Gestational trophoblastic disease (GTD) is a group of pregnancy-related conditions that develop inside a woman's uterus (womb). The abnormal cells start in the tissue that would normally become the placenta. The placenta is the organ that develops during pregnancy to feed the fetus.

1. Gestational
Trophoblastic Disease
MUKESH SAH, MD
PGI
GOODSAM MEDICAL CENTER

2. Gestational trophoblastic disease
 A group of diseases
originated from placental trophoblastic cells
 Gestational trophoblasitc disease (GTD)
 Hydatidiform mole (complete and partial)
 Invasive mole
 Choriocarcinoma
 Placental-site trophoblastic tumor (PSTT)
 Gestational trophoblastic neoplasia (GTN)
 Non-gestational trophoblastic tumor
 Uncommon, derived from germ cells in ovarian or testicular
histologically
clinically

3. Development and differentiation of
gestational trophoblastic cells
 gestational trophoblastic cells evolved from extra-
embryonic cells
 At the time of implantation
cytotrophoblast outermost layer of the blastocyst
 7-8 days after implantation
syncytiotrophoblast implantation site
 Before villi formation previllous trophoblast
 2 weeks after pregnancy, primary villi formation
Villous surface villous trophoblast
Other parts extravillous trophoblast

5. Development and Differentiation of
gestational trophoblastic cells
 Cytotrophoblast
trophoblast stem cells
proliferability and differentiability
 Syncytiotrophoblast
differentiated mature cells
synthesize pregnancy-related hormones
material exchange between the fetus and the
mother
 Two differentiated forms of Cytotrophoblast
villous surface area Syncytiotrophoblast
extravillous Intermediate trophoblast

6. Hydatidiform mole

7. Hydatidiform mole
 Complete moles
Hydropic degeneration of all villi
Villous edema, trophoblastic hyperplasia, fetal-
derived
blood vessels disappear in stroma
 Partial moles
combine embryo or fetus
Villous edema partially, trophoblastic proliferation
lighterly, fetal-derived blood vessels present stroma

8. Complete moles Partial moles

9. Hydatidiform mole
Related Factors
 Complete moles
 Area common in Latin America, Asia
uncommon in North America and Europe
 Race differences of the same race in different regions
 Nutrition and Economy lack of Vit A
 Age < 20 or >35 years
 The fertilization of an empty egg
the fertilization of an empty egg by a haploid sperm
Diploid genome 90% of the time (usually 46,XX)
 Genomic imprinting disorder

10. Hydatidiform mole
 Partial moles
 high-risk factors are still unknown
 "Haploid egg" fertilization
usually two sperm fertilize a normal egg
a triploid karyotype (69 chromosomes ), with the
extra haploid set of chromosomes derived from
father

11. Complete Partial
Karyotype
46, XX(90%)
46, XY(10%)
Triploid
(69XXY, 69XXX)
Embryo Absent Present
Villi Hydropic Few hydropic
Trophoblasts Diffuse hyperplasia
Mild focal
hyperplasia
Villus outline regular irregular
Blood vessel absence presence
Comparison of complete and partial
hydatidiform moles

12. Hydatidiform mole
Clinical Presentation
 Complete moles
 Abnormal vaginal bleeding during early pregnancy( 8-
12week)
most common symptom
 Uterine enlargement exceeding normal pregnant uterus
 Others
Abdominal pain
Pregnancy-induced hypertension
Theca lutein ovarian cyst
Hyperthyroidism (CHM)
 Partial moles
 Mild symptoms, Confused with abortion easily

13. Hydatidiform mole
hCG regression pattern after hydatidiform
Mean time of the hCG regressed to normal
— 9 weeks no more than 14 weeks
Abnormal hCG regression pattern after hydatidiform
signifies the presence of GTN
 Complete mole
 15% local invasion and 4% distant metastasis
 High –risk :
①HCG>100,000U/L
② Enlargement of Uterine
③ Theca lutein ovarian cyst >6cm
 Partial mole
 4%local invasion and almost no distant metastasis
 High –risk :unclear

14. Hydatidiform mole
 Diagnosis
 Abnormal bleeding after amenorrhea
 Inappropriately enlarged uterus
 Absence of fetal heart sounds
not palpate fetus between 16-20th week
 Vaginal discharge hydatidiform-like tissue
Hydatidiform mole should be considered

15. Hydatidiform mole
 Diagnosis
 Ultrasound
Complete moles produce a characteristic vesicular
sonographic pattern, usually referred to as a “snowstorm”
pattern
 HCG
 Elevated above expected for gestational age
 Dynamic observation for 8-10 weeks, continued to rise
 HCG-related molecules
Hyperglycosylated HCG
free β-HCG subunit
 DNA karyotype
Complete moles — usually diploid
Partial moles — usually triploid

16. a “snowstorm” pattern

17. Hydatidiform mole
 Treatment
Suction curettage
 Molar pregnancy should be terminated as soon as
possible when diagnosis has been confirmed
 Suction curettage is a first choice, must be fully
done in operating room
 tissue from curettage should
be submitted to pathology

18. Hydatidiform mole
Treatment
 Theca lutein cysts of the ovary
do not need special treatment
 Prophylactic chemotherapy:
A controversial topic
only be offered to patients with high-risk factor or
impossible follow-up
 Hysterectomy
Only remove local invasion, but not distant metastasis
Only for old women without childbearing desire

19. Hydatidiform mole
Follow-up
 necessary for diagnosis of early GTN
 Methods:
 HCG
 Symptom: Abnormal uterine bleeding
 Pelvic examination
 Ultrasound, chest X-ray and CT
 Contraception:
 Condom and oral contraceptives, not IUD
 Duration for contraceptiom — 1 year

20. Gestational
Trophoblastic
Neoplasia

21. General Consideration
 Antecedent gestation
60% hydatidiform mole
30% follow abortion
10% term pregnancy or ectopic pregnancy
 from mole
— invasive mole
or choriocarcinoma
from Non-mole
— choriocarcinoma

22. Gestational Trophoblastic
Neoplasia
Pathogenesis
 Invasive mole
 Invasive mole is a hydatidiform mole that invades the
myometrium and may produce distant metastases.
 Microscopic finding are the same as in hydatidiform
mole
 Choriocarcinoma
 Gloss：invades the myometrium , penetrate the
serosa
and may produce distant metastases
 Microscopy：no villi, but instead sheets or foci of
trophoblasts on a background of hemorrhage and
necrosis

23. Invasive mole
Invasive mole
Invasive mole
Choriocarcinoma
Choriocarcinoma
Choriocarcinoma

24. invades the
myometrium
Lung
metastases
Brain
metastases
cervical metastases

25. Gestational Trophoblastic
Neoplasia
Clinical Manifestation
Nonmetastatic GTN
 the antecedent gestational event is usually HM
 Abnormal vaginal bleeding after mole
 Others:
 Enlarged uterus
 Theca lutein cysts of the ovary
 Abdominal pain
 Fake pregnancy symptoms

26. Gestational Trophoblastic
Neoplasia
Metastatic GTN
Usually chroriocarcinoma
 Primary symptoms
 Metastatic symptoms
 Lung metastases are frequently common
 vaginal metastases are the second common
 liver and brain metastases usually death cause
 other metastastic sites
spleen, kidney, bladder, gastrointestinal system,
and bone
Simultateously occur or not

27. Gestational Trophoblastic
Neoplasia
Diagnosis
 Symptoms and signs:
◆ Abnormal vaginal bleeding
after post-evacuation, abortion, term pregnancy
or ectopic pregnancy,
◆ Metastatic symptoms
GTT should be considered

28. Gestational Trophoblastic
Neoplasia
 HCG assay
Most important and sometimes only diagnostic evidence
Diagnostic criteria for post- HM GTN (FIGO2000)
hCG plateau for >4 values （±10％）， over 3 weeks
hCG increase of ≥10% over 2 weeks
hCG persistence after evacuation of mole for 6 months
Diagnostic criteria for non post-HM GTN
HCG elevated at 4w after abortion, term or ectopic pregnancy
Re-rising HCG titer after reaching normal levels

29. Gestational Trophoblastic
Neoplasia
 Chest X-ray
lung metastases
 CT
small lung metastases and brain metastases
 MRI
Liver and brain metastases
 Ultrasound
primary lesions of uterus and pevical metastases
Imaging supports diagnosis, but not necessary

30. Gestational Trophoblastic Neoplasia
 Histological diagnosis
 villus shape can be found in primary or metastatical
lesions
 Presence of villus shape Invasive mole
Absence of villus shape Choriocarcinoma
Histology is not necessary
for diagnosis of GTN

31. Anatomy staging of GTN (FIGO, 2000)
StageI Localized to the uterus
StageII Lesion diffused, but Localized to the genitalia
(accessory,vagina,broad ligament)
StageIII Lung metastasis, with or without genitalia change
StageⅣ Other metastasis
Gestational Trophoblastic Neoplasia
Stage I
Stage II
Stage III
Stage IV

32. WHO Prognostic Score Index
SCORE 0 1 2 4
Age(y) ＜40 ≥40 - -
Antecedent mole abortion term -
Interval (mo) ＜4 4～6 7～12 ≥13
Pretreatment b-hCG
(mIU/ml)
＜10３ 10３～10４ ＞ 10４～10
５
＞ 10５
Largest tumor (cm) － 3～4 cm ≥5cm -
Site of metastases Lung Spleen, Kidney Gastrointest
inal
Liver, brain
Number of metastases － 1～4 5～8 ＞8
Prior chemotherapy failed － － single
druug
＞2
* Total score≤6 low risk, ≥7 high risk

33. Gestational Trophoblastic Neoplasia
Treatment
 Chemotherapy combining surgery, radiotherapy
and other treatment
 Base on the assessment and stage, therapy stratified
Chemotherapy :
 Single-agent chemotherapy is applied in low-risk
gestational trophoblastic disease (MTX, Act-D, 5-Fu)
 High-risk patients commonly use combined
chemotherapy (EMA-CO)

34. Single agent chemotherapy
DAY Therapy Interval
1-5 MTX 0.4mg/kg im qd 14d
1、3、5、7 MTX1mg/kg im 14d
2、4、6、8 FA 0.1mg/kg im or po
1-5 Act-D10-12ug/kg ivgtt qd 14d
1-8 5-Fu 28-30mg/kg ivgtt qd 12－14d

35. Combined chemotherapy
Drugs Dose ,pathway,periods Interval
5-Fu+KSM 3weeks
5-Fu 26-28mg/kg·d，ivgtt for 8days
KSM 6g/kg·d， ivgtt for 8days

36. Combined chemotherapy
EMA-CO Interval 2weeks
the first part EMA
1st day VP16 100mg/m2 ivgtt
Act-D 0.5mg ivgtt
MTX 100 mg/m2 ivgtt
MTX 200mg/m2 ivgtt for 12hours
2nd day VP16 100mg/m2，ivgtt
Act-D 0.5mg ivgtt
CF15mg，im
（after 24hours from the use of MTX， once every 12hours，twice）
3rd CF15mg，im，once every 12hours，twice。
4th to 7th rest（no drug）
the second part CO
8th day VCR1.0mg/m2， ivgtt
CTX600mg/m2， ivgtt

37. PSTT
 A special type, more rarely in clinic
 Most of them have a good prognosis
 Form the intermediate trophoblast cells
 Clinical manifestations
 More common occur at reproductive period
women
 More common occur following term or ectopic
pregnancy
 Abnormal bleeding after amenorrhea

38. PSTT
 Diagnosis
HCG was negative
HPL mildly elevated
Confirmed by histology
 Treatment
Surgery is the preferred treatment
Chemotherapy is adjuvant therapy

39. THANK YOU !