2. GTD Overview
Heterogeneous group of related lesions
Arise from abnormal proliferation of trophoblast of
the placenta
Can follow any gestational event – abortion,
miscarriage, ectopic, normal pregnancy
Unique because the maternal lesions arise from
fetal (not maternal) tissue
Most GTD lesions produce (B-hCG)
Can be cured even in the presence of widespread
metastases
6. Hydatidiform Mole
North America: 0.6-1.1 per 1000 pregnancies
Asia: 2-10 per 1000 (3x Western countries)
Difference possibly related low dietary intake of
carotene (vitamin A deficiency) and animal fat
More common at reproductive extremes in age
(>35y or <20y)
7. Hydatidiform Mole
Risk Factors:
History of previous GTD
If one previous mole, 1% chance of recurrence (vs. 0.1% in
general population)
If 2 previous moles, risk of recurrence increases to 16-28%
Smoking
Vitamin A deficiency
Blood type:
A or AB are at slightly higher risk than those with type B or O
11. Diagnosis
Complete :
U/S usually very sensitive – generalized swelling (snow-storm )
partial mole
U/S may detect focal cystic spaces of varying diameter
Diagnosis on histology of curettings
12. Complete vs. partial mole
Partial
Complete
Feature
Triploid
(69,xxx or 69,
xxy)
Diploid(usually
46,xx or rarely
46,xy)
Karyotype
focal
diffuse
Swelling of chorionic villi
focal
diffuse
Trophoblastic hyperplasia
Present
absent
Embryonic tissue
usually<
100,000
Often > 100,000
hCG
<5%
15 - 20%
Trophoblastic sequelae
Rare
Up to 25%
Theca lutein cysts
Rare
Up to 25%
Medical complications
Small for dates
50% large for dates
Uterine size
13. Hydatidiform Mole Treatment
Evaluate for coexisting conditions:
- History and physical
- CBC, coagulation profile, serum chemistry
- thyroid function
- blood type and cross match
- chest radiography
- pelvic ultrasonography
Evacuation of mole
- Suction curettage
- Hysterectomy if completed childbearing
If Rh negative, give rhogham
15. Follow-Up Care – Molar
Pregnancy
80% of patients cured by evacuation
Follow B-hCG levels every two weeks until 3 consecutive tests
negative
Then monthly B-hCG every month for 6-12 months
More than half of patients will have complete regression of
hCG to normal within 2 months of evacuation.
Avoid pregnancy for at least 6 months after first normal B-hCG
(oral contraceptive pills is preferable)
Subsequent Pregnancies:
Send placenta for pathology
Check B- hCG 6 weeks postpartum
16. Prognosis
Complete mole has the latent risk of local invasion or
telemetastasis
The high-risk factors includes
β-HCG>100000IU/L
uterine size is > 20 weeks size.
the luteinizing cyst is >6cm
If >40 years old,the risk of invasion and metastasis may be
37%, If >50 years old,the risk of invasion and metastasis may
be 56%.
repeated mole: the morbidity of invasion and metastasis
increase 3~4 times
18. Risk Factors for GTN After Mole
Preevacuation uterine size greater than
gestationl age or larger than 20 weeks
gestation
Theca-lutein cysts larger than 6 cm
Age > 40 years
Serum hCG levels > 100,000 mIU/mL
Previous hydatidiform mole
19. Invasive Mole
Myometrial invasion by hydatidiform mole
Formerly known as chorioadenoma destruens
1 in 15,000 pregnancies
10-17% of hydatidiform moles will progress to invasive moles
20. Persistent Mole
Definition of persistent molar disease and
need for chemotherapy (at least one of the
following):
B-hCG plateau for ≥ 4 values for ≥ 3 weeks
B-hCG increase of ≥ 10% for ≥ 3 values for
≥ 2 weeks
B-hCG persistence 6 months after molar
evacuation
Histopathologic diagnosis of
choriocarcinoma
Presence of metastatic disease
21. Choriocarcinoma
Most aggressive type of GTN
Abnormal trophoblastic hyperplasia
Absence of chorionic villi
Direct invasion of myometrium
Most often develops from a complete hydatidiform mole
Vascular spread to distant sites:
Lungs
Brain
Liver
Pelvis and vagina
Spleen, intestines, and kidney
22. Choriocarcinoma
May come from any type of pregnancy
- 25% follow abortion or tubal pregnancy
- 25% with term gestation
- 50% from hydatidiform moles
2-3% of moles progress to choriocarcinoma
Incidence 1 in 40,000 pregnancies
Rarely, choriocarcinomas can develop in other parts of
the body in both men and women. These are not related
to pregnancy as ovaries and testicles
Nongestational choriocarcinoma tends to be less
responsive to chemotherapy and has a less favorable
prognosis than the gestational variant
23. Placental-Site Trophoblastic
Tumor (PSTT)
Originate from intermediate cytotrophoblast cells
Secrete human placental lactogen (hPL)
Less vascular invasion, necrosis and hemorrhage
than choriocarcinoma
Lymphatic spread
Arise months to years after term pregnancy but can
occur after spontaneous abortion or molar
pregnancy
24. Placental-Site Trophoblastic
Tumor (PSTT)
Most common symptom is vaginal bleeding
Tend to:
- Remain in uterus
- Disseminate late
- Produce low levels of B-HCG compared to other
GTN
- Be resistant to chemotherapy (treat with surgery)
26. Diagnosis of GTN
Increase or plateau in B-hCG after molar pregnancy
Pathologic diagnosis by D&C or biopsy of metastatic
lesions
WARNING: biopsy of metastatic lesions can result in
massive hemorrhage
Metastatic workup: CXR (or CT chest), CT
abdomen/pelvis +/- CT/MR of brain
27. Classification & Staging of GTD
FIGO Staging
Describes anatomic distribution of disease
World Health Organization (WHO) Scoring Index
Describes prognosis
28. FIGO Staging
Stage Description
I Disease confined to the uterus
II Disease extends outside the uterus but
limited to genital structures (adnexa,
vagina, and broad ligament)
III Disease extends to the lungs with or
without genital tract involvement
IV Disease involves any other metastatic sites
30. WHO Prognostic Score Index
Score
Characteristic 0 1 2 4
Age <40 ≥40 - -
Antecedent preg Mole Abortion Term -
Pregnancy to
treatment
Interval (months)
<4
months
4-6
months
7-12 months >12 months
Pretreatment hCG <103 103- 104 104-105 >105
Largest tumor size
(including uterus)
< 3cm 3-4 cm ≥5cm -
Site of metastases Lung Spleen,
kidney
GI tract Liver, brain
Number of metastases - 1-4 5-8 >8
Previous failed
chemotherapy
- - Single drug ≥2 drugs
31. Therapy for GTN
Single agent therapy for nonmetastatic (stage I) or low-risk metastatic (stage II
and III) with score <7 survival rates ~ 100%
Combination chemotherapy +/- radiation and/or surgery for high-risk metastatic
disease with score ≥7
32. Therapy: Nonmetastatic GTN
Single-agent with either methotrexate or
dactinomycin
Chemotherapy continued until hCG values
normal and then 2-3 cycles beyond
Change to alternative single-agent for hCG
plateaus above normal or toxicities
If significant elevation of hCG or new
metastases, switch to multiagent
85-90% cured with initial regimen, <5%
will require hysterectomy for cure
33. Therapy: Low-risk Metastatic
GTN
Low-risk metastatic disease can be treated with single-agent
therapy with 5-day regimens
Cure rates ~100% but 30-50% will be develop resistance to
first agent
If resistance to sequential single-agent chemotherapy (5-10%
of patients), switch to multiagent chemotherapy
34. Therapy: High-risk Metastatic GTN
Stage IV
Stage II/III with score > 7
Disease refractory to single-agent chemotherapy
Combination Chemotherapy:
EMACO:
Day 1: Etoposide, Methotrexate and Dactinomycin
Day 8: Cyclophosphamide and Vincristine
(Oncovorin)
Repeat q2 weeks until remission
Continue for at least 2-3 cycles beyond first normal
hCG
MAC (Methotrexate, Dactinomycin, Cyclophosphamide)
EMA/EP – EMA + Etoposide and Cisplatin
35. Metastatic Gestational Trophoblastic Tumors
Surgery
It is indicated for tumor resistant to chemotherapy and single
metastases persisting despite chemotherapy.
RT
RT, in combination with chemotherapy, is clearly indicated for the
primary management of patients with brain metastases.
36. PSTT Therapy
Hysterectomy
Chemotherapy for metastatic disease or
nonmetastatic disease with poor prognosis:
- Interval from index pregnancy > 2 years
- Deep myometrial invasion
- Tumor necrosis
- Mitotic count > 6 per 10 high-power fields
Survival rates:
~100% for nonmetastatic disease
50-60% for metastatic disease
37. Follow-up Care
After completion of chemotherapy, follow serial hCG every 2
weeks for three months, then monthly for one year
Physical examinations every 6-12 months and imaging as
indicated
38. Reproductive Performance
Most women resume normal ovarian function
Women who undergo chemotherapy are advised not to
conceive for one year after completion of treatment
No increase risk of stillbirths, abortions, congenital
anomalies, prematurity, or major obstetric complications
39. False Positive Serum hCG
Phantom hCG syndrome/ phantom
choriocarcinoma
3-4% of healthy individuals have human-
antimouse antibodies that can mimic hCG
immunoreactivity
To verify:
Urine hCG should be negative
Should not show parallel decrease with serial
dilutions
Test at national B-hCG reference lab
40. Summary
Hydatidiform mole is a benign condition, 80% cured with
suction D&C
Malignant GTN:
Persistent or invasive mole
Choriocarcinoma
PSTT
WHO score > 7 represents high-risk disease
GTN very sensitive to chemotherapy
