Table Of Content

i ii iii ColorAtlasofHematology PracticalMicroscopicandClinicalDiagnosis HaraldTheml,M.D. Professor,PrivatePractice Hematology/Oncology Munich,Germany HeinzDiem,M.D. KlinikumGrosshadern InstituteofClinicalChemistry Munich,Germany TorstenHaferlach,M.D. Professor,KlinikumGrosshadern LaboratoryforLeukemiaDiagnostics Munich,Germany 2ndrevisededition 262colorillustrations 32tables Thieme Stuttgart·NewYork iv LibraryofCongressCataloging-in-Publica- Important note: Medicine is an ever- tionDataisavailablefromthepublisher changing science undergoing continual development. Research and clinical ex- perience are continually expanding our knowledge,inparticularourknowledgeof Thisbookisanauthorizedrevised propertreatmentanddrugtherapy.Insofar translationofthe5thGermanedition asthisbookmentionsanydosageorappli- publishedandcopyrighted2002by cation,readersmayrestassuredthatthe ThiemeVerlag,Stuttgart,Germany. authors,editors,andpublishershavemade TitleoftheGermanedition: everyefforttoensurethatsuchreferences TaschenatlasderHämatologie areinaccordancewiththestateofknowl- edge at the time of production of the book. Translator:UrsulaPeter-CzichiPhD, Nevertheless,thisdoesnotinvolve,imply, Atlanta,GA,USA orexpressanyguaranteeorresponsibility onthepartofthepublishersinrespectto anydosageinstructionsandformsofappli- 1stGermanedition1983 cationsstatedinthebook.Everyuserisre- 2ndGermanedition1986 questedtoexaminecarefullythemanu- 3rdGermanedition1991 facturers’leafletsaccompanyingeachdrug 4thGermanedition1998 andtocheck,ifnecessaryinconsultation 5thGermanedition2002 withaphysicianorspecialist,whetherthe 1stEnglishedition1985 dosageschedulesmentionedthereinorthe 1stFrenchedition1985 contraindications stated by the manufac- 2ndFrenchedition2000 turersdifferfromthestatementsmadein 1stIndonesionedition1989 thepresentbook.Suchexaminationispar- 1stItalianedition1984 ticularly important with drugs that are 1stJapaneseedition1997 eitherrarelyusedorhavebeennewlyre- leased on the market. 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Coverdesign:Cyclus,Stuttgart Thisbook,includingallpartsthereof,isle- TypesettingandprintinginGermanyby gallyprotectedbycopyright.Anyuse,ex- DruckhausGötzGmbH,Ludwigsburg ploitation, or commercialization outside thenarrowlimitssetbycopyrightlegisla- tion,withoutthepublisher’sconsent,isille- galandliabletoprosecution.Thisappliesin particulartophotostatreproduction,copy- ing,mimeographing,preparationofmicro- ISBN3-13-673102-6(GTV) films, and electronic data processing and ISBN1-58890-193-9(TNY) 1 2 3 4 5 storage. v Preface OurCurrentEdition AlthoughthisisthesecondEnglisheditionofourhematologyatlas,this editioniscompletelynew.Asanimmediatesignofthischange,thereare nowthreeauthors.Thecompletelyupdatedvisualpresentationusesdig- italimages,andthecontentisorganizedaccordingtothemostup-to-date morphologicalclassificationcriteria. Inthisnewedition,ournewlyformedteamofauthorsfromMunich (the“MunichGroup”)hassuccessfullysharedtheirknowledgewithyou. HeinzDiemandTorstenHaferlacharenationallyrecognizedaslecturers ofthediagnosticscurriculumoftheGermanAssociationforHematology andOncology. Goals Mostphysiciansarefundamentally“visuallyoriented.”Apartfromimme- diatepatientcare,themicroscopicanalysisofbloodplaystothisprefer- ence. This explains the delight and level of involvement on the part of practitionersinthepursuitofmorphologicalanalyses. Specialization notwithstanding, the hematologist wants to preserve theopportunitytoperformgroundbreakingdiagnosticsinhematologyfor thegeneralpractitioner,surgeon,pediatrician,theMTAtechnician,andall medical support personnel. New colleagues must also be won to the cause. Utmost attention to the analysis of hematological changes is es- sentialforatimelydiagnosis. Even before bone marrow cytology, cytochemistry, or immunocyto- chemistry,informationbasedontheanalysisofbloodisofimmediaterel- evanceinthedoctor’soffice.Itiscentraltothediagnosisofthediseasesof the blood cell systems themselves, which make their presence known throughchangesinbloodcomponents. Theexhaustivequantitativeandqualitativeuseofhematologicaldiag- nostics is crucial. Discussions with colleagues from all specialties and teachingexperiencewithadvancedmedicalstudentsconfirmitsimpor- tance.Incaseswhereadiagnosisremainselusive,theawarenessofthe next diagnostic step becomes relevant. Then, further investigation throughbonemarrow,lymphnode,ororgantissuecytologycanyieldfirm results.Thispocketatlasoffersthebasicknowledgefortheuseofthese techniquesaswell. vi Preface Organization Reflectingourgoals,theinductiveorganizationproceedsfromsimpleto specializeddiagnostics.Bydesign,wesubordinatedthedescriptionofthe bonemarrowcytologytothediagnosticbloodanalysis(CBC).However, wehaverespondedtofeedbackfromreadersofthepreviouseditionsand have included the principles of bone marrow diagnostics and non- ambiguousclinicalbonemarrowfindingssothatfrequentandrelevant diagnosescanbequicklymade,understood,orreplicated. Thenosologyanddifferentialdiagnosisofhematologicaldiseasesare presentedtoyouinatabularform.Wewantedtoofferyouapocketbook foreverydaywork,notareferencebook.Therefore,morphologicalcuri- osities,oranomalies,areabsentinfavorofapracticalapproachtomor- phology. The cellular components of organ biopsies and exudates are brieflydiscussed,mostlyasareminderoftheimportanceofthesetests. Theimagesareconsistentlyphotographedastheynormallyappearin microscopy (magnification 100 or 63 with oil immersion lens, oc- casionallymaster-detailmagnificationobjective10or20).Eventhough surprisingperspectivessometimesresultfromviewingcellsatahigher magnification,thedownsideisthatthisbynomeansfacilitatestherecog- nitionofcellsusingyourownmicroscope. InstructionsfortheUseofthisAtlas Theorganizationofthisatlassupportsasystematicapproachtothestudy ofhematology(seeTableofContents).Theindexofferswaystoanswer detailedquestionsandaccessthehematologicalterminologywithrefer- encestothemaindescriptionandfurthercitations. Thebestwaytobecomefamiliarwithyourpocketatlasistofirsthavea cursorylookthroughitsentirecontent.Theimagesareaccompaniedby shortlegends.Onthepagesoppositetheimagesyouwillfindcorrespond- ingshortdescriptivetextsandtables.Thistextportiondescribescellphe- nomenaanddiscussesinmoredetailfurtherdiagnosticstepsaswellas thediagnosticapproachtodiseasemanifestations. Acknowledgments Twentyyearsago,ProfessorHerbertBegemanndedicatedtheforewordto thefirsteditionofthishematologyatlas.Heacknowledgedthat—beyond cellmorphology—thisatlasaimsattheclinicalpictureofpatients.Weare gratefulforbeingabletocontinuethistradition,andfortheimpulsesfrom ourteachersandcompanionsthatmakethispossible. Wethankourcolleagues:J.Rastetter,W.Kaboth,K.Lennert,H.Löffler, H.Heimpel,P.M.Reisert,H.Brücher,W.Enne,T.Binder,H.D.Schick,W. Hiddemann,D.Seidel. Munich,January2004 HaraldTheml,HeinzDiem,TorstenHaferlach vii Contents PhysiologyandPathophysiologyofBloodCells: MethodsandTestProcedures ............................ 1 IntroductiontothePhysiologyandPathophysiologyofthe HematopoieticSystem ....................................... 2 CellSystems .................................................. 2 PrinciplesofRegulationandDysregulationintheBloodCell SeriesandtheirDiagnosticImplications ........................ 7 Procedures,Assays,andNormalValues ....................... 9 TakingBloodSamples ......................................... 9 ErythrocyteCount ............................................ 10 HemoglobinandHematocritAssay ............................. 10 CalculationofErythrocyteParameters .......................... 10 RedCellDistributionWidth(RDW) ............................ 11 ReticulocyteCount ............................................ 11 LeukocyteCount .............................................. 14 ThrombocyteCount .......................................... 15 QuantitativeNormalValuesandDistributionofCellularBlood Components ................................................. 15 TheBloodSmearandItsInterpretation(DifferentialBloodCount, DBC) ......................................................... 17 SignificanceoftheAutomatedBloodCount ..................... 19 BoneMarrowBiopsy .......................................... 20 LymphNodeBiopsyandTumorBiopsy ......................... 23 Step-by-StepDiagnosticSequence ............................ 25 NormalCellsoftheBloodandHematopoieticOrgans . 29 TheIndividualCellsofHematopoiesis ........................ 30 ImmatureRedCellPrecursors:ProerythroblastsandBasophilic Erythroblasts ................................................. 30 MatureRedBloodPrecursorCells:PolychromaticandOrtho- chromaticErythroblasts(Normoblasts)andReticulocytes ....... 32 ImmatureWhiteCellPrecursors:MyeloblastsandPromyelo- cytes ........................................................ 34 viii Contents PartlyMatureWhiteCellPrecursors:MyelocytesandMetamyelo- cytes ........................................................ 36 MatureNeutrophils:BandCellsandSegmentedNeutrophils ..... 38 CellDegradation,SpecialGranulations,andNuclearAppendages inNeutrophilicGranulocytesandNuclearAnomalies ............ 40 EosinophilicGranulocytes(Eosinophils) ........................ 44 BasophilicGranulocytes(Basophils) ............................ 44 Monocytes ................................................... 46 Lymphocytes(andPlasmaCells) ............................... 48 MegakaryocytesandThrombocytes ............................ 50 BoneMarrow:CellCompositionandPrinciplesofAnalysis .... 52 BoneMarrow:MedullaryStromaCells ......................... 58 AbnormalitiesoftheWhiteCellSeries .................. 61 PredominanceofMononuclearRoundtoOvalCells ........... 63 ReactiveLymphocytosis ...................................... 66 ExamplesofExtremeLymphocyticStimulation:Infectious Mononucleosis ............................................ 68 DiseasesoftheLymphaticSystem(Non-HodgkinLymphomas) ... 70 DifferentiationoftheLymphaticCellsandCellSurfaceMarker ExpressioninNon-HodgkinLymphomaCells ................. 72 ChronicLymphocyticLeukemia(CLL)andRelatedDiseases .... 74 LymphoplasmacyticLymphoma ............................. 78 FacultativeLeukemicLymphomas(e.g.,MantleCellLymphoma andFollicularLymphoma) ................................... 78 Lymphoma,UsuallywithSplenomegaly(e.g.,HairyCellLeuke- miaandSplenicLymphomawithVillousLymphocytes) ....... 80 MonoclonalGammopathy(Hypergammaglobulinemia),Mul- tipleMyeloma*,PlasmaCellMyeloma,Plasmacytoma ......... 82 VariabilityofPlasmacytomaMorphology ..................... 84 RelativeLymphocytosisAssociatedwithGranulocytopenia (Neutropenia)andAgranulocytosis ............................ 86 ClassificationofNeutropeniasandAgranulocytoses ........... 86 Monocytosis ................................................. 88 AcuteLeukemias ............................................. 90 MorphologicalandCytochemicalCellIdentification ........... 91 AcuteMyeloidLeukemias(AML) ............................. 95 AcuteErythroleukemia(FABClassificationTypeM ) .......... 100 6 AcuteMegakaryoblasticLeukemia (FABClassificationTypeM ) ................................. 102 7 AMLwithDysplasia ........................................ 102 HypoplasticAML ........................................... 102 Contents ix AcuteLymphoblasticLeukemia(ALL) ........................ 104 Myelodysplasia(MDS) ...................................... 106 PrevalenceofPolynuclear(Segmented)Cells ................. 110 NeutrophiliawithoutLeftShift ................................ 110 ReactiveLeftShift ............................................ 112 ChronicMyeloidLeukemiaandMyeloproliferativeSyndrome (ChronicMyeloproliferativeDisorders,CMPD) .................. 114 StepsintheDiagnosisofChronicMyeloidLeukemia .......... 116 BlastCrisisinChronicMyeloidLeukemia ..................... 120 Osteomyelosclerosis .......................................... 122 ElevatedEosinophilandBasophilCounts ....................... 124 ErythrocyteandThrombocyteAbnormalities ........... 127 ClinicallyRelevantClassificationPrincipleforAnemias:Mean ErythrocyteHemoglobinContent(MCH) ....................... 128 HypochromicAnemias ....................................... 128 IronDeficiencyAnemia ....................................... 128 HypochromicInfectiousorToxicAnemia(SecondaryAnemia) ... 134 BoneMarrowCytologyintheDiagnosisofHypochromicAne- mias ....................................................... 136 HypochromicSideroachresticAnemias(SometimesNormo- chromicorHyperchromic) .................................... 137 HypochromicAnemiawithHemolysis ......................... 138 Thalassemias ............................................... 138 NormochromicAnemias ..................................... 140 NormochromicHemolyticAnemias ............................ 140 HemolyticAnemiaswithErythrocyteAnomalies ................ 144 NormochromicRenalAnemia(SometimesHypochromicor Hyperchromic) ............................................... 146 BoneMarrowAplasia ......................................... 146 PureRedCellAplasia(PRCA,Erythroblastopenia) ............. 146 AplasiasofAllBoneMarrowSeries(Panmyelopathy,Pan- myelophthisis,AplasticAnemia) ............................. 148 BoneMarrowCarcinosisandOtherSpace-OccupyingProcesses .. 150 HyperchromicAnemias ...................................... 152 ErythrocyteInclusions ....................................... 156 HematologicalDiagnosisofMalaria ............................ 158