Gestational Gestational Trophoblastic DiseaseTrophoblastic Disease

DefinitionDefinition

A clinical spectrum including all A clinical spectrum including all neoplasm derived from neoplasm derived from abnormal trophoblastic abnormal trophoblastic proliferation proliferation

ClassificationClassification

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 Placental-site trophoblastic tumortumor

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

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

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

The microscopic appearance of hydatidiform mole:

•Hyperplasia of trophobasitc cells

•Hydropic swelling of all villi

•Vessles are usually absent

IncidenceIncidence• 1:20001:2000 pregnancies in United States and pregnancies in United States and

Europe, but Europe, but 10 times 10 times more in Asia. 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 The incidence is higher toward the beginning and more toward the end of the beginning and more toward the end of the childbearing period.childbearing period.

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

PathologyPathology

The 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 fluid.filled with fluid.• There is There is no vasculature in the chorionic no vasculature in the chorionic

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

• High hCG causes High hCG causes multiple theca lutein multiple theca lutein cystscysts 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 Cysts may reach a large size (10 cm or more.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

))ii ( (Complete moleComplete mole::• The whole conceptus is transformed The whole conceptus is transformed

into a mass of vesicles. into a mass of vesicles.

• No embryoNo embryo is present. is present.

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

))ii ( (Complete moleComplete mole::

Complete moleComplete mole

(ii) Partial mole(ii) Partial mole

- A part of trophoblastic tissue only shows molar changes.

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

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

Partial mole

(ii) Partial mole(ii) Partial mole

Differentiation between complete and partial Differentiation between complete and partial molemole

FeatureFeatureComplete MoleComplete MolePartial MolePartial Mole

Embryonic or Embryonic or foetal tissuefoetal tissue

AbsentPresent

Swelling of the Swelling of the villivilli

DiffuseFocal

Trophoblastic Trophoblastic hyperplasiahyperplasia

DiffuseFocal

KaryotypeKaryotypePaternal 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 usually of short period

(2-3 months).(2-3 months).

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

3.Symptoms of 3.Symptoms of preeclampsiapreeclampsia may be may be present as headache, and oedemapresent as headache, and oedema

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

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

• Prune juicePrune juice disharge may occur. disharge may occur.

• The blood is brown because it has retained for The blood is brown because it has retained for sometime in the uterine cavity. sometime in the uterine cavity.

• passage of vesicles passage of vesicles is diagnostic. is diagnostic.

• The blood may be concealed causing The blood may be concealed causing enlargment & tenderness of the uterus. enlargment & tenderness of the uterus.

(A) Symptoms(A) Symptoms

5. 5. Abdominal painAbdominal pain : may be : may be

- dull-aching - dull-aching due to rapid distension of the due to rapid distension of the uterus by the mole or by cocealed uterus by the mole or by cocealed haemorrhage.haemorrhage.

- - ColickyColicky due to starting expulsion, due to starting expulsion,

- 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.Pre-eclampsia in 20-30% of cases, usually

before 20 weeks’ gestation.

2.Pallor indicating anemia may be present.

3.Hyperthyroidism in 3-10% of cases manifested by enlarged thyroid gland, tachycardia (due to chorionic thyrotropin secreted by trophoplast &HCG also has a thyroid stimulating effect.

4.Breast signs of pregnancy.

Abdominal examinationAbdominal examination1.1.The uterus isThe uterus is > >the period of amenorrhoea the period of amenorrhoea in in

50%50% of cases, of cases, corresponds to it in 25%corresponds to it in 25% and and smaller in 25%smaller in 25% with inactive or dead mole. with inactive or dead mole.

2.2.The uterus isThe uterus is doughydoughy in consistency due to in consistency due to absence of amniotic fluid and its distension absence of amniotic fluid and its distension with vesicles. with vesicles.

3.3.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 1.Passage of vesicles (sure

sign).

2.Bilateral ovarian cysts in 50% of cases.

3.No internal ballottement.

1.1.Urine pregnancy test:Urine pregnancy test: is positive in high dilution. is positive in high dilution. • 1/200 is highly suggestive, 1/200 is highly suggestive, • 1/500 is surely diagnostic. 1/500 is surely diagnostic. • In normal pregnancy it is positive in In normal pregnancy it is positive in

dilutions up to 1/100.dilutions up to 1/100.

2. 2. Serum b -hCG levelSerum b -hCG level is highly elevated ( > 100.000 is highly elevated ( > 100.000

mIU/m1).mIU/m1).

(C) Investigations(C) Investigations

(C) Investigations(C) Investigations3. 3. UltrasonographyUltrasonography revealsreveals::

• The characteristic intrauterine The characteristic intrauterine "" snow snow stormstorm" " appearance,appearance,

• no identifiable foetus,no identifiable foetus,

• bilateral ovarian cysts may be detected.bilateral ovarian cysts may be detected.

4. 4. X-rayX-ray to the abdomen: to the abdomen: shows no foetal shows no foetal skeleton.skeleton.

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

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

HCG of 280,000 mIU/ml

Complete Mole

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

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

A real-time ultrasound of a hydatidiform mole.

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

Complications1.1. Haemorrhage.Haemorrhage.2.2. InfectionInfection due to absence of the amniotic sac and due to absence of the amniotic sac and

due to the large surface area left after expulsion due to the large surface area left after expulsion or evacuation of the mole.or evacuation of the mole.

3.3. Perforation Perforation of the uterus. Spontaneous by a of the uterus. Spontaneous by a perforating mole or during evacuation.perforating mole or during evacuation.

4.4. Pregnancy induced Pregnancy induced hypertensionhypertension5.5. Hyperthyroidism.Hyperthyroidism.6.6. Subsequent development of Subsequent development of choriocarcinomachoriocarcinoma in in

about about 5%5% of cases and of cases and invasive mole invasive mole in about in about 10%10% of cases. of cases.

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

Treatment

When the diagnosis of hydatidiform mole is established, the molar pregnancy should be evacuated.

Suction dilation and curttage to remove benign hydatidiform mole

An oxytocic agent 20 units oxytocin in 500 m1 of 5% glucose should be infused intravenously after the start of evacuation and continued for several hours to enhance uterine urettage :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 number equal to the period of amenorrhoea in weeks e.g. Nweeks e.g. Noo. 10 Hegar for 10 weeks’ . 10 Hegar for 10 weeks’ amenorrhoeaamenorrhoea

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

(I) Suction evacuation(I) Suction evacuation

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

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

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

The material removed is sent for histological

examination to exclude malignancy .

Curettage• After evacuation ,After evacuation ,

• the uterus is the uterus is gently curettedgently curetted with a with a sharp curette.sharp curette.

• Some advise Some advise curettage one week aftercurettage one week after evacuation to ensure complete evacuation to ensure complete removal, but the is not the routine removal, but the is not the routine practicepractice..

Theca lutein cystsTheca lutein cysts

• They are hormone dependent.

• Disappear spontaneously after evacuation of the mole.

• So, they are not removed surgically unless 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)HysterotomyIt may be needed for evacuation of It may be needed for evacuation of

a large mole to minimize and a large mole to minimize and facilitate control of bleeding.facilitate control of bleeding.

(III) HysterectomyIt should be considered in women over

40 years who have completed their family for fear of

developing

choriocarcinoma.

)IV (Medical induction

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

Follow upFollow up As choriocarcinoma may complicate As choriocarcinoma may complicate

the vesicular mole after its the vesicular mole after its evacuation, evacuation, detection of serum ß-detection of serum ß-hCG by radioimmunoassay is hCG by radioimmunoassay is essentialessential

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 radioimmunoassay every week till the test becomes negative for 3 successive test becomes negative for 3 successive weeks, then the test is repeated every weeks, then the test is repeated every month for one year.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 upFollow up

Follow upFollow up- Persistent high level Persistent high level indicates remnants of indicates remnants of

molar tissues which necessitate molar tissues which necessitate chemotherapy ( methotrexate) with or chemotherapy ( methotrexate) with or without curettage. Hysterectomy is without curettage. Hysterectomy is indicated if women had enough children.indicated if women had enough children.

- Rising hCG level Rising hCG level after disappearance after disappearance means developing of choriocarcinoma or means developing of choriocarcinoma or a new pregnancy. a new pregnancy.

It is expected that urine pregnancy It is expected that urine pregnancy test is negative 4 weeks after test is negative 4 weeks after evacuation evacuation

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

Follow up Follow up

Contraception during follow upContraception during follow up

• The combined pill is started when the The combined pill is started when the beta-HCG becomes negative.beta-HCG becomes negative.

• Till this happens, the condom can be Till this happens, the condom can be used.used.

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

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

IUD during follow upIUD during follow up

Invasive moleInvasive mole or or Chorioadenoma Chorioadenoma

DestruensDestruens

Definition Definition

• It is a trphoplastic tumour with It is a trphoplastic tumour with penetration of the myometrium by the penetration of the myometrium by the chorionic villi.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 typicalA 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 moleblood flow suggest an invasive mole..

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

Early features suggesting persistant GTN or post molar syndrome include

1. Recurrent Or Persistent Vaginal Bleedig

2. Subinvoluation

3. Amenorrhoea

4. Persistence of ovarian enlargement.5. No malignancy in endometrial biopsy

Chemotherapy •Started if persistant or malignant disease

developThe level of serum HCG doubles in 2 weeks),

after exclusion of a new pregnancy plateaus failure HCG to decrease over 3

weeks) or the test for the hormone becomes positive

after being negative or If metastases appear.

Definition A malignant form of GTD which can

develop from a hydatidiform mole or from placental trophoblast cells associated with a healthy fetus ,an abortion or an ectopic pregnancy.

Symptoms and signs • Bleeding

• Infection

• Abdominal swelling

• Vaginal mass

• Lung symptoms

• Symptoms from other metastases

Doppler image of choriocarcinoma