Gestational Trophoblastic Disease (GTD) Part I: Molar Pregnancy

August 3, 2011

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

Gestational Trophoblastic Disease
(GTD)
Part I : Molar Pregnancy
Dr. Mohamed El Sherbiny
MD Ob.& Gyn. Senior Consultant
Damietta, Egypt

Part I: Molar Pregnancy

Definitions
Gestational Trophoblastic Disease (GTD)
It is a spectrum of trophoblastic diseases that includes:
• Complete molar pregnancy
• Partial molar pregnancies
• Invasive mole
• Choriocarcinoma
• Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy.
RCOG Guideline No. 38 .2010

 

Definitions
Gestational Trophoblastic Neoplasia (GTN)
=Malignant Gestational Trophoblastic Disease
It is a spectrum of trophoblastic diseases that develops malignant sequelae. GTN includes:
• Persistent post molar GTD
• Invasive mole
• Choriocarcinoma
• Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy.
Disaia &Creasman Clinical Gynecological Oncology 2007 Cunningham et al Williams Obsterics 23rd , 2010

Gestational Trophoblastic Disease
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- hCG 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.

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.

FeaturePartial moleComplete mole
 Most commonly 69, XXX or - XXYMost commonly 46, XX or -,XY
Karyotype  
Pathology  
FetusOften presentAbsent
Amnion, fetal RBCUsually presentAbsent
Villous edemaVariable, focalDiffuse
Trophoblastic proliferationFocal, slight-moderateDiffuse, slight-severe
Clinical presentation  
DiagnosisMissed abortionMolar gestation
Uterine sizeSmall for dates50% large for dates
Theca lutein cystsRare25-30%
Medical complicationsRare10-25%
Postmolar CTN2.5-7.5%6.8-20%

Epidemiology& Risk Factors
Incidence:USA 1/1000 South East 1/100 (Hospital)
• 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

Epidemiology & Risk Factors
Partial moles have been linked to:
• Higher educational levels
•Smoking
•Irregular menstrual cycles
•Only male infants are among the prior live births

Karyotype

Pathology of Molar Pregnancy

Complete H. Mole
Microscopically Enlarged, edematous villi and abnormal trophoblastic proliferation that diffusely involve the entire villi
No 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 produced
Uterine enlargement in excess of gestational age.
Theca-lutein cyst associated in 30%

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"

 

Pathogenesis of Choriocarcinoma
– Aneuploidy
– (Not a multiplication of 23 chromosome )

 

Partial H. Mole
Microscopically: 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

Partial Hydatidiform Mole
Trophoblastic proliferation are slight and focal

 

 

Fetal hand demonstrating syndactyly. The fetus had a triploid karyotype, and the chorionic tissues were a partial mole

 

 

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 ; 2010
Some 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 cysts
Very rarely Acute respiratory failure
Neurological symptoms such as seizures (?metastatic disease).
RCOG Guideline No. 38 ; 2010

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?

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 ws
hCG levels > 2 multiples of the median may be of value in the diagnosis
RCOG Guideline No. 38 ; 2010

U/S& hCG
Definite diagnosis on first U/S examination
• U/S alone: 68%
• U/S + hCG > threshold of 82,350 mIU/mL: 89%
Disaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007

hCG mIU/mLWeeksComplete mole
Detection Level>53-4
Choriodecidual thickening1004
Gestational sac (D Zone)1000 -15004-5
Yolk sac70005- 6
Heart motion10,0006
Embryonic Movem. >> 10.0006- 7
Maximum level50,000to 100,0008-10

 

Complete Molar Pregnancy

Complete hydatidiform mole. The classic "snowstorm" appearance is created by the multiple placental vesicles.

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 abortions
Disaia &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 1
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?

What Does The Differential Diagnosis Include 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 Be Most 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?

What Is The Ultrasonogaphic Differential Diagnosis For This Case?
U/S DD :
1-Missed abortion
2-Degenerated fibroid

Differential Diagnosis:
Long standing missed abortion with cystic degeneration of the placenta

What Is The Recommended Subsequent Test ?
subunit hCG
The 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 Most Likely Diagnosis?
• The snowstorm pattern on U/S &
• The abnormally high hCG level are diagnostic of
Vesicular Mole
Probably 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 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 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 Best Method Of Evacuating A Molar Pregnancy?
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

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/S
RCOG Guideline No. 38 ; 2010

Return to Case Scenario 1
Suction curettage has been performed using 10mm canula under U/S guidance
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 :

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

Meticulous histopathological examination revealed:
• Villi have extensive stromal edema
• Abnormal 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
hCG 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 hCG ≥ 105. Although hysterectomy does not eliminate possibility of GTN this, it markedly reduces its likelihood.

Second Uterine Evacuation :There is no clinical indication for the routine use of second uterine evacuation
RCOG Guideline No. 38 ; 2010
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. * *
American College of Obstetricians and Gynecologists, 2004*

Is Anti-D Prophylaxis Required For This Case?

No


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

Post-evacuation Surveillance
Why?
• To determine when pregnancy can be allowed
• To detect persistent trophoblastic disease (i.e. GTN)

The Post-evacuation Surveillance. How?
• A baseline serum -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 hCG estimation and U/S examination ± D&C are advised
RCOG Guideline No. 38 ; 2010

 

What Is The Optimum Follow-up Period Following Normalization of 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 Period After 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 ; 2010
At this period levels of hCG are monitored every month
Practically once hCG has normalized after molar evacuation, the possibility of GTN developing is very low.

What Is Safe Contraception Following GTD?
• Barrier methods until normal β hCG level.
• Once hCG 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 hCG levels are normal to reduce uterine perforation.
RCOG Guideline No. 38 ; 2010

Case Scenario 2
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

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.

 

• 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 twin
The mole is mostly complete ,to be confirmed histopathologicaly (After termination). U/S Fetal screening: No detectable anomalies
Follow up is recommended .

How Can We Council The Couple?
1-Counseling for the increased risk of perinatal morbidity :
• Bleeding
•Pre-eclampsia 5-20%
• 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 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 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
• hCG level levels consistent with GTN.
• Evidence of metastases (choriocarcinoma)
• Accidental hemorrhage
Garner UpToDate ,2010

Thank You