1. Gestational Trophoblastic Disease
Chapter 22
Gestational Trophoblastic Disease
Women’s Hospital, School of Medicine Zhejiang University
Xiaodong Cheng

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  
clinically
histologically

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 Partial 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. Partial moles
Complete 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. Comparison of complete and partial hydatidiform moles
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

12. Hydatidiform mole Partial moles 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 HCG DNA karyotype
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
Choriocarcinoma
Invasive mole
Choriocarcinoma
Invasive mole
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)
Gestational Trophoblastic Neoplasia
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
Stage III
Stage I
Stage II
Stage IV

32. Prognostic scoring system for GTT (FIGO,2000)
score 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
＞ 10４～10５
＞ 10５
Largest tumor (cm) －
3～4 cm
≥5cm
Site of metastases
Lung
Spleen, Kidney
Gastrointestinal
Liver, brain
Number of metastases
1～4
5～8 ＞8
Prior chemotherapy failed
single ＞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
MTX 0.4mg/kg im qd d
1、3、5、 MTX1mg/kg im d
2、4、6、 FA 0.1mg/kg im or po
Act-D10-12ug/kg ivgtt qd d
Fu mg/kg ivgtt qd －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 Treatment Surgery is the preferred treatment
HCG was negative
HPL mildly elevated  Confirmed by histology
Treatment
Surgery is the preferred treatment
Chemotherapy is adjuvant therapy

39. Thank you !