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 pregnancy

Partial molar pregnancies

Invasive mole

Choriocarcinoma

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 GTD

Invasive mole

Choriocarcinoma

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

Karyotype

Most commonly69, XXX or - XXY

Most commonly46, XX or -,XY

Pathology

Fetus Often present Absent

Amnion, fetal RBC Usually present Absent

Villous edema Variable, focal Diffuse

Trophoblastic proliferation Focal, slight-moderate Diffuse, slight-severe

Clinical presentation

Diagnosis Missed abortion Molar gestation

Uterine size Small for dates 50% large for dates

Theca 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 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

How Do Molar Pregnancies Present To The Clinician?

Some women will present early with passage of molar tissue

Rarer presentations include:Hyperthyroidism

Early 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

examination

U/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 3-4

Choriodecidual 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 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

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

abortion

2-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 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.

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 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

Should Products Of Conception Be Examined Histologically?

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 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 low

IUCD 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 mole

Other placental abnormalities

Rtroplacental hematoma

Degenerating 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/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 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 dioploidy

β hCG level levels consistent with GTN.

Evidence of metastases (choriocarcinoma)

Accidental hemorrhage

Garner UpToDate ,2010

When Must Pregnancy Be Terminated ?

Thank You

Thank You

Egypt