XXVI Congress of the IAP: Abstracts 27 predict lymph node metastasis, since a positive lymph node may not always be clinically CD44v6 in comparison with that in primary carcinoma. or radiologically evident. Recent studies have shown that D2-40, a monoclonal antibody Conclusion: (1) CD44v6 is relatively more expressed in lymph node metastases than in that reacts with an oncofetal antigen present in fetal germ cells, is a highly sensitive and primary breast carcinoma. (2) Ductal proliferative processes are associated with CD44v6 specifi c lymphatic endothelial immunohistochemical marker. In this study, we investigated expression in the luminal cells. (3) CD44v6 may play a role in breast cancer lymph node the value of lymphatic invasion detected by D2-40, to predict lymph node metastasis in the metastasis. Studies into the role that CD44v6 plays in breast carcinogenesis and lymph invasive breat carcinomas. node metastasis by correlating the expression of bFGF and MMP-9 with that of CD44v6 Design: A total of 40 cases of invasive ductal breast carcinoma (IBC) with axillary lymph are currently in progress. node metastasis (22) and those without axillary lymph node metastasis (18) were retrieved from the hospital database. Immunostaining for D2-40 was performed on an automated Cancer Epidemiology immunostainer with appropriate positive and negative controls. The H and E and immunostained slides were examined blindly (without the knowlege of the status of lymph 112 EPIDEMIOLOGY OF CANCERS IN HASSAN II UNIVERSITY HOSPITAL node metastasis) by two pathologists to identify lymphatic invasion. Statistical analysis IN FES 2003-2005 was performed using Chi-Square test. Afaf Amarti; Laila Chbani; Hind Fatemi; Kawtar Znati, Medicine Faculty, Fès, Morocco Results: D2-40 highlighted the lymphatic endothelial cells in all 40 cases. Lymphatic Background: About 57% of all cancers occur in developing countries, however little is invasion was identifi ed in 18/22 (82%) cases of IBC with axillary node metastasis. In known about their epidemiology because of the lack of cancer registries in these countries. contrast, the lymphatic invasion was present in only 2 /18 cases (11%) of IBC without In our practice, no cancer registry is available in Morroco and published data is based on axillary node metastasis, which was statistically signifi cant (P<0.05) between the two hospital series. groups of breast cancer patients. With H and E examination, lymphatic invasion was Design: To assess for the fi rst time the epidemiology of cancers in our region based on the observed in only 14/22 (63%), including 2/22 (9%) cases suspicious for lymphatic invasion data of the pathology laboratory of Hassan II University of Fes. in IBC with axillary node metastasis. 1/18 (6%) case was detected to have lymphatic Results: From October 2003 to December 2005 1019 cases of cancer were collected. 55% invasion on the H and E slides in IBC without axillary node metastasis. were men and 45% women and the mean age was 53 years. The most frequent tumors were Conclusion: Our results indicate that the lymphatic invasion detected by D2-40 of digestive and cutaneous origin (18,3% each)followed by breast and cervical carcinoma immunostain, is highly predictive of axillary lymph node metastasis. In addition, D2-40 second (13,4%). Cervico-facial tumors came in the third place with 11% of all cancers staining increases the sensitivity of recognizing lymphatic invasion over routine H and (larynx and nasopharynx tumors having the same frequency). E examination. We recommend that D2-40 immunostain may be helpful to determine if Conclusion: Authors emphasize the need for cancer registries in developing countries as lymph node resection is of value in patients with invasive breast carcinoma. cancer is a prominent public health problem and epidemiologic data can better prepare the health system to take care of cancer patients. 110 BP1 EXPRESSION IS NOT INVOLVED IN THE EVOLUTION OF INVASIVE BREAST CARCINOMA ACQUIRING METASTATIC POTENTIAL Gang Yue; Gang Yue; Marino Leon; Reda Saad; Yulin Liu; Jan Silverman, Allegheny Cardiovascular General Hospital, Pittsburgh, PA, United States Background: BP1 is a novel member of the homeobox genes associated with early 113 POSTNATAL PROLIFERATION OF MYOCARDIAL CELLS IN TWO hematopoiesis and has been described in the evolution/carcinogenesis of some malignant DIFFERENT REGIMENS OF PRESSURE OVERLOAD FOR PREPARATION OF neoplasms. Overexpression of BP1 was recently reported in the progression of breast THE SUB-PULMONARY VENTRICLE carcinoma (Breast Cancer Research and Treatment. 90:241-7, 2005). However, the Maria Cristina Abduch; Renato Assad; Miguel Quintana; Acrisio Valente; Lea Demarchi; involvement of BP1 in the evolution of breast carcinoma acquiring metastatic potential Vera Aiello, Heart Institute (InCor), University of Sao Paulo School of Medicine, São has not been studied. In this study, we examine the expression of BP1 in invasive breast Paulo, Brazil carcinoma (IBC) with positive lymph node and compare the fi nding with invasive breast Background: Pulmonary artery banding (PAB) is sometimes required in patients with carcinoma without lymph node metastasis. transposition of the great arteries to prepare the sub-pulmonary ventricle, in order it Design: A total of 40 cases of invasive breast carcinoma with axillary lymph node undergoes an increase in mass and becomes suitable for the arterial switch operation. metastasis (22) and those without axillary lymph node metastasis (18) were retrieved from Controversy exists regarding the occurrence and extension of myocyte hyperplasia the hospital database. Immunostaining for BP1 antibody were performed on an automated after the neonatal period in response to that pressure overload, as well as about the best immunostainer with appropriate positive and negative controls. For the staining intensity, a regimen of ventricular preparation. This study is aimed at analyzing experimentally the score index of 0, 1, 2, and 3 corresponding to negative, weak, moderate, and strong staining cell proliferation rate in right ventricles submitted to different types of PAB: continuous was used. Statistical analysis was performed with Chi-Square test. and intermittent. Results: The positive BP1 staining is observed in all 40 (100%) cases of IBC with and Design: Twenty one healthy, 30 to 60-days-old goats (beyond the neonatal period) were without lymph node metastasis with a predominantly cytoplasmic pattern. There is no divided in three groups: control (n=7, no surgical procedure), continuous stimulation (n=7, statistical difference in staining intensity between these two groups of IBC. Besides tumor submitted to PAB by surgical implantation of a external device, infl ated continuously cells, BP1 also stains benign ductal epithelial cells in all 30 (100%) cases of IBC that and progressively for fi ve days- total 96 hours), and intermittent stimulation (n=7, PAB, contain benign breast tissue with a predominantly nuclear pattern. stimulated intermittently- 12 hours/day, for fi ve days- total 48 hours). Bidimensional Conclusion: Our results indicate that BP1 expression is not correlated with axillary lymph echocardiography was performed every day in animals from both stimulated groups, in node metastasis of invasive breast carcinoma. In addition, in contrast to the recent report, order to evaluate the thickness of the RV free wall and to calculate the RV mass. At the end there is no statistically signifi cant difference in BP1 expression between nonneoplastic of the experiment, the goats were sacrifi ced, the hearts excised and histological sections breast tissue and invasive breast carcinoma. (5-ìm- thick) from the right ventricle (RV), left ventricle (LV) and ventricular septum were submitted to imunohistochemistry with the monoclonal antibody Ki- 67 to identify 111 CD44V6 IS A MARKER OF METASTATIC POTENTIAL IN BREAST cell proliferation. Labeled cardiomyocytes and interstitial/vessel cells were quantifi ed CANCER microscopically (number/ high power fi eld). Comparisons between groups regarding the Wenyong Zhang; Elizabeth Hyjek; Gabriel Sica; Syed Hoda, Weill Medical College of number of labeled cells were performed using analysis of variance test. Cornell University, New York, NY, United States Results: Both stimulated groups showed signifi cant increase in the RV free wall thickness Background: CD44 glycoproteins are cell surface receptors involved in cell-cell and cell- and mass at the last day of the experiment, compared to the basal values. The number extracellular matrix interaction and are involved in tumor invasion and metastasis. CD44 of proliferating RV cardiomyocytes in the continuous stimulation group was signifi cantly splice variant 6 (CD44v6) is implicated in metastasis of pancreatic and breast cancer cell higher when compared to the respective LV and to both ventricles of the controls (p=0.023). lines. In humans, over-expression of CD44v6 has been associated with poor prognosis When comparing the intermittent stimulation group with the controls, no difference was in some tumors. Thus far, the role of CD44v6 in the breast carcinogenesis and tumor detected in the rate of proliferating RV cardiomyocytes. Neither signifi cant difference was progression is unclear. found regarding the number of labeled septal myocytes in both stimulated groups compared Design: Seventeen patients with lymph-node-positive breast carcinoma were investigated. to controls. On the other hand, numbers of proliferating RV interstitial/vessel cells were We are addressing the following questions: (1) whether the expression pattern of CD44v6 signifi cantly higher in both stimulated groups when compared to the respective LVs and differs in normal breast tissue, ductal hyperplasia, in situ carcinoma and invasive carcinoma to the controls (p<0.05). The same cells from the right half of the ventricular septum also ; (2) whether there is a difference in CD44v6 expression between the primary and the showed an increased proliferation rate when compared to the control animals (p=0.001). metastatic breast carcinoma to the regional lymph nodes; (3) whether CD44v6 expression Conclusion: Under the conditions of the present study, the continuous pressure overload is correlated with the expression of basic fi broblast growth factor (bFGF) and matrix imposed to the RV increased signifi cantly the proliferation of RV cardiomyocytes and metalloproteinase-9 (MMP-9), two CD44 binding proteins that are potentially associated interstitial/vessel cells, while intermittent stimulation was not capable of enhancing the with tumor growth and cancer metastasis. Immunohistochemical staining was done on proliferation of cardiomyocytes but elicited interstitial/vessel cells hyperplasia. At present, paraffi n tissue sections of the primary tumors and the lymph node metastases using anti- we cannot answer if a longer period of intermittent stimulation would have resulted in a CD44v6, anti-bFGF and anti-MMP-9 antibodies. Immunostains were evaluated both for similar rate of proliferating cardiomyocytes. Moreover, the ideal proportion of proliferated the strength of staining (negative, weak, strong) and the percentage of positively-stained cells (cardiomyocytes related to interstitial/vessels cells) remains to be determined. cells. Results: (1) In normal breast tissue, CD44v6 antibody stained myoepithelial cells, but 114 MORPHOLOGIC ALTERATIONS IN DILATED TRICUSPID VALVES not luminal cells (0/17). In 15/16 (94%) atypical hyperplasia/usual hyperplasia and 12/13 Peter Baker, Children`s Hospital, Columbus, OH, United States (92%) DCIS/LCIS, CD44v6 antibody stained both myoepithelial and luminal cells. 10/17 Background: Tricuspid valve (TV) regurgitation (3+ to 4+) is present in up to 14% of (59%) invasive carcinoma showed positive CD46v6 staining. (2) 12/17 (71%) metastatic patients at 1 week after TV annuloplasty and up to 32% at 5 years. Mortality associated breast carcinoma to the regional lymph nodes stained positive for CD44v6. Among the with reoperation is up to 37%. The most common etiology for TV regurgitation is right 12 CD44v6-positive metastatic carcinoma, 8/12 (67%) showed increased expression of ventricular and TV annular dilation. Anatomic alterations in dilated TV`s relative to non- dilated valves have not been well characterized. Better understanding of these alterations 28 XXVI Congress of the IAP: Abstracts may provide a basis for improved valve function following surgical intervention. anatomical collection of acquired heart-vessels diseases coming from routine autopsy. Design: Hearts were obtained at autopsy in 2 groups: control, with TV circumference < Design: A Museum for the Anatomical Collection of heart diseases has been set up and 11.0 cm (n=17, 10 males and 7 females, mean age 59.5 years), and dilated TV, with TV equipped with fl owing cupboards with book shelves. Each specimen has been transferred circumference > 13.0 cm (n=19, 16 males and 3 females, mean age 61.7) years. Annular in a single jar or double sack with only a small amount of formalin to avoid evaporation. length, maximum base to free edge length and maximum chordal length were measured Identifi cation of each specimen is warranted by a stick on label, including registration on each TV leafl et. Dilation of each cardiac chamber was graded (0-3+). Statistics were number, date as well as Pathologic codes. A nosologic system to classify acquired heart- performed using Student`s t-test and Pearson`s correlation coeffi cient. vessels diseases has been put forward with 12 main categories, accordingly to the main Results: Heart weights were greater in the dilated TV group (527 v 409 grams, p=.002). morbid entity (ie. Pericardium, Coronary artery, Myocardium, Endocardium-aorta, mitral, Dilation of the right atrium was absent (n=14) or mild (n=3) in the controls and moderate tricuspid, pulmonary, parietal-, Conduction system, Tumors, Vessels, Miscellanea), each (n=11) or severe (n=8) in the dilated TV group. Dilation of the right ventricle was absent subdivided in subcategories, including normal hearts. An electronic Access database in all control hearts and moderate (n=12) or severe (n=7) in the dilated TV group. Mean management system has been set up for data storage and retrieval. TV circumference was 13.8 cm in the dilated TV group (range 13.0 to 15.0) and 10.8 Results: A total of 850 cases, referring to the routine cardiovascular autopsies performed cm in the controls (range 10.0-11.0) Annular lengths were greater in all leafl ets of the in the 9 years time interval from 2002 to 1994, have been entered in the database and dilated TV group compared with controls (anterior 4.5 v 3.9 cm, p<.001: posterior 5.8 v archived in the Cardiovascular Registry. Pericardial disease was present in 25%, coronary 3.7 cm, p<.001: septal 3.4 v 3.1 cm, p<.001). The annular length as a percentage of TV artery in 67%, myocardial in 43% (including 26% hypertensive heart disease), valve in circumference was increased in the posterior leafl et of the dilated TV group (42.2% v 20%, conduction system in 4.3%, tumors in 1.8% and vessels in 20%. Cardiac surgery 34.6%, p<.001) and decreased in the anterior (33.0% v 36.4%, p<.001) and septal leafl ets procedures consisted of aortic valve replacement in 65 (7.6%), mitral valve in 38 (4.5%), (24.8% v 29.1%, p<.001). Compared with controls, the annular lengths of the anterior, aorto-coronary bypass grafts in 122 (14%), and aorta vascular prosthesis in 37 (4.3%). septal and posterior leafl ets increased 15%, 9% and 56% respectively. Within the dilated As far as interventional procedures, a pacemaker was present in 26 (3%) and coronary TV group, increasing TV circumference correlated with increasing annular lengths for the stent/PTCA in 76 (8.9%). Fort-fi ve (5.3%) were normal hearts. As far as miscellanea is anterior (r=.523, p<.05), posterior (r=.759, p<.001) and septal leafl ets (r=.545, p<.05); concerned, a patent foramen ovale was documented in 164 (19%), left ventricular false anterior leafl et base to free edge length (r=.460, p<.05) and grades of right ventricular tendons in 216 (25%), an aneurysm of the fossa ovalis in 62 (7.3%) and a Chiari network in (r=.498, p=.03) and right atrial dilation (r=.693, p+.001) Chordal lengths were not 26 (3%). A total of 180 specimens have been selected and collected separately for teaching increased in the dilated TV group. purposes. Conclusion: Dilated TV`s are characterized by increased annular lengths of all leafl ets. Conclusion: Protocols and electronic databases as well as an “ad hoc” Museum for the However, there is disproportionate expansion of the posterior leafl et annulus. Increasing collection of acquired heart diseases at the University of Padua have been developed. TV annular length correlated with increasing base to free edge length only in the anterior A Cardiovascular Registry of more than 3000 either congenital and acquired diseases leafl et. Accounting for altered anatomic relationships in dilated TV`s may reduce TV will represent the source of continuous consultation by scientists and students as part of regurgitation following surgical repair. the long-standing patavian tradition of pathologic studies in the fi eld of cardiovascular diseases. 115 HISTOPATHOLOGIC SUBSTRATE FOR CLINICAL MANIFESTATION AND IMAGING IN HERITABLE CARDIAC CONDUCTION SYSTEM AND 117 INHERITED CARDIOMYOPATHIES ARE A MAJOR CAUSE OF SUDDEN MYOCARDIAL DISEASE CARDIAC DEATH IN YOUNG PEOPLE Peter Baker; Elizabeth Sparks, Children`s Hospital, Columbus, OH, United States; Subha Cristina Basso, University of Padua, Pathology, Padova, Italy; Domenico Corrado; Barbara Raman; Charles Wooley, The Ohio State University, Columbus, OH, United States Bauce, University of Padua, Cardiology, Padova, Italy; Elisa Carturan, University of Background: The pathologic basis for conduction system and myocardial disease (CMD) Padua, Pathology, Padova, Italy; Andrea Nava, University of Padua, Cardiology, Padova, has not been well characterized in patients with LMNA mutation. Autosomal dominant Italy; Gaetano Thiene, University of Padua, Pathology, Padova, Italy lamin-CMD was identifi ed in a family of German descent. The pedigree spans 9 generations Background: Inherited arrhythmic cardiomyopathies, either structural or non structural and contains over 1000 family members. LMNA encodes lamin A/C, an intermediate (long QT, short QT, Brugada syndromes and catecholaminergic ventricular tachycardia) fi lament nuclear envelope protein. In this family, CMD is initially characterized by are genetically determined heart muscle diseases associated with electrical cardiac atrial arrhythmias and over several decades, affected members develop progressive dysfunction. The aim of the present study was the establish the prevalence of inherited atrioventricular (AV) block and ventricular myopathy. cardiomyopathies as a cause of sudden cardiac death (SCD) in a series of young people Design: The hearts of 8, late-stage, genotype-affected patients were studied at autopsy (7 (aged 1-35 yrs) who suffered cardiac arrest. males, 1 female; ages 45-74 years, mean = 59). Death was due to congestive heart failure Design: In the time interval 1980-2001, 449 (138 female and 311 male, mean age 24±8.5 (n=2), metastatic carcinoma (n=1) or sudden cardiac death (n=5). Sections for histology yrs) consecutive cases of SCD in the young in Northeast of Italy have been prospectively were taken from the atria, right ventricle, left ventricle (anterior, lateral, and posterior), studied according to a detailed pathology protocol. This included gross and histologic interventricular septum (mid and basilar), sinoatrial (SA) node and AV node, and stained study of the heart specimens, conduction system investigation when deemed necessary, as with H&E and Mason’s Trichrome stains. Myocyte hypertrophy, fi brosis and myocyte well as clinico-pathologic correlation. degeneration were graded 0 (absent) to 3 (severe). Echocardiography had been performed Results: Cardiac arrest was mechanical in 30 (7%) due to aortic rupture (20), pulmonary on 7 of the 8 autopsy patients. embolism (6), and haemorrhagic shock (4). In the remaining 419 (93%) SCD was Results: All 8 patients presented with fatigue and bradycardia and two had pacemaker arrhythmic and major causes included atherosclerotic coronary artery disease (CAD dependent heart rate. Atrial fi brillation was fi rst detected 5 to 26 years (mean = 13) prior 73,16%), arrhythmogenic right ventricular cardiomyopathy (ARVC 59, 13%), myocarditis to death. Echocardiography demonstrated moderate to severe left atrial dilation, (mean (47, 10%), valve disease (47, 10%), hypertrophic cardiomyopathy (45, 10%), conduction ratio of observed: upper limit of normal = 1.3), reduced left ventricular ejection fraction system disease (31, 7%), dilated cardiomyopathy (24, 5%), non-atherosclerotic CAD (range 17-28%, mean = 22%) and absent or mild left ventricular dilation (mean ratio of either congenital (21, 5%) or acquired (10, 2%), and postoperative congenital disease (7, observed: upper limit of normal = 1.05). At autopsy, heart weights ranged from 540 to 1.5%). Mean age of patients who died suddenly due to atherosclerotic CAD was higher of 650 grams (mean = 585). Atrial dilation was moderate (n=1) or severe (n=7) whereas left that of patients with other cardiovascular substrates (29.8 vs 23.2, p<0.0001). Altogether, ventricular dilation was mild (n=2) or moderate (n=6). The coronary arteries had <70% SCD was due to structural arrhythmogenic cardiomyopathies in 128 cases (30% of luminal narrowing with no evidence of ischemic heart disease. Histologic sections from arrhythmic SCD). Moreover, no evidence of structural heart disease was found both at the atria, left ventricle and interventricular septum showed severe myocyte hypertrophy. gross and histologic investigation in 39 arrhythmic SCD cases (9%) (“mors sine materia”). Fibrosis and myocyte degeneration were more prominent in the atria than in the ventricles Noteworthy, unexplained SCD has been recently demonstrated to be often related to ionic (p<.001). Severe fi brosis was present in the mid-myocardium of the posterior left ventricle channel gene mutations. and basilar interventricular septum. The SA and AV nodes had moderate (n=3 and n=5, Conclusion: More than one third of arrhythmic SCD in the young are due to respectively) or severe (n=5 and n=3, respectively) fi brosis. cardiomyopathies which are frequently genetically determined and thus potentially Conclusion: Histopathologic changes provide a substrate for development of atrial and heritable. This high prevalence underlies the need to reach a correct fi nal diagnosis to start ventricular arrhythmias, AV block, and reduced left ventricular systolic function. Clinically a widespread cardiological and molecular screening of family members of SCD victims signifi cant and characteristic patterns emerged including prominent atrial myocyte for preventive purposes. Moreover, since SCD may remain unexplained after a careful degeneration, SA and AV node fi brosis and regional distribution of ventricular fi brosis. gross and histologic examination and the diagnosis can be reached only through genetic Further correlations of histopathology with clinical and imaging fi ndings will provide the screening, there is the need to perform a post-mortem molecular investigation either in the basis for clinical staging and management. blood or in tissue samples retrieved at autopsy.

116 THE “CARDIOVASCULAR REGISTRY” AT THE UNIVERSITY OF 118 SURGICAL PATHOLOGY AND ETIOLOGY OF 278 CONSECUTIVELY PADUA: THE ANATOMICAL COLLECTION OF ACQUIRED HEART-VESSELS REMOVED MITRAL VALVES WITH PURE REGURGITATION DISEASE Pornsuk Cheunsuchon; Tuenjai Chuangsuwanich; Malee Warnnissorn; Punnarerk Cristina Basso; Aierkeen Abudureheman; Gaetano Thiene, University of Padua, Pathology, Thongcharoen; Suthipol Udompanthurak, Siriraj Hospital, Mahidol University, Padova, Italy Bangkoknoi, Thailand Background: The Institute of Pathological Anatomy of the University of Padua holds Background: In contrast to mitral stenosis, in which post-infl ammatory disease accounts one of the largest anatomical collection of cardiac specimens. The collection started in for over 99% of valves, the causes of pure mitral regurgitation (MR) are multiple. The the 70’s at the dawn of cardiac surgery and includes nearly all nosographic entities of etiology includes fl oppy valve, post-infl ammatory disease, infective endocarditis, papillary both congenital and acquired heart disease representing nearly the whole epidemiological muscle dysfunction and other disorders. In the past two decades, the majority of mitral spectrum of modern cardiovascular pathology. Three separate collections, including 1400 valves excised surgically because of MR have gradually shifted from rheumatic to so- congenital heart disease, 480 juvenile (<35 yrs) sudden death and 600 cardiac transplantation called fl oppy valves. And there has been a tendency to remove only portions of the mitral have been previously classifi ed. The aim of the present work was to reassemble also the valve in cases of pure MR, particularly from the posterior leafl et, resulting in an increase XXVI Congress of the IAP: Abstracts 29 of partially excised specimens. Thus, determination of etiology of the disease on gross Histogenesis of these tumors is still unclear. They are thought to arise from subendothelial inspection may be diffi cult in some cases. The objective is to study the pathology, etiology resided cells, which are presumably of pluripotential origin. Cytogenetical and molecular and prevalence of mitral valve (MV) disease with pure MR from surgically removed mitral abnormalities of these tumors reveal its true neoplastic origin. In our opinion reported case valve specimens. can be considered malignant myxoma with solitary bone metastasis. Design: All native surgically excised mitral valve specimens with pure MR received during June 1999 to August 2003 (51months) were studied macroscopically and microscopically. 121 DANON DISEASE: A VERY UNSUAL CAUSE OF HYPERTROPHIC The functional disorder was determined by echocardiography and the etiology determined CARDIOMYOPATHY. PATHOLOGICAL FEATURES AND MOLECULAR according to the macroscopic, microscopic and clinical fi ndings. ANALYSES ON EXPLANTED HEART Results: Among 278 MV specimens from 274 patients (241 isolated MV, 36 with Paola Francalanci, Children Hospital Bambino Gesù, Rome, Italy; Federico Zara; Claudio concomitant aortic valves and 1 with concomitant tricuspid valve from patients aged 9- Bruno, Unit of Muscular and Neurodegenerative Disease, Istituto G. Gaslini, University of 83 years, mean age 48.2 years), 118 cases (43.1%) were classifi ed as fl oppy valve (age Genova, Genova, Italy; Luigi Ballerini; Stefania Petrini; Margherita Verardo; Francesco range 18 – 83 years, mean age 57.4 years), 85 cases (31 %) as post-infl ammatory disease Callea; Enrico Bertini, Bambino Gesù Children`s Hospital, Rome, Italy presumably rheumatic fever associated (age range 13-73 years, mean age 36.4 years), 33 Background: Danon disease is a X-linked cardioskeletal myopathy due to primary cases (12 %) as infective endocarditis and post-infective endocarditis (IE-postIE) (age range defi ciency of lysosome-associated membrane protein-2 (LAMP-2), one of the proteins 15 - 67 years, mean age 44.6 years) and 38 cases (13.9 %) classifi ed as miscellaneous group thought to protect the lysosomal membrane from proteolytic digestion. including dilated ring and undetermined etiology. Among fl oppy valves, 70 cases (59.8 Design: A boy presented at 4 months with hypotonia, cardiomegaly and cardiac failure. %) had diffuse myxoid change and 54 cases (45.3 %) showed chordal rupture. In post- Two dimensional echocardiography showed marked cardiomegaly with severe hypertrophic infl ammatory disease, 43 cases (51.2 %) revealed moderate to marked neovascularization, cardiomyopathy. Immunohistochemical, electron microscopy and molecular analyses of 70 cases (82.4 %) revealed mild to moderate chronic infl ammatory cell infi ltration. Aschoff muscle biopsy and of explanted heart were carried out. bodies were found in 2 cases. In IE and post-IE group gram positive cocci organism was Results: On muscle biopsy, all muscle fi bers immunohistochemistry showed complete found in 69.6 % and chordal rupture was found in 24.2 %. In miscellaneous group, 3 absence of LAMP-2, and some fi bers presented increased expression of LIMP-1 (lysosomal cases were related to Marfan syndrome and 3 cases the etiology was undetermined. In integral membrane protein). Ultrastructural examination displayed numerous vacuoles comparison with post-infl ammatory disease, the posterior leafl et in fl oppy valve had containing degenerating mitochondrion, glycogen and lipids. These features suggested a signifi cantly longer basal-free edge length (mean basal-free edge length of fl oppy valve Danon disease. The diagnosis was confi rmed by the identifi cation of a skipping mutation = 14.5 mm. p < 0.001), more frequent chordal rupture and older mean age of the patients. (c.928G>A) in exon 7 in the LAMP-2 gene, leading to a stop codon mutation. Patient Among completely and partially excised specimens with post-infl ammatory disease, there harbored a de novo mutation because it was not found in his healthy mother. Because of the were no signifi cant differences in microscopic fi ndings (neovascularization and chronic unexpected spontaneous improvement of muscle weakness a second muscle biopsy was infl ammatory cell infi ltration). performed at age 3 ½ years. The histological pattern showed a mild increase in glycogen Conclusion: Floppy valve, post-infl ammatory disease and infective endocarditis are the and rare vacuoles. Immunohistochemistry confi rmed complete absence of LAMP- three main diseases in surgically removed mitral valves with pure regurgitation with fl oppy 2 expression. At 6 years the child underwent a cardiac transplantation. Histopathology valve as the most common cause. Macroscopic and microscopic examinations together showed myocyte hypertrophy, extensive sarcoplasmic vacuolation, glycogen storage, and with clinical information, echocardiographic fi ndings and operative details are important in prominent interstitial fi brosis. LAMP-2 staining was lacking the characteristic lysosomal the evaluation of the etiology of the disease especially in partial specimens. perinuclear granular pattern, while LIMP-1 immunostaining was strongly expressed similar to the muscle. One year after transplantation the child shows a good cardiac function and 119 AUTOPSY FINDINGS OF CHILDREN DYING OF CONGENITAL HEART the neurological follow-up demonstrates no muscle weakness. DISEASE Conclusion: Early pathological and genetic diagnosis of Danon disease is not only Andrew Dettrick; Edwina Duhig, QHPS, The Prince Charles Hospital, Chermside, mandatory for genetic counseling but also for performing a timely cardiac transplantation, Australia the only effective therapy in this disorder. The overexpression of LIMP-1 in muscle and Aim: To determine how often myocardial infarction is found at autopsy in paediatric heart might play a pathogenetic role in Danon disease. patients dying of congenital heart disease and determine which cardiac anomalies and surgical procedures are most common. 122 IMMUNE MODULATORS IN SURGICALLY RESECTED VALVES OF Method: We reviewed the autopsy fi ndings from cases of children dying of congenital CHRONIC RHEUMATIC VALVULTIS heart disease at our institution over the last 5 years (Jan 2000 – June 2005 inclusive). Shivali Gupta; Kim Vaiphei; H Vohra; R. H. Singh; A Aggarwal, PGIEMR, Chandigarh, Twenty-two (22) cases were included. India Results: Myocardial infarction was the cause of death in 11/22 (50%) cases and some Background: The most serious sequele of rheumatic fever is the valvular lesions evidence of myocardial ischaemia was found in 17/22 (77%). Hypoplastic left heart resulting in permanent deformity and functional deformity. Unrevealing the sequence sequence is the most frequent fatal anomaly. The Norwood procedure is the most common of infl ammatory process in development of valvulitis would be a crucial step in better surgical procedure associated with death. Almost all patients dying of congenital heart understanding the basis of the disease process. disease have cardiomegaly, often massive. Chylothorax and thrombo-embolic events are Design: To delineate repertoire of the infi ltrating lymphocytes and expression of adhesion common complications. molecules in surgically resected valves of chronic rheumatic valvulitis. In fi ve patients, Discussion: Myocardial infarction is a frequent fi nding in this group and more frequent atrial appendages were also available for the study. Both fresh frozen tissue and formalin than the literature would suggest. Possible risk factors for myocardial infarction include fi xed paraffi n embedded tissue were used for the study. Sub-typing of the lymphocytes cardiomegaly, relatively frequent thromboembolic events, stress of surgery/anaesthesia and expression patterns of adhesion molecules were carried out on sections stained with and pre-existing cyanosis (hypoxia). Data regarding the value and impact of paediatric peroxidase anti-peroxidase technique. Monoclonal antibodies used were CD4, CD8, CD19, autopsies are surprisingly lacking in the literature, especially in congenital heart disease CD18, CD11a , CD11b, CD11c, L- selectin, VCAM-1 and ICAM-1. patients. Despite vast improvements in prognosis of patients with congenital heart disease, Results: All valves on histology showed extensive collagenisation, vascularisation there are still a signifi cant number of deaths in these children. The level of agreement and calcifi cation in some with mild to moderate degree of chronic infl ammatory cell between the pre-mortem and post-mortem fi ndings regarding anatomy and cause of death infi ltration. The atrial appendages had heavier infl ammatory cell infi ltration compared to is high. Nevertheless, the autopsy often provides extra information which may be clinically the corresponding valves of the same patients. The infi ltrating lymphocytes of the valves signifi cant. The rate of “full” autopsies is disappointingly low. and atrial appendages were positive for CD4, CD8, CD11a, 11b, 11c, CD18 and L-selectin. There was a strong expression for ICAM-1 by the valvular endothelial lining cells. The 120 UNUSUAL CASE OF CARDIAC MYXOMA atrial appendage showed much stronger expressions. CD19 staining was negative in all Patrik Flodr; Milada Duskova, Faculty of Medicine, Olomouc, Czech Republic the cases studied. Backround: Cardiac myxoma represents one of the most common benign cardiac tumors. Conclusion: In rheumatic valvulitis, adhesion molecules appear to play important roles in Myxomas form polypoid mass localized mainly in the left atrium near the fossa ovalis. pathogenesis of the disease via T-cell mediated immune response. Microscopic evaluation reveals elongated, fusiform or stellate cells arranged singly, in cords or in vasoformative structures. Mitosis are very rare. Thick vessel with prominent 123 ORGANOSPECIFIC MORPHOMETRIC STANDARDS TO ESTIMATE muscular wall and thin vessels without pericytes can be present. Rarely, well-defi ned HYPERTENSIVE ANGIOPATHY columnar cells forming glands are encountered and may show cytologic atypia with mitotic Alex Gutsol, University of Manitoba, Kharkov National University, Winnipeg, MB, activity. Immunohistologically, they are positive for CK7, AE1/AE3, 4betaE12, Cam 5.2, Canada; Shyamala Dakshinamurti, University of Manitoba, Winnipeg, MB, Canada EMA, CEA and focal for CK20. Background: Despite obvious needs pathologists still don’t have reliable quantitative Design: We present a case of 60 years old man with atypical cardiac myxoma and solitary criteria to estimate arterial remodeling in different pathological processes. As it is already bone metastasis, which occurred thirteen months after the diagnosis of cardiac tumor obvious for heart pathology, a muscular propulsion contracting structure can exhibit was made. Both myxoma and bone metastasis showed similar histologic appearance and hypertrophic, restrictive or dilational myopathy. We hypothesized that similar processes the same immunoprofi le. Following imaging disclosed no another tumor and now, three are possible in arterial system as a part of very different remodeling processes for essential years after the initial diagnosis of atypical myxoma, patient is without any sign of other and symptomatic hypertension, vasculitis, atherosclerosis, congestive heart failure but neoplasia. adequate morphometric methods are needed. Results: Histopathologic fi nding revealed tumor, which apart from typical myxoma Design: We analyzed 100 autopsies (ages 40-70 years), 30 cases were considered structures formed irregular spaced glands. Epithelium of these glands showed cytologica normotensive, 70 had essential hypertension. Animal models were used as experimental atypia and increased proliferative activity (Ki67 20%). Immunohistochemically it showed vasorenal hypertension (VRH) created in 60 rats (ages 12-24 months), and 60 spontaneous positive staining for AE1/AE3, CEA and was negative for TTF1. hypertensive rats (SHR, ages 12-24 months). The arterial vessels in the brain, heart, kidney, Conclusion: Only few cases of cardiac myxomas with malignant features were presented liver, pancreas, spleen, lung, skin, skeletal muscle were analyzed on 4 µm paraffi n sections and labelled as primary cardiac adenocarcinomas, but none of them metastasize. stained with H&E, Masson`s thrichrome and Verhoeff’s Van Gieson staining for elastin. 30 XXVI Congress of the IAP: Abstracts Three random tissue blocks, ten random tissue slides were scanned to measure only clear anticoagulated plasma samples at Biosite Diagnostics and the Stroke Index calculated by transversal sections of arteries and arterioles with external diameter (ED) ≤ 150 µm. the software on the instrument. A two-tailed Student`s t-test was used to assess changes Results: Every organ has a specifi c three-dimensional arterial tree as the structural base pre- and post-marathon by Microsoft Excel software. providing organ specifi c hemodynamics. Quantifi cation of three-dimensional remodeling Results: Mean values for MMP-9 (p<0.001), D-dimer (p<0.001), and BNP increased in the arterial tree is impossible with just mean values of common using internal diameter (p=n.s.), whereas S100 beta decreased (p=n.s.) between pre- and post-marathon values. (ID) / wall thickness (WT) or similar ratios. Analysis with the complex profi le method Also, the values pre- and post-marathon for the stroke marker index increased from 0.97 substantiate that using only ID/WT or ED/ID mean value ratio gives false results because (normal) to 3.5 (low risk) [p< 0.001]. Before the race, only one of the runners had a of random or specifi c to organs domination of arteries from bigger or smaller clusters. measurable level of TnT (0.014 ng/ml), whereas after the race 21 (70%) exhibited The calculation of the equation of the regression of ID on ED or WT gives very reliable measurable troponin values. The mean values for troponin-T increased from <0.01 ng/mL (p<0.001) equations describing hemodynamicaly specifi c arterial tree (e.g. in the brain as to 0.03 ng/mL (p< 0.0001) between pre- and post-marathon samples. Troponin T values ID = 0.57ED - 0.65; the heart as ID =0.50ED - 0.9; the kidney as ID = 0.50ED - 2.43 for the after the race correlated only loosely with the stroke marker index value (r-squared=0.33). human). These equations are also specifi c for human or rat organs and prove that the ratio No adverse medical events occurred in our cohort of patients during or after the race. ID/WT must not be averaged through random measured “small arteries” even for vessels Conclusion: These results provide strong evidence of subclinical myocardial injury in in relatively narrow range cluster with ED ≤ 150 µm. Normal nomograms for ∆ID/ ∆ED/ non-elite marathon runners. The signifi cance of the increase in stroke index following ∆WT values have to be scaled to adequately analyze narrowing, dilation, hypertrophic or competition is not clear given the concomitant increases in troponin in this population. The atrophic process in arterial walls. This three-step method allows us to show organ specifi c elevation in stroke index most likely represents a confl uence of biochemical anomalies that three-dimensional changes in small arterial vessels for essential human, VRH or SHR does not indicate the presence of an acute cerebrovascular event. The signifi cance of the hypertension. elevations in the stroke index and two of its component markers is not resolved and needs Conclusion: Adequate morphometric analysis of arterial remodeling must consist of the further clarifi cation three-step method including creation of the complex profi le, calculation of the equation of the regression and drawing of the nomogram. It prepares easy to use standards for 126 PLAQUE EROSION AND HEMORRHAGE ON THE CAROTID analysed organs and animals and allows to estimate hypertrophic or dilational patterns ENDARTERECTOMY SPECIMENS MAY RESULT FROM PLAQUE RUPTURES of remodeling. PREVIOUSLY OCCURRED IN THE PERIOD OF MILD LUMINAL STENOSIS Hiroaki Murakami; Chikao Yutani; Shinobu Doi, Okayama University of Science, 124 C4D STAINING IN CARDIAC ALLOGRAFTS: EXPERIENCE WITH 1103 Okayama, Japan; Hatsue Ishibashi-ueda; Naoaki Yamada; Hiroaki Naito; Koji Iihara; ENDOMYOCARDIAL BIOPSIES FROM 442 PATIENTS Susumu Miyamoto; Kazuyuki Nagatsuka, National Cardiovascular Center, Osaka, Japan Chi K. Lai; Jon A. Kobashigawa; Juan C. Alejos; Elaine F. Reed; William D. Wallace; Background: Although patho-etiological mechanism of atherosclerotic plaque rupture Peter Shintaku; Michael C. Fishbein, David Geffen School of Medicine at UCLA, Los was well known, the mechanism of plaque erosion and hemorrhage has remained Angeles, CA, United States unclear. We histopathologically examined plaque erosion and hemorrhage on the carotid Background: C4d deposition in peritubular capillaries of renal allografts is a marker endarterectomy (CEA) specimens. of humoral rejection (HR)(antibody-mediated rejection) and is associated with a worse Design: Atherosclerotic plaques from 32 patients undergoing CEA were examined outcome. Although similar fi ndings are observed in cardiac allografts, there are no data histologically, with sections obtained every 3 to 5 mm after fi xation and decalcifi cation. regarding the pattern of C4d staining in a large population of cardiac transplant patients. Hemorrhage with glycophorin A, vascular endothelial cell with CD34, macrophage with Our objective was to correlate C4d staining patterns with acute cellular rejection (ACR), CD68 were examined with use of immunohistochemical staining. Hemorrhages, thrombi, Quilty lesion (QL), and HR in endomyocardial biopsies (EMBs). calcifi cations and foam cell infi ltration were carried out semi-quantitative analysis, and Design: We reviewed all EMBs results in which C4d staining was performed from 1/2001 fi brous caps were divided into myxomatous degeneration and fi brous components. An to 9/2005. C4d detection was performed by immunofl uorescence studies of frozen tissue acute plaque rupture consisted of a luminal platelet-fi brin-rich thrombus continuous (IF), immunoperoxidase staining of paraffi n-embedded tissue (IP), or both at the time of with an underlying lipid-rich core through a disrupted thin fi brous cap. Plaque erosion EMBs. was defi ned as an acute thrombus in direct contact with the intimal plaque. Stable plaque Results: There were 1103 EMBs from 442 pts: 288 males and 154 females, ranging in (non-ruptured group) was defi ned as cross-sectional luminal narrowing in the absence of age from 2 wks to 78.0 yrs (mean = 41.4 ± 23.1 yrs). Of these, 118 EMBs from 64 pts had a luminal thrombus. histologic and immunohistochemical evidence for HR. Of the EMBs with C4d positivity Results: 1. Non-ruptured group showed severe luminal stenosis, however it showed mild by IF, 22/412 (5.3%) had no histologic fi ndings of ACR, QL, or HR; 11/107 (10.3%) had hemorrhage in plaque. In this group, thick fi brous capsule may prevent plaque rupture. ACR only; 16/207 (7.7%) had QL only; 9/145 (6.2%) had both ACR and QL; and 45/83 2. Rupture sites in plaque ruptured group did not show severe luminal narrowing, (54.2%) had HR. Of the EMBs with C4d positivity by IP, 2/38 (5.3%) had no histologic lipid-content was large, and foam call infi ltration was remarkable, and associated with fi ndings of ACR, QL, or HR; 0/22 (0.0%) had ACR only; 4/65 (6.2%) had QL only; 0/31 hemorrhages and thrombi. 3. Plaque erosion was seen in 7 cases of 32examples (22%), (0.0%) had both ACR and QL; and 43/83 (58.9%) had HR. For the diagnosis of HR, IF for also degree of stenosis was most severe. Infl ammatory cell infi ltration with of the moderate C4d had a sensitivity of 54.2%, specifi city of 93.3%, positive predictive value of 43.7%, degree was seen in the capsule area, and the area of myxomatous degeneration occupied and negative predictive value of 95.5%. For IP, these values were 58.9%, 96.1%, 87.8%, large part in the capsule. and 83.3%, respectively. In 63 EMBs from 52 pts negative for HR, C4d was positive by Conclusion: 1. Plaque rupture occurred in mild stenosis might be responsible for results IF or IP. of hemorrhage followed by thrombus-formation in the plaque. 2. It is most likely that Conclusion: 1) C4d positivity by IF or IP is very specifi c for HR; 2) C4d negativity has thrombi on the plaque erosion could be associated with myxomatous degeneration, as a a high negative predictive value for HR, and 3) almost half of EMBs with HR are C4d wound heeling process of previous plaque ruptures. 3. In order to prevent plaque rupture, negative. The effect of therapy on HR and C4d detection, and whether histologic HR or it is necessary to evaluate lipid-rich core even in the time of mild stenosis even in early C4d positivity correlates better with antibody status and outcome are under study. stage of atherosclerosis.

125 MEASUREMENT OF A PLASMA STROKE BIOMARKER PANEL AND 127 CARDIAC MYXOMA CELLS EXHIBIT EMBRYONIC ENDOCARDIAL CARDIAC TROPONIN T IN MARATHON RUNNERS BEFORE AND AFTER STEM CELL FEATURES THE 2005 BOSTON MARATHON Augusto Orlandi; Alessandro Ciucci; Amedeo Ferlosio, Anatomic Pathology Institute, Tor Elizabeth Lee-Lewandrowski; Kent Lewandrowski, Division of Laboratory Medicine, Vergata University, Rome, Italy; Robert Genta; Giulio Gabbiani, Department of Pathology, Department of Pathology, Massachusetts General Hospital, Boston, MA, United States University of Geneva, Geneva, Switzerland; Luigi Giusto Spagnoli, Anatomic Pathology Background: Athletes are known to exhibit a number of laboratory test abnormalities Institute, Tor Vergata University, Rome, Italy following competition including markers refl ecting rhabdomyolysis and myocardial Background: The origin of myxoma, the most frequent tumour of the heart, remains ischemia (creatine kinase and its isoenzyme CK-MB, troponin-I and T), left ventricular uncertain. Previous phenotypic characterizations have shown heterogeneous results and function (B-type natriuretic peptides), D-dimer, CRP, and other hemostatic/infl ammatory the most recent hypothesis suggests that cardiac myxoma originates from a primitive markers. While the signifi cance of these changes is unclear, it has been postulated that pluripotential cardiogenic cell. elevations in cardiac troponins may refl ect reversible myocardial stunning or minor Design: We investigated the expression of actin isoforms and stem cardiac markers in 30 myocardial damage indicating true ischemic injury and cell death. Biochemical evidence cases of left atrial myxomas by immunohistochemistry and in eight consecutive tumours of injury to non-cardiac organs in otherwise healthy athletes is sparse. Recently, Biosite by RT-PCR. Diagnostics developed a rapid immunoassay multimarker stroke panel for the detection Results: In all cases, á-smooth muscle actin (á-SMA) protein and/or transcripts were of stroke in symptomatic patients. The Triage stroke panel consists of S100 beta, matrix detected, whereas á-cardiac actin was observed in few cases and á-skeletal actin always metalloproteinase-9 (MMP-9), BNP, and D-dimer. The sample is interpreted by a software absent. Besides classical aspects, vascular-like structures were characterized by cells algorithm (MultiMarker Index) that analyzes information from the four biomarkers to yield expressing CD34 and less frequently á-SMA. Confocal microscopy showed the focal a stroke index ranging from 0-10 with two cutoffs of <1.3 (low risk) and >5.9 (high risk) co-expression of CD34 and á-SMA in myxoma cells, suggesting a gradual loss of stem for stroke. The purpose of this study is to examine markers of cardiovascular injury and endothelial markers and the acquirement of myocytic antigens. In order to confi rm stress (troponin and BNP) and the results of the stroke panel among non-elite runners this hypothesis, early cardiac differentiative markers were also investigated. RT-PCR completing the 2005 Boston Marathon. documented the presence of transcripts for Sox9 (100%), Notch1 (87.5%), NFATc1 Design: Thirty-fi ve marathon runners scheduled to run the 109th 2005 Boston Athletic (37.5%), Smad6, metalloproteinases 2 and 1 alone or in variable combinations and the Association Marathon were recruited. We excluded subjects with a history of cardiovascular absence of ErbB3 and Wilms’ Tumour transcription factor 1. Myxoma cells maintained disease. A comprehensive general health exam was performed for each subject. Whole phenotypic heterogeneity in vitro, including the expression of á-SMA and the presence blood samples were collected before and immediately following the race and processed of stress fi bres. immediately. Plasma samples were tested immediately for troponin T using a Roche Elecsys Conclusion: These fi ndings document in cardiac myxoma cells the phenotypic markers 2010 immunoassay analyzer. The Biosite Triage stroke panel was performed on EDTA of the embryonic endothelial-to-mesenchymal transformation preceding terminal XXVI Congress of the IAP: Abstracts 31 differentiation of endocardial cushions, supporting the hypothesis that cardiac myxoma Conclusion: The presence of cardiac involvement by amyloid is the most important cells may derive from adult developmental remnants. prognostic factor in patients with amyloidosis. Previous reports have shown that SSA results in slowly progressive heart failure whereas AL amyloidosis produces rapid 128 INTRAPARENCHYMATOUS ARTERIAL AND CAPILLARY progression of heart failure. This morphometric study showed all patients with heart MORPHOLOGICAL CHANGES IN HYPERTENSIVE PATIENS DEAD WITH failure, with and without amyloidosis, displayed greater luminal areas than normal INTRACEREBRAL HAEMORRHAGE controls. Moreover, a twofold dilatation of the vessels in the subepicardium compared to Iancu Emil Plesea, University of Medicine and Pharmacy, Department of Pathology, those in the subendocardium was noted only in patients with AL amyloidosis. This may Craiova, Romania; Stelian Danut Enache; Alexandru Camenita, Emergency County be due to the degree of intramural vascular involvement by amyloid in these patients, University Hospital, Department of Neurosurgery, Craiova, Romania; Oltin Tiberiu Pop, which concomitantly decreases the transmural perfusion pressure leading to compensatory University of Medicine and Pharmacy, Department of Pathology, Craiova, Romania; expansion of the subepicardial vessels. These fi ndings may explain the dismal outcome of Mihaela Tenovici, National Railways System Universitary Hospital, Department of patients with AL amyloidosis. Pathology, Craiova, Romania; Cornelia Enache, Emergency County University Hospital, Department of Neurology, Craiova, Romania 130 ISOLATED SEIZURES IN THE YOUNG AND PARADOXICAL Background: The rupture of a intraparenchymal vascular wall usually hides or at least EMBOLISM modifi es the real vascular pathology making thus diffi cult the study of the main cause James Southern, Medical College of Wisconsin, Brookfi eld, WI, United States; Lynda of primary intracerebral haemorrhage. Therefore the purpose of this study was to assess Biedrzycki, Waukesha County Medical Examiner`s Offi ce, Waukesha, WI, United States the alterations of intraparenchymal arterial and capillary in patients suspected of primary Background: Embolic strokes are usually associated with carotid atherosclerotic disease intraparenchymal hematoma, which died and were autopsied in order to confi rm the or cardiac disease with associated luminal thrombi. In the young , underlying carotid diagnosis. disease or cardiac disease with associated cardiac atrial mural thrombus may be absent Design: 82 hypertensive cases were selected which died with stroke and were confi rmed and in this setting, intra cardiac shunts- atrial or ventricular septal defects and the potential with intracerebral haemorrhage by autopsy. The studied material consisted of nervous tissue shunt of a patent foramen ovale- are associated with the stroke event. situated near and distant from the haemorrhagic lesion. The specimens were processed Design: A 32-years-old white male collapsed while conversing by telephone with a witness- by the classical histological technique (neutral buffered formalin fi xing and paraffi n described `seizure` and died despite resuscitation efforts in the fi eld and continuing in the embedement) and stained with usual stainings (H-E, van Gieson and Goldner trichromes) emergency room. Childhood medical problems were restricted to `asthma`. He reportedly and with immunohistochemical stains for basement membranes and endothelial cells. had a previous possible seizure two years earlier but was not treated for that event and had Results: Penetrating arteries and intraparenchymal arterioles showed the entire spectrum no recurrences until his fatal collapse. In the week prior to his collapse, he had a severe of lesions due to arterial hypertension including all steps of vascular wall degeneration: nosebleed and complained of headaches. thickening and folding of the inner elastica, hypertrophy of the middle smooth muscle Results: At autopsy, the interatrial septum had a patent foramen ovale. A bifurcated layer, progressive and exgtensive fi brosis, starting from the outer adventicial layer with thrombus with one round end was present in the foramen extending 0.7 cm into the simultaneous smooth muscle atrophy and, fi nally, hyaline degeneration of the collagen right atrium and 2.5 cm into the left atrium. The bifurcated end was leftward. Gross fi bres which replaced the middle and outer vascular wall layers. All these alterations and microscopic examination of the brain did not demonstrate infarct or identifi able had a focal irregular distribution, not related with the proximity of haemorrhagic focus. intravascular thromboembolism in the proximal cerebral circulation. No thrombi were Capillary walls showed also interesting morphological changes, consisting of focal or found in the deep leg veins. circumferential thickening due to the densifi cation of the type IV collagen material from Conclusion: The paradoxical embolism in transit through the foramen ovale highlights the the basement membrane structure. The CD 34 immunostaining showed that endothelial potential risk of embolic stroke to the greater than 1/3 of the human population with this cells kept their structural integrity. normal cardiac anatomic variation. Additionally the occurrence of isolated single seizures Conclusion: The sequence of cerebral vascular wall degenerative lesions results in in young adulthood warrants full evaluation including cardiac examination. hyalinization of excessive fi brillar material from arteriolar wall or from basement membranes. Hyalin material is weakening the wall resistance when exposed to the stress 131 FATAL HEMORRHAGE ASSOCIATED WITH PERCUTANEOUS caused by blood pressure high values in hypertension and, correlated with a minimal VASCULAR CLOSURE DEVICE resistance of the surrounding cerebral parenchyma, can explain why the cerebral James Southern, Medical College of Wisconsin, Brookfi eld, WI, United States; Lynda parenchyma is the only tissue in which blood pressure variations can determinate vascular Biedrzycki, Waukesha County Medical Examiner`s Offi ce, Waukesha, WI, United States rupture and cerebral haemorrhage. The more adequate term for describing the vascular Background: Achieving hemostasis following femoral arterial access for cardiac wall changes seems to be sclerosis (arteriolar and even capillary) with hyalinosis. angiography/ angioplasty has traditionally been done by manual application of direct pressure to the arterial puncture site. Non-manual external pressure devices have functioned 129 HISTOMORPHOMETRIC ANALYSIS OF INTRAMYOCARDIAL poorly due to easy displacement by even small patient movements. Percutaneous arterial VESSELS IN PATIENTS WITH CARDIAC AMYLOIDOSIS: EPICARDIUM VS puncture closing devices have been introduced to close the defects without the prolonged, ENDOCARDIUM staff intensive interaction. Preeti Sharma, University of Alabama at Birmingham, Birmingham, AL, United States; Design: The Angio-Seal™ (St. Jude Medical Inc., St. Paul, Minn.) consists of an absorbable Saeed Payvar, University of Texas Southwestern Medical Center, Dallas, TX, United polymer anchor placed within the lumen of the artery used for vascular access attached by States; Silvio Litovsky, University of Alabama at Birmingham, Birmingham, AL, United suture to an absorbable sponge outside the artery. An Angio-Seal™ device was placed States to close a right femoral artery puncture site following angiography and double coronary Background: Cardiac amyloidosis is defi ned by the histological presence of insoluble stent placement in a 71 years-of-age woman. She developed worsening hypotension fi brillar proteins around myocytes and within or around intramyocardial vessels. In a not responsive to inotropic agents over 1 1/2 hours following her procedure leading to recent abstract (Laboratory Investigation 2006; 86 (Suppl 1): 7A), we found that patients cardiorespiratory arrest with unsuccessful attempted resuscitation. with primary amyloidosis (AL) showed focally transmural intramyocardial vascular Results: At autopsy, massive retroperitoneal hemorrhage centered on the right side and involvement by amyloid with thickening of the media and narrowing of the lumens. In extended leftward in the pelvis. Left and right external iliac and common femoral arteries contrast, in patients with senile systemic amyloidosis (SSA), the vessel thickness was not and veins were explored in continuity from the lumbar region to the upper mid thighs. Soft affected by the amyloid deposition, as it was concentrated largely in the adventitia and tissue hemorrhage surrounded the right neural-vascular bundle at and proximal to arterial external media. To our knowledge, previous studies have examined the vascular deposition and venous puncture sites. Two venous puncture wounds were present in the right femoral of amyloid only qualitatively. The purpose of this study was to evaluate, in quantitative vein, one with a 3 lumen catheter in place. The right femoral artery had four puncture terms, the luminal areas of intramyocardial vessels in patients with cardiac amyloidosis sites- a 2 mm puncture at 3.1 cm proximal, a 3 mm puncture at 2.5 cm proximal and paired in order to elucidate the relationship between vascular deposition of amyloid and the 1 mm punctures at 2.3 and 2.2 cm proximal to the origin of the deep femoral artery and pathophysiology of myocardial perfusion in this condition. distal to the inguinal ligament. The Angio-Seal™ device was deployed and embedded in Design: The autopsy fi les at our institution from 1981 to present were reviewed to identify the hemorrhagic soft tissue with its anchor adjacent to but not in the femoral artery wall all individuals with the postmortem fi nding of cardiac amyloidosis. A total of 20 cases with or lumen. confi rmed cardiac amyloid by Congo red staining and typical apple-green birefringence Conclusion: While hemorrhage has been listed as one of the complications following use under polarized light were included. Each case was classifi ed into a particular amyloid of this device, failure to anchor the device in the vessel wall has not been cited specifi cally. syndrome (SSA, n=7, AL, n=11, secondary, n=1 and familial, n=1) according to careful While improper insertion of the device appears to be a rare event, confi rmation of proper review of hospital records. Histomorphometric analysis using Bioquant Image Analysis device deployment is a reasonable precaution, considering the potential severe morbidity was performed in SSA and AL amyloidosis patients, 8 normal controls, and 5 patients or morality associated with an open arterial defect. Exploration of the insertion site during with heart failure without amyloidosis. The luminal areas of multiple vessels (5-6 vessels/ postmortem examination will will help determine the frequency and clinical signifi cance zone) were measured from the outer third (subepicardium), middle third, and inner third of device failure. (subendocardium) of the left ventricular free wall. Results: Histomorphometric analysis revealed patients with AL amyloidosis, SSA, and 132 CYCLOOXYGENASE-2, AKT AND ERK 1/2 IN TERMINAL HEART heart failure without amyloidosis possessed greater luminal vascular areas than normal FAILURE AND AFTER LEFT VENTRICULAR MECHANICAL UNLOADING controls. The ratio of subendocardial to subepicardial vascular luminal areas was compared Jeremias Wohlschlaeger; Klaus J. Schmitz, Institute of Pathology, University Hospital in the above-mentioned groups. The median of this ratio was 0.53 (CI95% 0.23-0.79) in AL Essen, Essen, Germany; Bodo Levkau, Institute of Pathophysiology, Department of Internal amyloidosis patients, 1.03 (CI95% 0.70-1.82) in SSA patients, 0.81 (CI95% 0.67-1.20) in Medicine, University Hospital Essen Essen, Germany; Christof Schmid, Department of normal controls and 0.62 (CI95% 0.30-2.53) in heart failure without amyloidosis patients. Heart-, Thoracic and Vascular Surgery, University Hospital Münster, Münster, Germany; This ratio was compared among the four groups using the Kruskal-Wallis analysis of ranks Kurt W. Schmid; Hideo A. Baba, Institute of Pathology, University Hospital Essen, Essen, test. The chi-square test for the difference was 9.289, p-value=0.0257, indicating there was Germany a signifi cant difference among the four groups. Background: Among other infl ammatory factors, increased expression of cyclooxygenase- 32 XXVI Congress of the IAP: Abstracts 2 (COX-2) has been reported in chronic heart failure (CHF). In vitro and animal studies approximately 5% of which were reported as ASC-US (ASC/SIL = 2.5). BV was reported demonstrated that COX-2 is involved in the development of cardiac hypertrophy during the in 6% of cases. Overall 34.8% women with ASC-US were HPV+, and 23.7% were progression of CHF. COX-2 expression is regulated through multiple signalling pathways HRHPV+. Women under 30 had a 50% overall and a 36.9% HRHPV positivity, while including the PI3K/Akt pathway. Left ventricular assist devices (LVAD) treatment leads women >=30 had signifi cantly lower overall HPV+ (24.3%) and HRHPV+ (14.7%) rates. to restoration of basic cardiac function in a subgroup of patients, which is refl ected by The 357 (6.1 %) women that had BV reported had both signifi cantly higher HPV+ rates decreased cardiac hypertrophy and numerous molecular changes (“reverse remodeling”). (51% vs. 33.7%, p<0.001) and HRHPV rates (38.1% vs. 22.8%) than women with no BV This study investigates the expression of COX-2, phosphorylated Akt and Erk 1/2 in CHF reported. The difference was more marked in women under 30 who had a 63.18% vs. before and after LVAD. 48.79% HPV+ rate and a 49.75% vs. 35.65% HRHPV+ rate when women with ASC-US Design: In paired myocardial tissue of 38 patients before and after LVAD, the protein with and without BV were compared. expression of COX-2, p-Akt (Thr 308) and (Ser 473) and p-Erk 1/2 was demonstrated Conclusion: The rate of HPV+ and HRHPV+ was higher in women with ASC-US that also by immunohistochemistry and quantifi ed by morphometry before and after LVAD. had BV reported as compared with women with LBPT reported as ASC-US without BV. Immunodoublestaining was used to investigate a potential co-localisation of COX-2 and Possible explanations include the presence of similar risk factors for the two infections, p-Akt (Thr 308). a possible increased susceptibility to HPV infection or persistent infections conferred by Results:There is a signifi cantly decreased protein expression of COX-2, p-Akt (Thr 308) the loss of H2O2-producing lactobacilli or other changes in the vaginal milieu caused by and (Ser 473), p-Erk 1/2 and cardiac hypertrophy after mechanical unloading. Moreover, BV. Alternatively the higher prevalence of HPV in ASC-US with BV may be related to a signifi cant correlation between COX-2 and immunoexpression of p-Akt (Thr 308) as the potential obscuring of HPV-related cytologic changes by the presence of a fi lm of well as cardiomyocyte diameter, but not for p-AKT (Ser 473) and p-Erk 1/2 in CHF was coccobacillary microorganisms that renders an accurate interpretation of koilocytic observed before LVAD. However, this correlation was lacking after LVAD support. Co- changes diffi cult resulting in a diagnosis of ASC-US instead of LSIL. localisation of COX-2 and p-Akt (Thr 308) could be demonstrated in only in a subset of cardiomyocytes. 135 TELECYTOLOGY: DEVELOPMENT AND IMPLEMENTATION OF A Conclusion: LVAD treatment is associated with a signifi cant decrease of COX-2, p-Akt CLINICAL SERVICE FOR USE FROM REMOTE SITES (Thr 308) and (Ser 473) and p-Erk 1/2 as well as cardiac hypertrophy. The signifi cant Anuradha Arcot; Karlene Hewan-Lowe; James Finley, Brody School of Medicine at East correlation of COX-2 and p-Akt (Thr 308) in CHF may suggest a cross talk between the Carolina University, Greenville, NC, United States two molecules in the progression of cardiac hypertrophy. Background: We describe our experience with the establishment of a telecytology service for use at a small community hospital remotely located (150 miles) from our tertiary care 133 EFFECTS OF LOW-INTENSITY LASER ON PATHOLOGICAL CHANGES medical center. Utilizing a commercial robotic microscope (Coolscope-Nikon®) with a OF AORTIC ATHEROSCLEROSIS IN RABBITS JIANZHONG ZHANG, digital camera and network broadband (T1) connection, rapid assessment of adequacy of SHIQUAN XU, YINGQI LIU, ET AL. DEPARTMENT OF PATHOLOGY, 306 fi ne needle aspiration (FNA) biopsy specimens from a variety of sites was performed. HOSPITAL OF PLA, BEIJING 100101, CHINA The system allows multiple users to access the images simultaneously for subspecialty Jianzhong Zhang, Beijing 306 Hospital, Beijing, China consultation, obviating the need for an on-site expert. Background: Biological effect and its mechanism of low-intensity laser on atherosclerosis Design: FNA biopsies were performed by a radiologist using ultrasound or CT guidance was not well elucidated. It was to observe the effects of low-intensity laser (650nm/mw) on at the remote hospital. Cytologic smears (CS) were prepared either by a medical the pathological changes of aortic atherosclerosis in a rabbit model. technologist or an on-site pathologist. The medical technologists received prior training Design:Thirty-six male Zelanian rabbits were randomly and equally divided into 4 groups: in smear preparation, staining technique and basic operation of the robotic microscope. A control, laser radiation, simvastatin treatment and laser plus simvastatin. All the animals cytopathologist at the tertiary care medical center then viewed the slide preparations for were fed with high-fat diets during the experiment. Blood sampling was taken for lipid adequacy, rendered a preliminary interpretation and assessed the need for additional passes assay at 60th day. The animals were terminated at 61st day and aortas removed for gross for special studies. This was accomplished using a web browser and graphic user interface. and microscopic examinations, and Sudan III staining and morphometry analysis. The The initial cytologic preliminary interpretations rendered for 11 cases were compared to pathological changes were graded mild, intermediate and severe according to the varying the fi nal diagnosis and if available, surgical pathology diagnosis. Diagnostic accuracy and severity of atherosclerosis in aorta. the time from start to rendering a preliminary interpretation were monitored for each case. Results:There were no signifi cant differences (p>0.05) in blood fat level between the Results: Eleven telecytology cases (FNA biopsies of 4 thyroid lesions, 2 liver lesions, four groups before the experiment, but signifi cant difference (p>0.05) existed in serum 1 scapular bone lesion, 1 paraspinal mass, 1 enlarged peripancreatic lymph node and triglyceride after the treatments. LDL-C in control group was signifi cantly higher than CS of 2 breast lesions) reviewed had good correlation between the initial and the fi nal those in laser radiation, simvastatin treatment and laser plus simvastatin groups (p<0.01). diagnosis with no discrepancies. The time taken to render a preliminary diagnosis has There were also a signifi cant difference in HDL-C level among laser radiation group, been comparable to routine methods except for paucicellular specimens especially FNA laser plus simvastatin group and control group (p<0.01). The pathological changes were biopsies of thyroid lesions. Other problems encountered include web access issues and correlated with blood-fat levels. The mild atherosclerosis was found in the treated groups, slow response time for each web command execution. but severe or intermediate atherosclerosis mostly existed in control group. Conclusion: Our study demonstrates that telecytology is comparable to conventional Conclusion:Low-intensity laser only or combined with the drug can signifi cantly decrease methods of slide examination except for paucicellular specimens where it approximately blood-lipid levels and severity of the pathological changes of aortic atherosclerosis in this doubled the time needed to scan the slide prior to rendering a preliminary diagnosis. Web animal model. access issues were addressed by adjusting browser settings and managing cookies. The slow command execution time remains an issue with the current system, but may improve with Cytopathology newer software/systems in the future. In order to operationalize the system, it is necessary to have well trained personnel at the remote site. Overall, we feel that telecytology will be a cost effective tool that will support expansion of tertiary care pathology services to 134 WOMEN WITH LIQUID-BASED PAP TESTS (LBPT) INTERPRETED remote sites. AS ATYPICAL CELLS OF UNDETERMINED SIGNIFICANCE (ASC-US) ARE MORE LIKELY TO BE HUMAN PAPILLOMAVIRUS (HPV) POSITIVE WHEN 136 ARE WOMEN WITH LIQUID-BASED PAP TESTS (LBPT) INTERPRETED COCCOBACILLI CONSISTENT WITH BACTERIAL VAGINOSIS (BV) ARE AS NO EVIDENCE OF INTRAEPITHELIAL LESION OR MALIGNANCY (NILM) ALSO PRESENT MORE LIKELY TO HAVE HUMAN PAPILLOMAVIRUS (HPV) INFECTIONS Mariam Alsharif; Anthony-Osei Safo, University of Minnesota Medical Center, WHEN MICROORGANISMS ARE REPORTED? Minneapolis, MN, United States; Dan McKeon, University of Minnesota Medical Center, Gregory Ausmus, University of Minnesota Department of Laboratory Medicine and Fairview, Minneapolis, MN, United States; Kay Savik; Evin Gulbahce, University of Pathology, Minneapolis, MN, United States; Dan McKeon, University of Minnesota Minnesota Medical Center, Minneapolis, MN, United States; Stefan E. Pambuccian, Medical Center, Fairview, Minneapolis, MN, United States; Kay Savik, University of University of Minnesota Department of Laboratory Medicine and Pathology, Minneapolis, Minnesota, Minneapolis, MN, United States; H. Evin Gulbache, University of Minnesota MN, United States Department of Pathology and Laboratory Medicine, Minneapolis, MN, United States; Background: BV, a condition diagnosed in the Pap test based primarily on the Stefan E. Pambuccian, University of Minnesota Department of Laboratory Medicine and identifi cation of clue cells is a common, complex polymicrobial disorder characterized Pathology, Minneapolis, MN, United States by decreased lactobacilli and increased colonization by several facultative or strictly Background: A recently recommended screening strategy is to test women older than 30 anaerobic microorganisms, mainly Gardnerella vaginalis, Prevotella spp, Bacteroides with a combined LBPT with HPV DNA test. Most of such Pap tests are reported as NILM, spp, and Mobiluncus spp, that is associated with a variety of obstetric and gynecologic but some of these may also show the presence of microorganisms such as coccobacilli complications. BV has recently been shown to be associated with an increased risk of (bacterial vaginosis, BV), Candida (CAND), Trichomonas (TV), and herpes simplex prevalent and incident HPV infection. The aim of this study was to test the hypothesis that (HSV). The presence of these infections may result in mild cytologic changes that are women with ASC-US LBPT results also showing BV have an increased prevalence of HPV usually not pronounced enough to warrant a diagnosis of ASC or above. To our knowledge, infections on refl ex HPV DNA testing. the interaction between such infections and HPV infection in the setting of a normal LBPT Design: LBPT (SurePath®) interpreted as ASC-US according to the Bethesda 2001 system, has not been studied. While some of these microorganisms are sexually transmitted and that had PCR-based HPV DNA testing with MY09/11 primers and genotyping by RFLP may refl ect a possible co-infection with HPV, others could either refl ect or result in a performed between 12/01/02 and 5/31/05 were reviewed. HPV genotypes were assigned lowered local immunity that may increase the susceptibility for HPV infection or delay its to risk groups according to Munoz et al, 2003, with probable high risk types included as clearance. The aim of this study was to test the hypothesis that women with NILM LBPT high risk HPV (HRHPV). Age, HPV DNA test results (presence/absence, risk type and results with microorganisms show an increased prevalence of HPV infections. genotype) as well as, when available follow-up biopsy results were tabulated. Design: LBPT (SurePath®) interpreted as NILM according to the Bethesda 2001 system Results: A total of 5807 LBPT classifi ed as ASC-US from women aged 12-89 (mean that had PCR-based HPV DNA testing with genotyping by RFLP between 12/01/02 and 35+/-13), of which 3452 were over age 30 had HPV DNA tests performed during this 30 5/31/05 were reviewed. HPV genotypes were assigned to risk groups according to Munoz month interval. During this period, our laboratory processed more than 120,000 LBPT,