Gestational Trophoblastic Disease ppt

8/12/2019 Gestational Trophoblastic Disease ppt

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Fetal Medicine

Gestational Trophoblastic Disease

Jeannet E. Canda, RN,MAED

NDDUCollege of Nursing


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Gestational Trophoblastic Disease (GTD)is a relatively rare event with a calculated incidence of 1/714 livebirths.

There is evidence of ethnic variation in the incidence of GTD in theUK, with women from Asia having a higher incidence compared withnon-Asian women (1/387 versus 1/752 live births).

This may under-represent the true incidence of the diseasebecause of problems with reporting, particularly with regard topartial moles.


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Hydatiform mole

Invasive mole

Choriocarcinoma

Placental site trophoblastic tumor

Partial

Complete

GESTATIONAL TROPHOBLASTIC DISEASE


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Epidemiology

The incidence of molar pregnancy varies in different parts of the

world.

Women of Asian origin: 1 in 550 to 1 in 600.

Women of European origin: 1 in 1200 live births


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Age is probably the most important factor in the incidence ofdeveloping complete hydatidiform mole.

Where the incidence for women aged 25 to 29 is standardized

as 1, the risk is

6 X in women who become pregnant under 15 years

411 X in patients who become pregnant over the age of 50

Epidemiology


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North America and Europe:

Partial mole 1/700

Complete mole 1/1500-2000

Asian Countries:

Partial mole 1/120

Complete mole 1/350-500

HYDATIDIFORM MOLE

Incidence


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1. Maternal age > 40 years

< 15 years

2. Paternal age > 45 years

3. Previous hydatidiform mole 1st

1-2%2nd 15-28%

4. Vitamin A deficiency

HYDATIDIFORM MOLE

Risk factors


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Background

Hydatidiform mole is subdivided into complete and partial molebased on genetic and histo-pathological features.

Complete moles are diploid andro-genetic in origin no evidence of fetal tissue.

Arise as a consequence of

1. duplication of the haploid sperm following fertilisation of an emptyovum ( diandry)2. Some complete moles arise after dispermic fertilisation of an

empty ovum. (dispermy)

Molar PregnancyComplete Mole


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Emptyovum

Empty

ovum

46XX

46XX

or 46XY

23X or Y23X

23XComplete Mole

(46XX diploid)

Complete Mole (46XXor 46XY, diploid)

A single sperm fertilizes an

empty ovum, with duplicationof the 23X haploid set ofchromosomes, giving rise to ahomozygous diploid complete

mole.

Two sperms with twoindependent haploid sets ofchromosomes fertilize anempty ovum, producing a

dyspermic complete mole witheither 46XX or 46XY

karyotype.

COMPLETE MOLE

Modified from Cheung, 1995


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Complete molar pregnancy

Complete hydatidiform mole forms a multivesicular mass withdiffuse hydropic villi and a variable degree of trophoblasticproliferation.

There is usually no evidence of a foetus. This conceptus is diploid

and androgenetic in origin.

The incidence of a GT Tumour is approximately 1000X more likelyfollowing a complete hydatidiform mole than after a full-term

pregnancy.One possible explanation is that genomic imprinting plays arole in tumourigenesis since the complete mole is androgenetic inorigin.


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l d


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F l M d


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F l M di i


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Triploid in origin with usually two sets of paternal haploid genes and

one set of maternal haploid genes.

They occur, in almost all cases, following dispermicfertilisation of an ovum. There is usually evidence of a fetusor fetal red blood cells.

In some cases failure of meiosis I or II in the ovum leads to

Triploidy with 46 maternally derived chromosomes and 23paternal

Partial Molar Pregnancy

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23X 23X

Dyspermy23X/23Y or23X/23X

23Y

Partial Mole (69XXY,or 69XXX, or 69XYY

triploid)

PARTIAL MOLE

23X

23X

23Y

69XXY

Fertilization of a normal 23X haploid ovum by two sperms, producing atriploid partial mole with either 69XXY, 69XXX or 69XYY karyotype

Modified from Cheung, 1995

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Fetal or embryonic tissue absent present

Hydatiform swelling of chorionic villi extensive focal

Trophoblastic hyperplasia extensive focal

Scalloping of chorionic villi absent present

Trophoblastic stromal inclusions absent present

Karyotype 46XX (90%); Triploid (69 XXY)

46XY (10%)

Complete mole Partial mole

Cohn DE, Herzog TJ. Curr Opin Oncol 2000 Sep; 12(5):492-6

FEATURES OF PARTIAL AND COMPLETE MOLE

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Persistent GTD

The term persistent "gestational trophoblastic disease" is widelyused to describe the situation where a woman has had ahydatidiform mole and still has persistently raised human chorionicgonadotrophin (hCG) estimations

Since in the majority of cases the disease either remitsspontaneously or can be successfully treated without furtherpathological sampling, it is difficult to say exactlyin whatproportion of patients their hydatiform mole modulates to

choriocarcinoma.This event probably happens in 3% to 5% of patients who have hada complete hydatidiform mole

F t l M di i


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Gestational Trophoblastic Disease

Persistent GTD may develop

1. After a molar pregnancy,

2. After a non-molar pregnancy3. After a live birth (~ 1/50 000)

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Gestational Trophoblastic Tumours

Overview

GTT are unique in cancer biology in that they follow

1. either a normal or abnormal pregnancy,

2. the tumours contain paternal genes and are therefore anallograft in the maternal host.

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Invasive Hydatidiform Mole

Invasive hydatidiform mole (complete or partial) is common since

molar trophoblast invades the myometrium in most cases.

Pathologically invasive hydatidiform mole can be diagnosed only

when sufficient myometrium is made available to the pathologist

either on curettings or by hysterectomy

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Invasive Hydatidiform Mole

An invasive mole retains hydropic villi, which penetrate theuterine wall.

Can cause uterine rupture and can be life threatening.

Hydropic villi may embolize to distant organs, but this tumordoes not have metastatic potential.

Cure is possible by hysterectomy or chemotherapy.

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Choriocarcinoma

It is an unusual tumour in that it stimulates virtually no stromal

reaction and is therefore essentially a mixture of haemorrhage and

necrosis with tumour cells scattered within the mass.

Tumour cells can be scanty and present problems of pathologicalinterpretation if the possibility of choriocarcinoma has not been

raised.

The pathology of choriocarcinoma is reflected in its clinicalbehaviour with widespread intravascular dissemination to lungs,

brain and other sites.

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Choriocarcinoma

Is a very aggressive malignant tumor and arises either from

gestational chorionic epithelium or less frequently, from

totipotential cells within gonads or elsewhere.

Incidence is 1/ 30,000 pregnancies in US.

More common in Asian and African countries.

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Choriocarcinoma

Most cases are discovered by the appearance of a bloody, brownishdischarge, accompanied by a rising titer of HCG, particularly thebeta subunit.

Usually appear as very hemorrhagic, necrotic masses within theuterus.

Widespread dissemination via blood, lung (50%), vagina (30-40%),

brain, liver and kidney.

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Placental site trophoblastic tumours

Placental site trophoblastic tumours are now recognised as aseparate entity.

1. rare and2. are composed mainly of cytotrophoblastic cells

3. tend to be locally invasive4. less widely metastatic than choriocarcinoma

The optimal management of patients with placental sitetrophoblastic tumours is unclear.

This is because(i) the tumours are rare and(ii) their biological behaviour does appear to be variable.

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Where the disease is localised to the uterus, hysterectomy is thetreatment of choice.

A small number of patients treated with intensive chemotherapyinitially have achieved complete remission but the chemosensitivityof placental site trophoblastic tumours appears to be quite variable

Placental site trophoblastic tumours

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Clinical presentation

The most common presentation of a patient with a GTD is1. vaginal bleeding towards the end of the first trimester of

pregnancy.2. nausea and vomiting and3. uterus larger for dates than for a normal pregnancy.

Since the quantity of hCG produced by a normal pregnancy can varyover quite a wide range, the initial hCG estimation is not helpful in

differentiating between a pregnancy and a hydatidiform mole.

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COMPLETE HYDATIFORM MOLE

CLINICAL FEATURES

Vaginal bleeding (anemia) 97%

Excessive uterine size 50%

Theco-lutein ovarian cysts 50%

Preeclampsia 27%

Hyperemesis 25%

Hyperthyroidism 7%

Trophoblastic embolization 2%(respiratory distress)

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The increasing performance of ultrasound examination,

either routinely in the first trimester or for management of

early pregnancy complications, allows evacuation of mostpregnancies affected by hydatiform mole prior to

development of the classic sonographic and pathological

features.

ULTRASOUND FINDINGS

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Multiple hypoechoic areas extensive focal

Increased echogenicity extensive focalEnlarged uterine volume present absent

Theca-lutein cysts present absent

> gestational sac - present

< Uterine artery PI present -

Complete mole Partial mole

ULTRASOUND FINDINGS

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Diagnosis of Gestational Trophoblastic Disease

Increasing use of ultrasound in early pregnancy has led to the

earlier diagnosis of molar pregnancy.

The majority of histologically proven complete moles however are

associated with an ultrasound diagnosis of delayed miscarriage oranembryonic pregnancy

The ultrasound features of a complete mole are reliable but the

ultrasound diagnosis of a partial molar pregnancy is more complex.RCOG, February 2004

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Management of GTD

Suction curettage is the method of choice of evacuation for

complete molar pregnancies.

Because of the lack of fetal parts a suction catheter, up to a

maximum of 12 mm, is usually sufficient to evacuate all completemolar pregnancies

Medical termination of complete molar pregnancies, including

cervical preparation prior to suction evacuation, should be avoidedwhere possible because of the potential to embolise and

disseminate trophoblastic tissue through the venous system

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In partial molar pregnancies where the size of the fetal partsdeters the use of suction curettage, medical termination can beused.

These women may be at an increased risk of requiring treatmentfor persistent trophoblastic neoplasia, although the proportion ofwomen with partial molar pregnancies needing chemotherapy is low(0.5%)

Management of GTD

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Gestational Tropholastic Neoplasia-Requirement for diagnosis

1. 4 or more values of hCG plateau over ay least 3 weeks

2. A rise of hCG of 10% or greater for > 3 values over at least 2weeks

3. Presence of Choriocarcinoma

4. Persistence of hCG 6 months after mole evacuation

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Women scoring >7 (high risk) receive combination chemotherapy.

IV Etoposide, Methotrexate, Actinomycin D for 2 daysfollowed by Cyclophosphamide and Vincristine (Oncovin) (EMA-CO)

one week later.

The course is then repeated after six days.Charing Cross Hospital, London

Treatment of persistent GTD

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Future pregnancy

Women should be advised not to conceive until their hCG levels

have been normal for six months.

Women who undergo chemotherapy are advised not to conceive for

one year after completion of treatment

Risk of a further molar pregnancy is low (~ 2%)

>98% of women who become pregnant following a molar pregnancy

will not have a further mole or be at increased risk of obstetric

complications.

If a further molar pregnancy does occur, in 6880% of cases it will

be of the same histological type

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Follow-up and Fertility after Chemotherapy

Approximately 90% of patients who want to become pregnant

following chemotherapy have succeeded and there is no evidence of

increase in foetal abnormalities.

Occasionally a G.T.T. can occur or recur after a subsequent normalpregnancy

This emphasises the importance of reconfirming that hCG levels

return to normal after any subsequent pregnancy in a woman who

has had a trophoblastic disease event

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Contraception and hormone replacementtherapy

The COC-pill, if taken while hCG levels are raised, may increase theneed for treatment.

However, it can be used safely after the hCG levels have returnedto normal.

Other forms of hormonal contraception do not appear to be linkedto an increased need for treatment.

The small potential risk of using emergency hormonalcontraception, in women with raised hCG levels, is outweighed by

the potential risk of pregnancy to the woman.

Hormone replacement therapy may be used safely once hCG levelshave returned to normal.

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Survival

The overall survival in the Charing Cross series, with a maximum

follow-up of 15 years is ~ 94%

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The successful outcome in patients with GTT depends on severalfactors:-

(i)Need for a national registration scheme of patients at risk ofdeveloping a GTT(ii)The ability to monitor the disease and its response totreatment with serial hCG estimations.(iii)The intrinsic biological property of GTT in being inherentlyvery sensitive to a range of chemotherapeutic agents.

Survival

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Gestational Trophoblastic Disease ppt