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

2. Molar Pregnancy

3. Gestational Trophoblastic Disease (GTD)
Definitions
Gestational Trophoblastic Disease (GTD)
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.

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

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

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. Features Of Partial And Complete Hydatidiform Moles
Partial mole
Complete mole
Karyotype
Most commonly
69, XXX or - XXY
46, XX or -,XY
Pathology
Fetus
Often present
Absent
Amnion, fetal RBC
Usually present
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
10-25%
Postmolar CTN %
6.8-20%

8. Epidemiology& Risk Factors
Incidence:USA 1/ 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 8

9. Epidemiology & Risk Factors
Partial moles have been linked to:
Higher educational levels
Smoking
Irregular menstrual cycles
Only male infants are among the prior live births

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

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

12. Pathogenesis of Partial H. Mole
Karyotype
Pathogenesis of Partial H. Mole

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. Vesicles
Maternal side
Partial Hydatiform Mole 16

17. Partial H. mole.

18. Presentation The classic features are Irregular vaginal bleeding
Hyperemesis
Excessive uterine enlargement &
Early failed pregnancy.
Breathlessness due to anaemia
Abdominal pain
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 Pregnancy21 21

22. Complete hydatidiform mole
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.
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. Management
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.

29. Is That The Same For Partial Mole?
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 %.

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?
For 6 months from the date of uterine evacuation.
For 6 months from normalization of the β hCG level. B
For 12 months from the date of uterine evacuation. (For Nigeria)

33. What Is Safe Contraception Following GTD?
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.

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

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

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 hemorrhage. 39

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

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

45. FIGO Anatomic Staging Of GTN
Disease confined to the uterus
Stage 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

46. Staging : FIGO Risk factor affecting staging Stage 1-4 1 risk factor b
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. FIGO Prognostic Scoring For GTN (2000(4 2 1
FIGO SCORING
>40
<40
Age (years) --
Term
Abortion
Mole
Antecedent pregnancy
≥13
7to <13
4to <7
<4
Pregnancy to treatment
Interval (months)
> 100,000
10, ,000
,000
<1000
Pretreatment serum hCG (iu/l) ≥5
3 to<5
< 3
Largest tumour size, including uterus (cm)
Liver & brain
Gastro-intestinal
Spleen & Kidney
Lung
Site of metastases
>8
5-8
1-4
Number of metastases
≥2 Drugs
Single drug
Previous failed chemotherapy
Total Score Survival : ≤ 6 = Low risk (100%) ≥7 = High risk. (95%)

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

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
Monthly hCG level until normal for 24 months

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

53. Thank you