GTD

*

It is a clinical term used to indicate closely related conditions characterized by active abnormal proliferation of trophoblastic cells
Definition :


What does it include? hydatidiform mole (HM)(partial & complete) invasive mole (IM) Choriocarcinoma (CH) Placental-site trophoblastic tumor (PSTT, borderline, very rare)

Incidence:

1:2000 pregnancies in United States and Europe
1:200 in Asia
10 times more in women over 45 years old.
The increasing use of ultrasound in early pregnancy has probably led to the earlier diagnosis of molar pregnancy

1-Maternal age :↑<16, ↑↑↑>45 years.2-Women who have had a previous molar gestation. .3- low nutritional and socioeconomic factors. (contraversial) dietary protein deficiency low dietary intake of carotene4-The ABO blood group: appear to be a factor in choriocarcinoma development, i.e. women with blood group A have been shown to have a greater risk than blood group O women . RISK FACTORS:


It is a neoplastic proliferation of the trophoblast in which the terminal villi are transformed into vesicles filled with clear viscid material.
Hydatidiform Mole



Hydatidiform mole can be subdivided into: complete and partial mole Based on: Genetic and Histopathological features

A hydatidiform mole is an abnormality of fertilization

It is the result of fertilisation of anucleated ovum ( has no chromosomes) with a sperm which will duplicate giving rise to 46 chromosomes of paternal origin only.
It is the result of fertilisation of an ovum by 2 sperms so the chromosomal number is 69 chromosomes
COMPLETE MOLE
PARTIAL MOLE

Differentiation Between Complete And Partial Mole

Partial Mole
Complete Mole
Feature
Present
Absent
Embryonic or foetal tissue
Focal
Diffuse
Swelling of the villi
Focal
Diffuse
Trophoblastic hyperplasia
Paternal and maternal 69 XXY or 69 XYY
Paternal 46 XX (96%) or 46 XY (4%)
Karyotype
Rare (< 0.5% of cases)
In up to 20% of cases
Persistent trophoblastic disease


complete hydatidiform mole(CHM):
the entire uterus filled with abnormal vesicles, no signs of fetus.

partial hydatidiform mole

Normal trophoblastic
partial hydatidiform mole
complete hydatidiform mole


trophoblastic proliferation is considered the most important single criteria The initial histologic features of any lesion identified as GTN are less important than the clinical data and hCG level. So the subsequent management depends more on the hCG results than the histological reports.

High hCG causes:

multiple theca lutein cysts in the ovaries in about 50% of cases.
exaggeration of the normal early pregnancy symptoms and signs
Pathology

The majority of the patients with complete hydatiform mole are diagnosed prior to 16 weeks of gestation, or often earlier nowadays. The clinical presentation of CHM has changed considerably over the past few decades. Excessive uterine size, anaemia, hyperemesis, preeclampsia, theca lutein cysts, hyperthyroidism and metastatic disease are seen far less often.
Clinical Features



Patients with a complete mole present with: vaginal bleeding, uterine enlargement greater than expected for gestational age and an abnormally high level of serum hCG. Medical complications include pregnancy induced hypertension, hyperthyroidism, hyperemesis, anaemia and the development of ovarian theca lutein cysts. The ovarian hyperstimulation and enlargement of both ovaries may subsequently lead to ovarian torsion or rupture of theca lutein cysts.

Bleeding : Bleeding in early pregnancy after variable period of amenorrhea is the most common clinical sign of the mole (occurs in 90% of cases), with the passage of the vesicles.


Hyperemesis gravidarum: occurred in 25% of women with complete mole. particularly with excessive uterine size & markedly elevated hCG

Uterine enlargement: The uterus is commonly “large for date”in 50% of case of moles ,although, in a small proportion of cases the uterus corresponding to the gestational age or smaller than date. The uterus having a doughy consistency. The fetal parts are not palpable, and fetal heart is absent.

Theca lutein ovarian cysts: - 50% of patients with complete mole - result from high hCG levels, cause ovarian hyperstimulation - after molar evacuation, cysts normally regress spontaneously within 2 to 4 months


Pre-eclampsia: Occur in association with the moles with range widely from 12-54%, these due to differing times of diagnosis, the longer pregnancy progresses, the greater chance to developing pre-eclampsia. If the signs of pre-eclampsia appears early in pregnancy, the possibility of hydatidiform mole should be looked for with out delay.


Hyperthyrodism: Develop in small proportion of women ,and this may be due to thyrotrophic effects of the human chorionic gonadotrophin , which may lead to goitre, fine tremor ,supra-ventricular tachycardia, and weight loss.


DIC can develop in long-standing hydatidiform moles , when there is embolization of trophoblastic tissue to the lung, leads to thromboplastic substances which stimulate fibrin,and platelet deposition.


Partial H-mole • Do not have the dramatic clinical feature • In general, patients have the sign and symptoms of incomplete or missed abortion • partial mole can be diagnosed after histologic review of the tissue obtained by curettage

Diagnosis

History and examination Ultrasound B-hCG histopathology
Diagnosis


Ultrasonography: It is a reliable and sensitive technique for the diagnosis of complete molar pregnancy. Because the chorionic villi exhibit diffuse hydatidiform swelling. Complete moles produce a characteristic vesicular sonographic pattern, usually referred to as a “snowstorm” pattern.

*

Partial Hydatidiform Mole

Ultrasonography may also contribute to the diagnosis of partial molar pregnancy by demonstrating focal cystic spaces in the placental tissues and an increase in the transverse diameter of the gestational sac.
Ultrasound has limited value in detecting partial molar pregnancies.
U/S evaluation.

Partial mole

Complete mole



The clues for the sonographer in this diagnosis are the presence of a fetus (although usually with severe, but nonspecific, abnormalities) in combination with a formed placenta containing numerous cystic spaces
U/S evaluation.
Partial Hydatidiform Mole

Other investigation

For medical complication: Preeclampsia Hyperthyroidism Electrolyte imbalance Anemia Coagulation study For malignant GTN(invasive mole, choriocarcinoma, PSTD): Chest radiograph Liver function tests

* Management

Emptying uterine cavity Follow up
Management

Evacuation of Molar Pregnancies 

once the diagnosis is confirmed the uterine cavity should be emptied as soon as possible.

1. Complete HM

Suction curettage is the method of choice of evacuation for complete molar pregnancies.

The risk of bleeding with or without perforation is significant but uterine evacuation for a complete mole is superior to both medical evacuation of the uterus (may lead to increased risk of dissemination) and hysterectomy.


Medical termination of complete molar pregnancies, including cervical preparation prior to suction evacuation should be avoided where possible. because of the potential to embolise and disseminate trophoblastic tissue through the venous system.
oxytocic infusions are only commenced once evacuation has been completed. If the patient is experiencing significant haemorrhage prior to evacuation and some degree of control is required then use of these agents will be necessary according to the clinical condition.


Suction curettage is the method of choice for evacuation of partial molar pregnancies except when the size of the fetal parts deters the use of suction curettage, then medical termination can be used. .
2. Partial HM

There is no clinical indication for the routine use of a second uterine evacuation in the management of molar pregnancies. This may be recommended in selected cases with persisting mild symptom and lower level of hCG.
Evacuation of Molar Pregnancies

Hysterectomy: For older patient with localized disease who complete her family & desire sterilization. - the ovaries may be preserved, even though prominent theca lutein cysts are present - hysterectomy does not prevent metastasis, so, still required follow up with hCG levels

management of luteinizing cyst: After molar evacuation, cysts normally regress spontaneously within 2 to 4 months

It is important that women who have had a hydatidiform mole: should have close follow-up by serum hCG levels after the evacuation of the uterus, to ensure early recognition of persistent trophoblastic tissue .
*/21 Follow up


*/21 1. symptom: abnormal vaginal bleeding, cough, hemoptysis, signs of metastasis 2. Human Chorionic Gonadotropin (hCG) Weekly until normal for 3 consecutive weeks then monthly until normal for 6 consecutive months 3. Contraception: patients should be used effective contraception during the entire interval of hCG follow up

Women with GTD should be advised to use barrier methods of contraception until hCG levels revert to normal. Once hCG level have normalised, the combined oral contraceptive pill may be used. There is no evidence as to whether single-agent progestogens have any effect on GTN. Intrauterine contraceptive devices should not be used until hCG levels are normal to reduce the risk of uterine perforation.

Pregnancy after hydatidiform mole

Should undertakeUltrasound during first trimesterβ hCG 6 wks after completion of pregnancy

* Prognosis

complete mole has the latent risk of local invasion or telemetastasisThe high-risk factors includesβ-HCG>100000IU/Luterine size is obviously larger than that with the same gestational time.the luteinizing cyst is >6cmIf >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

Indication of chemotherapy after the evacuation of the hydatidiform mole :

High (>2ooooIU/L in serum), static or rising hCG level after one or two uterine evacuation. Persistent uterine hemorrhage after evacuation of mole with raised hCG levels. Persistent hCG elevation 6 months after evacuation. Evidence of metastases: hepatic, brain, and pulmonary.

Hydatidiform mole (compiete or parial )

Evacuation by suction D&C (hysterectomy only sterllization desired )
Monitor serum B-hCG weekly Good contraception

hCG returns to negative

hCG levels q month X 6
May again attempt pregnancy if desired
hCG plateaus or rises
Exclude new pregnancy
Stage and treat with chemotherapy
Algorithm for management of a patient with hydatidiform mole

Key points:

Gestational trophoblastic disorders represent an abnormal proliferation of trophoblastic tissue, leading to often massive placental overgrowth, occasional invasion and rarely even metastases. Large differences in incidence between different racial groups have been reported. All secrete human chorionic gonadotrophin (hCG), making it a very useful tool to monitor treatment and screen for recurrence.

Hydatidiform mole is the commonest type of gestational trophoblastic disease. Treatment is by uterine evacuation by suction curettage. The risk of bleeding with or without perforation is significant. It is important to track hCG after uterine evacuation to ensure that there is no residual tissue and that there is no invasion.

Following a complete mole, the patient must wait at least 6 months from the hCG returning to 0 (or for 1 year following chemotherapy) before trying for a further pregnancy to minimize the risks of recurrence. There is an increased recurrence risk in subsequent pregnancies, the risk of a second mole is 2% and a third 20%. Follow-up with checking of hCG levels must be undertaken after any subsequent pregnancy.