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

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

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

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

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

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

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

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

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

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

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

Ultrasound: ovarian cancer

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

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

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.

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

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

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

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

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

Serous Serous tumorstumors

Serous cancerSerous cancer

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

Mucinous tumorsMucinous tumors

Mucinous cancerMucinous cancer

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

Endometrioid cancerEndometrioid cancer

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

Clear cell tumorsClear cell tumors

Brenner tumorBrenner tumor

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

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

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)

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 ％％

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

Histologic classificationHistologic classification

Germ cell tumorsGerm cell tumors dysgerminomadysgerminoma endodermal sinus tumorendodermal sinus tumor embryonal tumorembryonal tumor polyembryomapolyembryoma choriocarcinomachoriocarcinoma teratomasteratomas mixed tumormixed tumor

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

Mature Cystic Teratoma

Immature ovarian teratoma

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

dysgerminomadysgerminoma

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

Endodermal sinus tumorEndodermal sinus tumor

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

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 ”

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

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

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

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

Ovarian thecomaOvarian thecoma

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

FibromaFibroma

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

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

Krukenberg tumorsKrukenberg tumors

Thank Thank you !you !

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

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

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

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

Hydatidiform moleHydatidiform mole

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

Complete moles Partial moles

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

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

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

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

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

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

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

a “snowstorm” pattern

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

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

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

Gestational TroGestational Tro

phoblastic Neopphoblastic Neop

lasialasia

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

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

Invasive moleInvasive mole

Invasive moleInvasive mole

Invasive moleInvasive mole

ChoriocarcinomaChoriocarcinoma

ChoriocarcinomaChoriocarcinoma

ChoriocarcinomaChoriocarcinoma

invades the myometrium

Lung metastases

Brain metastases

cervical metastases

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

Thank Thank you !you !