1. Gestational Trophoblastic Disease
ASSOCIATE PROFESSOR
IOLANDA BLIDARU
MD, PhD

2. Gestational Trophoblastic Disease
Complete / Partial vesicular mole
Invasive mole (chorioadenoma destruens )
Placental-site trophoblastic tumor
Choriocarcinoma

3. HYDATIDIFORM MOLE

4. A benign tumor of the chorionic villi, characterized by:
Definition
A benign tumor of the chorionic villi, characterized by:
Marked proliferation of the trophoplast, (both the syncytium & cytotrophoplast).
Oedema or hydropic degeneration of the connective tissue stroma of the villi → distension → formation of vesicles.
Avascularity of the villi: the blood vessels disappear from villi (early death of the embryo)

5. Incidence 1:2000 pregnancies in US and Europe
10 times more in South-East Asia, West Africa and Mexico = 1/120-1/240 pregnancies
choriocarcinoma ► 1/15,000 pregnancies → 1/500 to 1/1000 pregnancies

6. RISK FACTORS race deficiency of protein or carotene
higher incidence toward the beginning and (more) the end of the childbearing period.
age: 10 times more in women over 45 years old
consanguinity
blood type: the malignant form ► more frequent in group A
viral infections
the ovarian theca-lutein cysts

7. 1. placental vascular deficiency 2. genetic hypothesis
PATHOGENESIS
1. placental vascular deficiency
2. genetic hypothesis
3. immunological theory .

8. Pathology
The uterus is distended by thin walled, translucent, grape-like vesicles of different sizes.
These are degenerated chorionic villi filled with fluid.
No vasculature in the chorionic villi → early death + absorption of the embryo.

10. Pathology
Trophoblastic proliferation ↑ secretion of hCG, thyroxine and P.
E production is low (absence of the fetal supply of precursors).

11. Pathology
High hCG →
multiple theca lutein cysts in the ovaries (about 50% of cases)
exaggeration of the normal early pregnancy symptoms and signs

12. Histologic section of a complete hydatidiform mole
Villi of different sizes
The large villous in the center exhibits marked edema
Marked proliferation of the trophoblasts

13. Types:
Complete mole
Partial mole

14. 1. Complete mole The whole conceptus a mass of vesicles. No embryo.
Result of fertilization of enucleated ovum (no chromosomes) with a sperm which will duplicate giving rise to 46 chromosomes of paternal origin only.

15. 1. Complete mole

16. 2. Partial mole
- A part of trophoblastic tissue only shows molar changes.
- There is a fetus or at least an amniotic sac.
- Result of fertilization of 1 ovum by 2 sperms - the chromosomal number is 69 chromosomes

18. 2. Partial mole

19. DIFFERENTIATION BETWEEN COMPLETE AND PARTIAL MOLE
Complete Mole
Feature
Present
Absent
Embryonic or fetal tissue
Focal
Diffuse
Swelling of the villi
Trophoblastic hyperplasia
Paternal and maternal 69 XXY or 69 XYY
Paternal 46 XX (96%) or 46 XY (4%)
Karyotype
Rare
5-10%
Malignant Changes

20. Diagnosis

21. (A) Symptoms Amenorrhoea: short period (2-3 months).
Exaggerated symptoms of pregnancy especially vomiting.
3.Preeclampsia (headache + oedema)

22. (A) Symptoms 4. Vaginal bleeding
separation of vesicles from uterine wall
brown blood - retained in the uterine cavity.
5. Enlargment & tenderness of the uterus (concealed blood).
6. Passage of vesicles is diagnostic.
7. Abdominal pain
- dull-aching (rapid distension of the uterus)
- colicky (expulsion)
- sudden and severe (perforating mole)
- ovarian pain torsion or stretching cystic ovary

23. (B) Signs

24. General examination
Pre-eclampsia (20-30% of cases), Hypertension + proteinuria.
Pallor (anemia).
Hyperthyroidism (3-10% of cases) due to chorionic thyrotropin & HCG.
Breast signs of pregnancy.

25. Abdominal examination
The uterus is larger than the amenorrhea (50%).
The uterus is doughy in consistency (absence of amniotic fluid + distension with vesicles).
Fetal parts and heart sound cannot be detected (except in partial mole).
Absence of external ballottement.

26. Local examination Passage of vesicles (sure sign).
Bilateral ovarian cysts in 50% of cases.
No vaginal ballottement.

27. (C) Investigations 3. X-ray to the abdomen: no fetal skeleton.
Serum b -hCG level is highly elevated (> mIU/m1).
2. Ultrasonography
characteristic intrauterine "snow storm" appearance
no identifiable fetus
bilateral ovarian cysts
3. X-ray to the abdomen: no fetal skeleton.
4. X-ray of the chest.

28. A real-time ultrasound of a hydatidiform mole.
The dark circles of varying sizes at the top center are the edematous villi.

30. Differential diagnosis
The increased uterine size
multiple fetuses
single macrosomic fetus
hydramnios
uterine myomas.
The uterine bleeding
spontaneous abortion
noncomplicated ectopic pregnancy
uterine fibroids
cancer of the uterine corpus

31. Complications Haemorrhage. Infection.
Perforation of the uterus (spontaneously or during evacuation).
Pregnancy induced hypertension.
Hyperthyroidism.
Subsequent choriocarcinoma in about 5% of cases and invasive mole in about 10% of cases.
Recurrent mole (1-2%).

32. Treatment
As soon as the diagnosis of vesicular mole is established the uterus should be evacuated.
The selected method depends on:
the size of the uterus
whether partial expulsion has already occur
the patient's age and fertility desire.
3.Cross - matched blood should be available before starting.

33. 1. Evacuation Suction - dilatation of the cervix + Suction
Curettage - D&C
Hysterotomy - large mole
- under i.v. oxytocin in saline solution;
- - The material removed is sent for histological examination.

34. 4. Hysterectomy
It should be considered in women over 40 years who have completed their family to prevent developing choriocarcinoma.

35. Follow up
ß-hCG is measured every week till the test becomes negative for 3 successive weeks, then every month for one year.
Pregnancy is allowed if the test remains negative for one year.

37. Follow up
Persistent high level remnants of molar tissues which necessitate: a. chemotherapy (methotrexate) b. hysterectomy, if women had enough children.
Rising hCG level after disappearance means developing of choriocarcinoma or a new pregnancy.

38. Contraception during follow up
The combined pill - when the beta-HCG becomes negative.
Till this happens, the condom can be used.

39. Invasive Mole or Chorioadenoma Destruens
a trophoblastic tumor with penetration of the myometrium by the chorionic villi;
locally malignant;
rarely metastasizes;
may lead to perforation of uterus.

40. Gestational Choriocarcinoma
Choriocarcinoma is evident in the fundus of the hysterectomy specimen
Hemorrhagic lesions 40

41. Gestational Choriocarcinoma
Sheets of anaplastic CT and ST cells with hemorrhage & necrosis.
Myometrial & blood vessels invasion and early metastases
No Villus formation
Syncytiotrophoblast
Cytotrophoblast 41

42. Metastatic Disease 1- Pulmonary (80 %) 2- Vaginal metastases (30 %)
In 4% of patients after molar evacuation but is seen more commonly after other GTDs
Sites of metastases
1- Pulmonary (80 %)
2- Vaginal metastases (30 %)
3- Hepatic (10 %)
4- Central nervous system (10 %) 42

43. Metastatic Disease
If the pelvic examination & chest X-ray are negative, it is very uncommon to have metastatic involvement of other sites 43

44. Chest X ray: widespread metastatic lesions.

45. GTN Vaginal Metastasis

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

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

48. 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
The FIGO GTN Description = FIGO stage: FIGO Score
FIGO Oncology Committee, 2002

49. Hysterectomy plus Chemotherapy is indicated:
WMethotrexate (MTX) is the first line of choice
Hysterectomy plus Chemotherapy is indicated:
If the patient does not wish to preserve fertility or
There is a resistance to chemotherapies
Methotrexate is less toxic than actinomycin D
Methotrexate or actinomycin D alone equally effective compared with a combination of the two.