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diagnostic criteria handbook in histopathology diagnostic criteria handbook in histopathology a surgical pathology vade mecum paul j tadrous copyright c 2007 by john wiley sons ltd isbn 978-0-470-51903-5

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diagnostic criteria handbook in histopathology a surgical pathology vade mecum by paul j tadrous mb bs msc phd mrcpath histopathology unit cruk london uk

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copyright c 2007 john wiley sons ltd the atrium southern gate chichester west sussex po19 8sq england telephone 44 1243 779777 email for orders and customer service enquiries cs-books@wiley.co.uk visit our home page on www.wileyeurope.com or www.wiley.com all rights reserved no part of this publication may be reproduced stored in a retrieval system or transmitted in any form or by any means electronic mechanical photocopying recording scanning or otherwise except under the terms of the copyright designs and patents act 1988 or under the terms of a licence issued by the copyright licensing agency ltd 90 tottenham court road london w1t 4lp uk without the permission in writing of the publisher requests to the publisher should be addressed to the permissions department john wiley sons ltd the atrium southern gate chichester west sussex po19 8sq england or emailed to permreq@wiley.co.uk or faxed to 44 1243 770620 designations used by companies to distinguish their products are often claimed as trademarks all brand names and product names used in this book are trade names service marks trademarks or registered trademarks of their respective owners the publisher is not associated with any product or vendor mentioned in this book this publication is designed to provide accurate and authoritative information in regard to the subject matter covered it is sold on the understanding that the publisher is not engaged in rendering professional services if professional advice or other expert assistance is required the services of a competent professional should be sought other wiley editorial offices john wiley sons inc 111 river street hoboken nj 07030 usa jossey-bass 989 market street san francisco ca 94103-1741 usa wiley-vch verlag gmbh boschstr 12 d-69469 weinheim germany john wiley sons australia ltd 33 park road milton queensland 4064 australia john wiley sons asia pte ltd 2 clementi loop #02-01 jin xing distripark singapore 129809 john wiley sons canada ltd 6045 freemont blvd mississauga ontario l5r 4j3 canada wiley also publishes its books in a variety of electronic formats some content that appears in print may not be available in electronic books anniversary logo design richard j pacifico library of congress cataloging-in-publication data tadrous paul joseph diagnostic criteria handbook in histopathology a surgical pathology vade mecum by paul j tadrous p cm includes bibliographical references and index isbn 978-0-470-51903-5 alk paper 1 histology pathological­handbooks manuals etc 2 pathology surgical­handbooks manuals etc 3 diagnosis surgical­handbooks manuals etc 4 histology pathological­examinations questions etc 5 pathology surgical­examinations questions etc 6 diagnosis surgical­examinations questionss etc i title [dnlm 1 diagnosis differential­handbooks 2 pathology surgical­methods­handbooks 3 histological techniques­methods­handbooks wo 39 t122d 2007 rb30.t33 2007 616.07 583­dc22 british library cataloguing in publication data a catalogue record for this book is available from the british library isbn 978-0-470-51903-5 hb isbn 978-0-470-77096-2 hb custom typeset in 10/12 in times new roman by aptara inc new delhi india printed and bound in great britain by antony rowe ltd chippenham wiltshire this book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper production 2007024036

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disclaimer while every effort has been made to ensure the information in this book is accurate and timely there is always the possibility that errors have been made or that medical opinion has changed since the time of writing the author cannot accept any liability for damages of any kind resulting from the use of information received from this book.

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dedication i dedicate this book to the memory of my father mr joseph zaki tadrous who sadly passed away at the age of 84 in march 2007.

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contents preface acknowledgements abbreviations and symbols general bibliography and suggested reading index to grading and classification systems frozen section index reader s index 1 advice for exam candidates 2 histological techniques 3 laboratory management 4 cut-up and reporting guidelines 5 paediatric and placental 6 vascular 7 heart 8 respiratory and mediastinum 9 bone marrow 10 lymphoreticular 11 alimentary tract 12 liver biliary tract and pancreas 13 central nervous system and skeletal muscle 14 eye and ear 15 renal medicine 16 urological 17 gynaecological 18 breast 19 endocrine 20 skin 21 soft tissues 22 osteoarticular 23 infection and immunity 24 cytopathology 25 autopsy ix xi xiii xxiv xxv xxvi xxvi 1 6 22 36 56 68 75 81 99 107 126 156 181 193 201 211 232 258 267 281 309 329 343 353 377

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contents viii index of general terms index of molecules index of eponyms 395 416 420 please note that full-colour versions of all figures within chapter 4 and also figures 5.3 8.1 11.3 14.1 16.1 17.1 and 23.1 can be found in the colour plate section of this book

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preface this book presents criteria for histopathological diagnosis in list form for rapid access it covers diagnostic surgical pathology cytology autopsy practice histological technique lab management rcpath guidance and uk law relevant to histopathology trainees and consultants in diagnostic practice and those needing a quick refresher in preparation for professional exams such as the mrcpath should find this book a useful companion while at the microscope the pathologist will often be able to suggest a limited list of conditions in the differential and may need a reminder of the diagnostic criteria of those conditions in order to decide on the preferred option one may go to a standard diagnostic text for this purpose but there is almost invariably a lengthy few paragraphs of prose to read in order to glean the required morphological points these words are not wasteful when learning about a condition for the first time as one needs a substantial background of information to appreciate the condition in its context however most pathologists will have already read a full account of most conditions and just need to be reminded of the major points for diagnosis these points are what this book aims to provide as an aid to rapid acquisition of diagnostic criteria and salient information on management law and technique it is not intended as an initial source text and is not a substitute for reading a full account in specialist reference texts this is not a comprehensive account of pathology ­ no attempt is made to cover very basic material and some of the rarer entities are pointed to via references this book focuses on r diagnostic criteria for each condition r immuno profiles of normal cells tissues and pathological entities where this is helpful r criteria for malignancy in otherwise benign lesions e.g what makes a malignant sft what are the r criteria for malignancy in a pilomatricoma when should you be worried with an ameloblastoma and when does mgus become myeloma differential diagnoses with notes on distinguishing features e.g how do you distinguish kaposi s sarcoma from kaposiform haemangioendothelioma or mucoepidermoid carcinoma from adenosquamous carcinoma or epithelioid haemangioendothelioma from epithelioid angiosarcoma or an atypical adenomatous hepatocellular nodule from hepatocellular carcinoma definition of terms and quantities needed for diagnosis for example what are the size and mitotic count criteria for placing gists into malignancy risk categories what is the definition of vertical and radial growth phases for melanoma what constitutes an inadequate cervical smear how big must a focus of atypical adenomatous hyperplasia be before it is considered bronchioalveolar carcinoma what makes a lymph node metastasis a micrometastasis and how does this differ from `isolated tumour cells present many of these have important management implications grading scoring classification and staging criteria for tumours and non-neoplastic conditions e.g transplant rejection hepatitis er and pgr receptor status spermatogenesis etc no attempt has been made to reproduce the tnm staging system as the uicc book is an excellent handy reference which all pathologists working with tumours should have some aspects of tnm have however been included in this book where it emphasises certain practical points e.g in chapter 4 cut-up and reporting guidelines a separate grading index page is provided for rapid access to the various schemes see page xxv dating criteria for endometria myocardial infarction thrombi and villi following intra-uterine death normal values and ranges e.g for pm weights placental weights weight ratios mitotic counts etc laboratory methods are covered from a pathologist s perspective laboratory management health and safety uk legislation and government initiatives budgetary control clinical governance etc and summary guidance from the rcpath national datasets for reporting cancers cut-up autopsy practice and reporting major types of specimen together with handy anatomical diagrams frozen section diagnosis ­a separate `frozen section index see page xxvi points to advice for peroperative diagnosis in all the chapters for rapid access to this information mnemonics and general advice in exam technique are offered for mrcpath exam candidates rrrrrrrr this book bridges the gap between specialist diagnostic texts with their reams of context and study books for trainees with their reams of aetiology pathogenesis and molecules by presenting diagnostic information in practical detail ­ but without the padding pjt london 2007

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acknowledgements the support of the pathological society of great britain and ireland in helping to get this book to press is gratefully acknowledged i would like to thank all my colleagues both junior and senior who contributed to this book by answering my queries and by giving me questions to answer a special thanks to all the pathologists who answered my specific questions regarding topics in their own field while i was researching this book ­ this was often in response to queries i had over individual patient s cases as well as specifically for the book they include in alphabetical order ­ and apologies for anyone i may have missed dr emyr wyn benbow dr ashish chandra prof h terry cook prof amar p dhillon prof cyril fisher prof andrew m hanby prof alec j howie prof stefan g h¨ bscher prof g¨ nter kl¨ ppel dr jay h u u o lefkowitch dr iain lindsay dr neil j sebire prof neil a shepherd prof sami shousha prof ian c talbot prof rosemary a walker and prof clive a wells thanks are also due to dr caroline brodie who proofread early drafts of some of the chapters and gave helpful feedback thanks also to all those who made their libraries and collections available to me including dr ann sandison dr josephine wyatt-ashmead dr neil j sebire dr alan w bates dr michael t sheaff dr malcolm galloway and dr juan piris finally i would like to thank all the staff at john wiley sons for their helpfulness and skill in taking this book from manuscript to press.

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abbreviations and symbols indicates a potential pitfall fracture and therefore `leading to `which leads to `which could lead to `resulting in `gives rise to increased increases higher hyper raised expanded enlargement decreased decreases lower hypo lowered reduced suppression deficiency greatly increased act 1 1 -antichymotrypsin at 1 1 -antitrypsin sma alpha smooth muscle actin gt -glutamyl transferase micrometer ca2 microcalcifications `or `divided by or `per and plus with `and or `lots thereof +ve positive +vity positivity -ve negative -vity negativity ± `with or without `may have/show ±ve positive or negative `less than or equal to `at most `less than `fewer than `less commonly than much less than `more than or equal to `at least `greater than `more than `more commonly than much greater than `not `does not equal `which is not the same as `is equal to `which is the same as `synonymous with `is approximately equal to `which is similar to `almost identical to `is proportional to `depends on `is related to `correlates with degrees diameter [i isochromosome e.g [i7q 1 primary secondary 2 3 tertiary 3 ohsd 3 -hydroxysteroid dehydrogenase 3d 3-dimensional 5-ht 5-hydroxy tryptophan 3ys 5ys 10ys aac 3 year survival 5 year survival 10 year survival advisory appointments committees for consultants aafb acid-alcohol-fast bacilli/bacillus aah atypical adenomatous hyperplasia aan atypical adenomatous nodule liver abs antibody antibodies ab alcian blue abc `aneurysmal bone cyst or `achievable standards benchmarks for reporting and criteria for evaluating cervical cytology or `avidin-biotin complex abdpas alcian blue diastase pas stain acc adrenocortical carcinoma ace angiotensin converting enzyme acei ace inhibitors ache acetylcholinesterase acis adenocarcinoma in situ acp association of clinical pathologists acs acute chest syndrome acth adrenocorticotrophic hormone ad autosomal dominant adcc adenoid cystic carcinoma adh atypical ductal hyperplasia or additional duty hours adi aids-defining illness/illnesses adp acute diffuse proliferative gn adpckd autosomal dominant polycystic kidney disease aec 3-amino-9-ethylcarbazole afe amniotic fluid embolism afip usa armed forces institute of pathology afp alpha-fetoprotein afx atypical fibroxanthoma ags antigens aids acquired immunodeficiency syndrome aih autoimmune hepatitis aiha autoimmune haemolytic anaemia ain anal intra-epithelial neoplasia aip acute interstitial pneumonitis aitcl angioimmunoblastic t-cell lymphoma ak actinic keratosis do not confuse with ka al amyloid light chain type alc anti-liver cytosol abs alcl anaplastic large cell lymphoma ald alcoholic liver disease alh atypical lobular hyperplasia

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abnormal location of immature precursors lesion alk anaplastic lymphoma kinase alk-1 alkm anti-liver kidney microsomal abs all acute lymphoblastic leukaemia alp alkaline phosphatase alt alanine aminotransferase ama anti-mitochondrial abs amacar -methylacyl coa racemase p504s also called amacr amd age-related macular degeneration aml acute myeloid leukaemia amls amyotrophic lateral sclerosis ana anti-nuclear abs anca anti-neutrophil cytoplasmic abs apc antigen presenting cell apr abdominoperineal resection apt anatomical pathology technician mortician apud amine precursor uptake and amino acid decarboxylation ar `autosomal recessive or `androgen receptor arch architecture ards adult respiratory distress syndrome arf acute renal failure arvd arrythmogenic right ventricular dysplasia asap atypical small acinar proliferation asapus atypical small acinar proliferation of uncertain significance asc adenosquamous carcinoma asgp-r anti-asialoglycoprotein receptor abs ash alcoholic steatohepatitis asma anti-smooth muscle auto abs asps alveolar soft part sarcoma assocd associated ast aspartate aminotransferase atn acute tubular necrosis av atrioventricular avm arteriovenous malformation b&l bernatz and lattes classification ba biological agents bac bronchioalveolar carcinoma bal bronchioalveolar lavage baus basal cell/layer abnormalities of un-determined significance bcc basal cell carcinoma bcda basal crypt dysplasia-like atypia bcg bacille calmette-gu´ rin e bcl b-cell lymphoma bcl bcp basal cell papilloma sk bcs budd-chiari syndrome bds bile ducts bfh benign fibrous histiocytoma bjp bence-jones protein alip blag bm bmi bms bmtx bna bnc bnli bo boo boop bp bph bpop bric bsg bta bttp bx bxo c282y ca ca1 ca2 caa caa cabg cae cah calla cam cam5.2 capd capss castle cavg c-c cb cbd cbs/wb benign lymphocytic angiitis and granulomatosis basement membrane body mass index weight in kg ÷ [height in m]2 normal is 18.5­25 biomedical scientist bone marrow transplantation borderline nuclear abnormalities borderline nuclear changes bna british national lymphoma investigation barrett s oesophagus bladder outflow obstruction bronchiolitis obliterans organising pneumonia blood pressure benign prostatic hypertrophy bizarre parosteal osteochondromatous proliferation benign recurrent intrahepatic cholestasis british society of gastroenterology bladder tumour ag british testicular tumour panel biopsy balanitis xerotica obliterans the haemochromatosis amino acid substitution carcinoma either alone or at the end of a subtype e.g adenoca adenocarcinoma cornu ammonis region 1 sommer s sector of hippocampus `calcium or `calcification congophilic amyloid angiopathy coloanal anastomosis not used in this book coronary artery bypass graft chloroacetate esterase chronic active hepatitis common all ag cd10 congenital adenomatoid malformation carol a makin 5.2 cytokeratin antibodies to ck8 and ck18 chronic ambulatory peritoneal dialysis columnar cell alteration with prominent snouts and secretion carcinoma showing thymus-like elements coronary artery vein graft central to central centroblast common bile duct ratio of brain weights post-fixation cerebellum brainstem ÷

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cc cc ccam ccc ccf ccl ccst ccsta cct cd cdc cdle cdna cdsc cea cemd cerad cf cfa cfv cga cgb cgin cgl chai chc chimp cibd cin circ cis cjd ck clh clin cll cm cmf cml cmml cmt cerebrum cerebellum brainstem collagenous colitis centrocyte congenital cystic adenomatoid malformation clear cell carcinoma congestive cardiac failure columnar cell lesions certificate of completion of specialist training see also cct clear cell sarcoma of tendon and aponeuroses certificate of completion of training successor to the older ccst `cluster of differentiation or `condenser diaphragm communicable disease control chronic discoid lupus erythematosus complementary dna communicable disease surveillance centre of the hpa carcinoembyonic antigen confidential enquiry into maternal deaths consortium to establish a registry for alzheimer s disease cystic fibrosis cryptogenic fibrosing alveolitis cresyl fast violet chromogranin a chromogranin b cervical glandular intraepithelial neoplasia chronic granulocytic leukaemia commission for healthcare audit and inspection `the healthcare commission formerly chimp choriocarcinoma commission for healthcare improvement now called chai chronic idiopathic inflammatory bowel disease cervical intraepithelial neoplasia circumscribed carcinoma in situ creutzfeldt-jakob disease cytokeratin chronic lobular hepatitis clinical features clinically chronic lymphocytic leukaemia complete hydatidiform mole cyclophosphamide methotrexate and fluorouracil chronic myeloid leukaemia chronic myelomonocytic leukaemia core medical training cmv cni cns coc cop copd cytomegalovirus calcineurin inhibitors central nervous system combined oral contraceptive cryptogenic organising pneumonia chronic obstructive pulmonary disease copmed conference of postgraduate medical deans www.copmed.org.uk corec central office for research ethics committees part of the npsa coshh control of substances hazardous to health regulations 2002 cpa clinical pathology accreditation cpam congenital pulmonary airway malformation cpc clinicopathological correlation cpd continuing professional development cph chronic persistent hepatitis cppd calcium pyrophosphate deposition disease cpr cardiopulmonary resuscitation cr congo red crest calcinosis raynaud phenomenon oesophageal dysfunction sclerodactyly and telangiectasias crf chronic renal failure crm circumferential margin csf cerebrospinal fluid csl complex sclerosing lesion ct computed tomography ctd connective tissue diseases cu copper cubp copper binding protein cusa cavitron ultrasonic surgical aspirator cva cerebrovascular accident cvid common variable immuno-deficiency cvs cardiovascular system cx cervix cervical cytol cytological d.p decimal places d/dg differential diagnosis dab 3,3 diaminobenzidine dad diffuse alveolar damage dapi 4 ,6-diamino-2-phenylindole dcis ductal carcinoma in situ dcts distal convoluted tubules dd diverticular disease defn definition dej dermoepidermal junction del deletion df dermatofibroma dfsp dermatofibrosarcoma protruberans dgh district general hospital dh dermatitis herpetiformis dic disseminated intravascular coagulation diff differentiated

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dip dlb dlbcl dm dmin doh dopa dpas dpn dpx desquamative interstitial pneumonitis dementia with lewy bodies diffuse large b-cell lymphoma diabetes mellitus double minutes department of health dihydroxyphenylalanine diastase periodic acid schiff deep penetrating naevus kirkpatrick lendrum s distrene phalate and xylene mountant dsrct desmoplastic small round cell tumour du duodenal ulcers dub dysfunctional uterine bleeding e.coli escherichia coli eaa extrinsic allergic alveolitis eae experimental autoallergic encephalomyelitis eam external auditory meatus eamf elastin associated microfilament protein eatl enteropathy-associated t-cell lymphoma see also ettl eba epidermolysis bullosa acquisita ebmt endocervical-type borderline mucincous tumour ebna ebv nuclear antigen ebv epstein-barr virus hhv4 ec enterochromaffin ecf extracellular fluid ecg electrocardiogram ecl enterochromaffin-like edta ethylene diamine tetra-acetic acid eed erythema elevatum diutinum eeg electroencephalogram egfr epidermal growth factor receptor em electron microscopy ema epithelial membrane antigen emh extramedullary haemopoiesis emm erythema multiforme minor emu early morning urine sample eortc european organisation for research into the treatment of cancer eos eosinophils epr electronic patient record eqa external quality assurance er oestrogen receptor ercp endoscopic retrograde cholangiopancreatography erpc evacuation of retained products of conception ers european respiratory society esp especially esr erythrocyte sedimentation rate estscle endometrial stromal tumour with sex cord-like elements et essential thrombocythaemia et seq `and sequelae ettl ev evg ewtd enteropathy-type tcl eatl epidermodysplasia verruciformis elastic van gieson european working time directive 93/104/ec 1998 f female unless otherwise specified f/u follow-up f1 foundation year 1 f2 foundation year 2 fa fibroadenoma faa formol acetic alcohol fab french-american-british fab `fragment ag binding of an immunoglobulin ig fab fc fap familial ademomatous polyposis fatwo female adnexal tumour of probable wolffian origin tpwo fb follicular bronchiolitis fc `fragment crystallisable part of the immunoglobulin s constant `tail fch fibrosing cholestatic hepatitis fcl follicular lymphoma old name follicle centre cell lymphoma fd fibrous dysplasia fdc follicular dendritic reticulum cells fde fixed drug eruption fe iron ffi familial fatal insomnia fhx family history figo international federation of obstetrics and gynaecology fish fluorescent in situ hybridisation fna fine needle aspiration fnclcc f´ d´ ration nationale des centres de e e lutte contre le cancer fob faecal occult blood fobt faecal occult blood test fps fee-paying services fs frozen section fsgn focal segmental glomerulonephritis fsgs focal segmental glomerulosclerosis fsh follicle stimulating hormone ftsta fixed term specialty training appointment fviiira factor 8-related antigen i.e von willebrand factor fxiiia factor 13a clotting cascade g1 g2 g3 grades 1 to 3 ga granuloma annulare gaf gomori s aldehyde fuchsin gant gastrointestinal autonomic nerve tumour gave gastric antral vascular ectasia gb gall bladder gbm `glioblastoma multiforme or `glomerular basement membrane in the literature ­ but not in this book g-csf granulocyte colony stimulating factor

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gc gct gfap gfr gh ghrh gi gip gist git glut1 gm-csf gmc gn gnrh go goj gord gos gp gpi gs gss gu gvhd gvhr h&e h/rs ha haart hav hb hb hbp hbv hc hca hcc hcg hcv hcw hd hdac8 hdv hefce hellp hepa her2 hev hfe giant cells giant cell tumour glial fibrillary acidic protein glomerular filtration rate growth hormone growth hormone releasing hormone gastrointestinal giant cell interstitial pneumonitis gastrointestinal stromal tumour gastrointestinal tract glucose transporter protein 1 granulocyte/monocyte colony stimulating factor general medical council glomerulonephritis gonadotropin releasing hormone gonadorelin galactose oxidase gastro-oesophageal junction gastro-oesophageal reflux disease galactose oxidase schiff general practitioner general paralysis of the insane glomerulosclerosis gerstmann-st¨ ussler-sheinker a syndrome genitourinary graft vs host disease graft vs host reaction in the skin haematoxylin and eosin hodgkin or reed-sternberg cell/s non-molar hydropic abortion highly active anti-retroviral therapy hepatitis a virus haemoglobin hepatitis b used as a combining form e.g hbeag for hepatitis b `e antigen hepatitis b surface protein hepatitis b virus hassall s corpuscles hepatocellular adenomas hepatocellular carcinoma human chorionic gonadotrophin hepatitis c virus health care worker hirschprung s disease histone deacetylase 8 hepatitis delta agent higher education funding council of england haemolysis elevated liver enzymes low platelets high efficiency particulate air human egfr 2 c-erbb-2 hepatitis e virus haemochromatosis gene hg hgf hgp hh hhv4 hhv8 histol hiv hl hla hlo hme hmfg hmw hnpcc hocm hpa hpc hpf hpl hpv hrct hrg hrt hs hse hsp hsr hsv hswa ht hta htlv-1 htt hus hut hvg hx hx i.m iata ibms ibmt ic icd icf ich icrs id ida hazard groups herpes gestationis factor horizontal growth phase hiatus hernia human herpes virus 4 ebv human herpes virus type 8 kshv histology human immunodeficiency virus hodgkin lymphoma human leukocyte antigen helicobacter-like organism hereditary multiple exostoses human milk fat globule-associated antigen types 1 and 2 high molecular weight hereditary non-polyposis colorectal carcinoma mutator phenotype hypertrophic obstructive cardiomyopathy health protection agency incorporates the former phls haemangiopericytoma high power field human placental lactogen human papilloma virus high resolution ct healthcare resource group hormone replacement therapy hereditary spherocytosis health and safety executive henoch-sch¨ nlein purpura o homogeneously staining regions herpes simplex virus health and safety at work act 1974 hypertension `hyalinising trabecular adenoma or `human tissue authority human t-cell lymphotrophic virus 1 hyalinising trabecular tumour haemolytic uraemic syndrome hyperplasia of usual type haematoxylin van gieson history histiocytosis x intestinal metaplasia international air transport association institute of biomedical science intestinal-type borderline mucinous tumour indeterminate colitis infection control department intracellular fluid intra-cranial haemorrhage integrated care record service identification iron deficiency anaemia

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