Gestational Trophoblastic Diseases DR. SAMAA NAZER Assistant Professor of Obstetrics & Gynecology Jeddah, Saudi Arabia

Content: Definitions Classifications Etiology of molar pregnancy Histologic classification Difference between complete mole and partial mole Genetic of trophoblastic disease Diagnosis Early management care Follow up Role of chemotherapy Malignant variant and its work up and management Differential diagnosis of bleeding in early pregnancy.

DEFINITION Refers to the spectrum of abnormalities of the trophoblast associated with pregnancy and they specifically secret human chorionic gonadotrophin. They are among the rare human tumours that can be cured even in the presence of wide spread dissemination.

GTD include Complete mole Partial hydatidiform mole Placental site trophoblastic tumour Choriocarcinoma Persistent GTT Follow: Molar pregnancy (common) Therapeutic or spontaneous abortion Ectopic pregnancy Term pregnancy

Epidemiology of molar pregnancy Geographic and racial distribution There is wide variation in the reported incidence of hydatidiform mole USA 0.75 to 1.0 per 1000 pregnancy South East Asia 1.5 to 2.5 times higher Rate 8 per 1000 pregnancy Prior hydatidiform mole The risk increase of subsequent mole by 20 to 40 times Poor nutrition, low socioeconomic state case control studies show low dietary intake of carotin, folic acid Deficiency may contribute the development of mole. Maternal age Extreme of age below 20 years or older than 40 years (due to defective fertilization)

Complete versus partial hydatidiform mole Complete mole a. Pathology - lack of embryonic or fetal tissue - chronic villi exhibit genaralized hydrobic swelling . - diffuse trophoblastic hyperplasia of the syncytiotrophoblast and cytotrophoblast. 2. Genetic. complete mole only paternal chromosome fertilize an empty egg which result in a chromosome of 46xx in 80% of cases 20% of cases the chromosome is 46 xy where Haploid sperm one x and one Y fertilized empty egg. Duplication of the paternal chromosome is called adrogenesis

Partial hydatidiform mole Pathology: Chorionic villi of varying size . Foccal hydatidiform swelling, cavitation, and trophoblastic hyperplasia limited to the syncytiotrophoblast. Marked villous scalloping Prominent stromal trophoblastic inclusions Identifiable embryonic fetal tissues. Genetic of partial mole: They are usually triploid and have 69 chromosomes of both maternal and paternal origin (69 xxx) (69 xxy). The most common mechanism of origin is a haploid egg being fertilized by two sperm. Another Mechanism is the abnormal diploid sperm fertilize the haploid egg

Choriocarcinoma They are malignancies that occur after or in association with pregnancy Other primary site Ovary Testes Choriocarcinoma occurs in about 3% - 5% of molar pregnancy The rate in United State is 1 per 20,000 pregnancies After normal pregnancy 1 per 40,000 term pregnancy Pathology Malignant cytotrophoblast and syncytiotrophoblast Chorionic villi are absent

Placental site trophoblastic tumour It is rare consist of groups of mononucleated and multinucleated trophoblastic cell at the implantation site Histochemical studies have shown that the cells tend to stain with human placental lactogen (HPL) than for BHCG and both should be monitored. The treatment is hysterectomy.

Clinical features of complete mole 1. Abnormal vaginal bleeding in early pregnancy (97%) 2. Lower abdominal pain Toxemia before 24 weeks of gestation (27%) Hyperemesis gravidarum Uteus large for date (50%) Hyperthyroidism (7%) Enlargement of the ovary (Theca lutein ovarian cyst) (20%) Absent of fetal heart tones and fetal parts. Expulsion of swollen villi Trophoblastic embolization (RDs) (2%)

Partial Mole In general patient presents with signs and symptoms of incomplete or missed abortion. The diagnosis by histologic review of the curettings

Prognosis 15% of patient of complete mole → uterine invasion 4% of complete mole → metastasis 4% of partial mole develop persistent tumour Diagnosis of complete mole: Ultrasound reliable and sensitive Finding: a. Absence of the fetus b. Snow storm – like pattern c. Ovarian enlargement B-HCG The level in normal pregnancy reach peak at 10-14 weeks rarely exceed level of 100,000 MIU/ML Level excess of 100,000 MIU/ML suggest GTD

Management of molar pregnancy I – Evaluation of the patient for: Anemia, hypertension, pulmonary insufficiency, hyperthyroidism, DIC, by doing: 1. CBC 2. Liver function test (LFT) 3. PT, PTT, fibrinogen 4. Renal function test 5. Thyroid function test (TFT) 6. Blood group Rh 7. Cross match 2 units of blood 8. Chest x-ray II – Treated by evacuation of the uterus: Using suction evacuation plus intravenous oxytocin III – If patient has completed child bearing hysterectomy in high risk patient

Follow up The patient should be carefully monitored for the potential development of malignant sequalae by serial determination of B-HCG . The risk of GTT is increased with : A large uterus High HCG level Lutein cyst History of molar pregnancy Age above 40 years HCG follow up is weekly until negative results then monthly up to 1 year and it has to be plotted in a curve. Pelvic examination every 2 weeks until normal then every 3 months. Oral contraceptive for 1 year.

Diagnosis of Abnormal Follow up Abnormal regression curve either plateau, or increasing Symptom of recurrence of patient start to complain of per vaginal bleeding Management: To do metastatic work up by: Pelvic examination Repeat chest x-ray B-HCG level Liver function test Renal function test CT scan of chest, abdomen and pelvis Neurological examination if any abnormality – CT scan of the brain Chemotherapy

Chemotherapy Indication Plateus or increasing HCG Metastatic disease is present Chorio carcinoma is diagnosed in tissue HCG level is still elevated after 6 months, after evacuation Abnormal regression curve

Gestational trophoblastic Neoplasia 1. ½ cases after molar pregnancy 2. ¼ cases after normal pregnancy 3. ¼ cases after abortion, ectopic pregnancy FIGO Classification: Stage I : Confined to the corpus Stage II : Metastasis outside the uterus to vagina, or pelvic structure Stage III : Metastasis on the lungs Stage IV : Distant metastasis

Prognostic classification of GTT I - Non metastatic GTT II – Metastatic GTT a. Good prognosis: 1. Disease present less than 4 month 2. Pre treatment B-HCG less than 40,000 MIU/ml 3. No prior chemotherapy b. Poor prognosis: 1. Disease present more than 4 months 2. Pre treatment B-HCG greater than 40,000 MIU/ml 3. Presence of metastatic to site other than lungs and vagina, i.e. liver and brain. 4. Failure of prior chemotherapy

Management Nonmetastatic and good prognosis metastatic GTT Single agent chemotherapy ( Methotrexate ) 2. Poor prognosis GTT Multiple agent chemotherapy More than one protocol most common is MAC: methotrexate, Actinomycin D, chlorambucil

Differential Diagnosis of bleeding in early pregnancy Abortion (different type) Ectopic pregnancy Molar pregnancy Chorio carcinoma Blood diseases Local causes

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