內(nèi)科學(xué)教學(xué)課件：39 淋巴瘤

Lymphoma

(淋巴瘤)

Definition：aheterogenousgroupofneoplasticdiseasesoflymphoidtissues

thatoriginateinlymphnodesor/andany

othersiteofthebody.Classification：

HodgkinLymphoma，HL(Hodgkin′sDisease,HD)

Non-HodgkinLymphoma,NHLHL8～11%;NHL90%±GeneralConsiderationsClinicalFeatures：

Painless,progressivelymphadenectasis

Involvementofextranodalorganorsite

Fever,weightloss,nightsweat,cachexiaEpidemiology:

Incidence

incities/inthecountry;male/female;ageGeneralConsiderations全世界各國惡性淋巴瘤發(fā)病情況(2002)美國日本中國歐洲占惡性腫瘤(位)7797男性5.95.45.6女性3.83.43.8發(fā)病人數(shù)/10萬人4.94.83.24.8年死亡病例（萬）2.91.23.6年發(fā)病人數(shù)(萬)5.82.68.2每年增長(%)433.7Hodgkinlymphoma，HL1.

Infection:

⑴Epstein-BarrVirus(EBV)⑵Humanimmunodeficiencyvirus（HIV）⑶Humanherpesvirus-6（HHV-6）⑷Measlesvirus（MV）2.

Geneticfactor：

Familyhistory，SpecificalleleEtiologyandPathogenesisPathologyandPathophysiology

HL:Reed-Sternberg(R-S)cellPathology

RyeClassification，1966LymphocytepredominanceNodularsclerosisMixedcellularityLymphocytedepletionPathologyandPathophysiologyWHOClassification,2008

NodularlymphocytepredominanceHodgkin'slymphomaClassicalHodgkin'slymphomaLymphocyte-richHodgkin'slymphomaNodularsclerosisHodgkin'slymphomaMixedcellularityHodgkin'slymphomaLymphocytedepletionHodgkin'slymphomaHL分型特點(diǎn)類型病理組織學(xué)特點(diǎn)臨床特點(diǎn)結(jié)節(jié)性淋巴細(xì)胞為主型(NLPHL)結(jié)節(jié)狀生長，RS細(xì)胞核大，分葉，核仁小而明顯，沒有核仁外暈輪，稱為“爆米花樣”細(xì)胞,位于濾泡樹突狀細(xì)胞組成的大網(wǎng)中。期間充滿淋巴細(xì)胞占4%-5%，年輕人多見，男性比女性多見，常累及外周淋巴結(jié)，縱隔累及較少，診斷時(shí)多為Ⅰ、Ⅱ期，預(yù)后可富于淋巴細(xì)胞型(LRCHL)結(jié)節(jié)狀或彌漫性，散在RS細(xì)胞，含豐富的淋巴細(xì)胞，不存在中性粒細(xì)胞和嗜酸性粒細(xì)胞占6%，男性多見，預(yù)后可結(jié)節(jié)硬化型(NSHL)包膜很厚，交織的膠原纖維將浸潤細(xì)胞分隔成明顯結(jié)節(jié)，RS細(xì)胞較大，呈腔隙型（陷窩細(xì)胞），淋巴細(xì)胞、組織細(xì)胞、漿細(xì)胞、中性及嗜酸性粒細(xì)胞多見發(fā)達(dá)國家中最常見類型（60%-80%），年輕人多見，常累及淋巴結(jié)、縱隔，診斷時(shí)多為Ⅰ、Ⅱ期，預(yù)后可混合細(xì)胞型(MCHL)多為彌漫性，浸潤細(xì)胞呈多形性，可伴血管增生和纖維化。淋巴細(xì)胞、漿細(xì)胞、中性及嗜酸性粒細(xì)胞與較多經(jīng)典的RS細(xì)胞混同存在占15%-30%，任何年齡都可發(fā)病，有播散傾向，預(yù)后相對較差淋巴細(xì)胞消減型(LDHL)RS細(xì)胞數(shù)量較多，多形性，而淋巴細(xì)胞減少占1%，好發(fā)于老年人，常累及腹部淋巴結(jié)、脾、肝和骨髓，診斷時(shí)多為Ⅲ、Ⅳ期，預(yù)后差NLPHL和CHL的區(qū)別NLPHLCHL總體形態(tài)結(jié)節(jié)性為主彌散型、濾泡間、結(jié)節(jié)性腫瘤細(xì)胞L&H細(xì)胞或爆米花樣細(xì)胞經(jīng)典RS細(xì)胞,單核或多核RS細(xì)胞、腔隙細(xì)胞背景淋巴細(xì)胞,組織細(xì)胞淋巴細(xì)胞,組織細(xì)胞,中性、嗜酸性粒細(xì)胞,漿細(xì)胞纖維化少見常見CD15-+CD30-+CD20+-/+CD45+-EMA+-EB病毒-+(<50%)Ig基因活性的,功能性的無活性的年齡分布單峰雙峰(結(jié)節(jié)硬化型)分布部位外周淋巴結(jié)縱隔,腹部,脾確診時(shí)分布一般為I期常為II或III期B癥狀<20%40%病程隱匿性侵襲性ClinicalFeaturesSystemicsymptomsLymphnodeenlargementInvolvementofextranodalorganorsite非霍奇金淋巴瘤與霍奇金淋巴瘤臨床表現(xiàn)比較臨床表現(xiàn)霍奇金淋巴瘤非霍奇金淋巴瘤發(fā)病年齡青年多見各年齡組(隨年齡增長多見)發(fā)生部位首發(fā)淺表LN腫大常見除淺表LN外,結(jié)外淋巴組織發(fā)生亦常見發(fā)展規(guī)律向鄰近LN延續(xù)性擴(kuò)散非鄰近淋巴結(jié)發(fā)展常見病變范圍局部淋巴結(jié)病變常見局部淋巴結(jié)病變少見發(fā)熱/皮膚瘙癢較多見/年輕女性多見于晚期/少見肝/骨骼/骨髓侵犯少見常見縱隔/脾侵犯常見，尤結(jié)節(jié)硬化型/常見

除淋巴母細(xì)胞型外，不常見/不常見腹塊腸系膜病變少見常見咽淋巴環(huán)罕見較常見消化道侵犯罕見常見中樞神經(jīng)侵犯少見偶見皮膚侵犯罕見T細(xì)胞型較多見LabandOtherFindingsPeripheralBloodandBoneMarrow

Eosinophilia；R－Scell ESR,LDH，β2-MGSerumAlkalinePhosphatase，BloodCalciumLabandOtherFindingsB-ultrasoundRadiologicImaging

ChestX-ray

CT

MRIPET-CTEndoscopyLabandOtherFindingsBiopsyImmunophenotype

MolecularDetection

NLPHLCHLCD15-+CD30-+CD20+-/+CD45+-Diagnosis

Painless,progressive

lymphadenectasis→Biopsy

BiopsyofOtherSites

BoneMarrowAspirationandBiopsyDiagnosisandDifferentialDiagnosis

Stagingoflymphoma

（AnnArbor,1971；Cotswold,1989）

StageDefinitionⅠInvolvementofasinglelymphnoderegionorofasingleextranodalorganorsite(ⅠE)ⅡInvolvementoftwoormorenoderegionsonthesamesideofthediaphragm,orlocalizedinvolvementofanextranodalsiteororgan(ⅡE)andoneormorelymphnoderegionsonthesamesideofthediaphragmⅢInvolvementoflymphnoderegionsonbothsidesofthediaphragmwhichmayalsobeaccompaniedbylocalizedinvolvementofanextranodalorgansorsite(ⅢE)orspleen(Ⅲs)orboth(ⅢsE)ⅣDiffuseordisseminatedinvolvementofoneormoredistantextranodalorganswithorwithoutassociatedlymphnodeinvolvement,anyInvolvementofliverorbonebarrowBSymptoms:fever>38℃,nightsweats,and/orweightloss>10%ofbodyinthe6monthsStagingoflymphomaDiagnosisand

DifferentialDiagnosisLymphadenitisTuberculouslymphadenitisSarcoidosisTumournodemetastases1.StageⅠ-Ⅱ：ABVD×4～6+Irradiation(20～30Gy,Involvedfields)2.StageⅢ-Ⅳ：ABVD×6～8，

Consolidationradiotherapy(Bulky)3.Refractoryandrelapsed:

⑴Theoriginaleffectiveregimens;⑵ICE,DHAP,ESHAP⑶Anti-CD30MonoclonalAntibody⑷HematopoieticStemCellTransplantation(HSCT)

Treatment霍奇金淋巴瘤的主要化療方案方案藥物劑量和用法ABVD阿霉素25mg/m2，靜注，第1天、15天博萊霉素10mg/m2，靜注，第1天、15天長春花堿6mg/m2，靜注，第1天、15天達(dá)卡巴嗪375mg/m2，靜注，第1天、15天ICE異環(huán)磷酰胺1.5g/m2，靜注，第1-3天卡鉑300mg，靜注，第2天依托泊苷100mg/m2，靜注，第1-3天DHAP地塞米松40mg，靜注，第1-4天順鉑100mg/m2，靜注，第1天阿糖胞苷2g/m2，靜脈滴注3小時(shí)，每12小時(shí)一次，第2天ESHAP依托泊苷40mg/m2，靜脈滴注2小時(shí)，第1-4天甲潑尼龍500mg/m2，靜脈滴注，第1-4天阿糖胞苷2g/m2，靜脈滴注3小時(shí)，第5天

順鉑25mg/m2，靜脈滴注，第1-4天（每3周為一周期）1.

TypesofTissuesandClinicalStage2.

InternationalprognosticfactorsforadvancedHL

Prognosisnon-Hodgkinlymphoma，NHL1.

Infection:

⑴EBV→BurkittLymphoma，TcellLymphoma,Immunodeficiencyassociatedlymphoma⑵Retroviruses：HTLV-Ⅰ→AdultT-cellleukemia/lymphoma(ATL)HTLV-Ⅱ→T-cellcutaneouslymphoma（granulomafungoides）HIVEtiologyandPathogenesis

⑶Humanherpesvirus-8（HHV-8)/Kaposisarcomaassociatedherpesvirus→Primaryeffusionlymphoma

（PEL）⑷Helicobacterpylori（HP）：StomachMALTlymphoma2.Environmentalfactor

andOccupationalexposure3.Immunocompromiceofhost:

Immunodeficiency/immunosuppression4.GeneticfactorEtiologyandPathogenesis

Pathology

ClassificationofNHL

Rappaport,1966Lukes

andCollins，1975IWF，1982

REAL，1994

WHO，2001，20082008WHO淋巴腫瘤新分類B淋巴母細(xì)胞白血病/淋巴瘤B淋巴母細(xì)胞白血病/淋巴瘤，NOSB淋巴母細(xì)胞白血病/淋巴瘤，具有重現(xiàn)性細(xì)胞遺傳學(xué)異常B淋巴母細(xì)胞白血病/淋巴瘤，具有t(9;22)(q34;q11.2);BCR-ABL1B淋巴母細(xì)胞白血病/淋巴瘤，具有t(v;11q23);MLL重排B淋巴母細(xì)胞白血病/淋巴瘤，具有t(12;21)(p13;q22);TEL-AML1(ETV6-RUNX1)B淋巴母細(xì)胞白血病/淋巴瘤，具有超二倍體B淋巴母細(xì)胞白血病/淋巴瘤，具有亞二倍體(亞二倍體ALL)B淋巴母細(xì)胞白血病/淋巴瘤，具有t(5;14)(q31;q32);IL3-IGHB淋巴母細(xì)胞白血病/淋巴瘤，具有t(1;19)(q23;p13.3);E2A-PBX1;(TCF3-PBX1)T淋巴母細(xì)胞白血病/淋巴瘤慢性淋巴細(xì)胞白血病/小淋巴細(xì)胞淋巴瘤B細(xì)胞幼淋巴細(xì)胞性白血病脾邊緣區(qū)淋巴瘤毛細(xì)胞白血病脾淋巴瘤/白血病，未分類*脾彌漫紅髓的小B細(xì)胞淋巴瘤毛細(xì)胞白血病-變異型淋巴漿細(xì)胞淋巴瘤華氏巨球蛋白血癥重鏈病Alpha重鏈病Gamma重鏈病Mu重鏈病漿細(xì)胞瘤骨的孤立性漿細(xì)胞瘤髓外漿細(xì)胞瘤粘膜相關(guān)淋巴組織結(jié)外邊緣區(qū)淋巴瘤(MALT淋巴瘤)結(jié)內(nèi)邊緣區(qū)淋巴瘤

兒童結(jié)內(nèi)邊緣區(qū)淋巴瘤

濾泡性淋巴瘤兒童濾泡性淋巴瘤原發(fā)于皮膚的濾泡中心淋巴瘤套細(xì)胞淋巴瘤彌漫大B細(xì)胞淋巴瘤(DLBCL)，NOS富含T/組織細(xì)胞的大B細(xì)胞淋巴瘤原發(fā)于中樞神經(jīng)系統(tǒng)的DLBCL原發(fā)于皮膚的DLBCL，腿型老年性EB病毒陽性的DLBCL與慢性炎癥相關(guān)的DLBCL淋巴樣肉芽腫病原發(fā)于縱隔（胸腺）的大B細(xì)胞淋巴瘤血管內(nèi)大B細(xì)胞淋巴瘤ALK陽性的大B細(xì)胞淋巴瘤漿母細(xì)胞性淋巴瘤HHV8相關(guān)的大B細(xì)胞淋巴瘤多中心Castleman病原發(fā)性滲出性淋巴瘤伯基特淋巴瘤B細(xì)胞淋巴瘤，不能分類型,，具有介于彌漫大B細(xì)胞淋巴瘤與伯基特淋巴瘤之間的特征B細(xì)胞淋巴瘤，不能分類型，具有介于彌漫大B細(xì)胞淋巴瘤與典型霍奇金病之間的特征T細(xì)胞幼淋巴細(xì)胞性白血病大顆粒T淋巴細(xì)胞白血病NK細(xì)胞性慢性淋巴細(xì)胞增殖性疾病侵襲性NK細(xì)胞白血病兒童系統(tǒng)性EB病毒陽性的T細(xì)胞淋巴增殖性疾病類水痘樣淋巴瘤成人T細(xì)胞白血病/淋巴瘤結(jié)外NK/T細(xì)胞淋巴瘤，鼻型腸道病相關(guān)性T細(xì)胞淋巴瘤肝脾T細(xì)胞淋巴瘤皮下脂膜炎樣T細(xì)胞淋巴瘤蕈樣真菌病Sézary綜合征原發(fā)于皮膚的CD30陽性的T細(xì)胞增殖性疾病淋巴瘤樣丘疹病原發(fā)于皮膚的間變性大細(xì)胞淋巴瘤原發(fā)于皮膚的γδT細(xì)胞淋巴瘤原發(fā)于皮膚的CD8陽性侵襲性嗜表皮的細(xì)胞毒性T細(xì)胞淋巴瘤原發(fā)于皮膚的CD4陽性小/中間T細(xì)胞淋巴瘤外周T細(xì)胞淋巴瘤，NOS血管免疫母細(xì)胞性T細(xì)胞淋巴瘤間變性大細(xì)胞性淋巴瘤，ALK陽性間變性大細(xì)胞性淋巴瘤，ALK陰性霍奇金淋巴瘤結(jié)節(jié)淋巴細(xì)胞為主型霍奇金淋巴瘤典型霍奇金淋巴瘤結(jié)節(jié)硬化型典型霍奇金淋巴瘤富含淋巴細(xì)胞的典型霍奇金淋巴瘤混合細(xì)胞性典型霍奇金淋巴瘤淋巴細(xì)胞消減型典型霍奇金淋巴瘤移植后淋巴細(xì)胞增殖性疾病(PTLD)早期損傷漿細(xì)胞增生感染性單核細(xì)胞增多樣PTLD多形性PTLD單一形態(tài)的PTLD(B-及T/NK-細(xì)胞型)#典型霍奇金淋巴瘤型PTLD#前體細(xì)胞侵襲性B細(xì)胞成熟T/NK細(xì)胞HL和PTLD惰性B細(xì)胞組織細(xì)胞和樹突細(xì)胞腫瘤組織細(xì)胞肉瘤朗格漢斯組織細(xì)胞增生癥朗格漢斯細(xì)胞肉瘤交指樹突細(xì)胞肉瘤濾泡樹突細(xì)胞肉瘤成纖維細(xì)胞性網(wǎng)狀細(xì)胞腫瘤中間性樹突細(xì)胞腫瘤播散性幼年性黃色肉芽腫未分類的:6%毛細(xì)胞白血病:0%脾邊緣區(qū)淋巴瘤:1%淋巴漿細(xì)胞性淋巴瘤:1%伯基特淋巴瘤:2%淋巴結(jié)邊緣區(qū)淋巴瘤:1%原發(fā)性中樞神經(jīng)系統(tǒng)淋巴瘤:3%非霍奇金淋巴瘤的類型（中國內(nèi)地）ClinicalFeaturesSystemicsymptomsLymphnodeenlargementInvolvementofextranodalorganorsite非霍奇金淋巴瘤與霍奇金淋巴瘤臨床表現(xiàn)比較臨床表現(xiàn)霍奇金淋巴瘤非霍奇金淋巴瘤發(fā)病年齡青年多見各年齡組(隨年齡增長多見)發(fā)生部位首發(fā)淺表LN腫大常見除淺表LN外,結(jié)外淋巴組織發(fā)生亦常見發(fā)展規(guī)律向鄰近LN延續(xù)性擴(kuò)散非鄰近淋巴結(jié)發(fā)展常見病變范圍局部淋巴結(jié)病變常見局部淋巴結(jié)病變少見發(fā)熱/皮膚瘙癢較多見/年輕女性多見于晚期/少見肝/骨骼/骨髓侵犯少見常見縱隔/脾侵犯常見，尤結(jié)節(jié)硬化型/常見

除淋巴母細(xì)胞型外，不常見/不常見腹塊腸系膜病變少見常見咽淋巴環(huán)罕見較常見消化道侵犯罕見常見中樞神經(jīng)侵犯少見偶見皮膚侵犯罕見T細(xì)胞型較多見LabandOtherFindingsPeripheralBloodandBoneMarrow

Lymphocytosis;ComplicatedleukemiaLDH，β2-MG,GlobulinSerumAlkalinePhosphatase，BloodCalcium，CoombsTestCerebrospinalfluid(CSF)LabandOtherFindingsPeripheralBloodandBoneMarrow

Lymphocytosis;ComplicatedleukemiaLDH，β2-MG,GlobulinSerumAlkalinePhosphatase，BloodCalcium，CoombsTestCerebrospinalfluid(CSF)LabandOtherFindingsB-ultrasoundRadiologicstudies

ChestX-ray

CTMRIPET-CTEndoscopy彌漫性大B細(xì)胞淋巴瘤患者，髂后上棘穿刺陰性。18F-FDGPET/CT顯像示廣泛骨病灶。PET(A)及PET/CT融合圖像(B)顯示胸骨及臨近軟組織、頸椎、骶骨18F-FDG異常攝取。隨后的活檢確診淋巴瘤。淋巴瘤患者申請PET/CT協(xié)助分期。(A)PET圖像示18F-FDG異常濃聚。(B)相應(yīng)區(qū)域CT未見明確病變。(C)PET/CT融合圖像準(zhǔn)確地將FDG異常濃聚區(qū)定位于左髂骨，導(dǎo)致分期改變和病人處理方案的改變。彌漫性大B細(xì)胞淋巴瘤患者治療前PET顯像(A)示頸部、縱隔和腹腔廣泛18F-FDG異常濃聚區(qū)，治療后隨訪PET顯像(B)顯示全身葡萄糖代謝正常，提示治療有效。LabandOtherFindingsBiopsyImmunophenotype

CytogeneticDetectiont(14;18)－Follicularlymphomat(11;14)－Mantlecelllymphomat(8;14)－Burkittlymphomat(2;5)－Anaplasticlargecelllymphomaabnormalitiesof3q27－DLBCLMolecularDetection

Heavy-chaingenerearrangementTCRgenerearrangementDiagnosis

Painless,progressive

lymphadenectasis→Biopsy

SkinLesion→Biopsy

BoneMarrowAspirationandBiopsyBiopsyofOtherSites

DiagnosisandDifferentialDiagnosis

Stagingoflymphoma

（AnnArbor,1971；Cotswold,1989）

StageDefinitionⅠInvolvementofasinglelymphnoderegionorofasingleextranodalorganorsite(ⅠE)ⅡInvolvementoftwoormorenoderegionsonthesamesideofthediaphragm,orlocalizedinvolvementofanextranodalsiteororgan(ⅡE)andoneormorelymphnoderegionsonthesamesideofthediaphragmⅢInvolvementoflymphnoderegionsonbothsidesofthediaphragmwhichmayalsobeaccompaniedbylocalizedinvolvementofanextranodalorgansorsite(ⅢE)orspleen(Ⅲs)orboth(ⅢsE)ⅣDiffuseordisseminatedinvolvementofoneormoredistantextranodalorganswithorwithoutassociatedlymphnodeinvolvement,anyInvolvementofliverorbonebarrowBSymptoms:fever>38℃,nightsweats,and/orweightloss>10%ofbodyinthe6monthsStagingoflymphomaDifferentialDiagnosis

Lymphadenectasis：LymphadenitisTuberculouslymphadenitisSarcoidosisTumournodemetastases

Fever：Septicaemia,Tuberculosis,RheumaticdiseaseExtranodalLymphoma:Other

malignanttumerDiagnosisandDifferentialDiagnosis1.Chemotherapyandradiotherapy

⑴Indolent:Observe；Chlorambucil，CTX，F(xiàn)ludarabine,FC±R;COP/CHOP±R

LocalIrradiation⑵Aggressive:Chemotherapy(CHOP,m-BACOD,COP-BlAM)±Radiotherapy

High-Aggressive：

High-doseChemotherapy，(HyperCVAD)Lymphomacellleukemia:Accordingtothetreatmentofleukemia，VDLP

TreatmentTreatment

⑶

Lymphomacellleukemia:Accordingtothetreatmentofleukemia，VDLP⑷Relapsed:ESHAP

非霍奇金淋巴瘤常