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Gestational TrophoblasticGestational TrophoblasticDiseasesDiseases

DR. SAMAA NAZER DR. SAMAA NAZER Assistant Professor of Obstetrics & Gynecology Assistant Professor of Obstetrics & Gynecology

Jeddah, Saudi Arabia Jeddah, Saudi Arabia

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Content: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.

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DEFINITIONDEFINITION

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.

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GTD includeGTD include

1. Complete mole

2. Partial hydatidiform mole

3. Placental site trophoblastic tumour

4. Choriocarcinoma

Persistent GTT Follow: Molar pregnancy (common) Therapeutic or spontaneous abortion Ectopic pregnancy Term pregnancy

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Epidemiology of molar pregnancy Epidemiology of molar pregnancy

1. Geographic and racial distribution There is wide variation in the reported incidence of

hydatidiform moleUSA 0.75 to 1.0 per 1000 pregnancy South East Asia 1.5 to 2.5 times higher Rate 8 per 1000 pregnancy 2. Prior hydatidiform mole

The risk increase of subsequent mole by 20 to 40 times3. Poor nutrition, low socioeconomic state case control

studies show low dietary intake of carotin, folic acid Deficiency may contribute the development of mole.

4. Maternal age Extreme of age below 20 years or older than 40 years (due to defective fertilization)

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Complete versus partial Complete versus partial hydatidiform mole hydatidiform mole

1. 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

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Partial hydatidiform mole 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 andpaternal 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

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ChoriocarcinomaChoriocarcinoma

They are malignancies that occur after or in association with pregnancy

Other primary site1. Ovary 2. TestesChoriocarcinoma 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 Pathology1. Malignant cytotrophoblast and syncytiotrophoblast 2. Chorionic villi are absent

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Placental site trophoblastic tumourPlacental 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.

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Clinical features of complete moleClinical features of complete mole

1. Abnormal vaginal bleeding in early pregnancy (97%)

2. Lower abdominal pain

3. Toxemia before 24 weeks of gestation (27%)

4. Hyperemesis gravidarum

5. Uteus large for date (50%)

6. Hyperthyroidism (7%)

7. Enlargement of the ovary (Theca lutein ovarian cyst) (20%)

8. Absent of fetal heart tones and fetal parts.

9. Expulsion of swollen villi

10. Trophoblastic embolization (RDs) (2%)

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Partial Mole Partial Mole

• In general patient presents with signs and symptoms of incomplete or missed abortion.

• The diagnosis by histologic review of the curettings

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PrognosisPrognosis 15% of patient of complete mole → uterine

invasion 4% of complete mole → metastasis 4% of partial mole develop persistent tumourDiagnosis of complete mole: 1. Ultrasound reliable and sensitive

Finding: a. Absence of the fetus b. Snow storm – like pattern c. Ovarian enlargement 2. B-HCG The level in normal pregnancy reach peak at 10-14

weeks rarely exceed level of 100,000 MIU/MLLevel excess of 100,000 MIU/ML suggest GTD

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Management of molar pregnancyManagement of molar pregnancyI – Evaluation of the patient for: Anemia, hypertension, pulmonary insufficiency,hyperthyroidism, DIC, by doing:1. CBC2. Liver function test (LFT)3. PT, PTT, fibrinogen 4. Renal function test 5. Thyroid function test (TFT)6. Blood group Rh7. Cross match 2 units of blood 8. Chest x-ray II – Treated by evacuation of the uterus: Using suction evacuation plus intravenous oxytocinIII – If patient has completed child bearing hysterectomy in high

risk patient

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Follow up 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. A large uterus

b. High HCG level

c. Lutein cyst

d. History of molar pregnancy

e. Age above 40 years

1. HCG follow up is weekly until negative results then monthly up to 1 year and it has to be plotted in a curve.

2. Pelvic examination every 2 weeks until normal then every 3 months.

3. Oral contraceptive for 1 year.

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Diagnosis of Abnormal Follow upDiagnosis of Abnormal Follow up 1. Abnormal regression curve either plateau, or increasing 2. Symptom of recurrence of patient start to complain of per

vaginal bleeding

Management: To do metastatic work up by: 1. Pelvic examination 2. Repeat chest x-ray 3. B-HCG level4. Liver function test5. Renal function test6. CT scan of chest, abdomen and pelvis 7. Neurological examination if any abnormality – CT scan of

the brain 8. Chemotherapy

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Chemotherapy IndicationChemotherapy Indication

1. Plateus or increasing HCG

2. Metastatic disease is present

3. Chorio carcinoma is diagnosed in tissue

4. HCG level is still elevated after 6 months, after evacuation

5. Abnormal regression curve

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Gestational trophoblastic NeoplasiaGestational 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

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Prognostic classification of Prognostic classification of GTTGTTI - 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

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ManagementManagement

1. 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

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Differential Diagnosis of bleeding in Differential Diagnosis of bleeding in early pregnancyearly pregnancy

1. Abortion (different type)

2. Ectopic pregnancy

3. Molar pregnancy

4. Chorio carcinoma

5. Blood diseases

6. Local causes

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