chapter 21 female genital tumor 6. ovarian tumor women’s hospital, school of medicine, zhejiang...
TRANSCRIPT
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Chapter 21 Chapter 21
Female Genital Female Genital
TumorTumor6. Ovarian 6. Ovarian
TumorTumorWomen’s Hospital, School of Medicine, Zhejiang universityWomen’s Hospital, School of Medicine, Zhejiang university
XingXing XieXie
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Ovarian tumorOvarian tumor
Common gynecologic malignant tumorsCommon gynecologic malignant tumors Occur in females of all agesOccur in females of all ages but different histological types in different abut different histological types in different a
ge-periodsge-periods Epithelial ovarian carcinoma with poor Epithelial ovarian carcinoma with poor
prognosisprognosis
5-year survival rate about 30-40%5-year survival rate about 30-40%
the mortality rate ranks first in the mortality rate ranks first in gynecological malignanciesgynecological malignancies
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General IntroductionGeneral Introduction
Histological classification Histological classification
very complicatedvery complicated Most histological types Most histological types in body organsin body organs The current classification The current classification
issued by WHO in 1973issued by WHO in 1973
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Histologic types of ovarian tuHistologic types of ovarian tumormor
Ovarain epithelial tumorOvarain epithelial tumor Germ cell tumorGerm cell tumor Sex-cord stromal cell tumorSex-cord stromal cell tumor Lipid (lipoid) cell tumorLipid (lipoid) cell tumor Gonadal blastomaGonadal blastoma Non-specific ovarian soft tissue tumorNon-specific ovarian soft tissue tumor Unclassified tumorUnclassified tumor Metastatic tumorMetastatic tumor Tumor-like lesionsTumor-like lesions
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Symptoms and signsSymptoms and signs
Benign tumorsBenign tumors No symptoms as tumor is small No symptoms as tumor is small Abdominal distention or pelvic mass Abdominal distention or pelvic mass
as tumor is as tumor is medium sizemedium size Gynecological examinationsGynecological examinations
A A spherical mass on one side of spherical mass on one side of the uterus, cystic, smooth the uterus, cystic, smooth surface, movablesurface, movable
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Symptoms and signsSymptoms and signs Ovarian cancerOvarian cancer early stageearly stage asymptomatic, oftenasymptomatic, often found occasionally by found occasionally by
gynecological examinations gynecological examinations Late stagesLate stages Abdominal distention, Abdominal distention, abdominal mass, ascitesabdominal mass, ascites End-stageEnd-stage Weight loss, severe anemia, cachexiaWeight loss, severe anemia, cachexia Transvagina-rectnum examinationTransvagina-rectnum examination Pelvic masses: bilateral , solid or semi-solid, notPelvic masses: bilateral , solid or semi-solid, not
movablemovable
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ComplicationsComplications pedicel retortionpedicel retortionCommon gynecological emergencyCommon gynecological emergency Frequency Frequency about 10%about 10% Usually occur in mass with a longer Usually occur in mass with a longer pedicle, mediupedicle, mediu
m size, good movability, and m size, good movability, and center deflection center deflection Blood flow blocked and Blood flow blocked and tumor necrosis atumor necrosis after retofter reto
rtionrtionSymptoms:Symptoms: one one side of lower abdomen pain side of lower abdomen pain
concomitantconcomitant nausea and vomit, nausea and vomit, Signs:Signs: Mass with high tension and tendernessMass with high tension and tenderness
Treatment Treatment emergency surgery oemergency surgery once diagnosednce diagnosed
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ComplicationsComplications RuptureRupture Frequency about 3%Frequency about 3% TraumaticTraumatic and and spontaneousspontaneous SymptomSymptom llower abdominal painower abdominal pain related to the size of rupture related to the size of rupture the quality and quantity of the quality and quantity of cyst fluidcyst fluid SignsSigns aabdominal tendernessbdominal tenderness muscle intensitymuscle intensity ascitesascites TreatmentTreatment emergency surgeryemergency surgery
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ComplicationsComplications InfectionInfection Due to rupture, retorsion or the near organs’ Due to rupture, retorsion or the near organs’
infectioninfection SymptomsSymptoms fever, abdominal pain fever, abdominal pain SignsSigns mass, amass, abdominal tenderness,bdominal tenderness, muscle intensitymuscle intensity TreatmentTreatment anti-infection, surgeryanti-infection, surgery Malignant changeMalignant change surgery surgery as soon as possibleas soon as possible
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DiagnosisDiagnosis Benign tumorsBenign tumors No specific symptomsNo specific symptoms A mass found occasionally by physical A mass found occasionally by physical
examinationexamination Ovarian cancerOvarian cancer No specific symptomsNo specific symptoms Gynecological examinationGynecological examination bilateral pelvic mass, bilateral pelvic mass, solid solid , poor , poor
movability, with ascites, uterus rectum nest movability, with ascites, uterus rectum nest nodulesnodules
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DiagnosisDiagnosis
Adjuvant examinationsAdjuvant examinations Imaging techniquesImaging techniques Ultrasonography Ultrasonography :: mainly used to diagnose primary lesionmainly used to diagnose primary lesion
accuracy rate above 90%accuracy rate above 90%
difficult to measure the diameter <1cm difficult to measure the diameter <1cm lesionlesion
Radiology (X-Ray, CT, MRI)Radiology (X-Ray, CT, MRI) mmainly used to diagnose the metastatic ainly used to diagnose the metastatic
lesionlesion
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Ultrasound: ovarian cancer
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DiagnosisDiagnosis Adjuvant examinationsAdjuvant examinations Tumor markersTumor markers §CA125§CA125 rise up in 80% epithelial cancersrise up in 80% epithelial cancers more used for disease monitoring and more used for disease monitoring and
prognosis evaluationprognosis evaluation §§AFPAFP rise in erise in endodermal sinus tumorndodermal sinus tumor §§hCG hCG ovarian choriacarcinomaovarian choriacarcinoma §§Sex hormoneSex hormone sex-cord stromal cell tumorsex-cord stromal cell tumor Laparoscopy Ascitic cytology
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Metastatic pathwayMetastatic pathway FeaturesFeatures Widely disseminated in abdominal cavity Widely disseminated in abdominal cavity Subclinical metastasisSubclinical metastasis
pathwayspathways spread directly and spread directly and abdominal cavity plantabdominal cavity plant lymph metastasislymph metastasis blood vessel metastasisblood vessel metastasis
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Clinical surgical-pathology staging (2000Clinical surgical-pathology staging (2000 ,, FIGO)FIGO)StageStage
II Growth limited to ovariesGrowth limited to ovaries
IAIA Growth limited to one side ovaries; no ascites. No Growth limited to one side ovaries; no ascites. No tumor on external surface; capsules intacttumor on external surface; capsules intact
IBIBGrowth limited to both ovaries; no ascites. No Growth limited to both ovaries; no ascites. No tumor on external surface; capsules intacttumor on external surface; capsules intact
ICIC
Tumor either IA or IB but with tumor on surface Tumor either IA or IB but with tumor on surface of one or both ovaries;or with capsule ruptured; of one or both ovaries;or with capsule ruptured; or with ascites containing malignant cells, or with or with ascites containing malignant cells, or with positive peritoneal washingspositive peritoneal washings
IIII Growth involving one or both ovaries with pelvic extension.Growth involving one or both ovaries with pelvic extension.
IIAIIAExtension and/or metastasis to the uterus and/or Extension and/or metastasis to the uterus and/or tubes.tubes.
IIBIIB Extension to other pelvic tissues.Extension to other pelvic tissues.
IICIIC
Tumor either Stage IIA or IIB, but with tumor on Tumor either Stage IIA or IIB, but with tumor on surface of one or both ovaries; or with capsule surface of one or both ovaries; or with capsule ruptured; or with ascites containing malignant ruptured; or with ascites containing malignant cells, or with positive peritoneal washings.cells, or with positive peritoneal washings.
IIIIII Tumor involving one or both ovaries with peritoneal implants outside pelvis and/or positive Tumor involving one or both ovaries with peritoneal implants outside pelvis and/or positive retroperitoneal or inguinal nodes. Superficial liver metastasis equals Stage III.retroperitoneal or inguinal nodes. Superficial liver metastasis equals Stage III.
IIIAIIIA
Tumor grossly limited to true pelvis with Tumor grossly limited to true pelvis with negative nodes, but with histologically confirmed negative nodes, but with histologically confirmed microscopic seeding of abdominal peritoneal microscopic seeding of abdominal peritoneal surfaces.surfaces.
IIIBIIIB
Tumor of one or both ovaries with histologically Tumor of one or both ovaries with histologically confirmed implants to abdominal peritoneal confirmed implants to abdominal peritoneal surfaces, none exceeding 2 cm in diameter Nodes surfaces, none exceeding 2 cm in diameter Nodes are negative.are negative.
IIICIIIC Abdominal implants >2 cm in diameter and/or Abdominal implants >2 cm in diameter and/or positive retroperitoneal or inguinal nodes.positive retroperitoneal or inguinal nodes.
IVIVGrowth involving one or both ovaries with distant metastasis. If pleural effusion present, must be Growth involving one or both ovaries with distant metastasis. If pleural effusion present, must be positive cytology to assign a case to Stage IV. Parenchymal live metastasis equals Stage IV.positive cytology to assign a case to Stage IV. Parenchymal live metastasis equals Stage IV.
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TherapyTherapy
Surgery Surgery ObjectivesObjectives To confirm the diagnosisTo confirm the diagnosis To resect tumorTo resect tumor To determine To determine surgical-pathology staging surgical-pathology staging of of
malignancymalignancy Chemotherapy and radiationChemotherapy and radiation for malignancyfor malignancy follow-up follow-up ovarian cancer is easy to recurrent and ovarian cancer is easy to recurrent and
should be long-term follow-upshould be long-term follow-up
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Epithelial tumorsEpithelial tumors The most common histological typeThe most common histological type accounting for 50-70% of the accounting for 50-70% of the
primary tumorprimary tumor 85-90% of malignant tumor85-90% of malignant tumor Derived from ovarian germinal Derived from ovarian germinal
epitheliumepithelium belong to the primitive body cavity epithebelong to the primitive body cavity epithe
lium lium have potential to have potential to differentiate into a differentiate into a
variety of variety of Mullerian epitheliaMullerian epithelia More common in older womenMore common in older women Can be divided into benign, borderline, Can be divided into benign, borderline,
malignant tumorsmalignant tumors
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Epithelial tumorsEpithelial tumors
Borderline tumorsBorderline tumors low malignant potential tumorslow malignant potential tumors pathological features of pathological features of
malignant tumor cells but no malignant tumor cells but no stromal invasionstromal invasion
clinically clinically slower development, feweslower development, fewer metastasis and more later recurrenr metastasis and more later recurrence ce
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Histological Histological classificationclassification
Epithelial tumorsEpithelial tumors Serous tumorsSerous tumors Mucinous tumorsMucinous tumors Endometrioid tumorEndometrioid tumor Brenner tumorBrenner tumor Mixed epithelial tumorsMixed epithelial tumors Undifferentiated carcinomaUndifferentiated carcinoma
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PathologyPathology
Serous tumorsSerous tumors cancer cell cancer cell differentiate into oviduct epithelialdifferentiate into oviduct epithelial Serous cystadenomaSerous cystadenoma Mostly unilateral, spherical, smooth, cystic, Mostly unilateral, spherical, smooth, cystic,
serous fluidserous fluidMicroscope:Microscope: simple columnar epithelium simple columnar epithelium
serous cystadenocarcinomaserous cystadenocarcinoma Mostly bilateral, semi-substantive, multiple antrum cMostly bilateral, semi-substantive, multiple antrum c
ystoid, cavity filled with papilla, crisp, bloody cyst fluystoid, cavity filled with papilla, crisp, bloody cyst fluidid
Microscope:Microscope: cubic or columnar epithelium, cubic or columnar epithelium, stratified, arranged in ≥4 layers, cellular atypia, stratified, arranged in ≥4 layers, cellular atypia, stromal invasionstromal invasion
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Serous Serous tumorstumors
Serous cancerSerous cancer
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PathologyPathologyMucinous tumorsMucinous tumorscancer cell cancer cell differentiate into enteric or differentiate into enteric or ccervical ervical
endometrial endometrial Mucinous cystadenomaMucinous cystadenoma Mostly unilateral, large size, cystic, and often have Mostly unilateral, large size, cystic, and often have
more capsules with the jelly-like mucusmore capsules with the jelly-like mucus Microscope:Microscope: simple columnar epithelium, can simple columnar epithelium, can
see goblet and argyrophil cellssee goblet and argyrophil cells If tumor rupture, tumor cells seed in peritoneal If tumor rupture, tumor cells seed in peritoneal
to form peritoneal myxomato form peritoneal myxoma Mucinous cystadenocarcinomaMucinous cystadenocarcinoma Mostly unilateral, cystic, cystic see the Mostly unilateral, cystic, cystic see the papillapapilla, bloo, bloo
dy cyst fluiddy cyst fluid Microscope:Microscope: columnar epithelium, stratified, columnar epithelium, stratified,
arranged in arranged in ≥≥ 3 layers, cellular atypia, stromal 3 layers, cellular atypia, stromal invasioninvasion
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Mucinous tumorsMucinous tumors
Mucinous cancerMucinous cancer
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PathologyPathology
Endometrioid tumorEndometrioid tumor Benign, borderline tumor is fewBenign, borderline tumor is few Endometrioid carcinomaEndometrioid carcinoma MostlyMostly unilateral, cystic or solid, with unilateral, cystic or solid, with
papilla, bloody cyst fluid. papilla, bloody cyst fluid.
Microscope:Microscope: similar to endometrial similar to endometrial cancercancer
Often Often concomitant with concomitant with endometrial endometrial cancercancer
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Endometrioid cancerEndometrioid cancer
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PathologyPathologyClear cell tumorsClear cell tumors Benign tumorsBenign tumors are few are few Clear cell carcinomaClear cell carcinoma MostlyMostly unilateral, cystic or solid unilateral, cystic or solid Microscope:Microscope: alveolar alveolar tumor cells withtumor cells with
abundant cytoplasm , atypia nuclearabundant cytoplasm , atypia nuclear Easy to lymph node and liver metastasisEasy to lymph node and liver metastasis Often concomitant with endometriosis and hypercOften concomitant with endometriosis and hyperc
alcemiaalcemia Brenner tumorBrenner tumor Differentiate and formate from transitional Differentiate and formate from transitional
epithelumepithelum Most are benign, unilateral, diameter <5cm, hardwMost are benign, unilateral, diameter <5cm, hardw
are qualityare quality
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Clear cell tumorsClear cell tumors
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Brenner tumorBrenner tumor
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Epithelial TumorsEpithelial Tumors
TreatmentTreatment benign tumorsbenign tumors Once diagnosed, surgical extensionOnce diagnosed, surgical extension reproductive period reproductive period womenwomen ovarian tumor resection or oophorectomyovarian tumor resection or oophorectomy perimenopausal and postmenopausal perimenopausal and postmenopausal
womenwomen ● ● adnexectomy adnexectomy ●● hysterectomy and bilateral salpingo-oophorechysterectomy and bilateral salpingo-oophorec
tomytomy Notices in surgeryNotices in surgery ①① differentiate the benign and malignant tumodifferentiate the benign and malignant tumo
rs rs during surgery (grossly, frozen section )during surgery (grossly, frozen section ) ② ② take out the tumor integrallytake out the tumor integrally
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Epithelial TumorsEpithelial TumorsTreatmentTreatment malignancymalignancy Principle: surgery combined with chemotherapy and radioPrinciple: surgery combined with chemotherapy and radio
therapytherapy surgerysurgery Early stage:Early stage: Staging surgery Staging surgery • Cytology for Cytology for ascites or peritoneal washings ascites or peritoneal washings • Complete pelvic and abdominal explorationComplete pelvic and abdominal exploration• OmentectomyOmentectomy• Back peritoneum lymph nodes excisionBack peritoneum lymph nodes excision• Hysterectomy + bilateral salpingoophorectomyHysterectomy + bilateral salpingoophorectomy• Conservative surgery Conservative surgery only for eligible only for eligible young women desiring childbearingyoung women desiring childbearing
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Epithelial TumorsEpithelial Tumors
TreatmentTreatment malignancymalignancy surgerysurgery Advanced stage: Advanced stage: Cytoreductive surgery (debulking surgeCytoreductive surgery (debulking surge
ry)ry) Resect primar and metastatic tuomrs aResect primar and metastatic tuomrs a
s much as possible , to minimize diames much as possible , to minimize diameter of residual tumor (<1cm)ter of residual tumor (<1cm)
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Epithelial TumorsEpithelial Tumors ChemotherapyChemotherapy Major adjuvant therapy, post-surgeryMajor adjuvant therapy, post-surgery Commonly used drugsCommonly used drugs cisplatin, carboplatin, paclitaxel, CTX, others.cisplatin, carboplatin, paclitaxel, CTX, others. Preferred to platinum-based combination chemotPreferred to platinum-based combination chemot
herapy herapy “ “Gold standard”: carboplatin and paclitaxel comGold standard”: carboplatin and paclitaxel com
binationbination RadiotherapyRadiotherapy For metastasis and recurrenceFor metastasis and recurrence Others Others immunotherapyimmunotherapyPrognosisPrognosis 5-year survival rate of Ia stage >905-year survival rate of Ia stage >90 %% 5-year survival rate of advanced stage <305-year survival rate of advanced stage <30 %%
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Ovarian germ cell tumorOvarian germ cell tumor
FeaturesFeatures From primitive germ cells in embryonic gonadFrom primitive germ cells in embryonic gonad Ability to produce diversity organizationsAbility to produce diversity organizations Frequency: account for 20~40% in all ovarian tuFrequency: account for 20~40% in all ovarian tu
morsmors More common in young women and girlsMore common in young women and girls Sensitive to chemotherapy Sensitive to chemotherapy ,, most can be reservmost can be reserv
ed for reproductive functioned for reproductive function Abnormal tumor markers: AFP, HCGAbnormal tumor markers: AFP, HCG
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Histologic classificationHistologic classification
Germ cell tumorsGerm cell tumors dysgerminomadysgerminoma endodermal sinus tumorendodermal sinus tumor embryonal tumorembryonal tumor polyembryomapolyembryoma choriocarcinomachoriocarcinoma teratomasteratomas mixed tumormixed tumor
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PathologyPathology
TeratomasTeratomas Comprised of multi-germ layer , rarely one layerComprised of multi-germ layer , rarely one layer Mostly are mature , few are immatureMostly are mature , few are immature Mature teratomasMature teratomas (( dermoid cystdermoid cyst )) benign tumorbenign tumor ,, the most common germ cell tumthe most common germ cell tumoror frequently single side, cystoid with smooth surfafrequently single side, cystoid with smooth surface, ce, contains tissues of fat, hair, teeth and bonecontains tissues of fat, hair, teeth and bone microscopymicroscopy : : scolex contains three layersscolex contains three layers malignant transformation: squamocarcinoma in malignant transformation: squamocarcinoma in scolex epilithiumscolex epilithium
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Mature Cystic Teratoma
Immature ovarian teratoma
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PathologyPathology
DysgerminomaDysgerminoma Moderate malignant tumorModerate malignant tumor Mostly occurs at puberty and child-bearinMostly occurs at puberty and child-bearin
g perildg perild Single side, solidSingle side, solid Microscopy Microscopy :: rotundity or mostly cornuarotundity or mostly cornua
l cellsl cells Extraordinary sensitive to radiotherapyExtraordinary sensitive to radiotherapy
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dysgerminomadysgerminoma
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PathologyPathology
Endodermal sinus tumorEndodermal sinus tumor Common in children and young womeCommon in children and young wome
nn Highly malignant, poor prognosis Highly malignant, poor prognosis Single side with large mass, fragile, obSingle side with large mass, fragile, ob
vious bleeding and necrosis;vious bleeding and necrosis; MicroscopyMicroscopy :: loose reticulate and enloose reticulate and en
dothelial sinus structuredothelial sinus structure Produce AFPProduce AFP
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Endodermal sinus tumorEndodermal sinus tumor
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TreatmentTreatment Benign tumorBenign tumor The same as epilithial tumors The same as epilithial tumors Malignant tumorMalignant tumor SurgerySurgery Lateral salpingoophorectomy regardless any stage as lLateral salpingoophorectomy regardless any stage as l
ong as opposite side ovary and uterus are not involvedong as opposite side ovary and uterus are not involved ChemotherapyChemotherapy Sensitive to chemotherapy : BEP BVP VACSensitive to chemotherapy : BEP BVP VAC RadiotherapyRadiotherapy sensitive for sensitive for DysgerminomaDysgerminoma ,, seldom used for young seldom used for young
agesages
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Sex cord-stromal tumorsSex cord-stromal tumors From sex cord and stromal tissues of embryoFrom sex cord and stromal tissues of embryo
nic gonadnic gonad Frequency: account for 5Frequency: account for 5 % % in all ovarian tuin all ovarian tu
morsmors Comprised or uni- or multi-cell componentsComprised or uni- or multi-cell components Mostly are benign or low malignant tumorMostly are benign or low malignant tumor Produce steroid hormones, with endocrine fuProduce steroid hormones, with endocrine fu
ntion, produce female or male features, also ntion, produce female or male features, also called “functioning ovarian tumor ”called “functioning ovarian tumor ”
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Histologic classificationHistologic classification
Sex cord-stromal tumorsSex cord-stromal tumors Granulosa cell -stromal cell tumorsGranulosa cell -stromal cell tumors Sertoli-stromal cell tumorsSertoli-stromal cell tumors GranudroblastomaGranudroblastoma
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PathologyPathology
Granulosa cell tumorsGranulosa cell tumors Adult form and child formAdult form and child form Adult formAdult form commoncommon low malignantlow malignant ,, produce E2produce E2 ,, female featufemale featu
resres solid or partly cysticsolid or partly cystic microscopy: Granulosa cell, Call-Exner bodymicroscopy: Granulosa cell, Call-Exner body Child formChild form seldom, highly malignantseldom, highly malignant
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Granulosa cell Granulosa cell tumortumor
Call–Exner bodies (sex cord-stromal tumors )
Granulosa Granulosa cell cell tumortumor
Granulosa cGranulosa cell ell tumortumor
stromal cell stromal cell tumorstumors
Granulosa cGranulosa cell ell tumortumor
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PathologyPathology
Ovarian thecoma (theca cell tumor)Ovarian thecoma (theca cell tumor) BenignBenign ,, seldom malignantseldom malignant Single side, solid.Single side, solid. MicroscopyMicroscopy short spindle cells, spiral arrangementshort spindle cells, spiral arrangement Female featuresFemale features
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Ovarian thecomaOvarian thecoma
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PathologyPathologyFibromaFibroma BenignBenign Single side, solid, hardnessSingle side, solid, hardness MicroscopyMicroscopy short spindle cells, knitting arrangemshort spindle cells, knitting arrangem
ent.ent. Meigs syndrome Meigs syndrome fibroma combination with ascites or hfibroma combination with ascites or h
ydrothorax, naturally disappear after tydrothorax, naturally disappear after tumor excisionumor excision
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FibromaFibroma
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TreatmentTreatment
Benign tumorBenign tumor surgery as same as epithelial tumorsurgery as same as epithelial tumor Malignant tumorMalignant tumor SurgerySurgery Conservative surgery for young women with staConservative surgery for young women with sta
ge I, desiring childbearingge I, desiring childbearing Radical surgery for othersRadical surgery for others ChemotherapyChemotherapy Combinated Chemotherapy Combinated Chemotherapy Regimens: as same as germ cell or epilithelial tuRegimens: as same as germ cell or epilithelial tu
morsmors
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Ovarian metastatic tumorsOvarian metastatic tumors OriginOrigin any organs’ tumorsany organs’ tumors commonly from breast, gastrointestinal and genital trcommonly from breast, gastrointestinal and genital tr
actact Krukenberg tumors (signet ring cell tumor)Krukenberg tumors (signet ring cell tumor)
From gastrointestinal From gastrointestinal Bilateral, solid, median size, without adhension Bilateral, solid, median size, without adhension ovary –shape or kidney-shape ovary –shape or kidney-shape
microscopymicroscopy :: signet ring cellssignet ring cells Surgery combined with chemotherapy and radiotherSurgery combined with chemotherapy and radiother
apyapy Poor prognosisPoor prognosis
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Krukenberg tumorsKrukenberg tumors
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Thank Thank you !you !
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Chapter 22Chapter 22
Gestational Trophoblastic DiseGestational Trophoblastic Diseasease
WomenWomen’’s Hospital, School of Medicine Zhejiang Universits Hospital, School of Medicine Zhejiang Universityy
Xing XieXing Xie
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Gestational trophoblastic diGestational trophoblastic diseasesease
AA group of diseases group of diseases originated from placental trophoblastic cellsoriginated from placental trophoblastic cells
Gestational trophoblasitc disease (GTD)Gestational trophoblasitc disease (GTD) Hydatidiform mole (complete and partial) Hydatidiform mole (complete and partial) Invasive moleInvasive mole Choriocarcinoma Choriocarcinoma Placental-site trophoblastic tumor (PSTT)Placental-site trophoblastic tumor (PSTT)
Gestational trophoblastic neoplasia (GTN)Gestational trophoblastic neoplasia (GTN)
Non-gestational trophoblastic tumorNon-gestational trophoblastic tumor Uncommon, derived from germ cells in ovarian or Uncommon, derived from germ cells in ovarian or
testiculartesticular
histologically clinically
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Development and Development and differentiation of gestational differentiation of gestational
trophoblastic cellstrophoblastic cells gestational trophoblastic cellsgestational trophoblastic cells evolved from evolved from extrextr
a-embryonic cellsa-embryonic cells At the time of implantation At the time of implantation cytotrophoblast cytotrophoblast outermost layer of the outermost layer of the
blastocyst blastocyst 7-8 days after implantation 7-8 days after implantation syncytiotrophoblast syncytiotrophoblast implantation site implantation site Before villi formation Before villi formation previllous trophoblastprevillous trophoblast 2 weeks after pregnancy, primary villi 2 weeks after pregnancy, primary villi
formation formation Villous surface Villous surface villous trophoblastvillous trophoblast Other parts Other parts extravillous trophoblastextravillous trophoblast
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Development and Differentiation Development and Differentiation of gestational trophoblastic cellsof gestational trophoblastic cells
CytotrophoblastCytotrophoblast trophoblast stem cells trophoblast stem cells
proliferability and differentiabilityproliferability and differentiability SyncytiotrophoblastSyncytiotrophoblast differentiated mature cellsdifferentiated mature cells synthesize pregnancy-related hormones synthesize pregnancy-related hormones
material exchange between the fetus and material exchange between the fetus and the motherthe mother
Two differentiated forms of Two differentiated forms of CytotrophoblCytotrophoblastast
villous surface area Syncytiotrophoblastvillous surface area Syncytiotrophoblast
extravillous Intermediate trophoblastextravillous Intermediate trophoblast
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Hydatidiform moleHydatidiform mole
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Hydatidiform mole Hydatidiform mole
Complete molesComplete moles Hydropic degeneration of all villiHydropic degeneration of all villi Villous edema, trophoblastic hyperplasia, fetal-Villous edema, trophoblastic hyperplasia, fetal-
derived derived
blood vessels disappear in stromablood vessels disappear in stroma Partial molesPartial moles
combine embryo or fetuscombine embryo or fetus Villous edemaVillous edema partially, t partially, trophoblastic rophoblastic
proliferation proliferation
lighterly, fetal-derived blood vessels lighterly, fetal-derived blood vessels presentpresent stromastroma
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Complete moles Partial moles
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Hydatidiform moleHydatidiform moleRelated FactorsRelated Factors Complete molesComplete moles
Area common in Latin America, AsiaArea common in Latin America, Asia uncommon in uncommon in North America and EuropeNorth America and Europe Race dRace differences of ifferences of the same race in the same race in different different
regionsregions Nutrition and EconomyNutrition and Economy lack of Vit Alack of Vit A Age Age < 20 or >35 years< 20 or >35 years The fertilization of an empty eggThe fertilization of an empty egg the fertilization of an empty egg by a haploid sperthe fertilization of an empty egg by a haploid sper
mm Diploid genome 90% of the time (usually 46,XX)Diploid genome 90% of the time (usually 46,XX) Genomic imprinting disorderGenomic imprinting disorder
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Hydatidiform moleHydatidiform mole Partial molesPartial moles high-risk factors are still unknownhigh-risk factors are still unknown "Haploid egg" fertilization"Haploid egg" fertilization usually usually two sperm fertilize a normal eggtwo sperm fertilize a normal egg a triploid karyotype (69 chromosomes ), with the a triploid karyotype (69 chromosomes ), with the
extra haploid set of chromosomes derived from fextra haploid set of chromosomes derived from fatherather
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CompleteComplete PartialPartial
Karyotype Karyotype 46, XX(90%) 46, XX(90%) 46, XY(10%)46, XY(10%)
TriploidTriploid
(69XXY, 69XXX)(69XXY, 69XXX)
Embryo Embryo AbsentAbsent PresentPresent
Villi Villi Hydropic Hydropic Few hydropic Few hydropic
TrophoblastsTrophoblasts Diffuse hyperplasia Diffuse hyperplasia Mild focal Mild focal hyperplasia hyperplasia
Villus outlineVillus outline regularregular irregularirregular
Blood vesselBlood vessel absenceabsence presencepresence
Comparison of complete and partiComparison of complete and partial hydatidiform molesal hydatidiform moles
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Hydatidiform moleHydatidiform moleClinical PresentationClinical Presentation Complete molesComplete moles Abnormal vaginal bleeding during early pregnancy( 8-1Abnormal vaginal bleeding during early pregnancy( 8-1
2week)2week) most common symptom most common symptom Uterine enlargement exceeding normal pregnant uterus Uterine enlargement exceeding normal pregnant uterus Others Others Abdominal painAbdominal pain Pregnancy-induced hypertensionPregnancy-induced hypertension Theca lutein ovarian cystTheca lutein ovarian cyst Hyperthyroidism (CHM)Hyperthyroidism (CHM) Partial molesPartial moles Mild symptoms, Confused with abortion easilyMild symptoms, Confused with abortion easily
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Hydatidiform moleHydatidiform molehCG regression pattern after hydatidiformhCG regression pattern after hydatidiform Mean time of the hCG regressed to normalMean time of the hCG regressed to normal — — 9 weeks no more than 14 weeks 9 weeks no more than 14 weeks Abnormal hCG regression pattern after hydatidiform Abnormal hCG regression pattern after hydatidiform signifies the presence of GTNsignifies the presence of GTN Complete moleComplete mole 15%15% l local invasion and 4% distant metastasis ocal invasion and 4% distant metastasis High –risk :High –risk :
①①HCG>100,000U/LHCG>100,000U/L② ② Enlargement of UterineEnlargement of Uterine③ ③ Theca lutein ovarian cyst >6cmTheca lutein ovarian cyst >6cm
Partial molePartial mole 4%l4%local invasion and almost no distant ocal invasion and almost no distant
metastasis metastasis High –risk :unclearHigh –risk :unclear
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Hydatidiform moleHydatidiform mole DiagnosisDiagnosis Abnormal bleeding after amenorrheaAbnormal bleeding after amenorrhea Inappropriately enlarged uterusInappropriately enlarged uterus Absence of fetal heart sounds Absence of fetal heart sounds not palpate fetus between 16-20not palpate fetus between 16-20thth week week Vaginal discharge hydatidiform-like Vaginal discharge hydatidiform-like
tissuetissue
Hydatidiform mole should be consideredHydatidiform mole should be considered
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Hydatidiform moleHydatidiform mole DiagnosisDiagnosis Ultrasound Ultrasound Complete moles produce a characteristic vesicular sonogComplete moles produce a characteristic vesicular sonog
raphic pattern, usually referred to as a “snowstorm” praphic pattern, usually referred to as a “snowstorm” patternattern
HCGHCG Elevated above expected for gestational ageElevated above expected for gestational age Dynamic observation for 8-10 weeks, continued to riseDynamic observation for 8-10 weeks, continued to rise HCG-related moleculesHCG-related molecules Hyperglycosylated HCGHyperglycosylated HCG free β-HCG subunitfree β-HCG subunit
DNA karyotype DNA karyotype Complete moles — usually diploid Complete moles — usually diploid Partial moles — usually triploidPartial moles — usually triploid
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a “snowstorm” pattern
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Hydatidiform moleHydatidiform mole TreatmentTreatmentSuction curettageSuction curettage Molar pregnancy should be terminated as Molar pregnancy should be terminated as
soon as possible when diagnosis has been soon as possible when diagnosis has been confirmedconfirmed
Suction curettage is a first choice, Suction curettage is a first choice, must must be fully done in operating roombe fully done in operating room
tissue from curettage should tissue from curettage should be submitted to pathologybe submitted to pathology
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Hydatidiform moleHydatidiform moleTreatmentTreatment Theca lutein cysts of the ovaryTheca lutein cysts of the ovary do not need special treatmentdo not need special treatment Prophylactic chemotherapy: Prophylactic chemotherapy: A controversial topic A controversial topic only be offered to patients with high-risk factor only be offered to patients with high-risk factor
or or impossible follow-upimpossible follow-up HysterectomyHysterectomy Only remove local invasion, but not distant metOnly remove local invasion, but not distant met
astasisastasis Only for old women without childbearing desireOnly for old women without childbearing desire
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Hydatidiform moleHydatidiform moleFollow-upFollow-up necessary for diagnosis of early GTNnecessary for diagnosis of early GTN Methods:Methods: HCGHCG Symptom: Abnormal uterine bleedingSymptom: Abnormal uterine bleeding Pelvic examination Pelvic examination Ultrasound, chest X-ray and CTUltrasound, chest X-ray and CT Contraception: Contraception: Condom and oral contraceptives,Condom and oral contraceptives, not IUD not IUD Duration for contraceptiom Duration for contraceptiom —— 1 year 1 year
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Gestational TroGestational Tro
phoblastic Neopphoblastic Neop
lasialasia
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General ConsiderationGeneral Consideration Antecedent gestation Antecedent gestation 60% hydatidiform mole 60% hydatidiform mole 30% follow abortion 30% follow abortion 10% term pregnancy or ectopic pregna10% term pregnancy or ectopic pregna
ncyncy from molefrom mole — — invasive mole invasive mole or choriocarcinoma or choriocarcinoma
from from Non-mole Non-mole
—— choriocarcinomachoriocarcinoma
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Gestational Trophoblastic NGestational Trophoblastic Neoplasiaeoplasia
PathogenesisPathogenesis Invasive moleInvasive mole Invasive mole is a hydatidiform mole that invades Invasive mole is a hydatidiform mole that invades
the myometrium and may produce distant metastthe myometrium and may produce distant metastases. ases.
Microscopic finding are the same as in hydatidifoMicroscopic finding are the same as in hydatidiform molerm mole
ChoriocarcinomaChoriocarcinoma GlossGloss :: invades the myometrium , penetrate the invades the myometrium , penetrate the
serosaserosa and may produce distant metastasesand may produce distant metastases MicroscopyMicroscopy :: no villi, but instead sheets or foci ono villi, but instead sheets or foci o
f trophoblasts on a background of hemorrhage anf trophoblasts on a background of hemorrhage and necrosisd necrosis
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Invasive moleInvasive mole
Invasive moleInvasive mole
Invasive moleInvasive mole
ChoriocarcinomaChoriocarcinoma
ChoriocarcinomaChoriocarcinoma
ChoriocarcinomaChoriocarcinoma
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invades the myometrium
Lung metastases
Brain metastases
cervical metastases
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Gestational Trophoblastic NGestational Trophoblastic Neoplasiaeoplasia
Clinical ManifestationClinical ManifestationNonmetastatic GTNNonmetastatic GTN the antecedent gestational event is usually the antecedent gestational event is usually
HMHM Abnormal vaginal bleeding after mole Abnormal vaginal bleeding after mole Others:Others: Enlarged uterus Enlarged uterus Theca lutein cysts of the ovaryTheca lutein cysts of the ovary Abdominal pain Abdominal pain Fake pregnancy symptomsFake pregnancy symptoms
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Gestational Trophoblastic NeoGestational Trophoblastic Neoplasiaplasia
Metastatic GTNMetastatic GTNUsually chroriocarcinomaUsually chroriocarcinoma Primary symptoms Primary symptoms Metastatic symptoms Metastatic symptoms
Lung metastases are frequently common Lung metastases are frequently common vaginal metastases are the second commonvaginal metastases are the second common liver and brain metastases usually death caliver and brain metastases usually death ca
use use other metastastic sites other metastastic sites spleen, kidney, bladder, gastrointestinal syspleen, kidney, bladder, gastrointestinal sy
stem, and bone stem, and bone
Simultateously occur or not
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Gestational Trophoblastic NeoGestational Trophoblastic Neoplasiaplasia
DiagnosisDiagnosis Symptoms and signs:Symptoms and signs:◆◆ Abnormal vaginal bleeding Abnormal vaginal bleeding after post-evacuation, abortion, term after post-evacuation, abortion, term
pregnancy or ectopic pregnancy, pregnancy or ectopic pregnancy, ◆ ◆ Metastatic symptoms Metastatic symptoms GTT should be consideredGTT should be considered
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Gestational Trophoblastic NeoplasGestational Trophoblastic Neoplasiaia
HCG assayHCG assay Most important and sometimes only diagnostic evidence Most important and sometimes only diagnostic evidence Diagnostic criteria for post- HM GTN (FIGO2000)Diagnostic criteria for post- HM GTN (FIGO2000) hCG plateau for >4 values hCG plateau for >4 values (( ±10±10 %), %), over 3 weeksover 3 weeks hCG increase of ≥10% over 2 weekshCG increase of ≥10% over 2 weeks hCG persistence after evacuation of mole for 6 monthshCG persistence after evacuation of mole for 6 months
Diagnostic criteria for non post-HM GTNDiagnostic criteria for non post-HM GTNHCG elevated at 4w after abortion, term or ectopic pregHCG elevated at 4w after abortion, term or ectopic preg
nancynancyRe-rising HCG titer after reaching normal levelsRe-rising HCG titer after reaching normal levels
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Gestational Trophoblastic NeoplasGestational Trophoblastic Neoplasiaia
Chest X-rayChest X-ray lung metastases lung metastases CTCT small lung metastases and brain metastases small lung metastases and brain metastases MRIMRI Liver and brain metastases Liver and brain metastases UltrasoundUltrasound primary lesions of uterus and pevical metastasprimary lesions of uterus and pevical metastas
es es Imaging supports diagnosis, but not Imaging supports diagnosis, but not
necessarynecessary
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Gestational Trophoblastic NeoplasGestational Trophoblastic Neoplasiaia
Histological diagnosisHistological diagnosis villus shape can be found in primary or villus shape can be found in primary or
metastatical lesionsmetastatical lesions Presence of villus shape Invasive molPresence of villus shape Invasive mol
e e Absence of villus shape ChoriocarcinAbsence of villus shape Choriocarcin
omaoma Histology is not necessary Histology is not necessary for diagnosis of GTNfor diagnosis of GTN
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Anatomy staging of GTN (FIGO, 2000)Anatomy staging of GTN (FIGO, 2000) StageIStageI Localized to the uterusLocalized to the uterus
StageIIStageII Lesion diffused, but Localized to the genitalia (aLesion diffused, but Localized to the genitalia (accessory,vagina,broad ligament)ccessory,vagina,broad ligament)
StageIIIStageIII Lung metastasis, with or without genitalia Lung metastasis, with or without genitalia changechange
StageⅣStageⅣ Other metastasisOther metastasis
Gestational Trophoblastic NeoplasiaGestational Trophoblastic Neoplasia
Stage I
Stage II
Stage III
Stage IV
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Prognostic scoring system for GTT Prognostic scoring system for GTT
(FIGO,2000)(FIGO,2000) scorescore 00 11 22 44
Age(y)Age(y) << 4040 ≥≥4040 -- --
Antecedent Antecedent molemole abortionabortion termterm --
Interval (mo) Interval (mo) << 44 44 ~~ 66 77 ~~ 1212 ≥≥1313
Pretreatment b-hCG (mIU/Pretreatment b-hCG (mIU/ml) ml)
<< 1010 33 1010 33~~ 1010 44 > > 1010 44~~ 101055
> > 1010 55
Largest tumor (cm) Largest tumor (cm) -- 33 ~~ 4 cm 4 cm ≥≥5cm5cm --
Site of metastases Site of metastases LungLung Spleen, KidneySpleen, Kidney GastrointestiGastrointestinal nal
Liver, brainLiver, brain
Number of metastases Number of metastases -- 11 ~~ 44 55 ~~ 88 >> 88
Prior chemotherapy failed Prior chemotherapy failed -- -- single single >> 22
* Total score≤6 low risk, ≥7 high risk
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Gestational Trophoblastic NeoplasGestational Trophoblastic Neoplasiaia
TreatmentTreatment Chemotherapy combining surgery, radiotherapy Chemotherapy combining surgery, radiotherapy
and other treatmentand other treatment Base on the assessment and stage, therapy stratifiBase on the assessment and stage, therapy stratifi
ed ed Chemotherapy : Chemotherapy : Single-agent chemotherapy is applied in low-risk Single-agent chemotherapy is applied in low-risk
gestational trophoblastic disease (MTX, Act-D, 5-gestational trophoblastic disease (MTX, Act-D, 5-Fu)Fu)
High-risk patients commonly use combined cheHigh-risk patients commonly use combined chemotherapy (EMA-CO)motherapy (EMA-CO)
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Single agent chemotherapySingle agent chemotherapy
DAY Therapy Interval DAY Therapy Interval
1-5 MTX 0.4mg/kg im qd 14d1-5 MTX 0.4mg/kg im qd 14d 11、、 33、、 55、、 7 MTX1mg/kg im 14d 7 MTX1mg/kg im 14d 22、、 44、、 66、、 8 FA 0.1mg/kg im or po 8 FA 0.1mg/kg im or po 1-5 Act-D10-12ug/kg ivgtt qd 14d 1-5 Act-D10-12ug/kg ivgtt qd 14d
1-8 5-Fu 28-30mg/kg ivgtt qd 121-8 5-Fu 28-30mg/kg ivgtt qd 12 -- 14d14d
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Combined chemotherapyCombined chemotherapy
Drugs Drugs Dose ,pathway,periodsDose ,pathway,periods Interval Interval
5-Fu+KSM5-Fu+KSM 3weeks3weeks
5-Fu5-Fu 26-28mg/kg·d26-28mg/kg·d ,, ivgtt for 8daysivgtt for 8days
KSMKSM 66g/kg·dg/kg·d , , ivgtt for 8daysivgtt for 8days
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Combined chemotherapyCombined chemotherapy
EMA-COEMA-CO Interval Interval 2weeks2weeks
the first part EMAthe first part EMA
11stst day VP16 100mg/m day VP16 100mg/m2 2 ivgttivgtt
Act-D 0.5mg ivgttAct-D 0.5mg ivgtt
MTX 100 mg/mMTX 100 mg/m2 2 ivgttivgtt
MTX 200mg/mMTX 200mg/m22 ivgtt for 12hours ivgtt for 12hours
22ndnd day VP16 100mg/m day VP16 100mg/m22 ,, ivgttivgtt
Act-D 0.5mg ivgttAct-D 0.5mg ivgtt
CF15mgCF15mg ,, imim
(( after 24hours from the use of MTXafter 24hours from the use of MTX , , once every 12hoursonce every 12hours ,, twictwicee ))33rdrd CF15mg CF15mg ,, imim ,, once every 12hoursonce every 12hours ,, twicetwice 。。44thth to 7 to 7thth rest rest (( no drugno drug )) the second part COthe second part CO
88thth day VCR1.0mg/m day VCR1.0mg/m22 , , ivgttivgtt
CTX600mg/mCTX600mg/m22 , , ivgttivgtt
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PSTTPSTT
A special type, more rarely in clinicA special type, more rarely in clinic Most of them have a good prognosisMost of them have a good prognosis Form Form the intermediate trophoblast the intermediate trophoblast
cellscells Clinical manifestationsClinical manifestations More common occur at reproductive period womMore common occur at reproductive period wom
en en More common occur following term or ectopic prMore common occur following term or ectopic pr
egnancyegnancy Abnormal bleeding after amenorrheaAbnormal bleeding after amenorrhea
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PSTTPSTT
DiagnosisDiagnosis HCG was negativeHCG was negative
HPL mildly elevatedHPL mildly elevated Confirmed by histologyConfirmed by histology
TreatmentTreatment
Surgery is the preferred treatment Surgery is the preferred treatment
Chemotherapy is adjuvant therapyChemotherapy is adjuvant therapy
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