Gestational trophoblastic disease (GTD) is a spectrum of conditions that includes complete and partial hydatidiform moles, invasive moles, choriocarcinoma, and placental site trophoblastic tumors. Complete molar pregnancies are most commonly diagnosed based on vaginal bleeding and uterine enlargement greater than expected for gestational age. Ultrasound typically shows a "snowstorm" appearance of multiple small cysts, while beta-hCG levels are often highly elevated. Surgical evacuation using suction curettage is the recommended treatment, with histological examination of the products of conception to confirm the diagnosis. Follow up of beta-hCG levels is needed to monitor for persistent trophoblastic
3. It is a spectrum of trophoblastic diseases
that includes:
Complete molar pregnancy
Partial molar pregnancies
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
Definitions
Gestational Trophoblastic Disease (GTD)
RCOG Guideline No. 38 .2010
The last 2 may follow abortion, ectopic or normal pregnancy.
4. It is a spectrum of trophoblastic diseases
that develops malignant sequelae. GTN
includes:
Persistent post molar GTD
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
Definitions
Gestational 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.
6. 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
8. 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.
9. Feature Partial mole Complete mole
Karyotype
Most commonly
69, XXX or - XXY
Most commonly
46, 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
rd
10. 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
11. 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
17. 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%
19. 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"
22. 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
23. Scalloping of chorionic villi
Partial Hydatidiform Mole
Trophoblastic proliferation are slight and focal
27. 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
How Do Molar Pregnancies Present
To The Clinician?
Some women will present early with passage of molar tissue
28. 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
How Do Molar Pregnancies
Present To The Clinician?
29. 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
30. 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%
31. 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?
32. 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
38. 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
39. 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?
41. 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
42. 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?
43. The most useful diagnostic
test is :
U/S
Which Diagnostic Test Would Be
Most Useful?
44. Complex intrauterine mass containing many small cysts
(Snowstorm appearance)
What is the most likely diagnosis?
Hydatidiform (Vesicular) mole
49. 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
50.
51. 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
54. 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 ?
60. 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.
65. 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
66. 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.
67. 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 2010Soper. Obstet Gynecol 108:176, 2006
Cunningham et al,Williams Obstetrics,23 ed ,2010
68. 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
70. 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*
71. 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
73. 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?
75. 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-
76. 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
77. 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.
78. 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
79. 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
80. What Is The U/S Differential Diagnosis?
US scanning revealed
81. Complete mole with a coexisting
normal twin
Partial mole
Other placental abnormalities
Rtroplacental hematoma
Degenerating myoma
What Is The U/S Differential Diagnosis?
82. 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?
83. 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
twin
The mole is mostly complete ,to be
confirmed histopathologicaly (After
termination).
U/S Fetal screening: No detectable
anomalies
Follow up is recommended .
84.
85. 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
86. 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 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
87. 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 ?