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It is a spectrum of trophoblastic diseasesthat includes:Complete molar pregnancyPartial molar pregnanciesInvasive moleChoriocarcinomaPlacental site trophoblastic tumourDefinitionsGestational Trophoblastic Disease (GTD)RCOG Guideline No. 38 .2010The last 2 may follow abortion, ectopic or normal pregnancy.
It is a spectrum of trophoblastic diseasesthat develops malignant sequelae. GTNincludes:Persistent post molar GTDInvasive moleChoriocarcinomaPlacental site trophoblastic tumourDefinitionsGestational Trophoblastic Neoplasia (GTN)=Malignant Gestational Trophoblastic DiseaseDisaia &Creasman Clinical Gynecological Oncology 2007Cunningham et al Williams Obsterics 23rd, 2010The last 2 may follow abortion, ectopic or normal pregnancy.
Over the last 30 years major advances have taken place inour understanding and management of gestationaltrophoblastic disease.1- It is now possible to diagnose a mole byultrasonography in minutes .2-It became the most curable gynec. malignancy.3-βhCG has very important role in the diagnosis,evaluation and follow up of GTN4- The cytogenetic profile has thrownlight on the etiology of the disease .Gestational Trophoblastic Disease
-Hydatidiform Mole(H. MOLE)=Vesicular Mole
Hydatidiform Moles (H.M.)Hydatidiform moles are abnormalpregnancies characterized histologicallyby :Trophoblastic proliferation &Edema of the villous stroma (Hydropic) .Based on the degree and extent of thesetissue changes, hydatidiform moles arecategorized as eitherComplete hydatidiform mole.Partial hydatidiform mole.
Feature Partial mole Complete moleKaryotypeMost commonly69, XXX or - XXYMost commonly46, XX or -,XYPathologyFetus Often present AbsentAmnion, fetal RBC Usually present AbsentVillous edema Variable, focal DiffuseTrophoblastic proliferation Focal, slight-moderate Diffuse, slight-severeClinical presentationDiagnosis Missed abortion Molar gestationUterine size Small for dates 50% large for datesTheca lutein cysts Rare 25-30%Medical complications Rare 10-25%Postmolar CTN 2.5-7.5% 6.8-20%Features Of Partial And Complete Hydatidiform MolesDisaia &Creasman Clinical Gynecological Oncology 2007rd
Epidemiology& Risk FactorsIncidence:USA 1/1000 South East 1/100 (Hospital)Risk Factors:Age: <20y (2fold) , > 40y(10 fold) & >50y (50% V.mole)Prior Molar PregnancySecond molar: 1% - Third molar : 20%!Diet:↑ in low fat Vit. A or carotene diet (complete mole)Contraception :COC double the incidencePrevious spontaneous abortion: double the incidenceRepetitive H. moles in women with different partnersCunningham et al,Williams Obstetrics,23 ed ,2010
Partial moles have been linked to:• Higher educational levels• Smoking• Irregular menstrual cycles• Only male infants are among theprior live birthsEpidemiology &Risk Factors
Homozygous 90%Pathogenesis of complete H. Mole
Pathogenesis of complete H. MoleHeterozygous 10%
Pathogenesis of Partial H. Mole
Complete H. MoleMicroscopically Enlarged, edematous villi and abnormaltrophoblastic proliferation that diffusely involve theentire villiNo fetal tissue, RBCs or amnion are producedMacroscopically, these microscopic changes transform thechorionic villi into clusters of vesicles with variabledimensions “ like bunch of grapes"No fetal or embryonic tissue are producedUterine enlargement in excess of gestational age .Theca-lutein cyst associated in 30%
1-Trophoblastic proliferation2-Hydropic DegenerationComplete hydatidiform mole: Microscopically Enlarged,edematous villi and abnormal trophoblastic proliferation thatdiffusely involve the entire placenta
Complete hydatidiform mole: Macroscopically, thesemicroscopic changes transform the chorionic villi into clusters ofvesicles with variable dimensions the name hydatidiform molestems from this "bunch of grapes"
Complete Hydatiform MoleUterine wall
Pathogenesis ofChoriocarcinoma–Aneuploidy–(Not a multiplication of 23chromosome )
Partial H. MoleMicroscopically: The enlarged, edematous villi andabnormal trophoblastic proliferation are slight andfocal and did not involve the entire villi.There is a scalloping of chorionic villiFetal or embryonic or fetal RBCsMacroscopically: The molar pattern did not involvethe entire placenta.Uterine enlargement in excess of gestational age isuncommon.Theca-lutein cysts are rareFetal or embryonic tissue or amnion
Scalloping of chorionic villiPartial Hydatidiform MoleTrophoblastic proliferation are slight and focal
Partial Hydatiform MoleVesiclesMaternal side
Fetal hand demonstrating syndactyly. The fetus had a triploid karyotype, and the chorionictissues were a partial mole
Partial H. mole.
The classic features areIrregular vaginal bleedingHyperemesisExcessive uterine enlargement &Early failed pregnancy.Clinicians should check a urine pregnancy testin women presenting with such symptoms.RCOG Guideline No. 38 ; 2010How Do Molar Pregnancies PresentTo The Clinician?Some women will present early with passage of molar tissue
Rarer presentations include:HyperthyroidismEarly onset pre-eclampsiaAbdominal distension due to theca lutein cystsVery rarelyAcute respiratory failureNeurological symptoms such as seizures (?metastatic disease).RCOG Guideline No. 38 ; 2010How Do Molar PregnanciesPresent To The Clinician?
What Is The Most Common PresentingSymptom Of A Complete Molar Pregnancy?A. HyperemesisB. Bilateral enlarged theca lutein cystsC. Vaginal bleedingD. Uterine enlargement> than expected for GAE. Pregnancy-induced hypertension
What Is The Most Common PresentingSymptom Of A Complete Molar Pregnancy?A. Hyperemesis 10%B. Bilateral enlarged theca lutein cysts 30%C. Vaginal bleeding 85%D. Uterine enlargement> than expected for GA 40%E. Pregnancy-induced hypertension 1%
U/S is helpful in making a pre-evacuationdiagnosis but the definitive diagnosis ismade by histological examination.U/S: Early detection reduced from 16 weeks(passage of vesicles) to 12 wsβhCG levels > 2 multiples of the median maybe of value in the diagnosisRCOG Guideline No. 38 ; 2010How Is Complete Mole Diagnosed?
In most patients with a partial mole,the clinical and U/S diagnosis isUsually missed or incomplete abortion.This emphasizes the need for athorough histopathologic evaluation ofall missed or incomplete abortionsHow Is Partial H .Mole Diagnosed?Disaia &Creasman Clinical Gynecological Oncologym 7thedd. 2007
Classically: A thickened, hydropicplacenta with fetal or embryonic tissueMultiple soft markers, including:Cystic spaces in the placenta andTransverse to AP dimension a ratio ofthe gestation sac of > 1.5, is requiredfor the reliable diagnosis of a partialmolar pregnancyRCOG Guideline No. 38 ; 2010How Is Partial H .Mole Diagnosed?
Partial Molar Pregnancies
A 24-year-old 2ndGravida ,Para 1 woman at 8 WsGA (Blood group: O, negative) complains of:1-Worsening nausea, and vomiting over the last2 weeks which is unlike her prior pregnancy .2-Irregular vaginal bleeding over the last 7 daysShe denies any abdominal or back cramps.What does the differential diagnosis include forthis patient?Case Scenario 1
The differential diagnosis of bleedingwith early pregnancy andprogressive vomiting are:Multiple pregnancy.Hydatidiform mole.Threatened abortion.Ectopic pregnancy.What Does The Differential DiagnosisInclude For This Patient?
The most useful diagnostictest is :U/SWhich Diagnostic Test Would BeMost Useful?
Complex intrauterine mass containing many small cysts(Snowstorm appearance)What is the most likely diagnosis?Hydatidiform (Vesicular) mole
What Would One Expect To See At Scan If Her Pregnancy Is Normal?Gestational (Chorionic) Sac
What Is The Ultrasonogaphic Differential Diagnosis For This Case?U/S DD :1-Missed abortion2-Degenerated fibroid
Differential Diagnosis: Long standing missed abortion with cystic degeneration of the placenta
β subunit hCGThen1-What is the most likely diagnosis?2-How can the patient be managed?What Is The Recommended Subsequent Test ?The B subunit hCG assay:195,000 mlU/mL
1-What Is The MostLikely Diagnosis?The snowstorm pattern on U/S&The abnormally high hCG level are diagnostic ofVesicular MoleProbably complete V. mole
Why It Is Probably Complete V. Mole? It demonstrates the typical U/S appearance of complete V. mole : a complex, echogenic intrauterine mass containing many small cystic spaces. Fetal tissues and amnionic sac are absent However the final differentiation is after histopathology.
There are 2 important basic lines :1-Evacuation of the mole2-Regular follow-up to detect persistent trophoblastic diseaseIf both basic lines are done appropriately, mortality rates can be reduced to zero.What Is The Plan of Management?
What Is The Best Method Of Evacuating ThisMolar Pregnancy?A. Cervical priming with misoprostol then suctionevacuationB. Suction evacuation to be repeated 1-2 weeks laterC. Single suction evacuationD. Medical trial with misoprostol &oxytocine beforesuctionC.What Is The Evidence ?
The Management Of Gestational Trophoblastic DiseaseRCOG Guideline No. 38 ; 2010What Is The Evidence ?
For Complete mole is: Suction curettageCervical preparation with prostaglandins or misoprostol , should be avoided to reduce the risk of embolisation (No sufficient studies) RCOG Guideline No. 38 ; 2010What Is The Best Method OfEvacuating A Molar Pregnancy?
For Partial mole: It depends on the fetal partsSmall fetal parts :Suction curettageLarge fetal parts: Medical (oxytocics) In partial mole the oxytocics is safe ,as the hazard to embolise and disseminate trophoblastic tissue is very low Also, the needing for chemotherapy is 0.1- 0.5%.RCOG Guideline No. 38 ; 2010Is That The Same For Partial Mole?
• The use of oxytocic infusion prior to completion of the evacuation is not recommended (fear of embolisation).• If the woman is experiencing significant haemorrhage prior to evacuation, surgical evacuation should be expedited and the need for oxytocin infusion weighed up against the risk of tumour embolisation.RCOG Guideline No. 38 ; 2010Can Oxytocic Infusions Be UsedDuring Surgical Evacuation?
Histological examination is indicated in:Failed pregnancies (missed or molar) :All medically or surgical managed casesProducts of conception, obtained after all repeat evacuations (post abortive or p.partum)There is no need after therapeutic termination : provided that fetal parts is identified on U/SRCOG Guideline No. 38 ; 2010Should Products Of Conception BeExamined Histologically?
Return to Case Scenario 1Suction curettage has been performedusing 10mm canula under U/S guidance10mmCanula up to a maximum of 12 mm, is usuallysufficient to evacuate all complete molar pregnancies.
Other seats of suction curettage
Suction curettage has been performedusing 10mm canula under U/S guidance :El SHERBINY HOSPEl SHERBINY HOSPCanula
Suction curettage can be performed under U/S guidance to:Facilitate the procedure Confirm complete evacuation of contents. Garner UpToDate 2010U/S Guided Suction Curettage
The Molar Content For Histopathological Examination
Meticulous histopathological examination revealed:Villi have extensive stromal edemaAbnormal trophoblastic proliferationNo embryonic or fetal tissue or RBCsThese findingsare diagnosticof:CompleteHydatidiformMole
The Case is Now Confirmed HistopathologicalAs A Complete H. MoleWhat Is The Most Appropriate Management?A- Surveillance :Weekly then monthly βhCGB-HysterectomyC-Transvaginal U/S examinationD-Repeated curettage &BiopsyE-Prompt chemotherapyA.
Hysterectomy may be preferred tosuction curettage at age ≥ 40 with nodesire for further pregnancies especiallywith other risk factors for GTN as : Large theca lutein cysts( >6 cm) Significant uterine enlargement Pretreatment βhCG ≥ 105.Although hysterectomy does not eliminatepossibility of GTN this, it markedlyreduces its likelihood.Garner UpToDate 2010Soper. Obstet Gynecol 108:176, 2006Cunningham et al,Williams Obstetrics,23 ed ,2010
Complete H. MoleAfter HysterectomyComplete H. Mole withlarge for date uterus&Theca-lutein cystPatient was 42 years5thG P5 initialBhCG:195,000mIU/mLComplete H. MoleAfter HysterectomyComplete H. Mole withlarge for date uterus&Theca-lutein cystPatient was 42 years5thG P5 initialBhCG:195,000mIU/mL
Theca-lutein cyst associated with a complete H. mole in >30%
Prophylactic Chemotherapy: The long-termprognosis for women with a H. mole is notimproved with prophylactic chemotherapy.Because toxicity—including death—may besignificant, it is not recommended routinely *It may be useful in the high-risk cases when follow-up are unavailable or unreliable. * *Second Uterine Evacuation :There is noclinical indication for the routine use ofsecond uterine evacuationRCOG Guideline No. 38 ; 2010American College of Obstetricians and Gynecologists, 2004*
When Anti-D Is Required?It is required in partial due to thepresence of fetal RBCsIn complete mole: if diagnosis is notconfirmed histopathologicallyRCOG Guideline No. 38 ; 2010Is Anti-D Prophylaxis Required ForThis Case?No
Post-evacuationSurveillanceWhy?To determine when pregnancycan be allowedTo detect persistenttrophoblastic disease (i.e. GTN)
A baseline serum β -hCG level is obtainedwithin 48 hours after evacuation.Levels are monitored every 1 to 2 weekswhile still elevated to detect persistenttrophoblastic disease (GTN).These levels should progressively fall toan undetectable level (<5 mu/ml).If symptoms are persistent, more frequent β hCGestimation and U/S examination ± D&C areadvisedRCOG Guideline No. 38 ; 2010The Post-evacuation Surveillance. How?
Cunningham et al,Williams Obstetrics,23 ed ,2010
Cunningham et al,Williams Obstetrics,23 ed ,2010The Scenario caseAt the 9 week follow up the β hCG level : 2u/LIs this level sufficient to stop follow up ?No4-
A. For 6 months from the date of uterineevacuation.B. For 6 months from normalization of the β hCGlevel.C. For 12 months from the date of uterineevacuation.What Is The Optimum Follow-up PeriodFollowing Normalization of β hCG?B
It depends upon when hCG has reverted to normal ≤ 56 days of the pregnancy event: Follow up is6 months from the date of uterine evacuation. >56 days of the pregnancy event :Follow up is6 months from normalization of the hCG level.RCOG Guideline No. 38 ; 2010What Is The Optimum Follow-up PeriodAfter Which Pregnancy Is Allowed?At this period levels of βhCG are monitored every monthPractically once βhCG has normalized after molarevacuation, the possibility of GTN developing is very low.
Barrier methods until normal β hCG level.Once βhCG level have normalized:Combinedoral contraceptive (COC ) pill may be used.If oral COC was started before the diagnosis ofGTD ,COC can be continue as its potential toincrease risk of GTN is very lowIUCD should not be used until β hCG levels arenormal to reduce uterine perforation.What Is Safe Contraception Following GTD?RCOG Guideline No. 38 ; 2010
A 34-year-old woman, married for 7 years3rd Gravida ,Para 0 at 14 Ws GA.The previous abortions were at 7&8 weeks.She complains of:1-Mild vaginal bleeding for 4 days2-Nausea, and moderate vomitingPulse 95/m, Bp 140/85Case Scenario 2
What Is The U/S Differential Diagnosis?US scanning revealed
Complete mole with a coexistingnormal twinPartial moleOther placental abnormalitiesRtroplacental hematomaDegenerating myomaWhat Is The U/S Differential Diagnosis?
Quantities serum β hCGFree T4Protein in urineRescanning after one week in atertiary or fetal medicine center fordiagnosis & screening.What Are The Required Investigations?
β hCG :80,000 mµ/mlFree T4 : 2µg/ml (N 0.3-1.7µg/ml)Protein in urine: NegativeU/S Tertiary center report:Molar pregnancy with a coexisting normaltwinThe mole is mostly complete ,to beconfirmed histopathologicaly (Aftertermination).U/S Fetal screening: No detectableanomaliesFollow up is recommended .
1-Counseling for the increased risk ofperinatal morbidity :• Bleeding• Pre-eclampsia5-20%• Hyperthyrodism 5%• premature labor 35%• Early fetal loss 40%• Live birth only :25%.2-Counseling for the increased risk of GTNoutcome and need of serial surveillance .How Cane We Council The Couple?RCOG Guideline No. 38 ; 2010
Garner UpToDate ,2010The Patients Elects To Continue ThePregnancy. How Can We Manage?Close maternal surveillance fordevelopment of preeclampsia orhyperthyroidism.Fetal karyotype may be considered iffollow up screening is not assuringSerial hCG level for detection of GTN.A chest x-ray to exclude pulmonarymetastases (choriocarcinoma)Postpartum: the placenta should be sentfor evaluation by a pathologist
Development of preeclampsia orhyperthyroidism.Fetal karyotype is not normal dioploidyβ hCG level levels consistent with GTN.Evidence of metastases(choriocarcinoma)Accidental hemorrhageGarner UpToDate ,2010When Must Pregnancy Be Terminated ?