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

Classifications
Gestational Trophoblastic Disease (GTD)
Invasive I-Pathologic Partial mole Chorio mole Complete mole Classification carcinoma
Placental site trophoblastic tumour

II-Clinical Classification
hCG based: WHO, FIGO, ACOG 2004 & RCOG 2010

Benign G.T.D.

G.T. Neoplasia Malignant G.T.D.

Non metastatic

Metastatic

Low risk

High risk

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.

Features Of Partial And Complete Hydatidiform Moles

Feature Karyotype Pathology
Fetus Amnion, fetal RBC Villous edema Often present Usually present Variable, focal Absent Absent Diffuse Diffuse, slight-severe

Partial mole
Most commonly 69, XXX or - XXY

Complete mole
Most commonly 46, XX or -,XY

Trophoblastic proliferation Focal, slight-moderate

Clinical presentation
Diagnosis Uterine size Theca lutein cysts Medical complications Missed abortion Small for dates Rare Rare Molar gestation 50% large for dates 25-30% 10-25%

Postmolar CTN 2.5-7.5% 6.8-20% Disaia &Creasman Clinical Gynecological Oncology 2007
rd

Epidemiology& Risk Factors

Incidence: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

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

Homozygous 90%

Pathogenesis of complete H. Mole

Heterozygous 10%

Pathogenesis of complete H. Mole

Pathogenesis of Partial H. Mole

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%

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. 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

Scalloping of chorionic villi

Trophoblastic proliferation are slight and focal

Vesicles

Maternal side
Partial Hydatiform Mole

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

Partial H. 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?

A. Hyperemesis B. Bilateral enlarged theca lutein cysts C. Vaginal bleeding 10% 30% 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 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

TVS Milestones Versus hCG hCG mIU/mL Weeks Detection Level >5 3-4
Choriodecidual thickening

100 7000

Gestational sac (D Zone) 1000 -1500

4-5
5- 6

Yolk sac

Heart motion
Maximum level

10,000
50,000to 100,000

6
6- 7

Embryonic Movem. > 10.000

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

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

Partial Molar Pregnancies

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?

Gestational (Chorionic) Sac

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 Likely Diagnosis?

The abnormally high hCG level are diagnostic of

Most

The snowstorm pattern on U/S&

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 ?

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 0.10.5%.
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

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 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 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.
Soper. Obstet Gynecol 108:176, 2006 Garner UpToDate 2010

Cunningham et al,Williams Obstetrics,23 ed ,2010

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

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 ; 2010

Prophylactic Chemotherapy: The long-term prognosis for women with a H. mole is not improved with prophylactic chemotherapy. Because toxicityincluding deathmay be significant, it is not recommended routinely *
It may be useful in the high-risk cases when followup 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
RCOG Guideline No. 38 ; 2010

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

Cunningham et al,Williams Obstetrics,23 ed ,2010

At the 9 week follow up the hCG level : 2u/L Is 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 Period Following Normalization of hCG?

A. For 6 months from the date of uterine evacuation. B. For 6 months from normalization of the hCG

level.
C. For 12 months from the date of uterine

evacuation.

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 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

US scanning revealed

What 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 hCG

Free T4
Protein in urine

Rescanning after one week in a

tertiary or fetal medicine center for

diagnosis & screening.

 hCG :80,000 m/ml Free T4 : 2g/ml (N 0.3-1.7g/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 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 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

Egypt