1. Gestational trophoblastic disease
Jolanta Zegarska MD,PhD
Department of Obstetrics, Gynecology and Gynecological Oncology.
Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun

2. Definition Gestational Trophoblastic Disease (GTD)
Represents a spectrum of diseases characterized by active abnormal proliferation of trophoblastic cells
Includes a unique spectrum of interrelated diseases:
Benign hydatiform mole
Invasive mole (Chorioadenoma destruens)
Choriocarcinoma
Placental site trophoblastictumor (very rare)

3. Epidemiology and Etiology
The incidence of molar pregnancy is about 1 in every 1500 to 2000 pregnancies (white woman)
Higher incidence among women in Asia (for example in Taiwan: 1 in every 125 to 200 pregnancies)
The cause of GTD is unknown
Most patients (80-90%) follow a benign course
The risk for the development of a second molar pregnancy is 1 to 3 % (40 times greater than the risk for developing the first molar pregnancy)
GTD occur more frequently in women younger than 20 years and older than 40 years

4. Relationship Abortion, delivery, ectopic pregnancy Hydatidiform mole
choriocarcinoma
Invasive mole
Abortion, delivery, ectopic pregnancy

5. Hydatidiform mole

6. Hydatidiform mole/definition
the placental trophoblastic cells proliferate abnormally
It is a neoplastic proliferation of the trophoblast in which the terminal villi are transformed into vesicles filled with clear viscid material
there is stromal edema
forms vesicula which is like grape on its appearance

7. Hydatidiform mole/classification
Hydatidiform mole is divided into
Complete mole
Incomplete/partial mole
Based on clinical, patomorphological and genetic features

8. Complete mole Most hydatidiform moles are complete
Have a 46 xx karyotype
Both of the x chromosomes are paternally derived
It results from the fertilization of an „empty egg” by haploid sperm 23x which then duplicates to restore the diploid chromosomal complement
Only a small percentage are 46 XY
Complete molar pregnancy is only rarely associated with a fetus, and this may represent a form of twinning

9. Complete mole/Genetic

10. Complete mole
Histopathologic findings associated with a complete molar pregnancy
Hydropic villi
Absence of fetal blood vessels
Hyperplasia of trophoblastic tissue
Invasive mole differs from hydadtidiform mole only in its propensity to invade locally and to metastasize

11. Complete mole/symptoms
Bleeding in the first half of pregnancy
Irregular bleeding
Heavy vaginal bleeding
Lower abdominal pain
Excessive nausea/ hyperemesis gravidarum
Preeclampsia
Irritability
Dizziness
Photophobia
Hyperthyroidism
Nervousness
Anorexia
Tremors

12. Complete mole/signs Tachycardia Tachypnea Hypertension
Absent fetal heart tones (and fetal parts)
Grape-like vesicles of the mole may be detected in the vagina
Enlarged uterus
50% patients with molar pregnancies
25% have size compatible and 25% have size smaller than gestational age
Ovarian enlargement by theca-lutein cyst
Occurs in about 1/3of women with molar pregnancies

13. Complete mole/diagnosis
Serum β-human chorionic gonadotropin (β-hcg) higher than normal pregnancy values
Ultrasonography
Reveals a „snowstorm” pattern
Chest film
Case courtesy of Dr Andrew Dixon, Radiopaedia.org

14. Complete mole / prognosis
Complete mole has the latent risk of local invasion or telemetastasis
The high-risk factors includes
β-HCG > IU/L
Uterine size is obviously larger than that with the same gestational time.
The luteinizing cyst is > 6cm
If > 40 years old, the risk of invasion and metastasis may be 37%, If > 50 years old, the risk of invasion and metastasis may be 56%.
Repeated mole: the morbidity of invasion and metastasis increase 3~4 times

15. Incomplete mole 10% of moles are incomplete Is not associated with age
Karyotype is usually a triploid
Often 69 XXY (80%)
These lesions often present with a coexistent fetus
The fetus usually has a triploid karyotype and is defective
A partial mole has some hydropic villi, whereas other villi are essentially normal
Fetal vessels are seen in a partial mole
The trophoblastic tissue exhibits less striking hyperplasia

16. Incomplete mole
Patients display most of the pathologic and clinical features of patients with complete mole, although usually in less severe form
Partial moles are usually diagnosed later than are complete moles
Partial moles generally present as spontaneous or missed abortion
Usually is not detected before the spontaneous termination of pregnancy
No luteinizing cyst

17. Incomplete mole
Ultrasonography performed for other indications may indicate possible molar degeneration of the placenta associated with the developing fetus
An amniocentesis should be performed to determine whether karyotype of the coexisting fetus is normal
Uterine size is usually normal or small for dates
Preeclampsia usually occurs between 17 and 22 weeks (about 1 month later than with complete mole)
Partial moles rarely metastasize, and only rarely is there a need for chemotherapy

18. Pathologic features
Complete mole incomplete mole Embryotic or fetal tissue - + Villus stromal edema diffuseed localized Trophoblastic hyperplasia diffuseed localized Villus outline regular irregular Villus stromal blood vessel - + Karyotype diploid triploid or tetraploid

19. Hydatidiform mole / treatment
Evacuation
Suction evacuation followed by sharp curettage of the uterine cavity
Regardless of the duration of pregnancy
Intravenous oxytocin
To help stimulate uterine contractions and reduce blood loss
Most patient have an uncomplicated course in the postoperative period
Some require blood, fresh frozen plasma or platelet transfusion
Rarely a patient can experience acute respiratory distress from trophoblastic embolization or fluid overload

20. Hydatidiform mole / follow up
Weekly serum analysis of β-hcg
The levels should steadily decline to undetectable levels
Usually within 12 – 16 weeks
Chemotherapy
Prophylactic chemotherapy is not indicated, because 90% have spontaneus remissions.
If the β-hcg levels plateau or rise at any time, chemotherapy should be initiated

21. Invasive mole

22. Invasive mole Usually a locally invasive tumor
It constitutes about 5 – 10 % of all molar pregnancies
Most of those with persistent β-hcg levels after molar evacuation
The lesion may:
Penetrate the entire myometrium
Rupture through the uterus
Result in hemorrhage into the broad ligament or peritoneal cavity
Rarely is associated with metastases
Vagina, lungs
Brain (rarely)

23. Invasive mole / Clinical manifestation
irregular vaginal bleeding
uterine subinvolution
theca lutein cyst does not disappear after emptying uterus
abdominal pain
metastatic focus manifestation

24. Invasive mole / Diagnosis
history and clinical manifestation
successive measurement of HCG
ultrasound examination
X-ray and CT
histologic diagnosis

25. Invasive mole
Histologic confirmation of invasive mole is almost always made at the time of hysterectomy
Hysterectomy is usually performed
in patients with persistent β-hcg levels following evacuation of molar pregnancy
In patients with persistent titers of β-hcg despite chemotherapy who have no evidence of metastatic disease
Hysterectomy is usually curative

26. choriocarcinoma

27. Choriocarcinoma
The frankly malignant form of gestational trophoblastic disease
Genetic analysis of choriocarcinomas usually reveals aneuploidy or polyploidy
Typical for anaplastic carcinomas
Appears grossly as a vascular-appearing, irregular and „beefy” tumor
Often growing through the uterine wall
Metastatic lesions appear hemorrhagic and have consistency of currant jelly
Histological consist of sheets of malignant cytotrophoblast and syncytiotrophoblast with no identifiable villi

28. Choriocarcinoma
50%gestational choriocarcinoma result from hydatidiform mole
Trophoblastic disease following a normal pregnancy is always choriocarcinoma
The tumor has a tendency to disseminate hematogenously, particularly to the lungs, vagina, brain, liver, kidneys and gastrointestinal tract
FIGO staging of gestational trophoblastic neoplasia

29. Choriocarcinoma / symptoms
Symptoms of metastatic disease
Vaginal bleeding
Uterine choriocarcinoma
Vaginal metastasis
Hemoptysis, cough, dyspnea
Result of lung metastasis
Headache, dizzy spells
Central nervous system metastases
Rectal bleeding, dark stools
Metastasis to gastrointestinal tract

30. Choriocarcinoma / signs
Uterine enlargement
Blood seen on examination with a speculum
Mass in vagina (metastatic tumor)
Acute abdomen
Rupture of uterus
Abdominal pain
Theca-lutein cyst
Neurologic signs
Partial weakness, paralysis, aphasia etc

31. Choriocarcinoma / diagnosis
Great imitator of the other diseases !!!!
May not be suspected
Unless it follows molar pregnancy
Screen for choriocarcinoma: β-hcg
Computer tomography (CT)
Pelvis
Abdomen
head
Cerebrospinal fluid β-hcg level
Ratio of serum to cerebrospinal fluid hcg levels of less than 40:1 suggest central nervous system involvement
β subunit does not cross the blood-brain barrier readily

32. Clinical features / poor prognosis
Urinary β-hcg level > IU/24 hr
Serum β-hcg level > IU
Disease presents more than 4 months from the antecedent pregnancy
Metastasis to the brain or liver
Regardless of β-hcg titer or duration of disease
Prior failure to respond to single-agent chemotherapy
Choriocarcinoma after a full-term delivery

33. Choriocarcinoma / treatment
Chemotherapy
Methotrexate
Actinomycin D
Cyclophosphamide
Modified Bagshave regimen (EMA-CO)
Surgery
Hysterectomy
Pulmonary resection
Radiotherapy (in conjunction with chemotherapy)
Brain
liver

34. Choriocarcinoma / prognosis
% of patients with GTN with good prognosis are cured
50 – 70 % patients with poor diagnosis are cured
Most patient who die have brain or liver metastases
Causes of death:
Vaginal bleeding.
Haemoptysis.
Intraperitoneal hemorrhage.
Peritonitis.
Metastasis to the vital organs e.g, brain.
Pulmonary complications

35. Prognostic scoring/FIGO/WHO
Scores 1 2 4
Age
<40
≥40 —
Antecedent pregnancy
Mole
Abortion
Term
Interval months from index pregnancy
<4
4–6
7–12
>12
Pretreatment serum β-hCG (iu/1)
<103
103–104
104–105
>105
Largest tumor size (including uterus)
<3
3–4 cm
≥5 cm
Site of metastases
Lung
Spleen, kidney
Gastrointestinal
Liver, brain
Number of metastases
1–4
5–8
>8
Previous failed chemotherapy
Single drug
≥2 drugs
Low-risk: individuals with a score ≤6

36. Choriocarcinoma / follow up
serum hcg levels should be measured
once per week until 4 normal values are obtained.
once per month for 1 year.
Patients with poor prognosis should be checked monthly for 2 years after 3-4 consecutive weekly normal serum hcg levels.
Levels should be checked every 3 months until 5 years
Patients should use a reliable method of contraception.
Advise not to be pregnant within 12 months after molar evacuation

37. Thank you