ASSOCIATE PROFESSOR IOLANDA BLIDARU MD, PhD

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. Definition A benign tumor of the chorionic villi, characterized by: • Marked proliferation of the trophoplast,(boththe 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 • 1:2000pregnancies 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. 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

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 • Serum b -hCG levelis highly elevated (> 100.000 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 ChorioadenomaDestruens • 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

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

42. Metastatic Disease 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 %)

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

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

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

49. 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.