a glistening and multilobular cut surface. Histologic examination reveals a well circumscribed nodule consisting of mucinous acini surrounding central ducts in a lobular arrangement. Connective tissue septa surround each individual lobule. The normal duct-acinar relationship is well maintained. There are associated features of focal squamous metaplasia, mucin extravasation and infiltration by muciphages and chronic inflammatory cells.

P269 ISOLATED HUMAN COLONIC CRYPT CELLS CONSISTENTLY EXPRESS GENES FOR IL-1a, IL-8, TNF-a AND IL-1RII BUT ARE UNRESPONSIVE TO TNF OR IL-1 STIMULATION S.R. Yana, H. Jamesb, H. Sappa, A.W. Stadnykb,c a Departments of Pathology, b Microbiology and Immunology, and cPediatrics Dalhousie University, Halifax, Nova Scotia, B3H 2Y9 Intestinal epithelial cells (IEC) are a source of multiple cytokines, including IL-1 and TNF. Increased tissue levels of these cytokines have been associated with inflammatory bowel disease. However, the cytokine profile and their regulation in human IEC are still poorly understood. In the current study, we assessed the cytokine gene expression and their possible regulation in freshly isolated human IEC. Colonic mucosa was obtained from human colonic tissues of normal appearing margins of colonic specimens immediately after surgical removal from patients with colorectal cancer. Mucosal crypts were isolated with the combination of

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DTT/EDTA treatment, physical shaking and filtration. Cellular proteins and mRNA were extracted from the crypt cells freshly isolated or after culture with or without stimuli. The proteins were used to assess activation of ERK1/2, p38 and IkBa by Western blotting while the mRNA for cytokine gene expression by RT-PCR. Results showed that freshly isolated human IEC expressed mRNA for IL-1a, IL-8, TNF-a and IL-1RII that were not changed by short term culture. In contrast, mRNA for INF-g and IL-10 were not detected in freshly isolated cells but induced by in vitro culture. High basal levels of phosphorylation of MAP kinases and IkBa were detected in freshly isolated cells and did not change after culture except for p38 which was further activated by culture. Most interestingly, IL-1b and TNF-a, which can cause a variety of biological changes in animal and human IEC lines, had no significant effects on levels of mRNA for the above cytokines and the phosphorylation of the enzymes mentioned above. In conclusion, isolated human IEC consistently express genes for IL-1a, IL-8, TNF-a and IL-1RII and in vitro culture induces mRNA for IFN-g and IL-10, but are unresponsive to TNF or IL-1 stimulation.

P270 HISTIOCYTOID SWEET’S SYNDROME: REPORT OF A CASE AND REVIEW OF THE LITERATURE S. Chow, S. Pasternak, S. Northgrave, N. Walsh Departments of Pathology, Capital District Health Authority, Halifax, NS, B3H 1V8 and Dermatology, Cape Breton District Health Authority. Sydney, NS, B1P 1P3 Sweet’s syndrome (SS), was first described in 1964 by Robert Douglas Sweet. The condition is characterized clinically by a cutaneous eruption of painful erythematous pseudovesicular plaques and/or nodules, accompanied by fever, leukocytosis and neutrophilia. Microscopically, lesional skin shows prominent edema of the papillary dermis beneath which is a dense diffuse infiltrate of polymorphonuclear leukocytes. SS can be idiopathic or associated with inflammatory conditions, such as viral infections, with malignancies of hematological or solid organ types, or with ingestion of various medications. In 2005 a group of European dermatopathologists described an unusual and previously under-recognized histopathological variant of SS and titled this ‘histiocytoid Sweet syndrome’ (HSS). The authors established that in some patients with early lesions of SS the dermal infiltrates were composed mainly of mononuclear cells resembling small histiocytes. While these cells stained

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positively for histiocytic markers, such as CD68, they also exhibited myeloperoxidase. The latter indicated that they were in fact immature myeloid cells. The authors postulated that, in some cases of early SS, immature myeloid cells can be released from the bone marrow and constitute the dermal infiltrates, to be replaced later by mature polymorphs. We report the case of a 58 year old woman who developed an eruption of erythematous pseudovesicular papules, mainly on the upper chest and back while on vacation in Cuba. The clinical differential diagnosis included polymorphous light eruption, a photosensitive drug eruption and Sweet’s syndrome. A punch biopsy of lesional skin revealed microscopic features of HSS. Detailed clinical and histopathological features of this case will be described in the interests of contributing to a scant literature on an unusual and under-recognized entity.

P271 EVALUATION OF THYROID FINE NEEDLE ASPIRATION BIOPSY FOLLOW-UP OUTCOMES FOR OUR INDETERMINATE CATEGORIES S. McRae, N. Chan, C.M. McLachlin, M.M. Weir Department of Pathology, London Health Sciences Centre &University of Western Ontario, London, Ontario, N6A 5A5 Objective: Our department implemented standardized thyroid fine needle aspiration biopsy (FNAB) reporting terminology in 2003 based on malignancy risk (low-5%, intermediate-15%, high 75-99%). An indeterminate (IND) category was created to include cystic contents (CC), follicular lesion (FL) and IND for papillary carcinoma (IPC). The purpose of this study is to examine the follow-up outcomes for our IND FNABs, in order to test their validity. Materials & Methods: We retrospectively evaluated cytology follow-up and surgical excision outcomes on all IND thyroid FNABs (CC, FL, IPC) from 2003-5. Terminology was based on: CC: cystic material with a paucity of epithelium; FL: equal small and large follicle architecture; IPC: focal nuclear atypia (grooves, pseudoinclusions). Results: The IND categories included 478 thyroid FNABs (445 patients) with 262 CC, 173 FL, and 43 IPC. Follow-up was obtained in 41% CC, 35% FL and 59% IPC. CC follow-up was: 9% papillary carcinoma (PC), 30% CC again, 40% benign, 14% intermediate risk and 7% unsatisfactory. FL follow-up was: 15% PC, 5% FL again, 70% benign, 8% intermediate risk, and 2% unsatisfactory. IPC follow-up was: 36% PC, 56% benign, 4% intermediate risk and 4% CC.

Conclusions: CC merits classification as IND and not negative, given the spectrum of benign and malignant lesions at follow-up. FL has a significant malignancy risk at follow-up, and may need to be recategorized. IPC has a significant malignancy rate, highlighting need for attention to even focal nuclear atypia. P272 QUANTITATIVE DETECTION OF CIRCULATING EPITHELIAL CELLS V. Iakovlev, R. Goswami, N. Arneson, J. Vecchiarelli, S.J. Done Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario Canada M5G 2M9 It has been known for over a century that breast cancer cells can be detected in the peripheral blood. Recently it was shown that the quantity of circulating tumor cells (CTCs) is an independent predictor for survival and treatment response. Real-Time PCR (RTPCR) is a sensitive technique for detection of CTCs. Free serum RNA, genomic DNA and non-specific RNA expression in leukocytes are thought to be the causes of false positive RT-PCR results. We decided to investigate whether the technique can be used to specifically quantitate CTCs. We tested CD44, Cytokeratin 19(CK19), Maspin and Mammaglobin genes for their robustness in amplification from serial dilutions of RNA extracted from the MDA-MB-231, UACC-812, T47D and HS578 T breast cancer cell lines. To simulate CTCs, serial dilutions of the T47D and HS578 T cell lines were added to freshly drawn peripheral blood from healthy volunteers. The samples were subjected to enrichment, RNA extraction and RT-PCR. To address the issue of false positive results we added extracted RNA to the peripheral blood and saline aliquots at different procedural steps and used RT-PCR to determine if added RNA was detectable. CK19 was the only gene reliably expressed in all four cell lines. We found that there was a linear relationship between the quantity of added cells and the cycle threshold values for Cytokeratin 19 gene. This relationship can be used for quantitative assays. The sensitivity threshold of the method was within 1–10 cell/ml of blood. We showed that a genomic DNA elimination step should be included in the RNA extraction protocol. Our results also showed that the RosetteSep (StemCell Technologies) gradient enrichment with cell pellet isolation procedures eliminates free RNA. This study shows that low levels of CTCs can be reliably detected and quantified. Validation of this technique is an important step for future studies of CTCs in breast cancer patients.

ARTICLE IN PRESS ABSTRACTS / Pathology – Research and Practice 202 (2006) 793–834

P273 ESTROGEN RECEPTOR AND HER-2NEU PROFILES IN BREAST CARCINOMA. THE CORRELATION WITH TUMOR GRADE, SIZE AND LYMPH NODE STATUS W.A. Mourad, N. Mohamed, A. Tulbah, M. Shoukri, T. Al-Tweigeri, A. Al. Sayed, D. Ajarim King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Background: Estrogen receptors (ER) in breast carcinoma usually indicates a well-differentiated tumor and good disease outcome whereas Her-2neu (HER2) expression is an indication of a more aggressive disease. We wanted to examine the combined profiles of ER and HER expression in breast carcinoma and its relationship to tumor grade and lymph node status (45 positive lymph nodes). Materials and Methods: We examined all cases of breast carcinoma excised between 2001 and 2002. ER and HER2 expression profiles were examined. These were correlated with tumor grade, size, lympho-vascular invasion and lymph node metastasis. Results: There were 243 cases of breast carcinoma. Four categories of tumor were identified: ER-/HER2+ and ER+/HER2- (n ¼ 87). ER-/HER2+ and ER-/ HER- groups had a higher incidence of grade 3 tumors than ER+/HER2+ and ER+/HER2- groups (73% and 76%, respectively, VS. 16% and 22%, respectively; p ¼ 0.00001). A higher incidence of larger tumor (42 cm) in the ER-/HER2+ group than the ER+ group (73 vs. 56%; p ¼ 0.003). No difference in lymph node metastasis and lympho-vascular invasion was identified between the different groups. Conclusion: In the context of ER and HER2 expression in breast carcinoma, ER may be more significant in predicting tumor behavior than HER2.

P274 PATHOLOGIC PROGNOSTIC INDICATORS IN NODE-POSITIVE INVASIVE UROTHELIAL ARCINOMA IN ADULT MALES W.A. Mourad, A.A. Mokhtar, M. Shoukri, R. Seyam, W.Al. Taweel, K. Al. Othman, K. Hanash Departments of Pathology, Urology and biostatistics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Certain pathologic parameters have been suggested to predict the behavior of urothelial carcinoma. We attempted to explore these indicators in male patients

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undergoing cystectomy and pelvic lymphadenectomy with positive lymph node metastasis. We examined seven pathologic parameters; including tumor size (45 cm vs.o5 cm), depth of invasion (muscularis propria vs. peri-vesical fat), lympho-vascular invasion, invasion of prostate/seminal vesicle, number of lymph node metastasis (X2 vs. o2), extranodal extension, and size of lymph node metastasis (X2 cm vs.o2 cm) in adult male patients who underwent radical cystectomy and pelvic lymphadenectomy with positive lymph node metastasis in our institution between 1999 and 2004. Correlation with survival was done. There were 31 patients with an age range of 32–77 years (median 59 years). Twenty cases (64.5%) were high-grade and 2 cases were low-grade urothelial carcinoma, 7 cases were high-grade squamous carcinoma and one case of adenocarcinoma. Twenty-one patients died of their disease and 10 are alive after a median follow-up of 11 months. Univariate and multivariate analyses showed that the only significant pathologic indicator is the depth of invasion of the tumor (p ¼ 0.03). None of the other variables reached any level of significance. Our findings suggest that, in adult male patients subjected to cystectomy and pelvic lymphadenectomy with positive lymph node metastasis, the depth of invasion is the only pathologic parameter predicting survival.

P275 CLINICO-PATHOLOGIC FEATURES OF HEPATIC NEOPLASMS IN EXPLANTED LIVERS W.A. Mourad, H. Khalaf, A. Tulbah King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Background: Hepatic neoplasm can be the primary indication for hepatic transplantation. The tumors can also be incidentally identified in explanted livers. We wanted to explore the clinico-pathologic features of hepatic neoplasm identified in explanted livers in our institution. Materials and methods: All explanted livers resected between 2001 and 2005 were evaluated for the presence of neoplasms and their clinicopathologic features. Results: Of 82 liver transplants seen in our institution 9 neoplasms (11%) were identified. Patient ages ranged from 5 to 63 years (median 56 years). The primary etiology of hepatic disease was hepatitis C virus in 6 cases, hepatitis B virus in one case and cryptogenic hepatitis in 2 cases. Serum alpha-fetoprotein was significantly elevated (4 40X normal) in only 2 cases

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ABSTRACTS / Pathology – Research and Practice 202 (2006) 793–834

and was less than twice the normal range in the rest of the cases. CA19-9 was not elevated in any of the cases; including the case of cholangiocarcinoma. The tumors included hepatocellular carcinoma (HCC) in 6 cases, one case of combined HCC and cholangiocarcinoma and one case of combined HCC and hepatoblastoma. Three tumors (30%) were incidentally identified. This included the hepatoblastoma and cholangiocarcinoma cases. The tumors ranged in size from 0.5 to 5 cm (median 1.4 cm) and were multifocal in 4 of the cases (40%). HCC were grade 1 in one case, grade 2 in eight cases and grade 3 in one case. One patient died of causes unrelated to the tumor and the remaining patients are alive with no evidence of disease at a median of 16.6 months. Conclusion: In our institution hepatic neoplasms can be seen in more than 10% of explanted livers. They can be incidentally identified, are frequently not associated with elevated serum levels of alpha-fetoprotein and CA19-9, are commonly multifocal and are associated with good prognosis. Thorough examination of the explanted liver is mandatory to identify microscopic neoplasms.

P276 PRIMARY MEDIASTINAL MIXED GERM CELL TUMOUR WITH RHABDOMYOSARCOMATOUS COMPONENT W. Lyew, G. Gohla Department of Pathology, St. Joesph’s Hospital, McMaster University, Hamilton, Ontario, Canada Mediastinal germ cell tumors are rare neoplasm representing less than 1% of all malignancies and only 3% of all germ cell tumors. They make 16% of mediastinal tumors in adults. Mediastinal germ cell tumors demonstrating malignant transformation is even more rare. We report a 27-year-old previously well male presented to Family Physician with a rapidly growing subcutaneous mass in left anterior chest wall. A CXR revealed a mass invading and destroying the fifth rib anteriorly as well as a large anterior mediastinal mass. No abnormalities in the testes were reported. The subcutaneous mass was biopsied and subsequently diagnosed as mixed germ cell tumor, predominately

yolk sac component. The patient was treated with chemotherapy followed by surgical excision of the mediastinal mass. Microscopic studies revealed a mixed germ cell tumor, predominantly mature teratoma with rhabdomyosarcomatous component. P277 ‘‘GRANULOMA ANNULARE’’ OF PENILE SKIN, A CASE REPORT AND LITERATURE REVIEW Wooje Jo, S. Salama Department of Laboratory Medicine, St. Joseph’s Hospital & McMaster University, Hamilton, Ontario, Canada, L8N 4A6 Granulomatous reactions of the genital skin are very rare and usually foreign body related. Penile necrobiotic reactions are even more rare. Most were penile necrobiosis lipoidica occurring in diabetic patients. We report a case of a penile granuloma annulare (GA), and discuss the differential diagnosis, proposed etiology, pathophysiology, and clinical outcome. A 20 year previously healthy male presented with a penile lesion. A skin biopsy showed areas of necrotic collagen associated with surrounding histiocytic inflammatory reaction showing focal palisading. The necrotic centers appeared mostly acellular or contained few neutrophils and nuclear fragments. There were also occasional eosinophils. No foreign material was demonstrated on polarizing microscopy. The stains were negative for acid fast bacilli and fungal organisms. There was increased dermal mucin in the areas of altered collagen, typical of GA. Literature review of necrobiotic lesions involving the penis revealed only 9 cases of GA. Most lesions spontaneously resolved, but recurred. The recurrent lesions resolved faster than the original lesions. Various topical and systemic medications, as well as surgical treatments have been utilized with varying results. The etiology remains unclear, although a number of unproven factors have been suggested, including ultraviolet light, fungal infections, arthropod bites, contact with irritant material, trauma, and viral infections. Several possible hypotheses have been proposed regarding pathogenesis, but the most likely mechanism remains unclear.