THE MANAGEMENT OF GESTATIONAL TROPHOBLASTIC NEOPLASIA 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

EPIDEMIOLOGY 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.

The incidence after a live birth is estimated at 1/50 000. 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.

Background Hydatidiform mole can be subdivided into complete and partial mole based on: Genetic and Histopathological features.

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:

Partial moles Are triploid in origin with two sets of paternal haploid genes and one set of maternal haploid genes.

Partial mole

Partial moles They occur, in almost all cases, following dispermic fertilization of an ovum. There is usually evidence of a fetus or fetal red blood cells.

The widespread use of ultrasound has led to earlier diagnosis of pregnancy and has changed the pattern of molar pregnancy.

symptoms of early pregnancy failure, 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 FACTORS Nulliparity Extremes 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.

Diagnosis of gestational trophoblastic neoplasia Early complete molar pregnancies are commonly associated with the ultrasound diagnosis of delayed miscarriage or anembryonic pregnancy. C

in Complete moles reveals: Ultrasonography in Complete moles reveals: The characteristic intrauterine " snow storm" appearance, No identifiable foetus, Bilateral ovarian cysts may be detected.

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. Ultrasonography has limited value in detecting partial molar pregnancies.

Diagnosis of gestational trophoblastic neoplasia 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. C

Diagnosis of gestational trophoblastic neoplasia Estimation of human chorionic gonadotrophin (hCG) levels may be of value in diagnosing molar pregnancies. C

Diagnosis of gestational trophoblastic neoplasia 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. C

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 curettage Is the method of choice of evacuation for complete molar pregnancies. C

Suction curettage 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.

Medical termination of complete molar pregnancies Including cervical preparation prior to suction evacuation, should be avoided where possible. C

Routine use of oxytocic agents There is theoretical concern, because of the potential to embolize and disseminate trophoblastic tissue through the venous system. C

Evacuation of molar pregnancies 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. C

Evacuation of molar pregnancies 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. C

Evacuation of molar pregnancies 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. C

Evacuation of partial mole In partial molar pregnancies where the size of the fetal parts deters the use of suction curettage, medical termination can be used. 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

Histological examination of products of conception 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. C

Histological examination of products of conception 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. C

Histological examination of products of conception Products of conception from therapeutic terminations of pregnancy should be examined if there is no evidence of fetal tissue. 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

The management of women with gynecological symptoms after evacuation of a molar pregnancy There is no clinical indication for the routine use of a second uterine evacuation in the management of molar pregnancies. D

The management of women with gynecological symptoms after evacuation of a molar pregnancy Uterine evacuation may be recommended, in selected cases, by the screening centre as part of the management of persistent trophoblastic neoplasia. 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 after a non molar pregnancy 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. C

Persistent GTN after a non molar pregnancy Persistent GTN should be considered in any woman developing acute respiratory or neurological symptoms after any pregnancy. C

Persistent GTN after a non molar pregnancy 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 . 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

Treatment of persistent GTN 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. 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 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. C

Future pregnancy Women should be advised not to conceive until the hCG level has been normal for six months. C

Future pregnancy 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. C

Future pregnancy Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment. C

Contraception and hormone replacement therapy 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. D

Thank you