Dr. Ahmed jasim
Objective of this lecture: To define GTD. To know the histological types of GTD. To study the incidence and the risk factors of GTD. To differentiate histopathologically between various types of GTD. To know the presentation of GTD.6. To know the ultrasonic and the laboratory findings. 7. To know the risk factors for malignant changes after any pregnancy. 8. To plan management and post treatment surveillance for benign GTD. 9. To diagnose malignant changes after evacuation of a mole.
10. To classify malignant GTD into low risk and high risk group. 11. To know the treatment of each group of malignant GTD.
DEFINITION GTD is a spectrum of neoplastic disorders that arise from placental trophoblastic tissue after abnormal fertilization. Malignant GTD almost always following complete molar pregnancy, but can occur after any gestation. e.g. abortion, ectopic, or term pregnancy. The maternal tumor arises from fetal not maternal tissue.
HISTOLOGICAL TYPES OF GTD Nonmalignant GTD: a. Complete hydatidiform mole. partial mole. 2. Malignant GTD which are a. Persistent /invasive GTD b. Choriocarcinoma c. Placental site trophoblastic tumor
GESTATIONAL TROPHOBLASTIC NEOPLASIA (GTN)
Complete vesicular mole Partial vesicular mole Invasive mole Placental-site trophoblastic tumor ChoriocarcinomaEPIDEMIOLOGY There is geographical variations in the incidence. Hydatidiform mole complicates 1-2 of 1000 pregnancies. Choriocarcioma occurs in 1 in every 30000 pregnancy Malignant GTD is the fourth common gynecological malignancy in Iraq after carcinomas of the ovary, endometrium and cervix.
Incidence:
1:2000 pregnancies in United States and Europe, but 10 times more in Asia. Predisposing factors include : Race,deficiency of protein or carotene The incidence is higher toward the beginning and more toward the end of the childbearing period. It is 10 times more in women over 45 years old.However, this may under represent the true incidence of the disease because of problems with reporting, particularly with regard to partial moles.
Persistent GTN may develop after a : Molar pregnancy, Non-molar pregnancy or Live birth. The incidence after a live birth is estimated at 1/50 000.
Hydatidiform mole can be subdivided into complete and partial mole based on: Genetic and Histopathological features.
Background
Complete moles
Complete moles are diploid and androgenetic in origin, with no evidence of fetal tissue.Complete moles
Usually arise as a consequence of duplication of the haploid sperm following fertilization of an ‘empty’ ovum. Some complete moles arise after dispermic fertilization of an ‘empty’ ovum.Complete mole:
Are triploid in origin with two sets of paternal haploid genes and one set of maternal haploid genes.Partial moles
Partial mole
They occur, in almost all cases, following dispermic fertilization of an ovum. There is usually evidence of a fetus or fetal red blood cells.Partial moles
The widespread use of ultrasound has led to earlier diagnosis of pregnancy and has changed the pattern of molar pregnancy.
The majority of women present with : symptoms of early pregnancy failure, while presentation with: Hyperemesis, Early severe pre-eclampsia and Hyperthyroidism is very rare.
RISK FACTORSNulliparityExtremes of maternal age( under 20 and over 35)The presence of enlarged theca lutien ovarian cysts.Abnormally elevated beta –hCG concentrations during pregnancy.History of previous GTD (double the risk).
PATHOLOGY In complete mole characterized by the lack of a fetus, trophoblastic hyperplasia, edematous chorionic villi, and a loss of normal villous blood vessels. Partial mole may contain some normal appearing chorionic villi and fetal tissue. The hydropic changes are focal and less prominent with little hyperplasia and no atypia of the surrounding trophoblast.
Choriocarcinoma: The lesion appears as sheets of anaplastic cytotrophoblasts and syncytiotrophblasts frequent mitoses, and multinucleated giant cells without chorionic villi.
CLINICAL FEATURES: Complete and partial mole present with: 1. bleeding in early pregnancy. 2. Hyperemesis gravidarum. 3. Uterine size greater than expected for gestational age and absent fetal heart sounds. 4. Early onset pre-eclampsia(< 24 weeks of gestation) 5. Thyrotoxicosis 6. Excessively elevated serum B-hCG(>100,000 mIU/mL)
CLINICAL FEATURES OF MALIGNANT GTD Persistent vaginal bleeding after evacuation of a mole or after any pregnancy. Secondary postpartum hemorrhage. 3. Symptoms of metastasis to the lung, brain, liver, and vagina. With all these features there is always elevated serum hCG level.
RISK FACTORS FOR DEVELOPING MALIGNANT GTD AFTER ANY TYPE OF PREGNANCY Maternal age over 35 years. Increasing parity. Prolonged use of oral contraception( over 5 years). Maternal type A blood group. History of prior GTD.
Early complete molar pregnancies are commonly associated with the ultrasound diagnosis of delayed miscarriage or anembryonic pregnancy.
Diagnosis of gestational trophoblastic neoplasia
C
Complete moles may be associated with suggestive ultrasonographic changes in the placenta.
Diagnosis of gestational trophoblastic neoplasia
C
in Complete moles reveals: The characteristic intrauterine " snow storm" appearance, No identifiable foetus, Bilateral ovarian cysts may be detected.
Ultrasonography
A real-time ultrasound of a hydatidiform mole. The dark circles of varying sizes at the top center are the edematous villi.
has limited value in detecting partial molar pregnancies.
UltrasonographyThe increasing use of ultrasound in early pregnancy has probably led to the earlier diagnosis of molar pregnancy.
Diagnosis of gestational trophoblastic neoplasia
C
However, the majority of histologically proven complete moles are associated with an ultrasound diagnosis of delayed miscarriage or anembryonic pregnancy.
Diagnosis of gestational trophoblastic neoplasia
C
The ultrasound features of a complete mole are reliable. But the ultrasound diagnosis of a partial molar pregnancy is more complex.
Diagnosis of gestational trophoblastic neoplasia
C
The finding of multiple soft markers, including both : cystic spaces in the placenta and a ratio of transverse to anterior-posterior dimension of the gestation sac of greater than 1.5 is required for the reliable diagnosis of a partial molar pregnancy.
Diagnosis of gestational trophoblastic neoplasia
C
Estimation of human chorionic gonadotrophin (hCG) levels may be of value in diagnosing molar pregnancies.
Diagnosis of gestational trophoblastic neoplasia
C
When there is diagnostic doubt about the possibility of a combined molar pregnancy with a viable fetus then ultrasound examination should be repeated before intervention.
Diagnosis of gestational trophoblastic neoplasia
C
The pregnancy should be allowed to proceed if the mother wishes, following appropriate counselling.
Twins, when there is one viable fetus and the other pregnancy is molar
C
The probability of achieving a viable baby is 40% and there is a risk of complications such as pulmonary embolism and pre-eclampsia.
C
Twins, when there is one viable fetus and the other pregnancy is molar
Evacuation of molar pregnancies
Surgical evacuation of molar pregnancies is advisable. Routine repeat evacuation after the diagnosis of a molar pregnancy is not warranted.C
Is the method of choice of evacuation for complete molar pregnancies.
Suction curettageC
Because of the lack of fetal parts a suction catheter, up to a maximum of 12 mm, is usually sufficient to evacuate all complete molar pregnancies.
Suction curettage
Including cervical preparation prior to suction evacuation, should be avoided where possible.
Medical termination of complete molar pregnancies
C
There is theoretical concern, because of the potential to embolize and disseminate trophoblastic tissue through the venous system.
Routine use of oxytocic agents
C
The contraction of the myometrium may force tissue into the venous spaces at the site of the placental bed. The dissemination of this tissue may lead to the profound deterioration in the woman, with embolic and metastatic disease occurring in the lung.
C
Routine use of oxytocic agents
It is recognized that significant haemorrhage may occur as a consequence of evacuating a large uterine cavity, It is recommended, where possible, that oxytocic infusions are only commenced once evacuation has been completed.
Evacuation of molar pregnancies
C
If the woman is experiencing significant haemorrhage prior to evacuation and some degree of control is required ,then use of oxytocic infusions will be necessary according to the clinical condition.
Evacuation of molar pregnancies
C
It is suggested that prostaglandin analogues should be reserved for cases where oxytocin is ineffective. Because evacuation of a large molar pregnancy is a rare event, advice and help from an experienced colleague should be sought where appropriate.
Evacuation of molar pregnancies
C
In partial molar pregnancies where the size of the fetal parts deters the use of suction curettage, medical termination can be used.
Evacuation of partial mole
C
Partial molar pregnancies
These women may be at an increased risk of requiring treatment for persistent trophoblastic neoplasia, although the proportion of women with partial mole needing chemotherapy is low (0.5%).
C
Histological examination of products of conception
All products of conception obtained after evacuation (medical or surgical) should undergo histological examination.C
In view of the difficulty in making a diagnosis of a molar pregnancy before evacuation, the histological assessment of material obtained from the medical or surgical management of incomplete abortions is recommended in order to exclude trophoblastic neoplasia.
Histological examination of products of conception
C
Because persistent trophoblastic neoplasia may develop after any pregnancy it is recommended that all products of conception obtained after repeat evacuation should undergo histological examination.
Histological examination of products of conception
C
Products of conception from therapeutic terminations of pregnancy should be examined if there is no evidence of fetal tissue.
Histological examination of products of conception
C
The management of women with gynecological symptoms after evacuation of a molar pregnancy
In cases where there are persisting symptoms, such as vaginal bleeding, after initial evacuation, consultation with the screening centre should be sought before surgical intervention.C
There is no clinical indication for the routine use of a second uterine evacuation in the management of molar pregnancies.
The management of women with gynecological symptoms after evacuation of a molar pregnancy
D
Uterine evacuation may be recommended, in selected cases, by the screening centre as part of the management of persistent trophoblastic neoplasia.
The management of women with gynecological symptoms after evacuation of a molar pregnancy
D
Persistent GTN after a non molar pregnancy
Women with persistent abnormal vaginal bleeding after a non molar pregnancy should undergo a pregnancy test to exclude persistent GTN.C
Persistent GTN can occur after nonmolar pregnancies. Vaginal bleeding is a common presenting symptom but symptoms from metastatic disease, such as dyspnoea or abnormal neurology, can occur.
Persistent GTN after a non molar pregnancy
C
Persistent GTN should be considered in any woman developing acute respiratory or neurological symptoms after any pregnancy.
Persistent GTN after a non molar pregnancy
C
The prognosis for women with GTN after nonmolar pregnancies may be worse (21% mortality after a live birth, 6% after a nonmolar miscarriage) and in part due to the delay in diagnosis .
Persistent GTN after a non molar pregnancy
C
Registration of women with molar pregnancy
Registration of any molar pregnancy is essential.C
Women with the following molar pregnancies should be registered and require follow up for 6–24 months as determined by the screening centre:Complete Hydatidiform molePartial Hydatidiform moleTwin pregnancy with complete or partial hydatidiform moleChoriocarcinomaPlacental site trophoblastic tumour. C
Treatment of persistent GTN
Women with persistent GTN should be treated at a specialist centre with appropriate chemotherapy.C
Treatment of persistent GTN
The need for chemotherapy following a complete mole is 15% and 0.5 % after a partial mole.C
Women with evidence of persistent GTN should undergo assessment of their disease followed by chemotherapy. Disease risk is scored according to the FIGO staging for GTN.
Treatment of persistent GTN
C
Women scoring six or less (low risk) receive intramuscular methotrexate on alternate days, followed by six rest days, with each course consisting of four injections.
Treatment of persistent GTN
C
Treatment of persistent GTN
Women who develop resistance to methotrexate are treated with a combination of intravenous dactinomycin and etoposide. Women scoring seven or more (high risk) receive combination chemotherapy.
C
Placental site trophoblastic tumour is now recognized as a variant of gestational trophoblastic neoplasia. Surgery and multi-agent chemotherapy play major roles in the clinical management of this tumour.
Placental site trophoblastic tumour
C
Future pregnancy
Women should be advised not to conceive until the hCG level has been normal for six months.C
The risk of a further molar pregnancy is low (1/55) and More than 98% of women who become pregnant following a molar pregnancy will not : Have a further mole or Be at increased risk of obstetric complications.
Future pregnancy
C
If a further molar pregnancy does occur, in 68–80% of cases it will be of the same histological type. Future pregnancy
C
After the conclusion of any further pregnancy (at any gestation) further urine or blood samples for hCG estimation are requested to exclude disease recurrence.
Future pregnancy
C
Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment.
Future pregnancy
C
Contraception and hormone replacement therapy
The combined oral contraceptive pill and hormone replacement therapy are safe to use after hCG levels have reverted to normal.C
The combined pills, if taken while hCG levels are raised, may increase the need for treatment. However, it can be used safely after the hCG levels have returned to normal.
Contraception and hormone replacement therapy
D
The small potential risk of using emergency hormonal contraception, in women with raised hCG levels, is outweighed by the potential risk of pregnancy to the woman.
Contraception and hormone replacement therapy
D