Gestational trophoblastic disease refers to a spectrum of conditions that result from abnormal proliferation of trophoblast tissue. This includes complete and partial hydatidiform moles, as well as invasive moles and choriocarcinoma. Complete moles are characterized by marked trophoblastic proliferation and swelling of the chorionic villi, resulting in vesicles within the uterus. The document discusses the incidence, pathology, diagnosis, treatment and follow up of molar pregnancies. Surgical evacuation is usually performed, and long term follow up is needed to monitor for recurrence and the potential development of choriocarcinoma.

1. Gestational Trophoblastic Disease Complete vesicular mole Partial vesicular mole Invasive mole Placental-site trophoblastic tumor Choriocarcinoma

2. Definition It is a benign neoplasm of the chorionic villi, characterized by: Marked proliferation of the trophoplast, both the syncytium & cytotrophoplast are affected. Oedema or hydropic degeneration of the connective tissue stroma of the villi which leads to their distension and formation of vesicles. Avascularity of the villi : the blood vessels disappear from villi explaining early death of the embryo

3. Incidence: 1:2000 pregnancies in United States and Europe, but 10 times more in Asia. Predisposing factors include : Race,deficiency of protein or carotene The incidence is higher toward the beginning and more toward the end of the childbearing period. It is 10 times more in women over 45 years old.

4. Pathology: The uterus is distended by thin walled, translucent, grape-like vesicles of different sizes. These are degenerated chorionic villi filled with fluid. There is no vasculature in the chorionic villi leads to early death and absorption of the embryo.

5. There is trophoblastic proliferation , with mitotic activity affecting both syncytial and cytotrophoblastic layers. This causes excessive secretion of hCG, chorionic thyrotrophin and progesterone. On the other hand, oestrogen production is low due to absence of the foetal supply of precursors. Pathology:

6. High hCG causes multiple theca lutein cysts in the ovaries in about 50% of cases. Cysts may reach a large size (10 cm or more. Cysts disappear within few months(2-3), after evacuation of the mole. High hCG also results in exaggeration of the normal early pregnancy symptoms and signs Pathology:

8. Histologic section of a complete hydatidiform mole stained with hematoxylin and eosin. Villi of different sizes are present. The large villous in the center exhibits marked edema with a fluid-filled central cavity known as cisterna. Marked proliferation of the trophoblasts is observed. The syncytiotrophoblasts stain purple, while the cytotrophoblasts have a clear cytoplasm and bizarre nuclei. No fetal blood vessels are in the mesenchyme of the villi.

9. Complete mole Partial mole Types:

10. (i) Complete mole: The whole conceptus is transformed into a mass of vesicles. No embryo is present. It is the result of fertilization of enucleated ovum ( has no chromosomes) with a sperm which will duplicate giving rise to 46 chromosomes of paternal origin only.

11. (i) Complete mole:

12. (ii) Partial mole - A part of trophoblastic tissue only shows molar changes. - There is a foetus or at least an amniotic sac. - It is the result of fertilization of an ovum by 2 sperms so the chromosomal number is 69 chromosomes

14. (ii) Partial mole

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

16. Diagnosis

17. (A) Symptoms : Amenorrhoea : usually of short period (2-3 months). Exaggerated symptoms of pregnancy especially vomiting. 3.Symptoms of preeclampsia may be present as headache, and oedema

18. 4. Vaginal bleeding : The main complaint, due to separation of vesicles from uterine wall, there may be a blood stained watery discharge, the watery part is from ruptured vesicles. Prune juice disharge may occur. The blood is brown because it has retained for sometime in the uterine cavity. The passage of vesicles is diagnostic. The blood may be concealed causing enlargment & tenderness of the uterus. (A) Symptoms:

19. 5. Abdominal pain : may be , - dull-aching due to rapid distension of the uterus by the mole or by cocealed haemorrhage. - colicky due to starting expulsion, sudden and severe due to perforating mole Ovarian pain due to stretching of the ovarian capsule or complication in the cystic ovary as torsion (A) Symptoms:

20. (B) Signs

21. General examination: Pre-eclampsia develops in 20-30% of cases, usually before 20 weeks’ gestation. Pallor indicating anemia may be present. Hyperthyroidism develops in 3-10% of cases manifested by enlarged thyroid gland, tachycardia (due to chorionic thyrotropin secreted by trophoplast &HCG also has a thyroid stimulating effect. Breast signs of pregnancy.

22. Abdominal examination: The uterus is larger than the period of amenorrhoea in 50% of cases, corresponds to it in 25% and smaller in 25% with inactive or dead mole. The uterus is doughy in consistency due to absence of amniotic fluid and its distension with vesicles. Foetal parts and heart sound cannot be detected except in partial mole. Absence of external ballottement.

23. Local examination : Passage of vesicles (sure sign). Bilateral ovarian cysts in 50% of cases. No internal ballottement.

24. Urine pregnancy test: is positive in high dilution. 1/200 is highly suggestive, 1/500 is surely diagnostic. In normal pregnancy it is positive in dilutions up to 1/100. 2. Serum b -hCG level : is highly elevated ( > 100.000 mIU/m1). (C) Investigations:

25. (C) Investigations: 3. Ultrasonography reveals : The characteristic intrauterine " snow storm " appearance, no identifiable foetus, bilateral ovarian cysts may be detected. 4. X-ray to the abdomen: shows no foetal skeleton. 5. X-ray of the chest: should be performed in every case of trophoplastic tumour.

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

27. Complications: Haemorrhage . Infection due to absence of the amniotic sac and due to the large surface area left after expulsion or evacuation of the mole. Perforation of the uterus. Spontaneous by a perforating mole or during evacuation. Pregnancy induced hypertension Hyperthyroidism . Subsequent development of choriocarcinoma in about 5% of cases and invasive mole in about 10% of cases. Recurrent mole may occur( 1-2% ).

28. 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 or not, the patient's age and fertility desire . Cross - matched blood should be available before starting.

29. - It is carried out under general anaesthesia , but not that which relax the uterus as halothane as it may induce severe bleeding. - An infusion of 20 units oxytocin in 500 m1 of 5% glucose should be maintained throughout the procedure. (I) Suction evacuation:

30. Dilatation of the cervix is done up to a Hegar's number equal to the period of amenorrhoea in weeks e.g. N o . 10 Hegar for 10 weeks’ amenorrhoea. The suction canula used will be of the same size also. (I) Suction evacuation:

31. (I) Suction evacuation: - A suction canula which may be metal or a disposable plastic (preferred) is introduced into the uterine cavity. The canula is connected to a suction pump adjusted at negative pressure of 300-500 mmHg according to the duration of pregnancy. The material removed is sent for histological examination.

32. Curettage After evacuation ,the uterus is gently curetted with a sharp curette. Some advise curettage one week after evacuation to ensure complete removal, but the is not the routine practice.

33. Theca lutein cysts They are hormone dependent. Disappear spontaneously after evacuation of the mole. So, they are not removed surgically unless complication occur as torsion or rupture.

34. (II)Hysterotomy: It may be needed for evacuation of a large mole to minimize and facilitate control of bleeding.

35. (III) Hysterectomy: It should be considered in women over 40 years who have completed their family for fear of developing choriocarcinoma.

36. (IV) Medical induction: Oxytocins and / or prostaglandins may be used to encourage expulsion of the mole but must always be followed by surgical evacuation.

37. Follow up : As choriocarcinoma may complicate the vesicular mole after its evacuation, detection of serum ß-hCG by radioimmunoassay is essential

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

39. Follow up : Persistent high level indicates remnants of molar tissues which necessitate chemotherapy ( methotrexate) with or without curettage. Hysterectomy is indicated if women had enough children. Rising hCG level after disappearance means developing of choriocarcinoma or a new pregnancy.

40. It is expected that urine pregnancy test is negative 4 weeks after evacuation and serum b -hCG is undetectable 4 months after evacuation. Follow up :

41. Contraception during follow up The combined pill is started when the beta-HCG becomes negative. Till this happens, the condom can be used. If the pill is used early the beta-HCG will take a longer time to become negative as oestrogen stimulates the growth of trophoplast.

42. The intrauterine device is not used because it may lead to irregular uterine bleeding which confuses the follow up Contraception during follow up

43. Invasive Mole or Chorioadenoma Destruens It is a trphoplastic tumour with penetration of the myometrium by the chorionic villi. It is locally malignant and rarely metastasizes. It may lead to perforation of uterus

44. Early features suggesting residual molar tissue include: recurrent or persistent vaginal bleeding, amenorrhoea, failure of uterine involution, persistence of ovarian enlargement.

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