11th Postgraduate Course for Training in Reproductive Medicine and Reproductive Biology

Gestational trophoblastic disease

D. Herbert

Definition

Originate from placental tissues

Rare human tumors curable even when metastatic

• Complete hydatidiform mole
• Partial hydatidiform mole
• Placental site trophoblastic tumors
• Choriocarcinoma

Pathology

· Complete mole

• Product of an abnormal conception lacking identifiable embryonic or fetal tissue.
• Chorionic villi with generalized hydropic swelling.
• Diffuse trophoblastic hyperplasia.
• Implantation-site trophoblast with diffuse and marked atypia.

• 90% : 46 XX
• 10% : 46 XY
• Entirely of paternal origin
• Mitochondrial DNA of maternal origin

· Partial mole

• Presence of identifiable embryonic or fetal tissues.
• Variation in size of chorionic villi, focal swelling, cavitation and trophoblastic hyperplasia.
• Implantation-site trophoblast with focal, mild atypia.

• growth retardation and multiple congenital malformations.
• Karyotype : 90-93% triploid
• One extra haploid set of paternal origin

· Choriocarcinoma

• Dimorphic population of cytotophoblast and syncitiotrophoblast without formed chorionic villi plus evidence of myometrial invasion.
• Hemorragic nodules and often extensive necrosis.
• Highly metastatic potential.
• Origin : any type of gestation

Karyotype : variable

· Placental site trophoblastic tumor

• Intermediate trophoblastic cell lineage
• Recognition difficult : differentiation from cytotrophoblast in continuous serie of stage.

• 90% benign
• 10% metastatic , killing

Origin : 95% after a term pregnancy
Extremely resistant to chemotherapy
Karyotype : variable

EPIDEMIOLOGY AND RISK FACTORS

· Hydatidiform mole

· Choriocarcinoma

Epidemiology not well understood

CLINICAL PRESENTATION

• Vaginal bleeding
• Uterine size palpably larger than gestational age
• Theca lutein ovarian cysts
• Preeclampsia
• Hyperemesis
• Spontaneous incomplete abortion (partial mole)
• Hyperthyroidism (rare)
• Respiratory insufficiency (rare)

METASTATIC DISEASE

• 4% after complete molar pregnancy.
• More commonly after nonmolar pregnancy.
• Often associated with choriocarcinoma, highly vascular and prone to severe haemorrage either spontaneously or during biopsy.

Most common metastatic sites

DIAGNOSIS

• Ultrasound
  • multiple small sonolucencies (3 to 5 mm diameter) = hydropic villae, without embryo (complete mole) .
  • " Snow storm pattern ".
• b HCG higher than gestational age.
• In placental site trophoblastic tumors : ­ HPL , not b HCG.

TREATMENT

· Hydatidiform mole (non metastatic)

D&C or hysterectomy if no desire of fertility.

• weekly ß HCG ® 3 normal values
• then 1x/month for 6 months
• Return to normal values within 9 to 11 weeks

WHO Prognostic Index Score to determine the resistance to chemotherapy

• Low risk : 0-4
• Intermediate risk : 5-7
• High risk : > 8

Persistent Gestational Trophoblastic Tumor

18-29% of complete moles (USA).

Diagnosis : if plateau of ß hCG for 3 consecutive weeks or if ­ ß hCG.

Histology may be different (Choriocarcinoma or placental site trophoblastic tumor).

Criteria of severity

• ß hCG > 100 000 mUI/ml at diagnosis
• ovarian thecomas> 6cm
• preeclampsia, hyperthyroidism, tumoral embolism

Risk of persistent trophoblastic disease then 40-50%

Risk diminishes to 10-15% with chemoprophylaxis (Methotrexate or Dactinomycin)

Staging : if pelvic examination and Chest X-Ray(or Chest CT-scan)in order,very low risk of finding metastases elsewhere.

CHEMOTHERAPY

• Score= 7 :low to intermediate risk,so monochemotherapy
• Score= 7 :high risk and therefore polychemotherapy.

Monochemotherapy

Methotrexate (MTX) ® 90% CR.

If failure with MTX, with further ttt® 100% CR.

5 drugs : etoposide,MTX,dactinomycin,cyclophophamide (EMA-CO).

83% CR versus 30-45% CR with monochemotherapy in " high risk " situations.

FOLLOW-UP

· b hCG weekly during treatment until 3 normal levels (3 weeks)
· b hCG every 2 weeks for the next 2-3 months.
· b hCG 1x/month for the next 6 months,then every 2 months.
· Follow-up after 1 year for all metastatic patients with b hCG 1x/year.
· Efficient birth control during the whole period of treatment and follow-up.
· Wait a minimum of one year of follow-up before starting a pregnancy.

• 68 % live births after complete mole
• 74 % live births after partial mole
• 68 % term live births after persistent GTT.

· Even with chemotherapy

· Risk subsequent molar pregnancy :

• 1% (after one mole)
• 15% to 28% after 2 molar pregnancies
• risk persistent GTT ­ 3x in patients with repeat mole

· Rate of stillbirth higher after persistent GTT than general population (odd ratio 2,9)

· Infertility rate same as in general population (4%)

· Rate of premature deliveries, ectopic gestations , congenital anomalies ,C-section same as general population.

References

• Berkowitz and Goldstein :NEJM 1996 pp1740-1748
• Society of Gynecologic Oncologists clinical Practice Guidelines : Oncology, 1998 pp455-461
• Rose : Seminars in Oncology 1995 pp 149-156
• Semer & Mcfee: Seminars in Oncology 1995 pp109-113
• Redline &Abdul-Karim : Seminars in Oncology 1995 pp 96-109
• Goldstein and Berkowitz :Seminars in Oncology 1995, Pp157-160
• Loret de Morla & Goldfarb : Seminars in Oncology 1995 pp193-197
• Berkowitz & al :Seminars in Oncology 2000, Pp678-685

Print this page

Edited by Aldo Campana,