Gestational trophoblastic disorders(GTD)

Dr.Fadia

Definition:

Abnormal proliferation of gestational trophoblastic tissue.

It forms a spectrum of inter-related diseases originating from the placental trophoblast.

Classification:

*WHO classification:

1. Premalignent:

*completemole (classical mole).

*partial mole.

2. Malignant disorders:

*choriocarcinoma.

*invasive mole.

*placental site tumors.

Incidence &Epidemiology:

  • The estimated incidence of complete mole is 1/ 1000-2000 pregnancy.
  • The incidence of partial mole is around 1/700 pregnancy..
  • The vast majority of complete & partial moles abort spontaneously during the first trimester& the incidence of molar pregnancy has been estimated to be 2% of all miscarriages.
  • The incidence of choriocarcinoma varies from 1/10000 to 1/50000 pregnancy (3-10% of hydatidiform mole).
  • Higher incidence in Africa & Asia.
  • The relative risk is highest in pregnancies at the extremes of reproductive age group (10 folds increase in those over 40).
  • Previous history of molar pregnancy increase incidence in subsequent pregnancy.
  • The ABO bloodgroup of the parents appears to be a factor in choriocarcinoma developments (high in A & low in O women).

Premalignant hydatidiform mole

1. Complete mole(CM):

*pathologically described as:

1. Diffuse trophoblastic hyperplasia.

2. Generilized swelling of the villous tissue.

3. No embryonic or fetal tissue.

4. Absence of blood vessels in the swollen villi.

*genetically:

The chromosomal composition in 85% is 46, xx, with both chromosomes being of paternal origin& 15% 46, xy.

*clinically patient present with:

  • Vaginal bleeding with or without passages of vesicles.
  • Uterine enlargement greater than expected for GA (larger than date).
  • No fetal heart sound
  • Associated medical complication which includes:

a.)Hyperemesis.

b.)Pregnancyinduced hypertension or early onset preeclampsia.

c.)Hyperthyroidism.

d.)Anemia.

e.)Development of theca lutein cyst.

f.)Risk of sever hemorrhage &or DIC.

  • Risk of progression to gestational trophoblastic neoplasia (GTN) is 18-29%.
  • The level of serum hCG is very high.
  • Ultrasound typically reveals a uterine cavity filled with multiple sonolucent area of varying size &shape (snow-storm appearance) without associated embryonic or fetal structure.

2.Partial mole(PM):

*pathologically:

1. Focal swelling of the villous tissue.

2. Focal trophoblastic proliferation.

3. There is embryonic or fetal tissue.

4. The abnormal villi are scattered within macroscopically normal placental tissue that tends to retain its shape.

*genetically:

The karyotype typically is triploid 69,xxy or 69,xyy.these are each composed of one maternal & 2 paternal sets of chromosomes.

*clinically the patient frequently present with:

  • Vaginal bleeding.
  • May be detected by routine ultrasound accidentally &resembles missed abortion.
  • Uterine size equal or smaller than dates.
  • Theca –lutein cyst are rare.
  • Medical complications are rare.
  • Risk of progression to GTN is 1-11%.

Investigation before evacuation:

  1. Blood group &Rh (to prepare blood before evacuation for risk of hemorrhage).
  2. Complete blood count (CBC).
  3. Pre evacuation serum hCG.
  4. RFT & serum electrolytes &LFT (elevated because of hyperemeseis).
  5. Measurements of BP & albumin in urine to exclude early onset pre- eclampsia.
  6. Thyroid function test if clinically suggestive thyrotoxicosis.
  1. ultrasound:
  2. Typical CM or PM. Picture.
  3. Presence of theca lutein cyst.
  4. The presence of secondary in the liver in GTN.

8. Chest x-ray (to exclude metastasis in GTN).

9. Coagulation profile to exclude DIC & the profiles are:

  • Prothrombinetime (PT).
  • Partial thromboplastine time (PTT).
  • Platelets count.
  • Serum fibrinogen.
  • FDP.

10. CT or MRI to evaluates the liver or brain if there clinical evidence of malignancy.

Treatment:

* Hydatidiform mole treatment consists of 2phases:

  1. Immediate evacuation.
  2. Subsequent evaluation for persistent trophoblastic proliferation or malignant changes.

* Evacuation is performed by suction evacuation & curettage under proper anesthesia regardless of the uterine size.

*compatible blood should be available before evacuation.

* Uterotonic drugs usually needed because of risk of hemorrhage (oxytocin, ergometrine, PG) &if used should be toward the end of evacuation to decrease the risk of trophoblastic migration.

* Antibiotic cover to decrease the risk of infection.

*anti D should be given after evacuation if the woman is Rh negative.

*histopathological examination of the sample to confirm GTD.

*complication of the operation includes:

1. Hemorrhage.

2. Perforation of the uterus.

3. Pulmonary complications due to trophoblastic embolization are frequently observed following evacuation &the prognosis depends on the severity of the symptoms.

4. Infection.

*secondary evacuation is indicated when there are retaind products of tissue or persistent spotting for 2 weeks.

*hysterectomy is indicated in:

  • No further pregnancy is desired.
  • Women aged 40 &over because of high risk of GTN (reduce the risk but not eliminate it).
  • Sever uncontrolled hemorrhage.
  • Invasive mole with evidence of perforation.
  • Malignant form of GTD with no further desire to conceive.

Follow-up evaluation of molar pregnancy:

  1. Prevent pregnancy for a minimum of 6 months using proper contraception.
  1. Monitor serum hCG level every 2 weeks until undetectable then monthly for 1 year &then every 3 months for one year.
  1. indications for chemotherapy:
  2. High levels of hCG (>20000IU/L) more than 4 weeks post evacuation.
  3. Progressively increasing hCG values at any time post evacuation.
  4. Any detectable level of hCG 4-6 months post evacuation.
  5. Metastases (brain, hepatic, pulmonary, renal, GIT)irrespective of hCGlevels.
  6. HCG level plateau in 3 consecutive serum samples.
  7. Malignant type of GTD.

Malignant trophoblastic disorders:

Invasive mole (chorioadenoma destruens)

  • Nearly always arise from a CM.
  • Characterized by invasion of the myometrium, which can lead to perforation of the uterus.
  • The incidence decrease because of early treatment &follow up of CM.
  • Histologicalsimilar to CM but with invasion of the myometrium.

Placental site trophoblastic tumors :

  • Most commonly follow a normal pregnancy but can occur after a non-molar abortion or a CM, &very rarely following a PM.
  • Form less than 2% of all GTD.

Choriocarcinoma:

  • Present the most frequent emergency medical problems in the management of trophoblastic disease.
  • It follow:
  • CM in 50%.
  • non-molar abortion in 25%
  • Term pregnancy in 25%.
  • Clinical presentation:

*locally from uterus =bleeding

*distant metastases=wide verity of symptoms depending on the site (lung, CNS, liver).

  • Diagnosis some times difficult &depends on high hCG&U/S with characteristic findings show the structure of the villous trophoblast, &occasionly by biopsy.
  • Treatment depends on FIGO scoring system to divide patient to high-risk & low risk group.
  • Chemotherapy (single or combination) is treatment of choice for low risk group methotrexate&folinic acid is treatment of choice in high risk group combination of chemotherapy is required (e.g. EMA/COregime =actinomycin,etoposide,methotrexate+vincristine&

cyclophosphamide).

  • Cure rate is very high with early diagnosis& proper treatment but the patient should be followed up for life (clinically &by serum hCG)to prevent recurrences.