DefinitionsGestational Trophoblastic Disease (GTD)It is a spectrum of trophoblastic diseases that includes: Complete molar pregnancy Partial molar pregnancies Invasive mole Choriocarcinoma Placental site trophoblastic tumourThe last 2 may follow abortion, ectopic or normal pregnancy. RCOG Guideline No. 38 .2010
Definitions Gestational Trophoblastic Neoplasia (GTN)=Malignant Gestational Trophoblastic DiseaseIt is a spectrum of trophoblastic diseases that develops malignant sequelae. GTN includes: Persistent post molar GTD Invasive mole Choriocarcinoma Placental site trophoblastic tumourThe last 2 may follow abortion, ectopic or normal pregnancy. Disaia &Creasman Clinical Gynecological Oncology 2007 Cunningham et al Williams Obsterics 23rd , 2010
ClassificationsGestational Trophoblastic Disease (GTD)I-Pathologic Partial mole Invasive Chorio Placental site trophoblasticClassification Complete mole mole tumour carcinoma Pe rsi st en tG G.T. NeoplasiaII-Clinical Benign TDClassification G.T.D. Malignant G.T.D.βhCG based:WHO, FIGO,ACOG 2004 & Metastatic Non metastaticRCOG 2010 Low risk High risk
Gestational Trophoblastic DiseaseOver 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 by ultrasonography 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 thrown light on the etiology of the disease .
Hydatidiform Moles (H.M.)Hydatidiform moles are abnormal pregnancies characterized histologically by : Trophoblastic proliferation & Edema of the villous stroma (Hydropic) .Based on the degree and extent of these tissue changes, hydatidiform moles are categorized as either Complete hydatidiform mole. Partial hydatidiform mole.
Features Of Partial And Complete Hydatidiform MolesFeature Partial mole Complete mole Most commonly Most commonly 69, XXX or - XXY 46, XX or -,XYKaryotypePathologyFetus 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% Disaia &Creasman Clinical Gynecological Oncology 2007 rd
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 incidence Previous spontaneous abortion: double the incidence Repetitive H. moles in women with different partners Cunningham et al,Williams Obstetrics,23 ed ,2010
Epidemiology & Risk FactorsPartial moles have been linked to:• Higher educational levels• Smoking• Irregular menstrual cycles• Only male infants are among the prior live births
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 proliferation 2-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"
Pathogenesis of Choriocarcinoma–Aneuploidy–(Not a multiplication of 23 chromosome )
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 RBCs Macroscopically: The molar pattern did not involve the entire placenta. Uterine enlargement in excess of gestational age is uncommon. Theca-lutein cysts are rare Fetal or embryonic tissue or amnion
Partial Hydatidiform Mole Scalloping of chorionic villiTrophoblastic proliferation are slight and focal
How Do Molar Pregnancies Present To The Clinician? The classic features are Irregular vaginal bleeding Hyperemesis Excessive uterine enlargement & Early failed pregnancy. Clinicians should check a urine pregnancy test in women presenting with such symptoms. RCOG Guideline No. 38 ; 2010Some women will present early with passage of molar tissue
How Do Molar Pregnancies Present To The Clinician?Rarer presentations include: Hyperthyroidism Early onset pre-eclampsia Abdominal distension due to theca lutein cystsVery rarelyAcute respiratory failureNeurological symptoms such as seizures (? metastatic disease). RCOG Guideline No. 38 ; 2010
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%
How Is Complete Mole Diagnosed?U/S is helpful in making a pre-evacuation diagnosis but the definitive diagnosis is made by histological examination.U/S: Early detection reduced from 16 weeks (passage of vesicles) to 12 wsβhCG levels > 2 multiples of the median may be of value in the diagnosis RCOG Guideline No. 38 ; 2010
U/S& βhCG Definite diagnosis on first U/S examination U/S alone: 68% U/S + βhCG > threshold of 82,350 mIU/mL: 89%Disaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007
How Is Partial H .Mole Diagnosed? In most patients with a partial mole, the clinical and U/S diagnosis is Usually missed or incomplete abortion. This emphasizes the need for a thorough histopathologic evaluation of all missed or incomplete abortionsDisaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007
How Is Partial H .Mole Diagnosed? Classically: A thickened, hydropic placenta with fetal or embryonic tissue Multiple soft markers, including: Cystic spaces in the placenta and Transverse to AP dimension a ratio of the gestation sac of > 1.5, is required for the reliable diagnosis of a partial molar pregnancy RCOG Guideline No. 38 ; 2010
Case Scenario 1A 24-year-old 2nd Gravida ,Para 1 woman at 8 Ws GA (Blood group: O, negative) complains of:1-Worsening nausea, and vomiting over the last 2 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 for this patient?
What Does The Differential DiagnosisInclude For This Patient?The differential diagnosis of bleeding with early pregnancy and progressive vomiting are:Multiple pregnancy.Hydatidiform mole.Threatened abortion.Ectopic pregnancy.
Which Diagnostic Test Would BeMost Useful?The most useful diagnostic test is : U/S
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
What Is The Recommended Subsequent Test ?β subunit hCGThe B subunit hCG assay: 195,000 mlU/mL Then 1-What is the most likely diagnosis? 2-How can the patient be managed?
1-What Is The MostLikely Diagnosis? The snowstorm pattern on U/S& The abnormally high hCG level are diagnostic of Vesicular 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.
What Is The Plan of Management?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 Best Method Of Evacuating This Molar Pregnancy?A. Cervical priming with misoprostol then suction evacuationB. Suction evacuation to be repeated 1-2 weeks laterC. Single suction evacuationD. Medical trial with misoprostol &oxytocine before suction C. What Is The Evidence ?
What Is The Evidence ?The Management Of Gestational Trophoblastic DiseaseRCOG Guideline No. 38 ; 2010
What Is The Best Method Of Evacuating A Molar Pregnancy?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 ; 2010
Is That The Same For Partial Mole?For Partial mole: It depends on the fetal parts Small fetal parts :Suction curettage Large 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 ; 2010
Can Oxytocic Infusions Be Used During Surgical Evacuation?• 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 ; 2010
Should Products Of Conception Be Examined Histologically?Histological examination is indicated in: Failed pregnancies (missed or molar) :All medically or surgical managed cases Products 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/SCOG Guideline No. 38 ; 2010 R
Return to Case Scenario 1Suction curettage has been performedusing 10mm canula under U/S guidance 10mm Canula up to a maximum of 12 mm, is usually sufficient to evacuate all complete molar pregnancies.
Suction curettage has been performedusing 10mm canula under U/S guidance : El SHERBINY HOSP Canula
U/S Guided Suction Curettage Suction curettage can be performed under U/S guidance to: Facilitate the procedure Confirm complete evacuation of contents. Garner UpToDate 2010
The Molar Content For Histopathological Examination
Meticulous histopathological examination revealed:Villi have extensive stromal edemaAbnormal trophoblastic proliferationNo embryonic or fetal tissue or RBCs These findings are diagnostic of: Complete Hydatidiform Mole
The Case is Now Confirmed HistopathologicalAs A Complete H. MoleWhat Is The Most Appropriate Management? A- Surveillance :Weekly then monthly βhCG B-Hysterectomy C-Transvaginal U/S examination D-Repeated curettage &Biopsy E-Prompt chemotherapy A.
Hysterectomy may be preferred to suction curettage at age ≥ 40 with no desire for further pregnancies especially with other risk factors for GTN as : Large theca lutein cysts( >6 cm) Significant uterine enlargement Pretreatment βhCG ≥ 105.Although hysterectomy does not eliminate possibility of GTN this, it markedly reduces its likelihood.Soper. Obstet Gynecol 108:176, 2006 Garner UpToDate 2010 Cunningham et al,Williams Obstetrics,23 ed ,2010
Complete H. Mole withlarge for date uterus&Theca-lutein cyst Complete H. Mole After HysterectomyPatient was 42 years5th G P5 initialBhCG:195,000mIU/mL
Theca-lutein cyst associated with a complete H. mole in >30%
Second Uterine Evacuation :There is no clinical indication for the routine use of second uterine evacuation RCOG Guideline No. 38 ; 2010Prophylactic Chemotherapy: The long-term prognosis for women with a H. mole is not improved with prophylactic chemotherapy. Because toxicity—including death—may be significant, it is not recommended routinely *It may be useful in the high-risk cases when follow- up are unavailable or unreliable. * *American College of Obstetricians and Gynecologists, 2004*
Is Anti-D Prophylaxis Required For This Case? NoWhen Anti-D Is Required?It is required in partial due to the presence of fetal RBCsIn complete mole: if diagnosis is not confirmed histopathologically RCOG Guideline No. 38 ; 2010
Post-evacuation SurveillanceWhy?To determine when pregnancy can be allowedTo detect persistent trophoblastic disease (i.e. GTN)
The Post-evacuation Surveillance. How? A baseline serum β -hCG level is obtained within 48 hours after evacuation. Levels are monitored every 1 to 2 weeks while still elevated to detect persistent trophoblastic disease (GTN). These levels should progressively fall to an undetectable level (<5 mu/ml). If symptoms are persistent, more frequent β hCG estimation and U/S examination ± D&C are advised RCOG Guideline No. 38 ; 2010
Cunningham et al,Williams Obstetrics,23 ed ,2010
At the 9 week follow up the β hCG level : 2u/LIs this level sufficient to stop follow up ? No 4- The Scenario case Cunningham et al,Williams Obstetrics,23 ed ,2010
What Is The Optimum Follow-up PeriodFollowing Normalization of β hCG?A. For 6 months from the date of uterine evacuation.B. For 6 months from normalization of the β hCG level.C. For 12 months from the date of uterine evacuation. B
What Is The Optimum Follow-up PeriodAfter Which Pregnancy Is Allowed?It depends upon when hCG has reverted to normal ≤ 56 days of the pregnancy event: Follow up is 6 months from the date of uterine evacuation. >56 days of the pregnancy event :Follow up is 6 months from normalization of the hCG level. RCOG Guideline No. 38 ; 2010At this period levels of βhCG are monitored every month Practically once βhCG has normalized after molarevacuation, the possibility of GTN developing is very low.
What Is Safe Contraception Following GTD? Barrier methods until normal β hCG level. Once βhCG level have normalized:Combined oral contraceptive (COC ) pill may be used. If oral COC was started before the diagnosis of GTD ,COC can be continue as its potential to increase risk of GTN is very low IUCD should not be used until β hCG levels are normal to reduce uterine perforation. RCOG Guideline No. 38 ; 2010
Case Scenario 2A 34-year-old woman, married for 7 years 3rd 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 140/85
US scanning revealedWhat Is The U/S Differential Diagnosis?
What Is The U/S Differential Diagnosis? Complete mole with a coexisting normal twin Partial mole Other placental abnormalities Rtroplacental hematoma Degenerating myoma
What Are The Required Investigations? Quantities serum β hCG Free T4 Protein in urine Rescanning after one week in a tertiary or fetal medicine center for diagnosis & screening.
β hCG :80,000 mµ/ml Free T4 : 2µg/ml (N 0.3-1.7µg/ml) Protein in urine: Negative U/S Tertiary center report:Molar pregnancy with a coexisting normal twinThe mole is mostly complete ,to be confirmed histopathologicaly (After termination).U/S Fetal screening: No detectable anomaliesFollow up is recommended .
How Cane We Council The Couple?1-Counseling for the increased risk of perinatal 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 GTN outcome and need of serial surveillance . RCOG Guideline No. 38 ; 2010
The Patients Elects To Continue ThePregnancy. How Can We Manage? Close maternal surveillance for development of preeclampsia or hyperthyroidism. Fetal karyotype may be considered if follow up screening is not assuring Serial hCG level for detection of GTN. A chest x-ray to exclude pulmonary metastases (choriocarcinoma) Postpartum: the placenta should be sent for evaluation by a pathologist Garner UpToDate ,2010
When Must Pregnancy Be Terminated ? Development of preeclampsia or hyperthyroidism. Fetal karyotype is not normal dioploidy β hCG level levels consistent with GTN. Evidence of metastases (choriocarcinoma) Accidental hemorrhage Garner UpToDate ,2010