Gestational Trophoblastic DiseaseGestational Trophoblastic Disease

1.1. Complete vesicular moleComplete vesicular mole

2.2. Partial vesicular molePartial vesicular mole

3.3. Invasive mole Invasive mole

4.4. Placental-site Placental-site trophoblastic tumortrophoblastic tumor

5.5. Choriocarcinoma Choriocarcinoma

DefinitionDefinitionIt is a benign neoplasm of the chorionic It is a benign neoplasm of the chorionic

villi, characterized by:villi, characterized by:1.1. Marked proliferation of the trophoplast,Marked proliferation of the trophoplast,bothboth 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

Incidence:Incidence:• 1:20001:2000 pregnancies in United States pregnancies in United States

and Europe, but and Europe, but 10 times10 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 beginning and more toward the end of the childbearing period.the childbearing period.

• It is It is 10 times10 times more in women over 45 more in women over 45 years old.years old.

PathologyPathology::• The uterus is distended by thin walled, The uterus is distended by thin walled,

translucent, grape-like translucent, 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 and absorption leads to early death and absorption of the embryo.of the embryo.

• There is There is trophoblastic proliferationtrophoblastic proliferation, , with mitotic activity affecting both with mitotic activity affecting both syncytial and cytotrophoblastic layers. syncytial and cytotrophoblastic layers.

• This causes This causes excessive secretion of excessive secretion of hCG, chorionic thyrotrophin and hCG, chorionic thyrotrophin and progesterone. progesterone.

• On the other hand, On the other hand, oestrogen oestrogen production is lowproduction is low due to absence of due to absence of the foetal supply of precursors.the foetal supply of precursors.

Pathology:

• High hCG causes High hCG causes multiple theca lutein multiple theca lutein cystscysts in the ovaries in about 50% of in the ovaries in about 50% of cases.cases.

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

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

• High hCG also results in High hCG also results in exaggeration exaggeration of the normal early pregnancy of the normal early pregnancy symptoms and signssymptoms and signs

PathologyPathology::

• Histologic section of a complete Histologic section of a complete hydatidiform mole stained with hydatidiform mole stained with hematoxylin and eosin. hematoxylin and eosin.

• Villi of different sizes are present.Villi of different sizes are present.• The large villous in the center The large villous in the center

exhibits marked edema with a exhibits marked edema with a fluid-filled central cavity known fluid-filled central cavity known as cisterna. as cisterna.

• Marked proliferation of the Marked proliferation of the trophoblasts is observed.trophoblasts is observed.

• The syncytiotrophoblasts stain The syncytiotrophoblasts stain purple, while the cytotrophoblasts purple, while the cytotrophoblasts have a clear cytoplasm and bizarre have a clear cytoplasm and bizarre nuclei. nuclei.

• No fetal blood vessels are in the No fetal blood vessels are in the mesenchyme of the villi. mesenchyme of the villi.

((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::

(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

(ii) Partial mole(ii) Partial mole

DIFFERENTIATION BETWEEN DIFFERENTIATION BETWEEN COMPLETE AND PARTIAL MOLE COMPLETE AND PARTIAL MOLE

FeatureFeatureComplete MoleComplete MolePartial MolePartial Mole

Embryonic or foetal Embryonic or foetal tissuetissue

AbsentPresent

Swelling of the villiSwelling of the villiDiffuseFocal

Trophoblastic Trophoblastic hyperplasiahyperplasia

DiffuseFocal

KaryotypeKaryotypePaternal 46 XX (96%) or 46 XY (4%)

Paternal and maternal 69 XXY or

69 XYY

Malignant ChangesMalignant Changes5-10%Rare

(A) (A) SymptomsSymptoms::1.1.AmenorrhoeaAmenorrhoea:: usually of short usually of short

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

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

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

• The The passage of vesiclespassage 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-achingdull-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 severesudden and severe due to perforating mole due to perforating mole

- Ovarian painOvarian 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:

General examinationGeneral examination::1.Pre-eclampsia develops in 20-30% of

cases, usually before 20 weeks’ gestation.2.Pallor indicating anemia may be present.3.Hyperthyroidism develops 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 examination:Abdominal examination:1.1.The uterus isThe uterus is larger larger than the period of than the period of

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

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

3.3.Foetal parts and heart sound cannot be Foetal parts and heart sound cannot be detected except in partial mole.detected except in partial mole.

4.4.Absence of external ballottement.Absence of external ballottement.

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 normal pregnancy it is positive

in dilutions up to 1/100.in dilutions up to 1/100.2. 2. Serum b -hCG levelSerum b -hCG level:: is highly is highly elevated ( > 100.000 mIU/m1).elevated ( > 100.000 mIU/m1).

(C) Investigations:(C) Investigations:

(C) Investigations:(C) Investigations:3. 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.

A real-time ultrasound of a hydatidiform mole.

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

Complications:1.1. HaemorrhageHaemorrhage..2.2. Infection Infection 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. PerforationPerforation 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. HyperthyroidismHyperthyroidism..6.6. Subsequent development of Subsequent development of choriocarcinomachoriocarcinoma in in

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

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

Treatment:1.1.As soon as the diagnosis of vesicular As soon as the diagnosis of vesicular

mole is established the mole is established the uterus should be uterus should be evacuated.evacuated.

2.2.The selected method depends on the The selected method depends on the sizesize of the uterus, whether of the uterus, whether partial partial expulsionexpulsion has already occur or not, the has already occur or not, the patient's agepatient's age and and fertility desirefertility desire..

3.3.Cross - matched Cross - matched bloodblood should be should be available before starting.available before starting.

- It is carried out under general anaesthesia, but not that which relax the uterus as halothane as it may induce severe bleeding.

- An infusion of 20 units oxytocin in 500 m1 of 5% glucose should be maintained throughout the procedure.

(I) Suction evacuation:(I) Suction evacuation:

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

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

Curettage• After evacuation ,the uterus is After evacuation ,the uterus is

gently curettedgently curetted with a sharp with a sharp curette.curette.

• Some advise Some advise curettage one week curettage one week afterafter evacuation to ensure evacuation to ensure complete removal, but the is not complete removal, but the is not the routine practice.the routine practice.

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.

(II)Hysterotomy:(II)Hysterotomy:It may be needed for It may be needed for evacuation of a large evacuation of a large mole to minimize and mole to minimize and

facilitate control of facilitate control of bleeding.bleeding.

(III) Hysterectomy:

It 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 As choriocarcinoma may complicate the vesicular complicate the vesicular mole after its evacuation, mole after its evacuation,

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

essentialessential

• ß-hCG is measured by ß-hCG is measured by radioimmunoassay every week radioimmunoassay every week till the test becomes negative till the test becomes negative for 3 successive weeks, then for 3 successive weeks, then the test is repeated every the test is repeated every month for one year.month for one year.

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

Follow upFollow up: :

Follow up :Follow up :- Persistent high levelPersistent high level indicates indicates

remnants of molar tissues which remnants of molar tissues which necessitate chemotherapy necessitate chemotherapy

( methotrexate) with or without ( methotrexate) with or without curettage. Hysterectomy is indicated if curettage. Hysterectomy is indicated if women had enough children.women had enough children.

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

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

and serum b -hCG is and serum b -hCG is undetectable undetectable 4 months4 months

after evacuation.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 is not used because it may not used because it may lead to irregular uterine lead to irregular uterine

bleeding which confuses bleeding which confuses the follow upthe follow up

Contraception during Contraception during follow upfollow up

Invasive Mole or Invasive Mole or Chorioadenoma DestruensChorioadenoma Destruens

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

• It is locally malignant and rarely It is locally malignant and rarely metastasizes.metastasizes.

• It may lead to perforation of It may lead to perforation of uterusuterus

Early features suggesting residual molar tissue

include:1. recurrent or persistent

vaginal bleeding,2. amenorrhoea,3. failure of uterine involution,4. persistence of ovarian

enlargement.