A Pattern Approach to Lymph Node Diagnosis PDF
Preview A Pattern Approach to Lymph Node Diagnosis
A Pattern Approach to Lymph Node Diagnosis A Pattern Approach to Lymph Node Diagnosis Anthony S.-Y. Leong, MB,BS,MD,FRCPA,FRCPath,FCAP,FASCP, FHKAM(Pathol),HonoraryFHKCPath,HonoraryFRCPT Director,PathologyLaboratories,SunwayMedicalCenter,PetalingJaya,Malaysia ProfessorofPathology,JeffreyCheahSchoolofMedicine,MonashUniversity,SunwayCampus,Malaysia Formerly MedicalDirector,HunterAreaPathologyService,Newcastle ProfessorandChair,DisciplineofAnatomicalPathology UniversityofNewcastle,NewSouthWales,Australia 123 AnthonyS.-Y.Leong,MD Director PathologyLaboratories SunwayMedicalCenter PetalingJaya Malaysia ProfessorofPathology JeffreyCheahSchoolofMedicine MonashUniversity SunwayCampus Malaysia [email protected] ISBN978-1-4419-7175-3 e-ISBN978-1-4419-7176-0 DOI10.1007/978-1-4419-7176-0 SpringerNewYorkDordrechtHeidelbergLondon LibraryofCongressControlNumber:2010935338 ©SpringerScience+BusinessMedia,LLC2011 Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewrittenpermissionofthe publisher(SpringerScience+BusinessMedia,LLC,233SpringStreet,NewYork,NY10013,USA),exceptforbrief excerptsinconnectionwithreviewsorscholarlyanalysis.Useinconnectionwithanyformofinformationstorageand retrieval,electronicadaptation,computersoftware,orbysimilarordissimilarmethodologynowknownorhereafter developedisforbidden. Theuseinthispublicationoftradenames,trademarks,servicemarks,andsimilarterms,eveniftheyarenotidentified assuch,isnottobetakenasanexpressionofopinionastowhetherornottheyaresubjecttoproprietaryrights. Whiletheadviceandinformationinthisbookarebelievedtobetrueandaccurateatthedateofgoingtopress,neither theauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityforanyerrorsoromissionsthatmay bemade.Thepublishermakesnowarranty,expressorimplied,withrespecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Thedevelopmentofsophisticatedancillarytechniquesforlymphnodediagnosishasmade hematopathologyaspecializeddisciplineinmanydevelopedcountries.Immunohistology, electron microscopy, and molecular diagnostic techniques are expensive procedures and requirespecializedresourcesandtechnicalskills,commoditiesthatarenotreadilyavailable in many laboratories other than those in large medical facilities. The general or commu- nity hospital pathologist is thus still required to make a histological diagnosis based on microscopic observations of the biopsied lymph node, or at least, to decide if the patho- logical changes represent a reactive or neoplastic process before referring the material for an expert opinion. Importantly, as the pathologist to first encounter the excised lymph node,heorsheisresponsiblefortriageofthespecimen.Thisrequiresfamiliaritynotonly withthedifferenttechnologiesemployedintheproperexaminationofthesampledmate- rial but also with the appropriate preparation of the specimen and what each adjunctive techniquehastooffer. There are many large and excellent textbooks on lymph node pathology that define anddescribediseasesoflymphnodesingreatdetail.Thesetaketheconventionalapproach ofseparatelydescribingeachofthereactiveandneoplasticentitiesthatinvolvethelymph node and lymphoid tissues, and their accompanying immunophenotypic profiles, and cytogenetic and molecular characteristics. This approach is contrary to the conventional method applied in histologic diagnosis which is one of pattern recognition performed through a systematic assessment of the various anatomical compartments of the tissue for changes in architecture, expansion of a population of normal cells, or accumulation or presence of abnormal populations of cells. In the lymph node, such anatomical compart- ments are not clearly visible. Such a method of assessment is even more important for the lymph node as anatomical compartmentalization reflects immune and cellular func- tion.Tothetraineeandgeneral/communitypathologist,thelymphnodemayrepresenta morass of small and large lymphocytes without clearly visible compartmentalization. This problem is further compounded by the fact that neoplastic lymphoid cells invariably have cytologic features similar and even identical to their normal counterparts, so that cellular density, composition, and compartmentalization become important aspects of the histo- logicassessment.Reactiveprocessescanproduceexuberantexpansionsofdifferentlymph node compartments, and the changes are dynamic, adding further to difficulties of diag- nosis. Thepatternapproachtolymphnodediagnosishasbeenpreviouslyproposedbutsuch an approach has not been adopted before in a textbook. The advent of immunohistology and the availability of a comprehensive range of sensitive antibodies that are immunore- active in routinely fixed, paraffin-embedded sections make it much easier to adopt such a diagnosticapproachwhichmoretrulyreflectsthemannerinwhichpathologistsroutinely examinelymphnodes.Invariably,assomeneoplasmsandmostreactiveconditionsinvolve more than one compartment and produce more than one pattern of change, there will be some degree of overlap with this method of diagnostic approach. However, in this book, this is kept to a minimum and each entity is discussed under its primary pattern v vi Preface of presentation and will be briefly mentioned, especially in differential diagnoses, when it producesalternativeandless-frequentpatternsofhistologicchange. Immunohistology is now an established ancillary diagnostic technique that is employed by most routine laboratories, although the range of antibodies available will vary.Wewillnotonlydiscusstheminimalrepertoireofantibodiesrequiredforlymphoma diagnosis but also provide detailed immunoprofiles for complete characterization of each neoplastic process. Clinical, molecular, and cytogenetic characteristics will also be dis- cussed as they often aid diagnosis and provide further understanding of the neoplastic process.Electronmicroscopy,whichislesscontributoryintheareaoflymphomadiagno- sis,willbetouchedonwhereappropriate. Itistheprimaryaimofthisbooktodemonstratethatasystematicapproachtolymph node examination can be achieved through recognition of morphological patterns pro- ducedbydifferentdiseaseprocesses.Alevelofconfidenceandfamiliaritywithlymphnode pathology can be attained through the adoption of such an approach that is employed largely in every other organ system in the body. This book is thus directed at trainee andgeneral/communitypathologistswhohavefirstcontactwiththeexcisedlymphnode and are required to make an initial judgment on the morphologic changes, especially if deciding to refer the specimen on for expert opinion. The classification system employed throughout this book is that of the 2008 World Health Classification. This book is not intended to supplant the many excellent texts available on lymph node pathology and is not intended to provide new information or knowledge. Its purpose is to instruct the reader in a method of examination that employs the recognition of patterns and colors. The discussion of each diagnostic entity is accompanied by ample color illustrations that highlight the diagnostic features. Inaddition, textboxes summarizing the salient features are provided. This is essentially a “how-to” manual that also integrates current informa- tion about specific neoplastic entities. References have been deliberately excluded as they distract from the primary purpose and the reader is referred to the 2008 WHO book for acomprehensiveandappropriatereferencelistingandtootherselectedreferences. AnthonyS.-Y.Leong,MD Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii SECTIONI 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Knowledge-BasedDiagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 SystematicExaminationoftheLymphNode . . . . . . . . . . . . . . . . . . . . 7 CellTypeIdentification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 CellSizeandCellularity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Immunohistology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 CytologicalPreparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 ThePatternApproachtoDiagnosis . . . . . . . . . . . . . . . . . . . . . . . . 14 SelectedReading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2. HandlingoftheLymphNodeBiopsy . . . . . . . . . . . . . . . . . . . . . . . 19 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 TheBiopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 LymphNodeTriage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3. ImmunohistologyandOtherDiagnosticTechniques . . . . . . . . . . . . . . . . 23 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Immunohistology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 BCellMarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 TCellMarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 NaturalKillerandT/NKCellMarkers . . . . . . . . . . . . . . . . . . . . . . . 38 PrecursorB-andTCellMarkers . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Monocyte/MacrophageMarkers . . . . . . . . . . . . . . . . . . . . . . . . . 39 LangerhansCell,FollicularDendriticCell,andInterdigitatingDendritic ReticulumCellMarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Markersof Reed–SternbergCellsinHodgkinLymphoma . . . . . . . . . . . . . 42 MiscellaneousMarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 MyeloidCellMarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 MastCellMarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 DiagnosticApproachwithImmunohistochemicalStains . . . . . . . . . . . . . . 47 StainingforFollicularDendriticCells . . . . . . . . . . . . . . . . . . . . . . . 47 ImmunohistologicalIdentificationofDiffuseLymphoidInfiltrates . . . . . . . . 49 HistochemicalStains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 FlowCytometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 MolecularDiagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 DetectionofClonality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 ImmunoglobulinHeavy-andLight-ChainGenes . . . . . . . . . . . . . . . . . 57 TCellReceptorChainGenes. . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 vii viii Contents GenotypeSubgroups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 ConventionalCytogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 FluorescenceInSituHybridization(FISH) . . . . . . . . . . . . . . . . . . . . 60 SouthernBlotAnalysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 PolymeraseChainReaction(PCR) . . . . . . . . . . . . . . . . . . . . . . . . . 60 GeneExpressionProfiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 4. AnatomicalandFunctionalCompartments . . . . . . . . . . . . . . . . . . . . . 63 BCellDifferentiationandCorrespondingBCellLymphomas . . . . . . . . . . . 64 TheCortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 TheLymphoidFollicle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 TCellDifferentiation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 TheParacortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 High-EndothelialVenules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 MedullaryArea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 ConnectiveTissueFramework . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 SECTIONII 5. NodularLymphoidInfiltrates . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 FollicularPattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 NeoplasticFollicles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 FollicularLymphoma(FL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 FollicularHyperplasiaVersusFollicularLymphoma . . . . . . . . . . . . . . . . 91 OtherFollicularPatterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 MantlePattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 MantleCellLymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 MarginalZonePattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 NodalMarginalZoneLymphoma(MonocytoidBCellLymphoma). . . . . . . . 107 NodularPattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 HeterogenousNodules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 PseudofollicularPattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 HodgkinLymphoma(HL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 ClassicalHodgkinLymphoma(CHL) . . . . . . . . . . . . . . . . . . . . . . . 116 Post-transplantLymphoproliferativeDisorders . . . . . . . . . . . . . . . . . . . 127 ColonizationofFolliclesbyNeoplasticCells . . . . . . . . . . . . . . . . . . . . 131 HomogenousNodules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 ReactiveHyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 FollicularandParacorticalHyperplasia . . . . . . . . . . . . . . . . . . . . . . . 136 Non-specificFollicularHyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . 137 ProgressiveTransformationofGerminalCenters(PTGC) . . . . . . . . . . . . . 137 RheumatoidLymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . . . . 138 ToxoplasmaLymphadenopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Human Immunodeficiency Virus/Acquired Immunodeficiency Disease Syndrome(HIV/AIDS)Lymphadenitis . . . . . . . . . . . . . . . . . . . 142 KimuraDisease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 CastlemanDisease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 SyphilisLymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 KikuchiDisease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Contents ix SystemicLupusErythematosus . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 InfectiousMononucleosisLymphadenopathy . . . . . . . . . . . . . . . . . . . 158 OtherViralLymphadenopathies . . . . . . . . . . . . . . . . . . . . . . . . . . 161 ParacorticalNodules/Expansion . . . . . . . . . . . . . . . . . . . . . . . . . . 165 DermatopathicLymphadenopathy(DL) . . . . . . . . . . . . . . . . . . . . . . 165 Drug-InducedLymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . . . 166 TheDiagnosticApproachtoNodularInfiltratesinLymphNodes . . . . . . . . . 167 AreTheyFolliclesorNodules? . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 AretheFolliclesReactiveorNeoplastic? . . . . . . . . . . . . . . . . . . . . . . 168 AreFolliclesInfrequentand“Constricted”? . . . . . . . . . . . . . . . . . . . . 168 AretheFolliclesExceptionallyLarge? . . . . . . . . . . . . . . . . . . . . . . . 169 DotheEnlargedGerminalCentersContainAtypicalCells? . . . . . . . . . . . . 169 AretheNodulesHomogenousorHeterogenousinComposition? . . . . . . . . . 169 HomogenousNodules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 HeterogenousNodules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 IfThereIsMarkedFollicularHyperplasia,CanaSpecificDiagnosisBeMade?. . . 170 DotheVagueNodulesRepresentParacorticalNodules? . . . . . . . . . . . . . . 171 6. DiffuseLymphoidInfiltrations . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 BCellNeoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 ChronicLymphocyticLeukemia/SmallLymphocyticLymphoma(CLL/SLL) . . 176 LymphoplasmacyticLymphoma(LPL) . . . . . . . . . . . . . . . . . . . . . . . 186 DiffuseLargeBCellLymphoma(DLBCL) . . . . . . . . . . . . . . . . . . . . 194 ClinicalSubtypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 BurkittLymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212 B Cell Lymphoma, Unclassifiable, with Features Intermediate Between DLBCLandBL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217 NodalInvolvementbyPrimaryExtranodalLymphomasandLeukemias . . . . . . 218 TCellandNKCellNeoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . 218 T-LymphoblasticLeukemia/Lymphoma(PrecursorTCellLymphoblastic Leukemia/Lymphoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219 PeripheralTCellLymphoma,NotOtherwiseSpecified(PTCL-NOS) . . . . . . . 223 AngioimmunoblasticTCellLymphoma . . . . . . . . . . . . . . . . . . . . . . 229 AnaplasticLargeCellLymphoma(ALCL),ALK-Positive . . . . . . . . . . . . . 238 Immunohistology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244 AnaplasticLargeCellLymphoma,ALK-Negative . . . . . . . . . . . . . . . . . 249 AdultTCellLeukemia/Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . 250 NodalInvolvementbytheCutaneousTCellLymphomas . . . . . . . . . . . . . 255 HistiocyticandDendriticNeoplasms . . . . . . . . . . . . . . . . . . . . . . . . 260 HistiocyticSarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262 LangerhansCellHistiocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 268 InterdigitatingDendriticCell(IDC)Sarcoma . . . . . . . . . . . . . . . . . . . 272 FollicularDendriticCell(FDC)Sarcoma . . . . . . . . . . . . . . . . . . . . . . 275 HodgkinLymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278 DiagnosticApproachtoDiffuseInfiltratesinlymphNodes . . . . . . . . . . . . 279 IstheInfiltrateTrulyDiffuse? . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 DoestheDiffuseInfiltrateInvolvetheNodePartiallyorCompletely? . . . . . . . 280 IstheInfiltrateMonomorphousorPolymorphous?AretheCellsSmallorLarge? . 281 x Contents 7. DefiningMicroscopicFeatures . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 GranulomasandFoamCells . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 InfectiveGranulomatousLymphadenitis . . . . . . . . . . . . . . . . . . . . . . 287 MycoticLymphadenitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 ProtozoanandParasiticLymphadenitides . . . . . . . . . . . . . . . . . . . . . 300 Non-infectiveGranulomatousLymphadenitis . . . . . . . . . . . . . . . . . . . 301 Granulomas,Non-necrotizing . . . . . . . . . . . . . . . . . . . . . . . . . . . 304 ForeignBodyandLipidGranulomatousLymphadenitis . . . . . . . . . . . . . . 307 LipidLymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310 SinusPattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 SinusHistiocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 Rosai–DorfmanDisease(SinusHistiocytosiswithMassiveLymphadenopathy) . . 316 Necrosis,Apoptosis,andInfarction. . . . . . . . . . . . . . . . . . . . . . . . . 317 ClearCells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319 MastCellDisease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 HairyCellLeukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 SpindledCells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324 InflammatoryMyofibroblasticTumor . . . . . . . . . . . . . . . . . . . . . . . 325 PalisadedMyofibroblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325 KaposiSarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 VascularProminence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 BacillaryAngiomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 VascularTransformationofLymphNodeSinuses . . . . . . . . . . . . . . . . . 331 Hemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 StarrySkyPattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 MottledPattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 Fibrosis/Hyalinization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 SignetRingCells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 BizarreorMultinucleatedCells . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 ExtramedullaryHematopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 ProminentEosinophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 ProminentNeutrophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338 ProminentPlasmaCells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339 InfiltrationofPericapsularFat . . . . . . . . . . . . . . . . . . . . . . . . . . . 339 Extraneous Cells – Pigmented Cells, Epithelial Cells, Foreign Material, DermatopathicLymphadenitis,Hemosiderin . . . . . . . . . . . . . . . . . 340 InclusionsofBenignExtraneousCells . . . . . . . . . . . . . . . . . . . . . . . 340 8. NodalInvolvementbyLeukemiasandExtranodalLymphomas . . . . . . . . . . 345 NodalInvolvementbyLeukemia . . . . . . . . . . . . . . . . . . . . . . . . . . 345 MyeloidLeukemia/MyeloidSarcoma . . . . . . . . . . . . . . . . . . . . . . . 345 PrimaryMyelofibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346 BandTCellProlymphocyticLeukemias . . . . . . . . . . . . . . . . . . . . . . 348 NKCellLymphoproliferativeDisorders . . . . . . . . . . . . . . . . . . . . . . 350 NodalInvolvementbyExtranodalLymphomas . . . . . . . . . . . . . . . . . . 351 SplenicBCellMarginalZoneLymphoma . . . . . . . . . . . . . . . . . . . . . 352 HairyCellLeukemia(HCL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353 Heavy-ChainDisease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
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