卵巢肿瘤教案

中南大学教案纸【科目】妇产科学【授课教师】陶光实【授课对象】2002级七年制.【授课地点】第1教室【授课章节】第三十二章【学时】2学时【授课内容】卵巢肿瘤【授课时间】2006.11.29一、教学目的与要求1.了解卵巢肿瘤的组织学分类，常见卵巢肿瘤的病理和临床特点。2．熟悉卵巢良、恶性肿瘤的鉴别诊断。3．掌握卵巢肿瘤的临床表现、诊断、鉴别诊断、治疗原则、常见并发症及其处理。4．熟悉妊娠合并卵巢肿瘤的危害及处理原则。二、教学重点重点：常见卵巢肿瘤的病理和临床特点；良、恶性肿瘤的鉴别诊断；常见的并发症及其诊断；恶性肿瘤的分期和处理原则。三、教学难点难点：卵巢肿瘤的分类；恶性肿瘤的分期和处理原则；常用化疗方案及药物。四、授课类型及方法1．大课讲授法。2．采用双语教学结合病例式、问题式、讨论式等教学方法，培养学生临床思维方式及解决实际问题的能力。3．一般了解的内容学生自习。五、教具多媒体课件、电脑、投影仪、激光笔、扬声器、粉笔及粉笔刷。六、教学内容与步骤分配时间导言（preambl）：卵巢肿瘤的现状、发病率及诊治情况。卵巢肿瘤（variantumor）一、卵巢的解剖及生理特点(anatomyandphysiology)2minComplexstructureandfunction：中南大学教案纸Celomicepithelium(体腔上皮)--单层立方.supportivestroma(支持间质)—白膜,性索间质,结缔组织,血管、神经和淋巴.Functionalgermcells(生殖细胞).Endocrineandreproductivefunction.二、卵巢肿瘤概论(generalconsideration)25min一).Incidence,Epidemiology●Morbidityisabout2.4-5.6%inourcountry.Ovariancanceristhesecondmostcommontumorinfemalepelvicreproductiveorgans,Accountsfor5%ofallcancersamongwomen.Generalconsideration,Theoverallriskofovariancancerisabout1.7%inthegeneralpopulation,itwilldevelopin1ofevery58women(1/58).In5%to7%thereisaninheritedpredispositionincreasingtheriskforotherfamilymembersinsomesyndromestoashighas50%.●Deaths----occuratrateof1every45minutes.●Liabletogettumors（多事之秋）.●Mostinkindsoftumors（种类之多居全身各器官肿瘤之冠）.●Deepinpelvic（深居盆腔），stealthilyoccuring(悄悄地来）.●Destituteinearlydiagnosismethods缺乏早期诊断方法.●Poorprognosisingynecologiconcology:5-yearssurvivalrateisabout30%（是预后最差的妇科肿瘤，死亡率是宫颈癌和内膜癌之和）.二).Classification（分类）ThesimplifiedWHOclassification（简化的WHO分类）iswidelyacceptedinourcountry.Accordingthehistogenensis（组织发生）ovarianneoplasmsareclassifiedintoninegroups（九大类）.三).Routeofmetastasis（转移途径）●Directspreading（直接蔓延）●Inta-abdominalimplantation（腹腔种殖）●Lymphogenousmetastasis（淋巴转移）●Hematogenousmetastasis（血行转移）Directspreadingandinta-abdominalimplantationarethemainroutesofmetastasis.中南大学教案纸四).Clinicalfeature(临床表现)1.Symptoms(症状):●Benign(良性):Inearlystagenosymptoms. Amassnearbytheuterusfoundduringroutinepelvicexamination(往往妇查时发现,在子宫一侧扪及包块).pressuresymptomssuchasabdominalswelling（腹脹）,frequencyofuring（尿频）andconstipation（便秘）.Symptomswhenoccuringcomplications.Malignant（恶性）:Inearlystagenosymptoms，whenappearingsymptoms,itisofteninlatestageabout70%ofpatients.Symptomsincluding:Vaginalbleeding---postmenopausal(绝经后)Abdominalswelling（腹脹）Abdominalmass(腹部包块）pressuresymptoms:abdominalpain(腹痛)lumbago（腰痛）lowerlimbs’painandedema(下肢疼痛或水肿）●三联症:A.Over40yearsage(40岁以上妇女)B.Symptomsofalimentarytract(不明原因胃肠道症状)C.Disorderofovarianfunction(卵巢功能紊乱)2．Sign(体征):Mass(Unilateralorbilateral,solid,immovable)扪及单侧或双侧包块,质硬,不活动。Ascites腹水征(+)Cancercellsinascites（腹水癌细胞,异常染色体核型）。五）.Complications（并发症）:1.Torsionofthepedicle(蒂扭转):Acutesymptomssuchassevereabdominalpain(腹痛)、nausea(恶心)、vomiting(呕吐)andfever(发热).Palpabledatendermass(压痛包块)inpelvicexamination(盆腔检查).中南大学教案纸Incidenceisabout10%ofovariantumors.Itisthemostcommonemergencydiseaseofgynecology,surgicaltreatmentshallbegivenassoonasdiagnosis(一经确诊需立即手术治疗.)Thepedicle(蒂)----theroundligamentofovary,infundibulopelvicligament,fallopiantube.手术注意点:钳夹前不可回复扭转,以防止发生栓塞脱落.2.Rupture（破裂）Spontaneous（自发性）rupture:肿瘤浸润、生长过速.Traumatic（外伤性）rupture:重击、分娩、性交、妇科检查及穿刺.eritonealirritation（腹膜刺激症）3.Infection（感染）:Seeninthepuerperium（产褥期）.bruisedduringlabor（分娩期损伤）.Temperatureishigher,cystmoretender（体温升高、囊肿变软）.Adhesion（粘连）oftenfollowtorsionorinfection(扭转和感染).4.Malignantchange（恶变）:Therateofmalignantchangeis:Serouscystadenoma(浆液性囊腺瘤)--30-45%mucinouscystadenoma(粘液性囊腺瘤)--15%Dermoidcyst(皮样囊肿)--2-5%Themajorsymptoms(主要症状)areabdominalswellingandpain六)．Staging（分期）:StagingClassificationusingtheFIGONonmenclature.Itissurgicalandbasedontheoperativefindings.七).Diagnosisanddifferentialdiagnosis(诊断及鉴别诊断):1.Diagnosis1).History(病史):不育、子宫内膜癌或乳腺癌病史、卵巢癌家族史.2).Clinicalsigns(临床依据):50-60岁围绝经期、腹胀、腹痛及胃肠不适、盆腹腔包块、子宫直肠窝结节、腹水.注意绝经后卵巢大小的生理变化，绝经晚期妇查扪及卵巢应高度怀疑,探查指征.3).Assistantdiagnosismethods(辅助诊断方法):中南大学教案纸①Ultrosography(B超):②Irradiation（放射检查):X-rayfilm:diagnosisofteratomaBariummeal(钡餐):排除胃肠道肿瘤或侵犯情况IVP(intravenouspyelogram)盆腔肾、尿管阻塞或移位Lymphangiography：淋巴有无转移CT：侵犯及转移情况，肠梗阻诊断③Cyologicexamination(细胞学检查):约80-90%腹水细胞学(+)④Laparoscopy(腹腔镜):比较直观,但有一定的限制.⑤Tumormarkers(肿瘤标志物):Epitheliumneoplasms(上皮性卵巢肿瘤)----CA125,LDHEndodermalsinustumor(内胚窦瘤)----AFP(未成数畸胎瘤,混和性无性细胞瘤含卵黄囊成分).Choriocarcinoma(卵巢绒癌)----HCGSexcordstromaltumors(性索间质肿瘤)----Estrogen2．Differentialdiagnosis1).benignovarianneoplasm:Non-neoplasticcystoftheovary.tuboovariancyst.Subserousmyomaofuterus（子宫肌瘤）.Earlypregnancy.Distendedbladder.Ascites（腹水）.2).malignantovarianneoplasm:Endometriosis(子宫内膜异位症).Pelvictuberculesis(盆腔结核).Tumorsofotherorgans-mesenteric（肠系膜）,renal,omental（网膜）andpancreatictumors.Retroperitonealtumors（腹膜后肿瘤）.Metastasistumors(转移性肿瘤).3).Differentiationbetweenbenignandmalignantovariantumors(良恶中南大学教案纸性卵巢性卵巢肿瘤鉴别诊断).4).DifferentiationDiagnosisofAdnexalMass(附件包块的鉴别诊断)●GynecologicOrigin(妇科来源)aUterineMasses(子宫包块)bOvarianMasses(卵巢包块)FunctionalCysts(功能囊肿)OvarianNeoplasms(肿瘤)cEndometriosis(子宫内膜异位症)dTubalMasses(卵管包块)●NongynecologicOriginaBowelbMiscellaneous八).Treatment(治疗):1.Forbenigntumors(良性):1).Observation（观察）:Under5cm---nonneoplasticandmaydisappearspontaneouslywithin60days（直径小于5CM可观察）.Ifenlargementsover5cm,treatmentrequired（直径大于5CM需治疗）.2).Surgicaltreatment(手术治疗).aSurgerymodelselectiondependuponages(根据年龄决定手术方式)bUnilateralcystectomyorcystoophorectomy（单側肿瘤或卵巢切除）cBilateralsalpingo-oophorectomyandhysterectomy（双附件和子宫切除）over50yearsofageserouscystadenomas术中注意排除恶性肿瘤,必要时送快速切片.2.Formalignantovariantumor(恶性):以手术(surgicaltreatment)和化疗(chemotherapy)为主,放疗(radiationtherapy),(immunotherapy)免疫治疗为辅的综合治疗.三、上皮性肿瘤(epithelialovariancancer)23min一).Serouscystoma1.serouscystadenoma（浆液性囊腺瘤）.Mostcommonofallbenignovarianneoplasm,Accountsfor25%ofbenignovariantumors.中南大学教案纸Unilocular（单房）ormultilocular（多房）.Bilateralin15%ofcases.Notexceed10cmindiameter.Thecystfluid（囊液）isusuallythinandserous（稀薄清亮）.Theliningepitheliumislowcolumar（上皮为低柱状排列）.Psammomabodies（沙粒体）aresometimespresentinthecystwall（囊壁）.2.Borderline（交界性）serouscystoma:Bilateral（双側）inmostofcases.Papillarygrowth（乳头生长）—External（外生）orEnternal（内生）Macroscopicfeatures（镜下特征）:Epitheliumcelllayers（上皮细胞层）<3；Lowgradeproliferativeactivity(低增殖活性)；Nuclearabnormalities（核异型）；Nostromainvasion(无间质浸润).3.Serouscystadnocarcinoma(浆液性囊腺癌）:Mostcommonofallmaliagnantovariantumor.Instituteabout40-50%.Usuallyappearduringthe40-60yearsandbilateral.Ascites（腹水）usuallypresentandimplyapoorprognosis（不良预后）.Microscopicfeatures:Theepitheliumishighlyintricate（高度紊乱）over4-5celllayersAnaplastic（异型）andatypicalstromalinvasion（典型间质浸润）.Thegeneral5-yearsurvivalrate（5年存活率）isabout20-30%.二).Mucinouscystomas1.Mucinouscystadenoma（粘液性囊腺瘤）:Accountfor20-30%.Usuallymultilocular（多房）andmaygrowtoaverylargesize.Cancerationrate（癌变率）is5-10%.Thecystfluidismucinousmateralasgelatinous（胶冻状粘液）.Spontaneousrupture（自发破裂）rateis2-5%.Ifrupture,theepitheliumcellsmayseedontotheperitoneumandproduceapseudumyxomaperitonei(假性腹膜粘液瘤）.中南大学教案纸Microscopicfeatures:Thecellsliningthecystcavityaretallandcolumnar（高柱状）.2.Borderlinemucinouscystadenoma:Majorsize,bilateral（双側）infewofcases,multilocular（多房）.Proliferativeactivity（增生活跃）.Nuclearabnormalities（核异型）.Epitheliumofcelllayers〈3.Nostromainvasion（无间质浸润）.Prognosisisbetter.3.Mucinouscystadenocarcinoma（粘液性囊腺癌）:Instituteabout10%ofallmalignantovariantumors.Unilateralinmostofcases（多为单側）.Majorsize,thecystcavityissolidlyfilledwithmassofpapillaryprojections（乳头状肿块）.Microscopicfeatures:Lesionwithmorethan4mitoses（核分裂）perhighpowerfield（每高倍视野）hasapoorprognosis,eveninstagIdisease.三）.上皮性卵巢癌的治疗(management)：1.早期患者（forstageI-II)----全面确定分期的探查手术（comprehensivestaginglaparotomy):a.腹部纵切口；b.全面盆腹探查；c.腹腔细胞学；d.大网膜切除；e.全子宫+双附件切除（卵巢动静脉高位结扎）；f.仔细探查及活检；g.盆腔及腹主动脉旁淋巴活检.2.晚期患者(forstageIIandover)----肿瘤细胞减灭术(cytoreductivesurgery,debulking):1).最大努力切除原发灶及一切转移瘤，使残余癌灶<1cm.●切除范围：a.足够大的腹部纵切口；b.腹水或腹腔冲洗液细胞学检查，全面盆腹探查；c.全子宫+双附或盆腔肿物切除（卵巢动静脉高位结扎）；d.大网膜切除，注意肝、脾区转移并切除；e.高危区转移灶切除及多点活检；f.肝、脾转移灶处理；g.盆腔及腹主动脉旁淋巴切除；h.阑尾切除及肠转移处理.2).再分期手术（restaginglaparotomy)中南大学教案纸3).开腹活检术4).中间性肿瘤细胞减灭术(intervalcytoredution)5).二次探查术(second-looklaparotomy)3.化疗(Chemotherapy)：主要辅助治疗。化疗敏感预防复发适合于各期患者,以铂类为主的化疗方案方案-----PC（顺铂+环磷酰胺）PT（顺铂+泰素）手术前化疗-----应在有病理结果后进行4).免疫治疗(Immunitherapy)：适合于各期患者，辅助性。四、Non-epithelialovarianneuplasm(非上皮性肿瘤)20min1.Ovariangermcelltumor（生殖细胞肿瘤）1).Teratoma（畸胎瘤）①Mature（成熟性）teratoma(orcystic[囊性]teratoma,dermoidcyst[皮样囊肿]):Comprises10-20%ofalltrueovarianneoplasm.Constituteabout85-97%ofovariangermcelltumor,about95%ofteratoma.Mostarefoundduringtheearlyreproductiveyears(20-40).Usuallyamoderatesizeandwithbilateralin10-17%,unilocular（单房）.Cystcontentsareusuallyskin,hair,adiposeandsebaceousmaterial,bone,teethandcartilage（软骨）.Oftenvisibleonx-rayfilm.Microscopically,variousofallthreegermcelllayers（3种胚层）maybefound.Cancerationrateis2-4%(mostinpostmenopause).Malignantchangeusuallysquamouscellcarcinomadevelopinginoneoftheepidermalelements（头节）ofthecyst.②Immatureteratoma（未成熟畸胎瘤）:Derivedfrom（起源于）allthreegermlayersusually2-3layers.Accountfor1-3%ofovarianteratoma.中南大学教案纸Thedegreeofmalignancyiscloselycorrelatedwiththeproportionofimmaturetissue（未成熟组织比例）,degreeofdifferentiation（分化程度）andneurepithelium（神经上皮）.Mostduringinjuvenility(meanageis11-19).2).Dysgerminoma（无性细胞瘤）About80%arefoundinpatientsunder25yearsofage.Comprisesabout5%ofallmalignantovarianneoplasms.Radiosensitiveand5-yearssurvivalrateis90%.3).Endodermalsinustumor(yolksactumor)[内胚窦瘤]Usuallyoccurinenfantandyoungwomen.ProducingAFP.poorprognosis.2.Ovariansexcordstromaltumor（性索间质肿瘤）1).Granulosacelltumor（颗粒细胞瘤）Institute3-6%ofovariantumors,80%ofsexcordstromaltumors.Usuallyoccuringin45-55yearsofage.Secreteestrogen,alsocalledfeminizingtumors（女性化肿瘤）.2).Thecacelltumor(卵泡膜细胞)SecreteestrogenSolidtumorBenign3).Fibroma(纤维瘤)Comprisesabout2-5%ofovariantumors.Benign,constitutetheMeigssyndrome(wheninconjunctionwithascitesandrighthydrothorax).3).Krukenbergstumor（库肯勃瘤）Fromcarcinomaofthestomach.Usuallybilateral,moderatesize.Cutsurfacetypicallyexhibitsgelatinousnecrosis（胶冻状坏死物）andmucin-filledcysticcavities.Singnetcell.病例讨论：中南大学教案纸患者女性，26岁，未婚。平素月经规律，7/35天,量中，有轻微痛经。2005-4出现月经紊乱4/15天，量少，无痛经。当地医院超声检查提示：双侧卵巢增大。于2005-5-30外院行腹腔镜检查术、术中见双卵巢肾形增大约右：6*5*4cm，左5*5*4cm。包膜均匀完整、但皮质略厚，表面散在毛细血管增生，余未见异常。行双卵巢活检术。术后病理报告：双侧卵巢Krukenberg瘤。术后严密随诊。术后2个月内无明显变化。术后4个月超声提示双侧卵巢增大、伴腹水症。查T由4个月前的1.663ng/ml上升至5.718ng/ml，伴毛发加重、闭经3月。复查胃镜显微结肠镜未见异常。2005-11-8在全麻下行次全子宫切除术、双附件切除术。手术顺利。术后病理报告：双卵巢krukenberg瘤。免疫组化显示肿瘤细胞：AE1：（-），AE3：（+），P170（-），CK7（灶状+），CK20（-），Inhibin（-），P53（-），Top-Ⅱa（+〈1%〉，CEA（灶状+）。后患者强烈要求出院，拒绝进一步检查。4.non-neoplasticcyst（非赘生性囊肿）oftheovary:1).Folliclecyst2).Granulosaluteincysts3).Thecaluteincysts4).Polycysticovary5).Endometriosis5.Treatment(治疗):1).良性生殖细胞及性索间质肿瘤：手术2).恶性生殖细胞及性索间质肿瘤：手术+化疗(VACBEPBVP)3).无性细胞瘤:辅加放疗4).转移性:肿瘤细胞减灭加原发灶切除五、Guidelinesonmanagementforovariantumor(卵巢肿瘤处理原则)20min1.卵巢囊性肿块:直径<5cm者，可定期观察2-3个月经周期。若>5cm直径则为手术指征。2.确诊为卵巢肿瘤者(混和性、实性肿块)原则上应手术切除肿瘤，术中鉴别良恶性，可疑恶性时立即冰冻切片病检确定手术范围。3.怀疑恶性肿瘤，尤其是实质性肿瘤，无论肿块大小均应及时手术。4.恶性肿瘤手术范围:原则上对早期卵巢癌应行全面确定分期的探查手术，晚期卵巢癌则行肿瘤细胞减灭术，术后辅以化疗，少数辅以放疗和免疫治疗的综合治疗方案。中南大学教案纸5.卵巢肿瘤并发症属急腹症，一旦确诊，无论良恶性及肿瘤大小均应立即手术。年青未生育的Ⅰa期，低度恶性肿瘤及生殖细胞肿瘤需保留生育功能者可行单附件切除术。6.保留生育功能的指征：1).上皮性卵巢肿瘤应具备以下条件:①年轻渴望生育；②Ia期；③细胞分化好（G1）或交界瘤；④对侧卵巢外观正常、活检阴性；⑤腹腔细胞学阴性；⑥高危区域探查及活检阴性；⑦有条件随诊；⑧完成生育后视情况再行手术切除子宫及对侧附件。2).生殖细胞肿瘤不论期别早晚都可保留生育功能3).颗粒细胞瘤如为单侧、包膜完整、肿瘤活动、对侧卵巢正常、内膜术前诊刮排除恶性者可保留生育功能。六、Etiologyandpathogenesisa(病因和发病机制)Geneticfactorssuchas:BRCA1[mutationin80%familyovarianarcinoma],BRCA2,P53[mutation14-44%],p16,NOEY2(normalovarianepithelialgenecloney2)[LOH>50%],Her-2/neuarenoticeableinnowadays,Telomeresandtelomerase.七、病例分析5min1、病史摘要：①患者×××，女，27岁，离异，2001年12月足月剖宫产1女婴。②患者因“下腹痛半月，发现盆腔包块8天”于2005-12-6收住院，患者月经规则，半月前出现下腹坠胀痛，程度轻，11月28日觉腹痛较前加重，伴肛门坠胀感，出现大便次数增多，2-3次/天，稀烂便，无粘液及脓血，无里急后重，无明显消瘦，门诊静滴药物抗感染治疗无好转。③体查：T36.3℃耻联上见一陈旧横形手术疤痕长8cm，下腹软，轻压痛，肝脾肋下未及，移动性中南大学教案纸浊音阴性，外阴发育正常，已婚式，阴道畅，宫颈光滑，有举痛及触痛，程度轻，子宫前位，大小、形状、边界不清，宫体压痛，右侧宫旁可扪及一囊实性包块，大小如8×5cm2，边界不清，活动差，局部压痛明显，左侧附件区轻压痛，触诊不清。④2001-11-28B超：子宫右后方囊实性包块⑤术前肝、脾、胆、肾、输尿管、膀胱B超未见异常，胸片、心电图、凝血4项、血常规、尿常规、大便常规等术前检查正常。⑥入院前及手术前均多次建议查肿瘤标志物明确肿瘤性质，患者均不同意。2、入院诊断：①盆腔包块查因：右侧卵巢肿瘤并感染？炎症包块？②疤痕子宫诊断依据：①下腹痛半月，发现盆腔包块8天；②右侧宫旁扪及一囊实性包块大小如8×5cm2，边界不清，活动差，局部压痛；③B超：子宫右后方囊实性包块可疑畸胎瘤。鉴别诊断：1).卵巢肿瘤并蒂扭转：支持点：下腹痛且发现盆腔包块，下腹轻压痛，以右下腹明显，右侧宫旁可扪及一囊实性包块大小如8×5cm2，边界不清，活动差，局部压痛明显，B超示卵巢畸胎瘤。不支持点：患者下腹痛无明显加剧，无恶心呕吐，腹软。结论：未能完全排除，需剖腹探查明确诊断。2).卵巢恶性肿瘤：支持点：下腹痛且发现盆腔包块，妇检：右侧宫旁可扪及一囊实性包块大小如8×5cm2，边界不清，活动差，B超：子宫右后方囊实性包块，左侧卵巢内囊性肿块（双侧卵巢均见包块）。不支持点：患者年龄27岁，发病以来无明显消瘦，胃纳可，B超提示右侧卵巢包块疑畸胎瘤，体查腹水征阴性。结论：未能排除，需术中标本冰冻