腫瘤學(xué)-犬肥大細(xì)胞

CanineMastCellTumors

犬肥大細(xì)胞瘤

FabienneMueller,Dr.med.vet.ResidentMedicalOncologySectionofDiagnosticImagingandRadio-OncologyVetsuisse-Faculty,UniversityofZurich?Jouschka“

10yearoldFSAirdaleTerrier1History

主訴Massehindleg

后腿腫塊Sinceseveralweeks

已發(fā)病幾周Changessize

大小發(fā)生改變Otherwisenoabnormalities 無(wú)其他異?，F(xiàn)象PhysicalExam

體檢BARNoabnormalitiesexceptmass 除腫塊外無(wú)異常Soft

腫塊柔軟Subcutaneous

位于皮下Notwellcircumscribed

界限不明顯DifferentialDiagnosis

鑒別診斷Mastcelltumor肥大細(xì)胞瘤Lipoma脂肪瘤Sebaceoushyperplasia/adenoma 脂肪增生/腺瘤a纖維肉瘤Melanoma黑素瘤Squamouscellcarcinoma鱗狀細(xì)胞癌Seroma,abscess…腫,膿腫…FineNeedleAspiration

細(xì)針抽吸術(shù)CytologicDiagnosis

細(xì)胞學(xué)診斷

?Mastcelltumor“(MCT)肥大細(xì)胞瘤MastCells

肥大細(xì)胞Derivedfromhematopoieticprecursors 來(lái)自造血細(xì)胞的前體Foundinliver,lung,skin,GItract,bonemarrow 可以在肝、

肺、皮膚、胃腸道以及骨髓中發(fā)現(xiàn)Integralininflammatoryandallergicresponses 可在炎癥及過(guò)敏反應(yīng)中出現(xiàn)GeneralMostcommonskintumorofdogs(16-21%)

狗常見(jiàn)的皮膚腫瘤(16%-21%)；Breedpredisposition:具有品種遺傳的特點(diǎn)...MastcelltumorsClinicalPresentation

臨床特征MastcelltumorsClinicalPresentation

臨床特征Location發(fā)病部位Headandneck頭頸部(13%)Thoraxandforelimb胸部及前肢(29%)Abdomenandhindlimb腹部及后肢(40%)Genitalorperianal生殖器或肛周(18%)

10%ofdogshavemultiplecutaneoustumors 10%的狗患有混合性的皮膚瘤BehavesimilartoloworintermediategradesolitaryMCT 行為與輕微或是中等程度的單個(gè)肥大細(xì)胞瘤相似

(MullinsMetal,JAVMA2006

Systemicmastocytosis全身性的肥大細(xì)胞增生病Usuallyassociatedwithcutaneoustumors通常伴有皮膚腫瘤FirstStep:GettingaDiagnosis

第一步:進(jìn)行診斷

Fineneedleaspiration

細(xì)針抽吸術(shù)-Usuallyeasydiagnosis

常用的簡(jiǎn)單方法-Nogradingoncytology!! 但不能在細(xì)胞學(xué)上分級(jí)：Biopsy

活組織檢查：-Antihistamines

抗組織胺類-Gradingonhistology->prognosis!!

組織學(xué)分類,以便判斷預(yù)后

Grade1:welldifferentiated

一級(jí):分化良好Grade2:moderatelydifferentiated

二級(jí):中等程度的分化Grade3:poorlydifferentiated；三級(jí):分化不明顯.MastcelltumorsStaging

診斷步驟Bloodwork

驗(yàn)血Thoracicradiographs 胸片Abdominalultrasound 腹部B超Palpationandaspirationofregionallymphnodes 局部淋巴結(jié)的觸診和穿刺(Buffycoatsmear)（淡黃層斑）；(Bonemarrow)（骨髓）MastcelltumorsParaneoplasticSyndroms

類腫瘤性綜合癥Heparin

肝素

->Bleedingtendency

出血傾向Histamine

組織胺

->GIulcers

胃腸道潰瘍Proteases

蛋白酶

->Woundhealingproblems： 創(chuàng)傷愈合問(wèn)題MastcelltumorsPrognosticFactors

影響預(yù)后的因素Established

已確定的Histologicgrade

組織學(xué)分級(jí)Clinicalstage

臨床階段Location

部位Breed

品種Growthrate

生長(zhǎng)速率Recurrence

血液循環(huán)PCNA

增殖細(xì)胞核抗原AgNORcount

銀染核區(qū)記數(shù)Intratumoralvesseldensity 瘤內(nèi)的脈管密度Unknown

未知的：c-KITC-試劑盒MMPs金屬蛋白酶P53P53MastcelltumorsPrognosticFactor–Grade

預(yù)后因素--腫瘤的等級(jí)PatnaikAKetal,VetPath1984Dogsaliveat1500days:1500日后存活的狗：

GradeI

一級(jí):93%

GradeII

二級(jí):

44%

GradeIII三級(jí):6%NorthrupNCetal,JVetDiagnInvest,2004Variationsamong10pathologistsingradingcaninecutaneousMCTs 十個(gè)病理專家對(duì)犬表皮肥大細(xì)胞瘤的分類中存在個(gè)體的差異Conclusion:significantvariationamongpathologists(p=0.001) 結(jié)論:在不同的病理專家存在顯著的差異(P=0.001)MastcelltumorsPrognosticFactor–Stage

預(yù)后因素--腫瘤的等級(jí)MastcelltumorsWHOstagingsystem: 世界衛(wèi)生組織的腫瘤分類等級(jí)stage0: pletelyexcisedtumor 0級(jí):不完全的體外腫瘤stageI:onetumorconfinedtothedermis Ⅰ級(jí):僅在皮膚上有一個(gè)腫瘤stageII: onetumorconfinedtothedermis+node Ⅱ級(jí):僅在皮膚及結(jié)節(jié)上有一個(gè)腫瘤stageIII:multipleorlargeinfiltratingtumors+/-node Ⅲ級(jí):有多發(fā)性或較大的浸潤(rùn)性瘤(結(jié)節(jié)上有或無(wú))stageIV:distantmetastasis Ⅳ級(jí):遠(yuǎn)端轉(zhuǎn)移

PrognosticFactor–Breed

預(yù)后因素--品種SharPei

沙皮犬

HigheroccurenceofgradeIIIMCTandinguinalMCT: 易發(fā)三級(jí)和腹股溝肥大細(xì)胞瘤(MillerDMJVetDiagnInvest1995)Boxer拳師犬HigheroccurenceofgradeIMCT(46%vs26%inotherbreeds) 易發(fā)一級(jí)肥大細(xì)胞瘤(高達(dá)46%,而其他型的為26%)(BostockDEJSmallAnimPract1973)MastcelltumorsPrognosticFactor–Location

預(yù)后因素–部位Controversial...

有爭(zhēng)議:Oralcavity,nailbed,inguinal,preputial,perineal 口腔的，指基部的，腹股溝的，包皮的，會(huì)陰的 ->Moremalignant(Turreletal,JAVMA1988)

更多的傾向于惡性 ->Similartootherlocations(Cahalaneetal,JAVMA2004) 同其他部位的相似MuzzleMCTshigherregionalmetastaticrate(Giegeretal,JVIM2003) 鼻口部肥大細(xì)胞瘤的轉(zhuǎn)移率高

VisceralMCT

內(nèi)臟肥大細(xì)胞瘤Verypoorprognosis

極度的預(yù)后不良Mastcelltumors

Treatment

治療

Surgery

手術(shù)療法Goal:cleanexcision 以徹底摘除腫瘤為目的.Radiotherapy

放射療法:Cleanupdirtymargins 清除污染緣.Chemotherapy

化學(xué)療法:MetastaticMCTs 轉(zhuǎn)移的肥大細(xì)胞瘤SupportiveCare

支持療法:

Preventparaneoplasticsyndromes 預(yù)防瘤外綜合征MastcelltumorsTreatment–Surgery

治療—手術(shù)

Goal:?Cleanmargins“,

目標(biāo):切緣干凈，徹底摘除

howmanycmrequired?? 干凈的切緣需要多少厘米?Verycontroversial!目前還存在很大的爭(zhēng)議Consensus:2cmlaterally,1fascialplaindeep 目前意見(jiàn)一致的是:外側(cè)2cm， 深至筋膜面.

Simpsonetal,JAVMA2004Fulcheretal,JAVMA2006...

MastcelltumorsTreatment–Surgery

治療—手術(shù)Consequenceofuncleanmargins? 如果邊緣不潔會(huì)有什么樣的后果Evenmorecontroversial!!! 同樣很有爭(zhēng)論?。?！Secondsurgery?Radiationtherapy?Nothing? 再次手術(shù)?放射療法?不作任何處理?Seguinetal,JVIM2006:-Only23%of30pletelyexcisedMCTsrecurred 30例不全摘除的肥大細(xì)胞瘤病例中只有23%的復(fù)發(fā).-Cellularproliferationmarkersmayindicatelikelyhoodofrecurrence 細(xì)胞增生可能表示著復(fù)發(fā)的可能性.Treatment–Radiotherapy

治療--放射療法Microscopicdisease病區(qū)微小時(shí)：Beforesurgery術(shù)前化療：-Onlymarginalexcisionnecessary只需切除病灶邊緣-Hopetoshrinktumor可望腫瘤縮小Afterpletesurgery在不完全摘除的手術(shù)之后也可化療

Measurabledisease病區(qū)較大時(shí)：Controversial療效有爭(zhēng)論 -Dobsonetal,VetCompOncol2004:OverallResponse88% CompleteRemission50% 有全身反應(yīng)的88%，完全減輕的50%。

MastcelltumorsTreatment–Chemotherapy

治療--化學(xué)療法Controversial!

有爭(zhēng)議！Consensus:

一致意見(jiàn)：GradeIIwithpoorprognosticfactors(location) Ⅱ級(jí)預(yù)后不良（視部位而定）GradeIIIDrugs:藥物：Prednisone強(qiáng)的松龍Vinblastine長(zhǎng)春新堿Lomustine環(huán)己亞硝脲...MastcelltumorsTreatment–SupportiveCare

治療--支持療法Mainlymeasurabledisease 一般在病變較大時(shí)用H1antagonist(Diphenhydramine)

H1對(duì)抗物（苯那君）；H2anatgonist(Ranitidine) H2對(duì)抗物（雷尼替丁）；Protonpumpinhibitor(Omeprazole) 氫離子泵抑制劑（奧美拉唑）。Mastcelltumors...backtoJouschka...

回到Jouschka

Stagingnegative

腫瘤分類為陰性

Problem:

問(wèn)題：?Clean“surgerynotpossible! 不可能實(shí)行“完全”的手術(shù)摘除

Options:

可供選擇的只有：Combinationsurgeryplusradiotherapy 綜合運(yùn)用放射療法和外科手術(shù)Amputation截肢術(shù)CombinationTreatment

綜合治療

Firstsurgery,thenradiotherapy

先手術(shù)后放療

Pro前提:

-Knowthegrade

知道瘤的等級(jí)

-Knowhistologicmargins

知道組織的邊緣

Contra相反:

-Biggerradiationflield

增大輻射的區(qū)域

-Woundhealingproblems(proteases!) 創(chuàng)傷的愈合問(wèn)題（蛋白酶）Firstradiation,thensurgery

先放療后手術(shù)

Pro前提:

-Smallerradiationfield

縮小輻射區(qū)域

-Hopefortumorsizereduction

希望腫瘤縮小

-Marginalexcisionpossible

邊緣切除的可能性

Contra相反:-Nograde

不知道等級(jí)

-Woundhealingproblemsinirradiatedskin 被照射皮膚區(qū)域的創(chuàng)傷愈合問(wèn)題RadiotherapyFirst...

首先進(jìn)行放射療法

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