Lecture for undergraduate medical student

1. Gestational Trophoblastic
Disease (GTD)
• Dr. Swati Singh
• Department of Obs and Gyn
• UDUTH

2. Molar Pregnancy

3. It is a spectrum of trophoblastic diseases that includes:
Complete molar pregnancy
Partial molar pregnancies
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy.
Definitions
Gestational Trophoblastic Disease (GTD)

4. Chorio
carcinoma
I-Pathologic
Classification
II-Clinical
Classification
βhCG based:
WHO, FIGO,
ACOG 2004 &
RCOG 2010
Benign
G.T.D.
G.T. Neoplasia
Malignant G.T.D.
Partial mole
Complete mole
Invasive
mole
MetastaticNon metastatic
Low risk High risk
Gestational Trophoblastic Disease (GTD)
Placental site
trophoblastic
tumour
Classifications

5. -
Hydatidiform Mole
(H. MOLE)
=
Vesicular Mole

6. Hydatidiform Moles (H.M.)
Hydatidiform moles are abnormal pregnancies
characterized histologically by :
Trophoblastic proliferation (Both
syncitiotrophoblast & cytotrophoblast)
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.

7. 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

8. Epidemiology& Risk Factors
Incidence:USA 1/1000 South East 1/500 (Hospital) and in
Nigeria 1/379.
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

9. 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

10. Homozygous 90%
Pathogenesis of complete H. Mole
Karyotype

11. Pathogenesis of complete H. Mole
Heterozygous 10%
Karyotype

12. Pathogenesis of Partial H. Mole
Karyotype

13. 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%

14. 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"

15. 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

16. Partial Hydatiform Mole
Vesicles
Maternal side

17. Partial H. mole.

18. The classic features are
Irregular vaginal bleeding
Hyperemesis
Excessive uterine enlargement &
Early failed pregnancy.
Breathlessness due to anaemia
Abdominal pain
Presentation
Some women will present early with passage of molar tissue

19. 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).

20. Clinical Findings
 Anemia
 Breathlessness
 Pseudo- Toxemia which consist of Systolic
hypertension edema and proteinuria
 The Uterus is doughy in consistence
 Absence of fetal part
 Enlarged Cystic Ovaries

21. Complete Molar Pregnancy

22. Complete hydatidiform mole. The classic "snowstorm"
appearance is created by the multiple placental vesicles.

23. 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

24. 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

25. 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

26. Differential diagnosis
• Multiple pregnancy.
• Hydatidiform mole.
• Threatened abortion.
• Ectopic pregnancy.

27. Partial Molar Pregnancies

28. 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.
Management

29. For Partial mole: It depends on the fetal parts
Small fetal parts :Suction curettage
Large 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%.
Is That The Same For Partial Mole?

30. Post-evacuation Surveillance
Why?
To determine when pregnancy
can be allowed
To detect persistent
trophoblastic disease (i.e. GTN)

31. The Post-evacuation Surveillance. How?
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

32. What Is The Optimum Follow-up
Period Following Normalization of β
hCG?
A. For 6 months from the date of uterine
evacuation.
B. For 6 months from normalization of the β
hCG level. B
C. For 12 months from the date of uterine
evacuation. (For Nigeria)

33. 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?

34. Part II: Gestational Trophoblastic
Neoplasia (GTN)

35. Nonmetastatic disease
 Locally invasive GTT develops in about 15%
 Patient usually present with
 Irregular vaginal bleeding
 Theca lutein cysts
 Uterine subinvolution or asymptomatic
enlargement
 Persistently elevated serum hCG level
 Persistent GTT
After hydatiaiform mole

36. Invasive Mole
Villus formation preserved
Trophoblast cells invade myometrium and blood vessels
Myometrium invaded
Myometrium
Villus

37. Invasive H. Mole
Myometrial invasion
Sometimes involving the peritoneum, parametrium, or
vaginal vault. Originate almost always from H. mole
Vesicles

38. Placental-site trophoblastic tumor
 Uncommon but important variant of
choriocarcinoma
 Characteristic
 Produce small amount of hCG and hPL
 Remain confined to the uterus
 Metastasizing late in their course
 Relatively insensitive to chemotherapy

39. Gestational Choriocarcinoma
Aneuploidy (not multiplication of 23 )
1 in 30,000 pregnancies in western world
1 in 300 to 1000 in Nigeria
40% after molar pregnancy: Easily Diagnosed
60% non-molar pregnancy: Difficult Diagnosis
The main presentations are often non-gynecologic
including hemoptysis or pulmonary embolism,
cerebral hemorrhage, gastrointestinal or urologic

40. Gestational Choriocarcinoma
Sheets of anaplastic cytotrophoblast and
syncytiotrophoblast cells with hemorrhage &
necrosis.
Myometrial & B. vessels invasion and early metastases
No Villus formation
Cytotrophoblast
Syncytiotrophoblast

41. Metastatic disease
 Metastatic GTT occur in about 4% after
complete mole
 Symptom of metastases may result from
spontaneous bleeding at metastatic foci
 The common site of metastases are
 Lung(80%)
 vagina(30%)
 pelvis(20%)
 liver(10%)
 brain(10%)

42. GTN Vaginal
Metastasis

43. Cranial MRI scan:
Large metastasis on the
left (black arrows)
Brain MRI of a patient
with a solitary brain
metastasis in remission

44. Autopsy specimen
Multiple
hemorrhagic
hepatic metastasis
CT Scan: Liver
metastsis

45. Disease confined to the uterusStage I
GTN extends outside of the uterus
but is limited to the genital
structures (adnexa, vagina, broad
ligament)
Stage II
GTN extends to the lungs, with or
without known genital tract
involvement
Stage III
All other metastatic sites (brain,
liver)
Stage
IV
FIGO Anatomic Staging Of GTN

46. Staging : FIGO
 Risk factor affecting staging
 hCG level > 100,000 mIU/ml
 Duration of disease longer than 6 months
from termination of pregnancy
 Stage 1-4
 Without risk factors a
 1 risk factor b
 With 2 risk factors c

47. 4210FIGO SCORING
>40<40Age (years)
--TermAbortionMoleAntecedent pregnancy
≥137to <134to <7<4Pregnancy to treatment
Interval (months)
> 100,00010,000-100,0001000-10,000<1000Pretreatment serum
hCG (iu/l)
--≥53 to<5< 3Largest tumour size,
including uterus (cm)
Liver &
brain
Gastro-
intestinal
Spleen &
Kidney
LungSite of metastases
>85-81-4--Number of metastases
≥2 DrugsSingle drug----Previous failed
chemotherapy
FIGO Prognostic Scoring For GTN (2000(
Total Score Survival : ≤ 6 = Low risk (100%) ≥7 = High risk. (95%)

48. Non metastatic GTD Metastatic
Single agent
Chemotherapy
Methotrexate or
Actinomycen D
Multi-agent
Chemotherapy
Low Risk ( ≤ 6) High Risk (≥7)
What Is The Optimum Treatment For GTN?
GTN

49. What is the best methotrexate regimen?
MTX:1mg/kg IM D:1, 3 ,5 ,7 alternating with
Folinic acid 0.1mg/kg IM D 2 , 4 , 6 , 8
followed by 6 rest days
Treatment is continued, until the hCG level
has returned to normal and then for a further
6 consecutive weeks.
As any chemotherapy treatment is reevaluated if FBC,
liver or kidney FT are affected or at drug resistance

50. Chemotherapy
 Combination chemotherapy
 Triple therapy : MTX, Act-D, cyclophosphamide
 EMA-CO : etoposide, MTX, Act-D,
cyclophosphamide, vincristine
 EMA-EP : etoposide and cisplatin on day 8
 Duration of therapy Until 3 normal hCG level
 After that, at least 2 additional course are
administered

51. Follow Up
 Stage 1-3 receive follow-up with
 Weekly hCG level until normal for 3 wks
 Monthly hCG level until normal for 12 months
 Effective contraception during the entire interval of
hormonal follow-up
 Stage 4 receive follow-up with
 Weekly hCG level until normal for 3 wks
 Monthly hCG level until normal for 24 months

52. Stage Survival Percent %
I 424/424 100
II 27/27 100
III 130/131 99
IV 14/18 78
What Is The Survival of GTN By
FIGO Stage?
Disaia &Creasman Clinical Gynecological Oncology 2007