2004 Summer Meeting - Amsterdam - The Pathological Society of ...

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157 Oxaliplatin Toxicity In The Liver J A Kitchen , A McGregor Histopathology department, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom Guidance issued by NICE in March 2002 recommends that oxaliplatin should be considered for use (in combination with 5FU/FA) in pre-operative chemotherapy to downstage potentially resectable colorectal carcinoma metastases in the liver. There is no literature on oxaliplatin hepatotoxicity except for a mention of altered serum liver enzyme and bilirubin chemistry in the manufacturer’s datasheet. However, consequent to our own anecdotal observations, we propose that oxaliplatin causes steatosis in the liver. Identifying possible hepatotoxicity is important, as steatosis may complicate the radiological assessment, and therefore also clinical management, of disease progression. We identified ten patients with post-oxaliplatin chemotherapy liver resections or biopsies, and a cohort of age, sex, and disease-matched patients who had not received oxaliplatin. Histological features of steatohepatitis were graded semiquantitatively. Steatosis was noted in 80% of the ‘oxaliplatin group’, including one patient with no fatty changes in a pre-chemotherapy biopsy, but moderate steatosis in a post-oxaliplatin resection specimen. The prevalence of steatosis in liver transplant donors is reported at 13-25% and 30% of cases in our control group showed steatosis. We conclude that oxaliplatin chemotherapy can cause steatosis in the liver of patients with metastatic colorectal carcinoma, a feature that may complicate subsequent radiological and clinical assessment. 158 Immunohistochemical study on L-type amino acid transporter 1(LAT1) expression for myelodysplastic syndrome I. Saito 1 , K. Taki 1 , A. Sakamoto 2 1 Musashino Red Cross Hospital, Tokyo, Japan, 2 Kyorin University School of Medicine, Tokyo, Japan Background: L-type amino acid transporter 1(LAT1) is one of the protein which plays as a transporter of amino acid for cell proliferation. In this study, we examined immunohistochemical expression for LAT1 using human bone marrow tissue with myelodysplastic syndrome. Materials and Methods: We use 26 case tissue specimens of clinically and histologically confirmed myelodysplastic syndrome (MDS) (FAB classification) (13 refractory anaemia: RA, 7 RA with excess of blasts: RAEB, 6 RAEB in transformation: RAEB-T cases). Immunohistochemical study was done by anti-LAT1 monoclonal antibody. Evaluation was given 3 categories, namely, strongly positive, weekly positive and negative. Results and Discussion: Positive immunoreactivity was found in the cytoplasm and cell membrane of immature myeloid blats. As to MDS, 25 cases (96.2%) revealed strongly positive and weakly positive. One case showed negative (4.8%). More than 90% of MDS cases showed immunohistochemical reactivity. Therefore, our data suggest a close relationship between LAT1 and neoplastic lesions of bone marrow. We believe that LAT1 immunoreactivity can be applied for histodiagnosis of MDS as a useful tool. 159 Clinical And Laboratory Presentation Of Chronic Lymphocytic Leukaemia L A Sanni , S O'Connor , A Jack Department of Histopathology, Algernon Firth Building, The General Infirmary at Leeds, Leeds LS1 3EX, Leeds, United Kingdom Patients with chronic lymphocytic leukaemia (CLL), the most common adult leukaemia in the western world, can either be asymptomatic or present with lymphadenopathy, hepatosplenomegaly, and non-specific symptoms of easy fatigability, weight loss and anorexia. The diagnosis is often made by lymph node (LN) biopsy or an absolute lymphocytosis greater than 5000 x 10 9 /L. However, the mode of clinical and laboratory presentation is a subject of controversy. We studied 67 patients (44 men and 23 women) with a primary diagnosis of CLL, made on a LN or other solid tissue. The median age of diagnosis was 70y (range 35 – 87y). Many patients had a raised lymphocyte count and LN biopsy was not essential for diagnosis. In 22% of cases (14/65), CLL was diagnosed incidentally during investigation for other malignancies. Almost all cases had a variable degree of marrow involvement (range 5-100%). The immunophenotype of IgM/D+, CD5+, CD79+weak, CD20+weak, CD23+, CD19+, CD22+, FMC7-, CD38- was present in 75% (50/67) of cases. ATM deletion, a poor prognostic marker, was present in 30% (7/23) of cases, when looked for. Our data suggest that even in patients with lymphadenopathy, diagnosis can be made on peripheral blood and marrow examination without recourse to LN biopsy. 160 Study of Plasmacytoid Dendritic Cells in Lymph Nodes Draining Breast Cancer by CD 123 Antibody. An Immunohistochemical and Flow Cytometry Study K Cox 1 , N M Aqel 2 , F Facchetti 4 , H Singhal 3 , M Burke 3 , S C Knight 1 1 Antigen Presentation Group, Imperial College, Harrow, United Kingdom, 2 Department of Cellular Pathology, Northwick Park Hospital, Harrow, United Kingdom, 3 Directorate of Surgery, Northwick Park Hospital, Harrow, United Kingdom, 4 Department of Pathology II, Brescia, Italy Plasmacytoid dendritic cells (PDC) constitute a distinct subset of antigen presenting cells. Morphologically similar cells can be found in histological sections of reactive lymph nodes (LN), close to High Endothelial Venules (HEV) in LN paracortex. We examined PDC in axillary LNs draining breast carcinoma by using an anti-CD123 antibody, both immunohistochemically on paraffin sections and flow cytometry. Paraffin sections from one LN of each patient were immunostained for CD 123. Cell suspensions were made from one fresh LN from each patient and then flow cytometry was employed to identify and isolate PDC. By using four-colour flow cytometry, PDC in axillary LN (n=19) were consistently identified. PDC are positive for HLA-DR & CD123 (high). They are negative for CD3, CD14, CD16, CD19, CD34, CD56 & CD11c. PDC stained strongly for CD123 in sections of LNs and were found in LN paracortex and scattered discretely in lymph node sinus system. Our findings suggest that: 1. Flow cytometry can be a useful tool in isolating PDC from LN, which can then be used in various functional studies 2. PDC have been identified, for first time, in paraffin sections of LNs draining breast carcinoma using anti-CD123 antibody 3. Identification of PDC in LN paracortex, discretely and close to HEV, confirms previous data on the localization of these cells in reactive LN 4. The identification of PDC in LN sinuses strongly suggests that at least some PDC migrate to LNs through the afferent lymphatics. 66
161 Human Intestinal Astrovirus Infection in an Immunocompromised Child Following Bone Marrow Transplantation NJ Sebire , M Malone , G Anderson , N Shah , HB Gaspar , WD Cubitt Great Ormond Street Hospital, London, United Kingdom Introduction: Astroviruses are rare causes of diarrhoea and vomiting in infants and the elderly, and may also cause symptoms in immune compromised individuals. Despite its recognition using rt-PCR and immunofluorescence methods in faecal samples, there is almost no data on their histopathological features in humans. We report the first case describing the histopathological, immunohistochemical and ultrastructural features of astrovirus infection in a human immunocompromised patient. Case Report. A 4 year old boy underwent bone marrow transplantation for complications of intractable enterocolitis of infancy. Approximately 6 months post-transplantation he presented with profuse diarrhoea. Investigation revealed the presence of adenovirus and astrovirus in faecal samples. Gastrointestinal biopsies were carried out to differentiate GVHD from infection as the cause of the diarrhoea. The gastric biopsies were normal. The duodenal and jejunal biopsies did not indicate GVHD, but showed villus blunting and irregularity of surface epithelium with a mild lamina propria mixed inflammatory reaction and no viral inclusions identified. Immunohistochemical staining for adenovirus was negative but staining for astrovirus demonstrated strikingly positive intestinal epithelial cells, predominantly located at the villus tips. Ultrastructurally, intracytoplasmic crystalline viral arrays were identified in surface enterocytes. Conclusion. Astrovirus infection may be a cause of diarrhoea in immunocompromised patients. Histopathological findings may be subtle and diagnosis requires immunostaining and/or electron microscopy. 162 Spiral Artery Associated Restricted Growth (SPAARG): Pathophysiology and Fetal Programming Implications Resulting from Low Intervillous Pressure NJ Sebire 1 , V Jain 2 , DG Talbert 2 1 Great Ormond Street Hospital, London, United Kingdom, 2 Imperial College, London, United Kingdom Introduction: Failure of adequate trophoblastic conversion of maternal spiral arteries results in high flow resistance and consequent reduction in fetal oxygen supply in intrauterine growth restriction (IUGR). In addition, raised spiral artery resistance reduces placental intervillous pressure affecting maternofetal water transfer. We examine the possible effects of reduced intravillous pressure using a pathophysiological computer model. Methods. A simulation of an experiment in which compression cuffs were placed around each spiral artery to progressively restrict flow, while observing various fetal and placental variables was carried out. Results. In normal circumstances, water moved to the fetus in the cotyledonary core villi, and to the mother in the outer villous layers. While the fetus was able to match villous capillary pressure to changes in intervillous pressure, net transplacental water movement was minimal. When spiral artery resistance was increased sufficiently to cause mean intervillous pressure to fall below that which the fetus could match, a net flow to the mother appeared resulting in oligohydramnios and continuing until the resulting fetal blood hemoconcentration produced a sufficient increase in colloid osmotic pressure to restrict further loss. Conclusion. Severe spiral artery flow restriction results in lowered mean intervillous pressure, net water loss from the fetus and haemoconcentration. Since systems within the developing feto-placental unit then operate in an abnormal ionic environment, axes such as the renin-angiotensin set-point may be affected. This may be a mechanism linking uteroplacental disease and IUGR to the fetal origins of adult disease. 163 Alveolar Septal Collapse (ASC) in the Transitional Human Lung: A Possible Common Mechanism in Sudden Unexpected Death in Infancy (SUDI) NJ Sebire 1 , DG Talbert 2 1 Great Ormond Street Hospital, Department of Paediatric Pathology, London, United Kingdom, 2 Institute of Reproductive Science, Imperial College, London, United Kingdom Introduction: Sudden unexpected death in infancy (SUDI) is a category used to represent the largest single group of infant deaths. We investigated a possible biomechanical mechanism which may be common in SUDI and may provide an explanation for the association of the known risk factors such as co-sleeping, prematurity, prone sleeping position, overwrapping, overheating and maternal smoking. Methods: On the basis of previously published data on lung development, surfactant function, connective tissue strength and elasticity, capillary pressures and biomechanical functions, a dynamic computer simulation was constructed to observe the consequences of altering various parameters. Results: Alveolar septal collapse occurs when the balance between surface tension causing them to collapse, (modified by surfactant function), is greater than support provided by capillaries and connective tissue. The pressures depend on both the surface tension itself and on the curvature of the surface such that collapse is much more likely at low volumes, which may lead to cyanosis and / or apnoea. Conclusion: The fundamental developmental instability of the lung predisposes to ASC, the risk being modified by other factors. SUDI may represent either intrinsic abnormality in pulmonary development or surfactant function, or, the combination of overheating, non-prone sleeping position and partial airway obstruction may act synergistically to precipitate ASC and death. Risk may be further modified by developmental factors such as prematurity and environmental cigarette smoke. This hypothesis provides a plausible biomechanical explanation linking many of the apparently unrelated epidemiological risk factors for SUDI. 164 Surface Cautery and Contamination of Postmortem Microbiological Samples: An Audit of Paediatric Autopsies NJ Sebire 1 , M Malone 1 , J Hartley 2 , AD Ramsay 1 , RA Risdon 1 1 Department of Histopathology, Great Ormond Street Hospital, London, United Kingdom, 2 Department of Microbiology, Great Ormond Street Hospital, London, United Kingdom Introduction: In our centre, paediatric post mortem examinations are carried out according to a comprehensive protocol, which includes collection of microbiology samples from CSF, blood, spleen and lung. Splenic and lung samples are obtained using a sterile blade and forceps, with or without preceeding surface cauterisation, according to pathologist preference. Methods. During a five-month period the microbiology results of all cases of non-forensic paediatric autopsies were reviewed and categorised according to the method used to obtain the specimen. Results. There were 70 reports reviewed. In all cases adequate microbiological samples were obtained from multiple sites as per standard protocol, including CSF, blood and tissue. In 21 cases surface spleen and lung cautery and splenic swab was used (the practice of one pathologist), and in 49 cases sterile instruments were used without prior surface cautery of spleen or lung. In seven cases the cause of death was sepsis, with pathogenic organisms isolated from multiple sites regardless of the technique used. The majority of spleen and lung samples demonstrated growth of contaminents or commensals such as coliforms, enterococci or upper respiratory tract commensals. Splenic samples showed no growth in 10/21 (48%) following cautery and swab versus 12/49 (24%) with ‘sterile’ tissue biopsy only. (z=1.9, P=0.05), whereas lung samples were sterile in 3/21 (14%) and 5/49 (10%) with and without cautery, respectively.(z=0.5, P=0.6). There was no relation between contamination and death to autopsy interval. (P=0.59) Conclusion. Microbiological sampling can provide essential information regarding cause of death in paediatric autopsies. Contamination is reduced using swabs versus tissue biopsy but surface cautery per se does not further reduce contamination risk. 67
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JOINT MEETING of the Pathological S
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Scientific Programme FEATURED TOPIC
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Scientific Programme GUEST LECTURES
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Scientific Programme TRAVEL (contin
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Scientific Programme AMSTERDAM PUBL
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Page 28 and 29: 5 Melanoma suppressor responses ind
Page 30 and 31: 13 Expression Of MHC Class I And II
Page 32 and 33: 21 Immunohistochemical Subtyping Of
Page 34 and 35: 29 Regional Quality Control by path
Page 36 and 37: 37 Nuclear Morphometry, Immortaliza
Page 38 and 39: 45 Dietary Fibre Accelerates Polyp
Page 40 and 41: 53 Intestinal Tumourigenesis : Navi
Page 42 and 43: 61 Expression Of The Transcription
Page 44 and 45: 69 Id2 expression is inversely corr
Page 46 and 47: 77 A Study of Insitu Hybridisation
Page 48 and 49: 85 Is There Agreement Between IMF-D
Page 50 and 51: 93 Recruiting Donors for Autopsy-ba
Page 52 and 53: 101 Workload Implications of Case R
Page 54 and 55: 109 Proposal for a Peer Standardise
Page 56 and 57: 117 Expression of hTERT in gastroin
Page 58 and 59: 125 Assessing Inter-observer Variat
Page 60 and 61: 133 Beta-catenin Expression In Gast
Page 62 and 63: 141 Infertile Males - Who Should Be
Page 64 and 65: 149 Papillary Mucinous Adenocarcino
Page 68 and 69: 165 The Association Between Early G
Page 70 and 71: 173 Cardiac abnormalities in a paed
Page 72 and 73: 181 Intraocular Ectopic Ependymoma
Page 74 and 75: 189 The Expression of S100A6 Protei
Page 76 and 77: 197 TSLC1 Is A Tumor Suppressor And
Page 78 and 79: 205 Wnt Expression In Colonic Subep
Page 80 and 81: 213 Microarray Based Comparative Ge
Page 82: 221 IMMUNOHISTOCHEMISTRY (IHC) ON B
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