Gestational Trophoblastic
Disease (GTD)
Part I : Molar Pregnancy
• Dr. Mohamed El SherbinyMD Ob.& Gyn. Senior Consultant
• Damietta, Egypt
Part I: Molar Pregnancy
It is a spectrum of trophoblastic diseases that includes:Complete molar pregnancyPartial molar pregnancies Invasive moleChoriocarcinoma Placental site trophoblastic tumour
DefinitionsGestational Trophoblastic Disease (GTD)
RCOG Guideline No. 38 .2010
The last 2 may follow abortion, ectopic or normal pregnancy.
It is a spectrum of trophoblastic diseases that develops malignant sequelae. GTN
includes:Persistent post molar GTDInvasive moleChoriocarcinoma Placental site trophoblastic tumour
DefinitionsGestational Trophoblastic Neoplasia (GTN)
=Malignant Gestational Trophoblastic Disease
Disaia &Creasman Clinical Gynecological Oncology 2007 Cunningham et al Williams Obsterics 23rd , 2010
The last 2 may follow abortion, ectopic or normal pregnancy.
Chorio
carcinoma
I-Pathologic Classification
II-Clinical ClassificationβhCG based: WHO, FIGO, ACOG 2004 & RCOG 2010
Benign G.T.D.
G.T. Neoplasia
Malignant G.T.D.
Partial moleComplete mole
Invasivemole
MetastaticNon metastatic
Low risk High risk
Gestational Trophoblastic Disease (GTD)Placental site trophoblastic tumour
Persistent GTD
Classifications
Over the last 30 years major advances have taken place in our understanding and management of gestational trophoblastic 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 GTN 4- The cytogenetic profile has thrown light on the etiology of the disease .
Gestational Trophoblastic Disease
-
Hydatidiform Mole
(H. MOLE)=
Vesicular Mole
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.
Feature Partial mole Complete mole
KaryotypeMost commonly69, XXX or - XXY
Most commonly46, XX or -,XY
PathologyFetus 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 Moles
Disaia &Creasman Clinical Gynecological Oncology 2007 Cunningham et al Williams Obsterics 23rd , 2010
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 Pregnancy
Second 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
Partial moles have been linked to:• Higher educational levels• Smoking• Irregular menstrual cycles• Only male infants are among the
prior live births
Epidemiology & Risk Factors
Karyotype
Homozygous 90%
Pathogenesis of complete H. Mole
Pathogenesis of complete H. Mole
Heterozygous 10%
Pathogenesis of Partial H. Mole
Pathology of Molar
Pregnancy
Complete H. MoleMicroscopically Enlarged, edematous villi and abnormal trophoblastic proliferation that diffusely involve the entire villiNo fetal tissue, RBCs or amnion are produced
Macroscopically, these microscopic changes transform the chorionic villi into clusters of vesicles with variable dimensions “ 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 Degeneration
Complete hydatidiform mole: Microscopically Enlarged, edematous villi and abnormal trophoblastic proliferation that diffusely involve the entire placenta
Complete hydatidiform mole: Macroscopically, these microscopic changes transform the chorionic villi into clusters of vesicles with variable dimensions the name hydatidiform mole stems from this "bunch of grapes"
Complete Hydatiform Mole
Uterine wall
Pathogenesis of
Choriocarcinoma–Aneuploidy –(Not a multiplication of 23 chromosome )
Partial H. MoleMicroscopically: The enlarged, edematous villi and abnormal trophoblastic proliferation are slight and focal and did not involve the entire villi.There is a scalloping of chorionic villi Fetal 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
Scalloping of chorionic villi
Partial Hydatidiform Mole
Trophoblastic proliferation are slight and focal
Partial Hydatiform Mole
Vesicles
Maternal side
Fetal hand demonstrating syndactyly. The fetus had a triploid karyotype, and the chorionic tissues were a partial mole
Partial H. mole.
The classic features areIrregular vaginal bleedingHyperemesisExcessive uterine enlargement &Early failed pregnancy.
Clinicians should check a urine pregnancy test in women presenting with such symptoms.
RCOG Guideline No. 38 ; 2010
How Do Molar Pregnancies Present To The Clinician?
Some women will present early with passage of molar tissue
Rarer presentations include:HyperthyroidismEarly onset pre-eclampsia Abdominal distension due to theca lutein cysts
Very rarelyAcute respiratory failure Neurological symptoms such as seizures (?
metastatic disease).
RCOG Guideline No. 38 ; 2010
How Do Molar Pregnancies Present To The Clinician?
What Is The Most Common Presenting Symptom Of A Complete Molar Pregnancy?
A. Hyperemesis
B. Bilateral enlarged theca lutein cysts
C. Vaginal bleeding
D. Uterine enlargement> than expected for GA
E. Pregnancy-induced hypertension
What Is The Most Common Presenting Symptom 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-evacuation diagnosis but the definitive diagnosis is made by histological examination.
U/S: Early detection reduced from 16 weeks (passage of vesicles) to 12 ws
βhCG levels > 2 multiples of the median may be of value in the diagnosis
RCOG Guideline No. 38 ; 2010
How Is Complete Mole Diagnosed?
U/S& βhCG Definite diagnosis on first U/S
examinationU/S alone: 68% U/S + βhCG > threshold of
82,350 mIU/mL: 89%
Disaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007
TVS “Milestones” Versus βhCG hCG mIU/mL Weeks
Detection Level >5 3-4Choriodecidual thickening 100 4
Gestational sac (D Zone) 1000 -1500 4-5
Yolk sac 7000 5- 6
Heart motion 10,000 6
Embryonic Movem. > 10.000 6- 7 Maximum level 50,000to 100,000 8-10
Complete Molar Pregnancy
Complete hydatidiform mole. The classic "snowstorm" appearance is created by the multiple placental vesicles.
Complete H.Mole (High-resolution) U/S Complex intrauterine mass containing many small cysts.
Complete H.Mole Associated theca-lutein cysts. U/S Power Doppler
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 abortions
How Is Partial H .Mole Diagnosed?
Disaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007
Classically: A thickened, hydropic placenta with fetal or embryonic tissue
Multiple soft markers, including:Cystic spaces in the placenta andTransverse 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
How Is Partial H .Mole Diagnosed?
Partial Molar Pregnancies
A 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 days
She denies any abdominal or back cramps.
What does the differential diagnosis include for this patient?
Case Scenario 1
The differential diagnosis of bleeding with early pregnancy and progressive vomiting are:
Multiple pregnancy. Hydatidiform mole.Threatened abortion.Ectopic pregnancy.
What Does The Differential Diagnosis Include For This Patient?
The most useful diagnostic test is :
U/S
Which Diagnostic Test Would Be Most 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 hCG
Then 1-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 Most Likely 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.
There are 2 important basic lines :
1-Evacuation of the mole
2-Regular follow-up to detect persistent trophoblastic disease
If 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 This Molar Pregnancy?
A. Cervical priming with misoprostol then suction
evacuation
B. Suction evacuation to be repeated 1-2 weeks later
C. Single suction evacuation
D. Medical trial with misoprostol &oxytocine before
suction
C.
What Is The Evidence ?
The Management Of Gestational Trophoblastic Disease
RCOG Guideline No. 38 ; 2010
What Is The Evidence ?
For Complete mole is: Suction curettage
Cervical preparation with prostaglandins or misoprostol , should be avoided to reduce the risk of embolisation (No sufficient studies)
RCOG Guideline No. 38 ; 2010
What Is The Best Method Of Evacuating 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 ; 2010
Is 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 ; 2010
Can Oxytocic Infusions Be Used During 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/S
RCOG Guideline No. 38 ; 2010
Should Products Of Conception Be Examined Histologically?
Return to Case Scenario 1Suction curettage has been performed using 10mm canula under U/S guidance
10mm
Canula up to a maximum of 12 mm, is usually sufficient to evacuate all complete molar pregnancies.
Other seats of suction curettage
Suction curettage has been performed using 10mm canula under U/S guidance :
El SHERBINY HOSPEl SHERBINY HOSP
Canula
Suction curettage can be performed under U/S guidance to:
Facilitate the procedure
Confirm complete evacuation of contents.
Garner UpToDate 2010
U/S Guided Suction Curettage
The Molar Content For Histopathological Examination
Meticulous histopathological examination revealed: Villi have extensive stromal edemaAbnormal trophoblastic proliferation No embryonic or fetal tissue or RBCs
These findings are diagnostic of:Complete Hydatidiform Mole
The Case is Now Confirmed Histopathological As A Complete H. Mole What 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.
Garner UpToDate 2010 Soper. Obstet Gynecol 108:176, 2006
Cunningham et al,Williams Obstetrics,23 ed ,2010
Complete H. Mole After Hysterectomy
Complete H. Mole with large for date uterus& Theca-lutein cyst
Patient was 42 years 5th G P5 initial BhCG:195,000mIU/mL
Complete H. Mole After Hysterectomy
Complete H. Mole with large for date uterus& Theca-lutein cyst
Patient was 42 years 5th G P5 initial BhCG:195,000mIU/mL
Theca-lutein cyst associated with a complete H. mole in >30%
Prophylactic 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. * *
Second Uterine Evacuation :There is no clinical indication for the routine use of second uterine evacuation
RCOG Guideline No. 38 ; 2010
American College of Obstetricians and Gynecologists, 2004*
When Anti-D Is Required?It is required in partial due to the
presence of fetal RBCs
In complete mole: if diagnosis is not confirmed histopathologically
RCOG Guideline No. 38 ; 2010
Is Anti-D Prophylaxis Required For This Case?
No
Post-evacuation Surveillance
Why? To determine when pregnancy
can be allowed To detect persistent
trophoblastic disease (i.e. GTN)
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
The Post-evacuation Surveillance. How?
Cunningham et al,Williams Obstetrics,23 ed ,2010
Cunningham et al,Williams Obstetrics,23 ed ,2010
The Scenario case
At the 9 week follow up the β hCG level : 2u/L
Is this level sufficient to stop follow up ?
No
4-
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.
What Is The Optimum Follow-up Period Following Normalization of β hCG?
B
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 ; 2010
What Is The Optimum Follow-up Period After Which Pregnancy Is Allowed?
At this period levels of βhCG are monitored every month Practically once βhCG has normalized after molar evacuation, the possibility of GTN developing is very low.
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 lowIUCD should not be used until β hCG levels are normal to reduce uterine perforation.
What Is Safe Contraception Following GTD?
RCOG Guideline No. 38 ; 2010
A 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 days
2-Nausea, and moderate vomiting
Pulse 95/m, Bp 140/85
Case Scenario 2
What Is The U/S Differential Diagnosis?
US scanning revealed
Complete mole with a coexisting normal twin Partial moleOther placental abnormalitiesRtroplacental hematomaDegenerating myoma
What Is The U/S Differential Diagnosis?
Quantities serum β hCG
Free T4
Protein in urine
Rescanning after one week in a tertiary or fetal medicine center for diagnosis & screening.
What Are The Required Investigations?
β hCG :80,000 mµ/mlFree 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 anomalies
Follow up is recommended .
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 .
How Cane We Council The Couple?
RCOG Guideline No. 38 ; 2010
Garner UpToDate ,2010
The Patients Elects To Continue The Pregnancy. How Can We Manage?
Close maternal surveillance for development of preeclampsia or hyperthyroidism.Fetal karyotype may be considered if follow up screening is not assuringSerial 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
Development of preeclampsia or hyperthyroidism.Fetal karyotype is not normal dioploidyβ hCG level levels consistent with GTN. Evidence of metastases (choriocarcinoma)Accidental hemorrhage
Garner UpToDate ,2010
When Must Pregnancy Be Terminated ?
Thank You
Egypt