肿瘤学-犬淋巴瘤

BabushkaSignalment 特征Female,8yearold,poodle

雌性，8岁，贵宾犬History病史PU/PDforthelastfewweeks

前几周多饮多尿Acutecollapse-immediatelypresentedtotheemergencyservice

严重虚脱－立刻送至急救PhysicalExam 体检Weakness 虚弱5%dehydration 5％脱水Nootherabnormalities 无其他异常DiagnosticPlan 诊断计划CBC 血常规Biochemistry 生化Urinalysis 尿检Results-CBC 全血细胞计数结果WBC-10.09白细胞计数RBC-6.26红细胞PCV-42红细胞压积容量Plts-159血小板Ts-6.8Results-Biochemistry生化结果Glu-101谷氨酸Creat-2.19Na+-151钠离子K+-3.9钾离子Ca++-1.91钙离子Results-UA尿检结果SG-1.018Ph-6.0Nosedimentorotherfindings

无沉淀，无其他异常ProblemList 问题列表Acutecollapse-weakness

急性虚脱－虚弱Hypercalcemia-PU/PD

高钙血症－多饮多尿Dehydration

脱水DDsforHypercalcemia

高钙血症鉴别诊断1 Laberror-alwaysmakesureitisrepeatable 实验错误－需要重复确认2 Physiologicgrowthofyounganimals年轻动物生长3 Dehydration(hyperproteinemia)脱水（高蛋白血症）4 Malignancytumors恶性肿瘤Lymphoma淋巴瘤,apocrineglandanalsacadenocarcinoma顶浆分泌腺和肛门腺癌,adenocarcinoma腺癌(thyroid甲状腺,mammarygland乳腺,nasal鼻,pulmonary肺),thymoma胸腺癌,squamouscellcarcinoma鳞状细胞癌,andprimaryhyperparathyroidism原发性甲状旁腺机能亢进.(Metstobone-rare成骨素－少见)5 Hypoadrenocortcism(Addison‘s)

肾上腺皮质功能不全（阿迪森）ConditionsAssociatedWithHypercalcemia(Cont.)高钙血症相关的情况6.Renalfailure肾衰7.HypervitaminosisD(cholecalciferolVD3)

高VD症d/tincreasedintestinalabsorptionofcalcium

帮助钙在肠内吸收8.

Primaryhyperparathyroidism-.

原发性甲状旁腺机能亢进olderdogsandcats,KeeshondandSiamesepredisposed.老龄犬猫，基丝犬，仙罗猫易得hypercalcemia,hypophosphatemia,ca-/pratio>33. 高钙血症，低磷血症（钙/鳞大于33）PTHlevel-usuallyelevated.甲状旁腺素水平－通常升高ConditionsAssociatedWithHypercalcemia(Cont.)9.

Skeletallesions(non-neoplastic)–骨骼损伤（无增生物）osteomyelitis–inflammation骨髓炎－炎症Boneresorbingfactorsproducedbymonocytesandactivatedlymphocytes单核细胞和核激活淋巴细胞产生各种骨吸收因子hypertrophicosteodystrophy肥大性骨营养不良disuseosteoporosis(immobilization)-萎缩性骨质疏松Increasedresorption,decreasedboneformation吸收增加，生成减少10.

Blastomycosis酵母病/Granulomatousdisorders肉芽肿病D/textrarenalproductionofcalcitriolbymononuclearcell,possiblyproductionof1,25-dihydroxyvitaminDbymononuclearcells钙三醇通过单核细胞后的肾外产物很可能就是1，25羟基维生素D3。DiagnosticPlan 诊断计划Thoracicradiographs

胸腔放射影像Abdominalultrasound

腹部超声ThoracicRadiographs胸部X光AbdominalUltrasound腹部超声Mesenteric,iliaclymphadenopathy

肠系膜，髂骨下淋巴结病Splenomegaly脾肿大Kidneys-rimsign肾－边缘明显Mediastinalmass纵隔块状DiagnosticPlan(Cont.)诊断计划Aspiratethemesentericlymphnode 抽吸肠系膜淋巴结Diagnosis诊断Lymphoma淋巴瘤Lymphoma淋巴瘤Origin-lymphoreticularcells

来源－淋巴网状内皮细胞Usuallyariseinlymphoreticulartissue-

通常在淋巴网状内皮细胞组织形成Lymphnodes,spleen,bonemarrow

淋巴结，脾脏，骨髓Mayariseinanytissue

可能在任何组织中形成Oneofthemostcommonneoplasms

最常见的肿瘤之一Primarily-middleagedtoolderdogs原发性：中年－老年犬Breeds–somearemorecommonlyaffected

种类：某些品种更易发Lymphoma淋巴瘤Etiology-unknown病因学－不明Pathology-病理学Classificationcanbebasedonanatomiclocationandhistologiccriteria

分类基于解剖学和历史标准Mostcommonforms最常见的形式-(inorderofdecreasingprevalence根据发病率由高到低)Multicentric(80%)多中心瘤,cranialmediastinal纵膈前肿瘤,GI胃肠,cutaneous表皮Arisefromclonalexpansionoflymphoidcellswithdistinctivemorphologicandimmunophenotypicfeatures.Classifications-grading,immuno根据克隆淋巴细胞形态学和免疫学特征，分为增生性和免疫性

Vallietal-2006Canineindolentnodularlymphoma

犬无痛结节状淋巴瘤Lymphomaswithalowmitoticrateandslowrateofclinicalprogression

淋巴瘤有丝分裂和临床症状发展均缓慢Usuallyariseafteralongperiodofbenignhyperplasia通常在良性的超常增生一段时间后产生Treatmentrequiresaspecific,ratherthangeneraldiagnosis,basedoncellmorphology,architecture,andphenotype治疗应该根据特异性而非一般诊断，即细胞形态，结构和免疫表型Classification分类Anatomic解剖学Multicentric多中心的Alimentary胃肠器官Mediastinal纵隔Cutaneous皮肤Other其他Cytologic细胞学Histologic组织学Immunophenotypic 免疫表型Anteriormediastinallymphoma.纵膈前淋巴瘤Anatomicclassificationassistsclinicianinunderstandingsigns.解剖学的分类有助于医师了解病症Multicentriclymphoma多中心淋巴瘤Dogswithmulticentriclymphomaareexaminedbecauseofgeneralizedperipherallymphadenopathy.由于全身性的淋巴结病而被检出患有多中心淋巴瘤的犬Mediastinallymphoma纵膈淋巴瘤DogswithmediastinallymphomahaveupperGIsignsorrespiratorysigns.Thereisofteneffusionandtumorsareoftenlargeatdiagnosis.有纵膈淋巴瘤的犬会有上消化道或呼吸道症状。诊断时，通常有渗出，肿瘤通常已很大

Alimentarylymphoma消化道淋巴瘤DogswithalimentarylymphomapresentwithGIsigns.TumorsariseinlymphoidtissuesofGItractandspreadtoabdominalnodes.有消化道肿瘤的犬通常表现消化道症状。肿瘤产生在胃肠道淋巴结，且可扩展至腹部淋巴结Cutaneouslymphoma皮肤淋巴瘤Epitheliotropic趋上皮的--TcellsT细(Mycosisfungoides真菌病)Nonepitheliotropic非趋上皮的--BcellsB细胞EpitheliotropiclymphomaisatumorderivedfromCD3andCD8+cellsinthedog.Non-epitheliotropiclymphomaaffectsthemid-deepdermis.在犬，趋上皮的淋巴瘤是来源于CD3和CD8＋的细胞。非趋上皮的淋巴瘤影响到真皮中层Cutaneouslymphoma皮肤淋巴瘤Clinicalappearancesofcutaneousormucosallymphomainthedog.犬皮肤或粘膜淋巴瘤临床表现Othersites其他部位CNS,ocular,renalandsplenicsitesoflymphoma.Virtuallyanyorganorsitemaybeaffected.中枢神经系统，眼，肾和脾淋巴瘤。事实上任何部位都可能发生Lymphoma淋巴瘤-ClinicalSigns临床症状Variableanddependontheextentofthelocationofthetumor.可见，肿瘤部位肿大Multicentric多中心-usuallygeneralizedpainless全身通常无痛Lymphadenopathy淋巴结病.Also-hepatosplenomegalyandbonemarrowinvolvementmayoccur.也有，肝脾大和骨髓受累Nonspecificsigns非特征性症状-anorexia,weightloss,vomiting,diarrhea,emaciation,ascites,dyspnea,PU,PD,andfevercanoccur.厌食，体重减轻，呕吐，腹泻，消瘦，腹水，呼吸困难，多饮，多尿，发烧GIoralimentary消化道–usuallynonspecificGIsigns.通常没有特征性的消化道症状Vomiting,diarrhea,weightlossandmalabsorption.呕吐，腹泻，体重减轻，吸收不良Mediastinal纵膈-Repiratorydistressassociatedwiththeextentofdisease,PU/PD.与疾病程度有关的呼吸困难，多饮，多尿Lymphoma淋巴瘤Differentialsforlymphadenopathy.与淋巴结病的鉴别Dependsonthesize,consistency,andthelocationoftheaffectednodes.依赖于大小，坚固程度和发病淋巴结的部位Infections.感染Bacterial,viral,rickettsial,parasitic,fungal.细菌，病毒，立克次氏体，寄生虫，真菌Metastatictumors转移性肿瘤(notgeneralized非全身性)Immunemediateddiseases.免疫介导性疾病Dermatopathies,vasculitis,polyarthritis,lupus.皮肤病，血管炎，多关节病，红斑狼疮Hematopoietictumors.造血系统肿瘤Lymphoma,leukemia,multiplemyeloma,histiocyticdisease.淋巴瘤，白血病，多发性骨髓瘤，组织细胞病Lymphoma-Diagnostics

淋巴瘤－诊断Afteradiagnosishasbeenmadetheextentofdiseaseshouldbedeterminedandcorrelatedtothestageofdisease疾病诊断后，要弄清疾病的程度和阶段CBC血常规Biochemistrypanel生化Urinalysis尿检Thoracicradiographs胸部X光Abdominalultrasound腹部超声Bonemarrowaspiration骨髓抽吸检查Lymphnodeaspirate淋巴结抽吸检查Immunohistochemistry免疫组织化学CanineLymphoma犬淋巴瘤-Staging疾病分期StageI-onelymphnode一个淋巴结StageII-morethanonelymphnodeonthesamesideofthediaphragm在膈膜的同一边有不止一个淋巴结StageIII-peripherallymphadenopathy,bothsidesofthediaphragm外周淋巴结病，膈膜的两边StageIV-liver,splenicinvolvement肝脾受累StageV-bonemarrow,otherunusualorgans其他不常见的器官AorBA或BLymphoma淋巴瘤-Treatment治疗Withouttreatmentmostdogsdieoftheirdiseasein4-6weeks.不治疗，大多数犬4-6周后死于疾病Consideredasystemicdiseaseandthereforerequiressystemictherapyinordertoachieveremissionandprolongedsurvival.应该当成全身疾病治疗，为了全身疾病得以缓和，延长寿命Therapyofchoice-systemicchemotherapy.全身化疗Manyprotocolshavebeendevelopedoverthelast15-20years.在最近15-20年里，出现了许多治疗方案Lymphoma淋巴瘤-Treatment治疗ImportantConsiderations商量很重要-youandtheclient你和宠物主人Examples例如-Prednisone泼尼松Cop强的松COPA环磷酰胺UWMadisonMediansurvivaltimes平均存活时间Treatment治疗Singleagentvs.Combinationchemotherapy简单用药，还是联合化疗Shortvs.Longwithmaintenance维持时间长，还是短Simon-JVIM.200612weekprotocol,77dogs.Sig.toxicosis.77只犬，治疗12周，明显中毒Median1stremission几乎第一天就缓和-243days(CR-76%)243天后（76％抗糖皮质激素）Siedlecki–CanVetJ.2006extendedmaintenancetherapy.39dogs.Min.toxicosis延长维持治疗时间，39只犬轻微中毒Mediansurvival-461days,CR-97%.平均存活时间461天（97％抗糖皮质激素）Treatment治疗Drugsused应用药物-L-asparginase,prednisone,cyclophosphamide,vincristine,adriamycin左旋阿胞糖苷，泼尼松，环磷酰胺，长春新碱，阿霉素MacDonaldetal-2005-doesElsparinfluenceefficacyortoxicity?左旋门冬酰胺酶能够改变药效或毒性吗？HalfBodyRadiation半体辐射Gustafsonetal-VCO,2004HalfBodyradiationinterposedwithinachemotherapyprotocolforcaninelymphoma(6dogs)犬淋巴瘤化疗过程中，插入半体辐射（6只犬）Theprotocolwasconsideredsafe治疗被认为是安全的Medianremissiontimefordogscompletingtheprotocol-455days完成治疗后犬的平均存活时间未455天Higherd/tadditionalcellkillfromRT辐射疗法会杀死其他细胞，所以死亡率较高ChemobeforeRT-topreventATLS在辐射治疗前给予化疗有助于阻止急性肿瘤溶解综合征AnotherStudy-WilliamsJVIM2004-52dogs.MedianOverallRemission-486days另外一项研究--WilliamsJVIM2004-52只犬。平均完全缓和时间—486天AutologousBoneMarrowTransplant自体骨髓移植Frimbergeretal.JVIM.2006Autologousbonemarrowtransplantforsupportofhighdosechemotherapychemotherapyattheendofa12week,5drugprotocol高剂量化疗12周，应用了5种药物后，只能采取自体骨髓移植28dogs28只犬Alldogs-CR所有犬—抗糖皮质激素Medianremissionduration-26.6weeks中数缓解期—26.6周Medianoverallsurvival-84.1weeks平均总存活天数---84.1周Lymphoma-PrognosticFactors淋巴瘤－影响预后的因子Immunophenotype免疫表型-mostimportantprognosticfactor最重要的影响因子TvsBT细胞，还是B细胞Immunhistochemistry免疫组化-CD3positive-TcellsCD3阳性－－T细胞CD79apositive-BcellsCD79a阳性－细胞Lymphoma-PrognosticFactorsStage阶段I-IIIbetterresponsetotreatmentthanV1-3阶段比4期治疗反应好Substage亚阶段systemicmanifestations-morelikelytofail全身表现的更易失败Histopathology组织病理学Highgradevslowgrade程度轻重Hypercalcemia高钙血症Gender性别Intactmaledogs-higherriskofdeath.Possibleroleoftestosteroneonchemosensitivity未去势的死亡的危险性高。可能是睾酮对化疗敏感性的影响Prolongedsteroidpretreatment延长的类固醇预处理P-glycoproteinexpressionP-糖蛋白的表达Cranialmediastinallymphadenomegaly纵膈前侧淋巴结病Anatomiclocation解剖学位置Lymphoma-PrognosticFactorsBreed-Boxers-品种—拳狮Lurieetal-VCO.Sept.2004TissuesectionsfromBoxerswerestainedforTandBlymphocytedistinction(50)对拳狮拳的组织切片进行T细胞和B细胞的鉴别染色FrequencyofTcelllymphomainboxers-82%T细胞的出现频率占82％significantlyhigherthan明显高于rottweilers-19%(37dogs)洛特维勒牧犬-19％（37只犬）goldenretrievers-50%(22dogs)金毛寻回猎犬-50%（22只犬）HypercalcemiaofMalignancy恶性肿瘤的高钙血症Themostcommonmetabolicemergencyinoncology肿瘤学上，最常见到代谢的急性紊乱Clinicalsigns临床症状-PU/PD,vomiting,hyposthenuria,dehydration多饮多尿，呕吐，低渗尿，脱水Interpretcalciuminrelationtoserumalbumin(ifitistotalCa)根据血清白蛋白计算钙（如果是总钙）Ca2+(mg/dl)-albumin(g/dl)+3.5(canine)EmergencyTreatmentforHypercalcemia高钙血症的紧急治疗Basicgoals基本目的-Correctdehydration纠正脱水-NaCl-2-3Xmaintenance维持量的2-3倍NaClEnhancerenalexcretionofcalcium增加肾脏钙的排泄-NaCl,Furosemide呋塞米,Glucocorticoids糖皮质激素Inhibitacceleratedboneresorption限制加速的骨吸收-calcitonin降血钙素,bisphosphonates二膦酸盐Treatunderlyingdisorder治疗根本疾病AcuteTumorLysisSyndrome急性肿瘤溶解综合征Aconditionofacutecollapsethatmayleadtodeathsoonaftertheadministrationofachemotherapeuticagenttoananimalwithachemosensitivetumor.一种急性虚脱，把化疗药物投服给化学敏感的肿瘤病例后，引起的急性死亡Humans人-lymphoma,leukemia,smallcelllungcancer淋巴瘤，白血病，小细胞性肺癌.Dog犬-lymphomaandleukemia淋巴瘤和白血病.AcuteTumorLysisSyndrome急性肿瘤溶解综合征Rapidtumorlysismaycauseanacutereleaseofintracellularphosphateandpotassium.Thisreleasecauseshypocalcemia,hyperkalemia,andhyperphosphatemia.Inhumans-hyperuricemiaisalsoseen.迅速的肿瘤溶解会引起细胞内磷和钾的释放。这种释放会导致低钙血症，高钾血症和高磷血症。在人，还可见高尿酸血症AcuteTumorLysisSyndrome急性肿瘤溶解综合征History病史-acutepensation急性呼吸困难,anorexia食欲缺乏,andcollapseafterchemotherapy化疗后虚弱Clinicalsigns临床症状-palemm,decreasedCRT,evidenceofdecreasedcardiacoutput,arrhythmias,vomiting,diarrhea,andevidenceoflysisoftumor粘膜苍白，心率、呼吸、脉搏减弱，心输出量减少，心律不齐，呕吐，腹泻和肿瘤溶解Diagnostics诊断-evidenceofmulti-organfailure,metabolicacidosis,hyperkalemia,hypophosphatemia,andazotemia.多器官衰竭，代谢性酸中毒，高血钾，低磷血症和氮血症AcuteTumorLysisSyndrome急性肿瘤溶解综合征Therapy治疗-preventionisessential.Restoretissueperfusionwithfluidsandstabilizecardiovascularsystem.Correctacid-basebalance,electrolyteimbalances,andazotemia.预防很重要。用液体恢复组织灌流，稳定心血管系统。纠正酸碱平衡，电解质平衡和氮血症Babushka(Cont.)BabushkawastreatedwiththeDavisprotocolfromSept.02toFeb.03.在9月2号到2月3号用戴维斯方法治疗BabushkaAtthatpointshepresentedforchemotherapy-notfeelingwell.一开始用化疗－感觉不好Diagnosticplan??诊断计划？？Babushka(Cont.)Ca++Significantlyelevated明显增加Creatinine肌酐Thoracicradiographs胸部放射照片Babushka(Cont.)Babushka(Cont.)Treatmentwasinitiatedwith

ElsparL-天冬酰胺酶CCNU(Lomustine)环己亚硝脲Prednisone用左旋门冬酰胺酶，氯乙环己亚硝脲和泼尼松开始治疗Potentialcomplications??潜在的并发症？？？Babushka(Cont.)AfewminutesaftershereceivedtheElsparshecollapsedinthereceptionarea接受左旋门冬酰胺酶几分钟后，迅速虚弱AreactiontotheElspar对左旋门冬酰胺酶的反应ShewastreatedwithfluidsandO2andrecoveredquickly用液体和氧气治疗后，迅速恢复ShewassenthomewithCCNUandprednisone给了些氯乙环己亚硝脲和泼尼松后带回家ChemotherapyInducedAnaphylaxisandHypersensitivity化疗导致过敏反应和超敏反应Anaphylaxisorananaphylaxis-likereactioncanoccurwithanydrug-mostcommon-Elspar.Duetoenzymeimmunogenicity.UsuallycausedbyIgE-mediatedmastcelldegranulation.Theexactmechanismisnotknown.AnaphylaxisusuallyoccurswithinsecondstominutesafteradministrationofElspar.过敏和过敏样反应可见于使用任何药物-左旋门冬酰胺酶最常见。由于酶的免疫原性，通常引起IgE介导的肥大细胞脱颗粒。确切的机制不明。过敏反应通常发生在左旋门冬酰胺酶投服后的几秒到几分钟内。ChemotherapyInducedAnaphylaxisandHypersensitivity化疗导致过敏反应和超敏反应Hypersensitivityreactionscanoccurwithanydrug-mostcommonly-doxorubicin-itisbelievedtoberelatedtomastcelldegranulation.Also-taxolandetoposide-duetothecarriers.超敏反应也可见于使用任何药物－最常见于阿霉素－认为与肥大细胞脱颗粒有关。也可见于紫杉酚和依托扑沙－由于载体Predisposingfactors-Elspar-duetopriorexposuretothedrug.Therouteofadministrationmaybeacontributingfactor.患病因素--左旋门冬酰胺酶—由于先前接触药物。给药途径或许是因素之一ChemotherapyInducedAnaphylaxisandHypersensitivity化疗导致过敏反应和超敏反应History病史-acutepensationandcollapsesoonaftertheadministrationofachemotherapeuticagent.化疗药物给药不久，出现急性的呼吸困难和虚弱Clinicalsigns临床症状-paleorcyanoticmm,decreasedCRT,evidenceofdecreasedcardiacoutput,alterationsinHRandcoolextremities.粘膜苍白或发绀，CRT减弱，心输出量减少，心律变化和四肢厥冷Diagnostics诊断-eliminateothercauses(CBC,C/S,U/A,cardiacevaluation).排出其他原因（CBC,C/S，尿液分析，心脏评估）ChemotherapyInducedAnaphylaxisandHypersensitivity化疗导致过敏反应和超敏反应Therapy治疗-.1.Eliminatetheunderlyingcause.排除潜在原因2.

Ensureapatentairwayandadequatecardiacoutput.确保气道通畅和足够的心输出3.Establishvascularaccess建立血管通路.4.

Initiatefluidtherapy.液体疗法5.

Treatwithdex,diphenhydramineandepinephrineifneeded.如果需要，用地塞米松，苯海拉明和肾上腺素治疗Babushka(Cont.)Aweeklatershewasnotfeelingwell. 1周后，它感觉不适Shedidnotwanttogetup,appearedlameanddidnotwanttoeat.

它不愿意起床，跛行，不愿饮食Differentials???鉴别诊断Babushka(Cont.)Differentials-鉴别诊断Noresponsetotreatment对治疗无反应(stilloutofremission仍然没有缓和)Sepsisduetotreatmentwithchemotherapy由于化疗引起的脓毒症CNSinvolvement中枢神经系统受累Other其他Diagnosticplan(inhercase)诊断计划Thoracicradiographs胸部放射照片Ca++CBCBabushka(Cont.)Results-结果CBC-WNL（withinnormallimits）正常Ca++-WNLTherefore-shehadmostlikelyrespondedtotreatment

因此，最可能是对治疗的反应Physicalexam-abscessonherleg 全身检查－腿部有脓肿

Theabscesswastreated-shecontinuedtreatmentwithCCNUandprednisone治疗脓肿－继续以氯乙环己亚硝脲和泼尼松治疗NeutropeniaandSepsis中性粒细胞减少症和脓毒症History病史-acutepensation,anorexia,andcollapseusually5-7daysafterthereceivingmyelosuppressivechemo.急性呼吸困难，厌食和治疗后通常5-7天虚弱ClinicalSigns临床症状-Pyrexia,brick-redmm,tachycardia,rapidCRT(hyperdynamicshock)ORpalemm,decreasedCRT,andevidenceofdecreasedcardiacoutput(hypodynamicshock).发烧，粘膜呈砖红色，心动过速，CRT增强（肌肉震颤）或粘膜苍白，CRT减弱和心输出量减少（肌肉震颤）Diagnostics诊断-evidenceofneutropenia,multi-organfailure,hypoglycemia,positiveculturesofblood,urine,pulmonaryairways,orothertissuesandmetabolicacidosis.中性粒细胞减少，多器官衰竭，低血糖，血液、尿液、肺泡和其他组织培养阳性，以及代谢性酸中毒NeutropeniaandSepsis中性粒细胞减少症和脓毒症Therapy治疗-1.Treattheunderlyingcause.治疗原发病2.Restoretissueperfusionwithfluidsandstabilizecardiovascularsystem以液体恢复组织的灌注，稳定心血管系统3.Correctacid-basebalance,electrolyteimbalances,andhypoglycemia纠正酸碱平衡和低血糖4.Initiateparenteralbactericidalantibiotictherapy使用杀菌性抗生素5.Considerhematopoieticgrowthfactorsupport,transfusionsoffreshwholeblood,(granulocytetransfusions)考虑补充造血因子和输新鲜的全血（粒细胞成分输血）Neu