Gestational trophoblastic disease for undergraduate

Gestational Gestational Trophoblastic DiseaseTrophoblastic Disease

Classification Classification

1.1. Hydatidiform (vesicular )mole Hydatidiform (vesicular )mole Complete and PartialComplete and Partial

2.2. Invasive mole Invasive mole

3.3. Choriocarcinoma Choriocarcinoma

4.4. Placental-site trophoblastic tumorPlacental-site trophoblastic tumor

Vesicular moleVesicular moleVesicular moleVesicular mole

Vesicular moleVesicular moleVesicular moleVesicular mole

It is a benign neoplasm of the chorionic villi It is a benign neoplasm of the chorionic villi characterized bycharacterized by

1.1. Marked proliferation of the trophoplast,both Marked proliferation of the trophoplast,both the syncytium & cytotrophoplast are affected.the syncytium & cytotrophoplast are affected.

2.2. Oedema or hydropic degeneration of the Oedema or hydropic degeneration of the connective tissue stroma of the villi which leads connective tissue stroma of the villi which leads to their distension and formation of vesicles.to their distension and formation of vesicles.

3.3. Avascularity of the villi: the blood vessels Avascularity of the villi: the blood vessels disappear from villi explaining early death of disappear from villi explaining early death of the embryothe embryo

• Hyperplasia of trophobasitc cells

• Hydropic swelling of all villi

• Vessels are usually absent

Normal villaVM

IncidenceIncidence 1:2000 pregnancies in United States and Europe, 1:2000 pregnancies in United States and Europe,

10 times more in Asia. 10 times more in Asia.

Predisposing factors includePredisposing factors include : :

Race, deficiency of protein or caroteneRace, deficiency of protein or carotene

The incidence is higher toward the beginning and The incidence is higher toward the beginning and more toward the end of the childbearing period.more toward the end of the childbearing period.

It is 10 times more in women over 45 years old.It is 10 times more in women over 45 years old.

PathologyPathologyThe uterus is distended byThe uterus is distended by thin walled, translucent, thin walled, translucent, grape-like grape-like vesiclesvesicles of of different sizes. different sizes. These are These are degenerated chorionic villidegenerated chorionic villi filled with filled with

fluid.fluid. There is There is no vasculature in the chorionic villino vasculature in the chorionic villi

leads to early death of the embryo.leads to early death of the embryo.

High hCG causes High hCG causes multiple theca lutein cystsmultiple theca lutein cysts in the ovaries in about 50% of cases.in the ovaries in about 50% of cases.

Cysts may reach a large size (10 cm or more.Cysts may reach a large size (10 cm or more.

Cysts disappearCysts disappear within few months(2-3),within few months(2-3), after evacuation of the mole. after evacuation of the mole.

PathologyPathology

(i) Complete mole(i) Complete mole The whole conceptus is transformed into a The whole conceptus is transformed into a

mass of vesicles.mass of vesicles.

No embryoNo embryo is present. is present.

It is the result of fertilization of enucleated It is the result of fertilization of enucleated ovum ( has no chromosomes) with a sperm ovum ( has no chromosomes) with a sperm which will duplicate giving rise to which will duplicate giving rise to 46 46 chromosomeschromosomes ofof paternal originpaternal origin only.only.

(i) Complete mole:(i) Complete mole:

Complete moleComplete mole

(ii) Partial mole(ii) Partial mole- A part of trophoblastic tissue only shows A part of trophoblastic tissue only shows

molar changes. molar changes.

- There is a fetus or at least an amniotic sac.There is a fetus or at least an amniotic sac.

- It is the result of fertilization of an ovum by - It is the result of fertilization of an ovum by 2 sperms so the chromosomal number is 69 2 sperms so the chromosomal number is 69 chromosomeschromosomes

Partial mole Partial mole

((ii) Partial moleii) Partial mole

Differentiation between complete and partial moleDifferentiation between complete and partial mole

FeatureFeature Complete MoleComplete Mole Partial MolePartial Mole

Embryonic or Embryonic or foetal tissuefoetal tissue

Absent Present

Swelling of the Swelling of the villivilli

Diffuse Focal

Trophoblastic Trophoblastic hyperplasiahyperplasia

Diffuse Focal

KaryotypeKaryotype Paternal 46 XX (96%) or 46 XY (4%)

Paternal and maternal 69 XXY

or 69 XYY

Malignant Malignant ChangesChanges

5-10% Rare

Diagnosis

(A) (A) SymptomsSymptoms1.1. AmenorrhoeaAmenorrhoea:: usually of short period (2-3 usually of short period (2-3

months).months).

2.2. Exaggerated symptomsExaggerated symptoms of pregnancy of pregnancy especially vomiting.especially vomiting.

3.Symptoms of preeclampsia may be present as 3.Symptoms of preeclampsia may be present as headache, and oedemaheadache, and oedema

4. 4. Vaginal bleedingVaginal bleeding : : The main complaint, due to separation of vesicles The main complaint, due to separation of vesicles

from uterine wall, there may be a blood stained from uterine wall, there may be a blood stained watery discharge, the watery part is from ruptured watery discharge, the watery part is from ruptured vesicles.vesicles.

Prune juicePrune juice discharg may occur. discharg may occur. passage of vesicles passage of vesicles is diagnosticis diagnostic. . The blood may be concealed causing enlargement The blood may be concealed causing enlargement

& tenderness of the uterus. & tenderness of the uterus.

(A) Symptoms(A) Symptoms

5. 5. Abdominal painAbdominal pain ::- dull-aching - dull-aching ,- ,- ColickyColicky or or Sudden And Severe Sudden And Severe due to perforating moledue to perforating mole

- Ovarian pain Ovarian pain due to stretching of the ovarian due to stretching of the ovarian capsule or complication in the cystic ovary as capsule or complication in the cystic ovary as torsiontorsion

(A) Symptoms(A) Symptoms

Signs

General examinationGeneral examination1.1. Pre-eclampsiaPre-eclampsia in 20-30% of cases, usually in 20-30% of cases, usually

before 20 weeks’ gestation.before 20 weeks’ gestation.

2.2. PallorPallor indicating anemia may be presentindicating anemia may be present..

3.3. HyperthyroidismHyperthyroidism in 3-10% of casesin 3-10% of cases4.4. ..5.5. Breast signsBreast signs of pregnancy.of pregnancy.

Abdominal examinationAbdominal examination

1.1. The uterus is >the period of The uterus is >the period of amenorrhoea in 50% of cases, amenorrhoea in 50% of cases, corresponds to it in 25% andcorresponds to it in 25% and smaller in 25% with inactive or dead mole.smaller in 25% with inactive or dead mole.

1.1. The uterus is doughy in consistency due to The uterus is doughy in consistency due to absence of amniotic fluid and its distension absence of amniotic fluid and its distension with vesicles. with vesicles.

2.2. Fetal parts and heart sound cannot be detected Fetal parts and heart sound cannot be detected except in partial mole.except in partial mole.

Local examination Local examination

1.1. Passage of vesicles (sure sign).Passage of vesicles (sure sign).

2.2. Bilateral ovarian cysts in 50% of cases.Bilateral ovarian cysts in 50% of cases.

3.3. No internal ballottement.No internal ballottement.

(C) Investigations(C) InvestigationsSerum b -hCG level Serum b -hCG level is highly elevated ( > 100.000 mIU/m1is highly elevated ( > 100.000 mIU/m1))

\\"" snow storm snow storm" appearance,on US " appearance,on US no identifiable fetus,no identifiable fetus,

X-rayX-ray of the chest: should be performed in of the chest: should be performed in every case of trophoplastic tumouevery case of trophoplastic tumour. r.

Partial Mole: Complex mass with many Partial Mole: Complex mass with many cystic areas (between arrowheads) and an cystic areas (between arrowheads) and an embryo (arrow) in a patient with a embryo (arrow) in a patient with a ββ-HCG -HCG

of 280,000 mIU/mlof 280,000 mIU/ml

Complete MoleComplete Mole

Complete mole: “snowstorm” Complete mole: “snowstorm” appearance with multiple cystic appearance with multiple cystic areas, no fetal tissue presentareas, no fetal tissue present

Corresponding T1 weighted Corresponding T1 weighted MRI (MRI can be helpful in MRI (MRI can be helpful in determining extent of determining extent of trophoblastic disease)trophoblastic disease)

A real-time ultrasound of a hydatidiform mole.

The dark circles of varying sizes at the top center are the edematous villi.

ComplicationsComplications1.1. Haemorrhage.Haemorrhage.2.2. InfectionInfection3.3. Perforation.Perforation.4.4. Pregnancy induced hypertensionPregnancy induced hypertension5.5. Hyperthyroidism.Hyperthyroidism.6.6. choriocarcinoma in about 5% of cases and choriocarcinoma in about 5% of cases and 7.7. invasive mole in about 10% of cases.invasive mole in about 10% of cases.

8.8. Recurrent mole may occur(1-2%).Recurrent mole may occur(1-2%).

Treatment Treatment

molar pregnancy should be evacuated.molar pregnancy should be evacuated. Suction dilation and curttageSuction dilation and curttage

20 units oxytocin in 500 m1 of 5% glucose20 units oxytocin in 500 m1 of 5% glucose should be infused IV after the start of should be infused IV after the start of evacuation and continued for several hours to evacuation and continued for several hours to enhance uterine contractilityenhance uterine contractility

Dilatation of the cervixDilatation of the cervix is done up to a Hegar's is done up to a Hegar's number equal to the period of amenorrhoea in weeks number equal to the period of amenorrhoea in weeks e.g. Ne.g. Noo. 10 Hegar for 10 weeks’ amenorrhoea. 10 Hegar for 10 weeks’ amenorrhoea

- The suction canula used will beThe suction canula used will be- of the same size also. of the same size also.

(I) Suction evacuation(I) Suction evacuation

(I) Suction evacuation(I) Suction evacuation- A suction canula which may be metal or a A suction canula which may be metal or a

disposable plastic (preferred) is introduced disposable plastic (preferred) is introduced into the uterine cavity. into the uterine cavity.

- The canula is connected to a suction pump The canula is connected to a suction pump adjusted at negative pressure of 300-500 adjusted at negative pressure of 300-500 mmHg according to the duration of pregnancymmHg according to the duration of pregnancy

The material removed is sent for The material removed is sent for histological examination to exclude histological examination to exclude

malignancy malignancy ..

CurettageCurettage After evacuation ,After evacuation , the uterus is gently curetted with a sharp the uterus is gently curetted with a sharp

curette.curette. Some advise curettage one week after Some advise curettage one week after

evacuation to ensure complete removal, evacuation to ensure complete removal, but the is not the routine practice.but the is not the routine practice.

Theca lutein cystsTheca lutein cysts They are hormone dependent.They are hormone dependent.

Disappear spontaneously after evacuation of Disappear spontaneously after evacuation of the mole.the mole.

So, they are not removed surgically unless So, they are not removed surgically unless complication occur as torsion or rupture.complication occur as torsion or rupture.

Large bilateral theca lutein cysts resembling ovarian germ cell tumors. With resolution of the human chorionic gonadotropin(HCG) stimulation, they return to normal-appearing ovaries.

Large bilateral theca lutein cysts resembling ovarian germ cell tumors. With resolution of the human chorionic gonadotropin(HCG) stimulation, they return to normal-appearing ovaries.

(II)Hysterotomy(II)Hysterotomymay be needed for evacuation of a large may be needed for evacuation of a large mole to minimize and facilitate control of mole to minimize and facilitate control of

bleeding.bleeding.

should be considered in women >40 years should be considered in women >40 years who have completed their family for fear who have completed their family for fear of developing of developing

choriocarcinoma.choriocarcinoma.

(III) Hysterectomy

(IV) Medical induction(IV) Medical induction

Oxytocins and / or prostaglandins may be Oxytocins and / or prostaglandins may be used to encourage expulsion of the mole used to encourage expulsion of the mole but must always be followed by surgical but must always be followed by surgical evacuation.evacuation.

Follow upFollow up

detection of serum ß-hCG by detection of serum ß-hCG by radioimmunoassay is essentialradioimmunoassay is essential

Normally B –subunit reach normal Normally B –subunit reach normal level 8-12 wks after evacuation level 8-12 wks after evacuation

ß-hCG is measured by ß-hCG is measured by radioimmunoassay every week till the test radioimmunoassay every week till the test

becomes negative for 3 successive weeks, then becomes negative for 3 successive weeks, then the test is repeated every month for one year.the test is repeated every month for one year.

Pregnancy is allowed if the test remains Pregnancy is allowed if the test remains negative for one year.negative for one year.

Follow up Follow up

Follow upFollow up- Persistent high level or Rising hCG level after Persistent high level or Rising hCG level after

disappearance means developing of disappearance means developing of choriocarcinoma or a new pregnancy.choriocarcinoma or a new pregnancy.

- Serum B-hCG is undetectable 4 months after Serum B-hCG is undetectable 4 months after evacuation.evacuation.

-

Contraception during follow upContraception during follow up

The combined pill is started when the beta-The combined pill is started when the beta-HCG becomes negative. Till this happens, HCG becomes negative. Till this happens, the condom can be used.the condom can be used.

If the pill is used early the beta-HCG will If the pill is used early the beta-HCG will take a longer time to become negative as take a longer time to become negative as oestrogen stimulates the growth of oestrogen stimulates the growth of trophoplast.trophoplast.

The intrauterine device is not used because The intrauterine device is not used because it may lead to irregular uterine bleeding it may lead to irregular uterine bleeding which confuses the follow upwhich confuses the follow up

IUD during follow upIUD during follow up

Invasive mole or Invasive mole or Chorioadenoma Chorioadenoma

DestruensDestruens

Definition Definition

It is a trphoplastic tumour with penetration It is a trphoplastic tumour with penetration of the myometrium by the chorionic villi.of the myometrium by the chorionic villi.

It is locally malignant It is locally malignant

and rarely metastasizesand rarely metastasizes..

It may lead to perforationIt may lead to perforation

of uterusof uterus

A case of invasive mole: inside the uterine cavity the typical A case of invasive mole: inside the uterine cavity the typical ““snow storm” appearance can be detected, The location ofsnow storm” appearance can be detected, The location of

blood flow suggest an invasive mole.blood flow suggest an invasive mole.

The same patient owing to the myometrial invasion. The same patient owing to the myometrial invasion. Reduced vascular resistance is detected in the uterine artery.Reduced vascular resistance is detected in the uterine artery.

Early features suggesting persistant GTN or Early features suggesting persistant GTN or post molar syndrome includepost molar syndrome include

1.1. Recurrent Or Persistent Vaginal BleedigRecurrent Or Persistent Vaginal Bleedig2.2. Subinvoluation Subinvoluation

3.3. Amenorrhoea Amenorrhoea

4.4. Persistence of ovarian enlargement.Persistence of ovarian enlargement.5.5. No malignancy in endometrial biopsyNo malignancy in endometrial biopsy

Chemotherapy Chemotherapy Started if persistant or malignant disease developStarted if persistant or malignant disease develop The level of serum HCG doubles in 2 weeks), after The level of serum HCG doubles in 2 weeks), after

exclusion of a new pregnancyexclusion of a new pregnancy plateaus failure HCG to decrease over 3 weeks) plateaus failure HCG to decrease over 3 weeks)

oror the test for the hormone becomes positive after the test for the hormone becomes positive after

being negative or being negative or If metastases appear. If metastases appear.

Definition Definition

A malignant form of GTD which can A malignant form of GTD which can develop from a hydatidiform mole or from develop from a hydatidiform mole or from placental trophoblast cells associated with a placental trophoblast cells associated with a healthy fetus ,an abortion or an ectopic healthy fetus ,an abortion or an ectopic pregnancy.pregnancy.

Symptoms and signs Symptoms and signs

BleedingBleeding InfectionInfection Abdominal swellingAbdominal swelling Vaginal massVaginal mass Lung symptomsLung symptoms Symptoms from other metastasesSymptoms from other metastases

Doppler image of choriocarcinoma