seminar on gestational trophoblastic disease (gtd) (f inal)

SEMINAR SEMINAR ONON

CHORIOCARCINOMACHORIOCARCINOMA

DEPARTMENT OF OBS & GYNAEN.S.C.B. MEDICAL COLLEGE, JABALPUR (M.P.)

Speaker

Dr. Monika Mourya

TYPES OF GTDTYPES OF GTD

BenignBenign

• Hydatidiform mole/molar pregnancy (complete Hydatidiform mole/molar pregnancy (complete

or incomplete)or incomplete)

MalignantMalignant

• Invasive mole Invasive mole

• Choriocarcinoma (chorioepithelioma)Choriocarcinoma (chorioepithelioma)

• Placental site trophoblastic tumorPlacental site trophoblastic tumor

PATHOLOGIC PATHOLOGIC CLASSIFICATIONCLASSIFICATION

CLINICAL CLINICAL CLASSIFICATIONCLASSIFICATION

Hydatidiform Hydatidiform molemole

*complete*complete

*incomplete*incomplete

Benign gestational Benign gestational trophoblastic diseasetrophoblastic disease

Invasive moleInvasive moleMalignant Malignant

trophoblastic diseasetrophoblastic diseaseNonmetastatic Nonmetastatic

Placental site Placental site trophoblastic trophoblastic tumortumor

Metastatic Metastatic

ChoriocarcinomChoriocarcinoma a High risk High risk Low riskLow risk

Pathologic and clinical classifications for gestational trophoblastic disease

Risk factor for malignant change Risk factor for malignant change

1.1. Pre-evacuation uterine size larger than expected for Pre-evacuation uterine size larger than expected for

gestational durationgestational duration

2.2. Bilateral ovarian enlargement (> 9 cm theca lutein Bilateral ovarian enlargement (> 9 cm theca lutein

cysts) cysts)

3.3. Age greater than 40 yearsAge greater than 40 years

4.4. Very high hCG levels(>100,000 m IU/ml)Very high hCG levels(>100,000 m IU/ml)

5.5. Medical complications of molar pregnancy such as Medical complications of molar pregnancy such as

toxemia, hyperthyroidism and trophoblastic toxemia, hyperthyroidism and trophoblastic

embolization (villi come out of placenta )embolization (villi come out of placenta )

6.6. repeat hydatidiform mole repeat hydatidiform mole

COMMON SITES FOR METASTATIC COMMON SITES FOR METASTATIC GESTATIONAL TROPHOBLASTIC GESTATIONAL TROPHOBLASTIC

TUMORSTUMORS

Site Site Per centPer cent

Lung Lung 60-9560-95

Vagina Vagina 40-5040-50

Vulva/cervixVulva/cervix 10-1510-15

Brain Brain 5-155-15

Liver Liver 5-155-15

Kidney Kidney 0-50-5

Spleen Spleen 0-50-5

Gastrointestinal Gastrointestinal 0-50-5

HYDATIDIFORM MOLEHYDATIDIFORM MOLE

(MOLAR PREGNANCY) (MOLAR PREGNANCY)

DEFINITION AND ETIOLOGY DEFINITION AND ETIOLOGY

Molar pregnancy is characterized Molar pregnancy is characterized

histologically by abnormalities of the histologically by abnormalities of the

chorionic villi consisting of varying degree of chorionic villi consisting of varying degree of

trophoblastic proliferation and edema of trophoblastic proliferation and edema of

villous stroma. villous stroma.

The etiology of hydatidiform mole The etiology of hydatidiform mole

remains unclear, but it appears to be due to remains unclear, but it appears to be due to

abnormal gametogenesis and fertilization. abnormal gametogenesis and fertilization.

2 types of H-mole 2 types of H-mole

Complete Mole : Complete Mole : In a ‘In a ‘complete molecomplete mole’ the mass of tissue is completely ’ the mass of tissue is completely

made up of abnormal cells made up of abnormal cells There is no fetus and nothing can be found at the time There is no fetus and nothing can be found at the time

of the first scan. of the first scan.

Partial Mole : Partial Mole : In a ‘In a ‘partial molepartial mole’, the mass may contain both these ’, the mass may contain both these

abnormal cells and often a fetus that has severe abnormal cells and often a fetus that has severe

defects. defects. In this case the fetus will be consumed ( destroyed) by In this case the fetus will be consumed ( destroyed) by

the growing abnormal mass very quickly. the growing abnormal mass very quickly.

Complete Mole Partial Mole

CYTOGENETICS CYTOGENETICS

Complete molar pregnancyComplete molar pregnancy

Chromosomes are paternal , diploidChromosomes are paternal , diploid

46,XX in 90% cases46,XX in 90% cases

46,XY in a small part46,XY in a small part

Partial molar pregnancyPartial molar pregnancy

Chromosomes are paternal and maternal, Chromosomes are paternal and maternal,

triploid. triploid.

69,XXY 80%69,XXY 80%

69,XXX or 69,XYY 10-20%69,XXX or 69,XYY 10-20%

COMPARATIVE PATHOLOGIC FEATURES OF COMPLETE AND COMPARATIVE PATHOLOGIC FEATURES OF COMPLETE AND PARTIAL HYDATIDIFORM MOLEPARTIAL HYDATIDIFORM MOLE

FeatureFeature Complete MoleComplete Mole Partial MolePartial Mole

KaryotypeKaryotype Usually diploid 46XXUsually diploid 46XX Usually triploidy 69XXX most common. Usually triploidy 69XXX most common.

VilliVilli All villi hydropin; no normal All villi hydropin; no normal adjacent villiadjacent villi

Normal adjacent villi may be present Normal adjacent villi may be present

vesselsvessels present they contain no fetal blood present they contain no fetal blood cellscells

blood cellsblood cells

Fetal tissueFetal tissue None presentNone present Usually presentUsually present

TrophoblastTrophoblast Hyperplasia usually present to Hyperplasia usually present to variable degreesvariable degrees

Hyperplasia mild and focalHyperplasia mild and focal

Uterine size Uterine size More than dateMore than date Less than date Less than date

Theca Lutein cyst Theca Lutein cyst 30-60% common 30-60% common Uncommon Uncommon

b HCGb HCG High more than 50 thousand High more than 50 thousand Less than 50 thousandLess than 50 thousand

Risk of persistent Risk of persistent GTNGTN

20%20% <5%<5%

Classical clinical Classical clinical symptoms symptoms

Common Common Uncommon Uncommon

Signs and Symptoms of complete Hydatidiform MoleSigns and Symptoms of complete Hydatidiform Mole

Vaginal bleedingVaginal bleeding

Hyperemesis ( severe vomit)Hyperemesis ( severe vomit)

Size inconsistent with gestational age( with no fetal heart Size inconsistent with gestational age( with no fetal heart

beating and fetal movement)beating and fetal movement)

PreeclampsiaPreeclampsia

Theca lutein ovarian cystsTheca lutein ovarian cysts

Signs and Symptoms of Partial Hydatidiform MoleSigns and Symptoms of Partial Hydatidiform Mole

Vaginal bleedingVaginal bleeding

Absence of fetal heart tonesAbsence of fetal heart tones

Uterine enlargement and preeclampsia is reported in Uterine enlargement and preeclampsia is reported in

only 3% of patients.only 3% of patients.

Theca lutein cysts, hyperemesis is rare.Theca lutein cysts, hyperemesis is rare.

Complete hydatidiform mole demonstrating enlarged villi of various

size

Partial hydartidiform mole

Here is a partial mole in a case of triploidy. Note the scattered grape-like masses with intervening normal-appearing placental tissue.

INCIDENCE INCIDENCE 1 out of 1500-2000 pregnancies in the U.S. and Europe1 out of 1500-2000 pregnancies in the U.S. and Europe

1 out of 500-600 (another report 1%) pregnancies in some 1 out of 500-600 (another report 1%) pregnancies in some

Asian countries. Asian countries.

Complete > incompleteComplete > incomplete

Repeat hydatidiform moles occure in 0.5-2.6% of patients, and Repeat hydatidiform moles occure in 0.5-2.6% of patients, and

these patiens have a subsequent greater risk of developing these patiens have a subsequent greater risk of developing

invasive mole or choriocarcinomainvasive mole or choriocarcinoma

There is an increased risk of molar pregnancy for women over There is an increased risk of molar pregnancy for women over

the age 40.the age 40.

Approximately 10-17% of hydatidiform moles will Approximately 10-17% of hydatidiform moles will

result in invasive moleresult in invasive mole Approximately 2-3% of hydatidiform moles progress Approximately 2-3% of hydatidiform moles progress

to choriocarcinoma ( most of them are curable) to choriocarcinoma ( most of them are curable)

CLINICAL RISK FACTORS FOR MOLAR CLINICAL RISK FACTORS FOR MOLAR PREGNANCYPREGNANCY

Age (extremes of reproductive years)Age (extremes of reproductive years)

<15<15

>40>40

Reproductive historyReproductive history

prior hydatidiform moleprior hydatidiform mole

prior spontaneous abortionprior spontaneous abortion

DietDiet

Vitamin A deficiencyVitamin A deficiency

Birthplace Birthplace

Outside North America( occasionally has Outside North America( occasionally has this disease) this disease)

Hydatidiform mole: specimen from suction curettage

A large amount of villi in the uterus.

The microscopic appearance of hydatidiform mole:

•Hyperplasia of trophobasitc cells

•Hydropic swelling of all villi

•Vessles are usually absent

Transvaginal sonogram demonstrating the “ snow storm” appearance.

Color Dopplor facilitates visualization of the enlarged spiral arteriesclose proximity to the “ snow storm” appearance

Sign and symptoms of H. Mole Sign and symptoms of H. Mole Symptoms Symptoms Vaginal bleeding -most presenting symptomVaginal bleeding -most presenting symptom Lower abdominal pain Lower abdominal pain Constitutional symptoms – hyperemisis gravidarum Constitutional symptoms – hyperemisis gravidarum Trophoblastic embolization – respiratory distress. Trophoblastic embolization – respiratory distress. 2% of patient with complete mole diagnosed in patient with excessive 2% of patient with complete mole diagnosed in patient with excessive

uterine size and markedly elevated HCG level. This patient may develop uterine size and markedly elevated HCG level. This patient may develop chest pain, dysnea, tachypnea, tachycardia, severe respiratory distress chest pain, dysnea, tachypnea, tachycardia, severe respiratory distress during and after molar evacuation. during and after molar evacuation.

Expulsion of grape like vesicles per vaginum is diagnostic of vesicular Expulsion of grape like vesicles per vaginum is diagnostic of vesicular mole. mole.

Signs Signs Pre-eclampsia 27% of patient with complete mole associated with Pre-eclampsia 27% of patient with complete mole associated with

hypertension, proteinuria, hyperreflexia, (eclamptic convulsion rarely hypertension, proteinuria, hyperreflexia, (eclamptic convulsion rarely occur).occur).

Hyperthyroidism – 7% of patient with complete molar gestation- patient Hyperthyroidism – 7% of patient with complete molar gestation- patient develop tachycardia, tremor, worm skin diagnosis confirmed by increase develop tachycardia, tremor, worm skin diagnosis confirmed by increase level of T3 and T4. level of T3 and T4.

Theca lutein ovarian cyst Theca lutein ovarian cyst

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.

Per abdomen findings Per abdomen findings Size of uterus more than that expected for period of Size of uterus more than that expected for period of

amenorrhoea 50% of cases. amenorrhoea 50% of cases. Feel of uterus is firm and elastic Feel of uterus is firm and elastic Fetal parts not felt nor any fetal movements, absence Fetal parts not felt nor any fetal movements, absence

of fetal heart sound. of fetal heart sound.

Vaginal Examination : Vaginal Examination : Internal ballottement can be elicited. Internal ballottement can be elicited. Unilateral/ bilateral enlargement (theca lutein cyst) of Unilateral/ bilateral enlargement (theca lutein cyst) of

ovary may be palpable in 25-50% of cases. ovary may be palpable in 25-50% of cases. Presence of vesicles in vaginal discharge is Presence of vesicles in vaginal discharge is

pathognomic of H mole. pathognomic of H mole. If the cervical os is open instead of membranes, blood If the cervical os is open instead of membranes, blood

clot or vesicles may be felt. clot or vesicles may be felt.

InvestigationsInvestigations

ABO/RH, CBCABO/RH, CBC

Hepatic, renal thyroid function test. Hepatic, renal thyroid function test.

Ultrasound – is the criterion standard for identifying Ultrasound – is the criterion standard for identifying

both complete and partial molar pregnancies. The both complete and partial molar pregnancies. The

classic image is of a “Snowstorm” pattern. classic image is of a “Snowstorm” pattern.

Quantitative estimation of HCG – rapidly increase Quantitative estimation of HCG – rapidly increase

value of serum HCG (HCG more than 1 l00,000 value of serum HCG (HCG more than 1 l00,000

m/IU/ml) are usual with molar pregnancies. Normal m/IU/ml) are usual with molar pregnancies. Normal

pregnancy value below 60,000m/IU/ml. pregnancy value below 60,000m/IU/ml.

A sonographic findings of a molar pregnancy. The characteristic “snowstorm” pattern is evident.

Transvaginal sonogram demonstrating the “ snow storm” appearance.

The most common symptom of a mole is vaginal The most common symptom of a mole is vaginal

bleeding during the first trimester bleeding during the first trimester

however very often no signs of a problem appear and the however very often no signs of a problem appear and the

mole can only be diagnosed by use of ultrasound mole can only be diagnosed by use of ultrasound

scanning. (rutting check)scanning. (rutting check)

Occasionally, a uterus that is too large for the stage of Occasionally, a uterus that is too large for the stage of

the pregnancy can be an indication. the pregnancy can be an indication.

DIAGNOSISDIAGNOSIS

DIFFERENTIAL DIAGNOSIS DIFFERENTIAL DIAGNOSIS •AbortionAbortion

•Multiple pregnancy Multiple pregnancy

•PolyhydroamniosPolyhydroamnios

•Fibroid or ovarian tumour with pregnancy. Fibroid or ovarian tumour with pregnancy.

COMPLICATIONS COMPLICATIONS

Immediate Immediate

•Haemorrhage and shock Haemorrhage and shock

•Sepsis Sepsis

•Perforation of uterusPerforation of uterus

•Pre-eclampsiaPre-eclampsia

•Acute pulmonary insufficiency Acute pulmonary insufficiency

•Co-agulation failureCo-agulation failure

LateLate

•Choriocarcinoma – following H mole ranges between 2-10%.Choriocarcinoma – following H mole ranges between 2-10%.

TREATMENT TREATMENT

Suction dilation and curettage :tSuction dilation and curettage :to remove benign hydatidiform moleso remove benign hydatidiform moles

When the diagnosis of hydatidiform mole is established, the molar When the diagnosis of hydatidiform mole is established, the molar

pregnancy should be evacuated. pregnancy should be evacuated.

An oxytocic agent should be infused intravenously after the start of An oxytocic agent should be infused intravenously after the start of

evacuation & continued for several hours to enhance uterine contractilityevacuation & continued for several hours to enhance uterine contractility

Hysterectomy (Removal of the uterus) Hysterectomy (Removal of the uterus) : used rarely to treat hydatidiform : used rarely to treat hydatidiform

moles if future pregnancy is no longer desired. moles if future pregnancy is no longer desired.

Chemotherapy with a single-agent drugChemotherapy with a single-agent drug

Prophylactic (for prevention) chemotherapy at the time of or immediately Prophylactic (for prevention) chemotherapy at the time of or immediately

following molar evacuation may be considered for the high-risk patients( to following molar evacuation may be considered for the high-risk patients( to

prevent spread of disease )prevent spread of disease )

Follow-up Protocols Follow-up Protocols History and clinical examination History and clinical examination Patients with hydatidiform mole are curative over 80% by Patients with hydatidiform mole are curative over 80% by

treatment of evacuation. treatment of evacuation. The follow-up after evacuation is key necessaryThe follow-up after evacuation is key necessary

Enquire about Enquire about uterine involution, ovarian cyst regression malignant deposit uterine involution, ovarian cyst regression malignant deposit

in ant vaginal wall, cessation of bleeding, persistent cough, in ant vaginal wall, cessation of bleeding, persistent cough, breathlessness or haemoptysis breathlessness or haemoptysis

Investigation : Detection of HCG in urine or serum, chest X-ray Investigation : Detection of HCG in urine or serum, chest X-ray before t/t and after evacuation to exclude metastases, there before t/t and after evacuation to exclude metastases, there after it should be done at 3after it should be done at 3rdrd, 6, 6thth & 12 & 12thth month. month.

Contraception should be practiced during this follow up period Contraception should be practiced during this follow up period combined oral pills and barrier method of contraception combined oral pills and barrier method of contraception used, IUCD is contraindication b/c of its frequent association used, IUCD is contraindication b/c of its frequent association of irregular bleeding surgical sterlization is another of irregular bleeding surgical sterlization is another alternative when she has completed her family. alternative when she has completed her family.

Invasive moleInvasive mole

DEFINITION DEFINITION

This term is applied to a molar pregnancy This term is applied to a molar pregnancy

in which molar villi grow into the myometrium in which molar villi grow into the myometrium

or its blood vessels, and may extend into the or its blood vessels, and may extend into the

broad ligament and metastasize to the lungs, broad ligament and metastasize to the lungs,

the vagina or the vulva. the vagina or the vulva.

Invasive mole: the tissue invades into the myometrial layer. No obvious borderline, with obvious bleeding.

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

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

Doppler image of invasive mole

CHORIOCARCINOMA CHORIOCARCINOMA

DEFINITIONDEFINITION

This is extremely malignant form of This is extremely malignant form of trophoblastic tumour may be considered trophoblastic tumour may be considered a carcinoma of chorionic epithelium, a carcinoma of chorionic epithelium, although an its growth and metastasis although an its growth and metastasis behave like sarcoma behave like sarcoma

Characterized by abnormal trophoblastic Characterized by abnormal trophoblastic hyperplasia and anaplasia , absence of hyperplasia and anaplasia , absence of chorionic villichorionic villi

Gross specimen of choriocarcinoma

Microscopic image of choriocarcinoma

absence of chorionic villiabsence of chorionic villi

Incidence : Incidence :

Occur in about 4% of patient after Occur in about 4% of patient after

evacuation of complete mole, but seems evacuation of complete mole, but seems

more after when GTT develop after non more after when GTT develop after non

molar pregnancy. molar pregnancy.

Patient develops choriocarcinoma – 50% Patient develops choriocarcinoma – 50%

after H. mole 15% after term pregnancy 25% after H. mole 15% after term pregnancy 25%

after abortion or ectopic pregnancy. after abortion or ectopic pregnancy.

SYMPTOMS AND SIGNS SYMPTOMS AND SIGNS

• BleedingBleeding

• InfectionInfection

• Abdominal swellingAbdominal swelling

• Vaginal massVaginal mass

• Lung symptomsLung symptoms

• Symptoms from other metastasisSymptoms from other metastasis

PATIENT MAY COMMONLY PRESENT WITH SIGN OF METASTASISPATIENT MAY COMMONLY PRESENT WITH SIGN OF METASTASIS

Pulmonary metastasis Pulmonary metastasis • 80% of patient with metastatic GTT lung involvement 80% of patient with metastatic GTT lung involvement

patient present with chest pain, cough, hemoptysis, patient present with chest pain, cough, hemoptysis, dyspnea.dyspnea.

Four principle pulmonary pattern Four principle pulmonary pattern • Alveolar or snow strom pattern.Alveolar or snow strom pattern.• Discrete rounded densities- cannon ball appearanceDiscrete rounded densities- cannon ball appearance• Embolic pattern caused by pulmonary arterial occlusion Embolic pattern caused by pulmonary arterial occlusion

Vaginal metastasis Vaginal metastasis • occur in about 30% occur in about 30%

Liver metastasis Liver metastasis • Occur in about 10% Occur in about 10%

Central Nervous SystemCentral Nervous System• Involve brain in 10% cases Involve brain in 10% cases

WHO Prognostic Scoring SystemWHO Prognostic Scoring System

ScoreScore Prognostic factorPrognostic factor 00 11 22 44

Age(years)Age(years) ≤≤3939 >39>39 —— ——

Pregnancy historyPregnancy history HydatidiforHydatidiform molem mole

Abortion,Abortion,

ectopicectopicTerm Term pregnancypregnancy ——

Interval (months) of Interval (months) of treatment treatment <4<4 4-64-6 7-127-12 >12>12

Initial hCG(mIU/ml)Initial hCG(mIU/ml) <10<1033 101033-10-1044 101044-10-1055 >10>1055

Largest tumor(cm)Largest tumor(cm) <3<3 3-53-5 >5>5 ——

Sites of metastasisSites of metastasis Lung Lung Spleen,Spleen,

kidneykidneyGI tract, GI tract, liverliver BrainBrain

No. of metastasisNo. of metastasis —— 1-41-4 4-84-8 88

Previous Previous (treatment)(treatment) —— —— Single drugSingle drug 2 or 2 or

moremore0-4 low risk, 5-7 intermediate risk, >8 high risk for death

FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOURTUMOUR

Stage I : Stage I : Disease confined to uterusDisease confined to uterus

Ia : Confined to uterus with no risk factorIa : Confined to uterus with no risk factor

Ib : Confined to uterus with 1 risk factorIb : Confined to uterus with 1 risk factor

Ic : confined to uterus with 2 risk factorIc : confined to uterus with 2 risk factor

Stage II : Stage II : GTT extending outside uterus but GTT extending outside uterus but

limited to genital str. (adenexa vagina broad limited to genital str. (adenexa vagina broad

ligaments)ligaments)

IIa : GTT involving genital tract with out risk IIa : GTT involving genital tract with out risk

factorfactor

Iib : GTT involving genital tract with 1 risk factorIib : GTT involving genital tract with 1 risk factor

IIC : GTT involving genital tract with 2 risk factor IIC : GTT involving genital tract with 2 risk factor

FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOURTUMOUR

Stage III : Stage III : GTT extending of lung with or withoutGTT extending of lung with or without

Known genital tract involvement Known genital tract involvement

IIIa : GTT extending to lung with no risk factorIIIa : GTT extending to lung with no risk factor

IIIb : GTT extending to lung with 1 risk factorIIIb : GTT extending to lung with 1 risk factor

IIIc : GTT extending to lung with 2 risk factorIIIc : GTT extending to lung with 2 risk factor

Stage IV: All other metastatic sites Stage IV: All other metastatic sites

IVa : All metastatic sites other site with out risk IVa : All metastatic sites other site with out risk

factorfactor

IVb : All metastatic sites other site with out 1 IVb : All metastatic sites other site with out 1

risk factorrisk factor

IVc: All other metastatic sites site with out 2 risk IVc: All other metastatic sites site with out 2 risk

factorfactor

Risk Factor ; HCG > 100;000mIU/mlRisk Factor ; HCG > 100;000mIU/ml

Duration of ds longer then 6 months from Duration of ds longer then 6 months from

formenation of antedent pregnancy. formenation of antedent pregnancy.

Diagnostic Evaluation Diagnostic Evaluation All Patients with persistent GTT should undergo All Patients with persistent GTT should undergo

careful pretreatment evaluation including the careful pretreatment evaluation including the

following –following –

Complete history and physical examination .Complete history and physical examination .

Measurement of serum HCG value.Measurement of serum HCG value.

. Hepatic, thyroid and renal function test.. Hepatic, thyroid and renal function test.

Determination of baseline peripheral WBC and Determination of baseline peripheral WBC and

platelet count.platelet count.

Once the diagnosis established the further Once the diagnosis established the further

examination should be done to determine the extent examination should be done to determine the extent

of disease (Chest X- ray, CT scan of abdomen, pelvis of disease (Chest X- ray, CT scan of abdomen, pelvis

and Head, MRI, USG)and Head, MRI, USG)

Management Management 1.1. Preventive and Curative Preventive and Curative

a.a. Preventive – Prophylactic CT in at risk women Preventive – Prophylactic CT in at risk women following evacuation of molar pregnancy.following evacuation of molar pregnancy.

Risk Women –Risk Women – Age of patient >35 years.Age of patient >35 years. Level of HCG > 100,000 IU/ 24 Hours.Level of HCG > 100,000 IU/ 24 Hours. Histological diagnosed infiltrative mole.Histological diagnosed infiltrative mole. Previous history of motor pregnancy.Previous history of motor pregnancy.- Meticulous follow up following evacuation of H. mole of Meticulous follow up following evacuation of H. mole of

at least one years to detect early evidence of at least one years to detect early evidence of trophoblastic reactivation.trophoblastic reactivation.

Single agent chemotherapy is highly effective in case of Single agent chemotherapy is highly effective in case of persistent trophoblastic disease. persistent trophoblastic disease.

- Selective hysterectomy in H. mole in patients of Selective hysterectomy in H. mole in patients of age>35years.age>35years.

Those who want to retain fertility Those who want to retain fertility

1. Single agent CT is preferred treatment in patients 1. Single agent CT is preferred treatment in patients

with stage I disease who want to retain fertility.with stage I disease who want to retain fertility.

When patients are resistant to single agent When patients are resistant to single agent

chemotherapy and desire to retain fertility chemotherapy and desire to retain fertility

combination chemotherapy should be administered.combination chemotherapy should be administered.

Stage II & III – Vaginal and pelvic metastatics.Stage II & III – Vaginal and pelvic metastatics.

Vaginal – In low risk cases.Vaginal – In low risk cases.

Single agent chemotherapy have 80% rate of Single agent chemotherapy have 80% rate of

remission.remission.

High risk patients managed with primary intensive High risk patients managed with primary intensive

combination chemotherapy. combination chemotherapy.

Curative Management -Curative Management -

Chemotherapy.Chemotherapy.

Surgery.Surgery.

Radiation.Radiation.

Management of various stages-Management of various stages-

Stage I: Stage I:

Initial – single agent chemotherapy or hysterectomy Initial – single agent chemotherapy or hysterectomy

with adjunctive chemotherapy .with adjunctive chemotherapy .

Resistant – Combination chemotherapy Resistant – Combination chemotherapy

Hysterectomy with adjunctive chemotherapy. Hysterectomy with adjunctive chemotherapy.

Local resection, pelvic infusion.Local resection, pelvic infusion.

Stage II & III-Stage II & III-

Low risk –Low risk –

Initial - Single agent chemotherapy.Initial - Single agent chemotherapy.

Resistant – Combination chemotherapy.Resistant – Combination chemotherapy.

High Risk – High Risk –

Initial – Combination chemotherapy.Initial – Combination chemotherapy.

Resistant – second line combination chemotherapyResistant – second line combination chemotherapy

Stage IV-Stage IV-

Initial - Combination Chemotherapy.Initial - Combination Chemotherapy.

Brain – Whole heat irradiation (3000 CGY)Brain – Whole heat irradiation (3000 CGY)

craniotomy to manage complications.craniotomy to manage complications.

Liver – Resection to manage complications.Liver – Resection to manage complications.

Resistant – second line combination chemotherapyResistant – second line combination chemotherapy

hepatic arterial infusion. hepatic arterial infusion.

Adjuvant chemotherapy is Adjuvant chemotherapy is adminstered for three resons adminstered for three resons

1.1. To reduce the likelihood of disseminating To reduce the likelihood of disseminating

viable tumour cell at surgery. viable tumour cell at surgery.

2.2. To maintain cytotoxic level of chemotherapy To maintain cytotoxic level of chemotherapy

in the blood stream and tissue in case viable in the blood stream and tissue in case viable

tumour cells are disseminated at surgery .tumour cells are disseminated at surgery .

3.3. To treat any occult metastasis that may To treat any occult metastasis that may

already present at the time of surgery.already present at the time of surgery.

Follow up-Follow up-

All patients with stage I through stage III disease All patients with stage I through stage III disease

should receive follow up with-should receive follow up with-

1.1. Weekly measurement of HCG level until they Weekly measurement of HCG level until they

are normal for 3 consecutive weeks.are normal for 3 consecutive weeks.

2.2. Monthly measurement of HCG value until level Monthly measurement of HCG value until level

are normal for 12 consecutive months. are normal for 12 consecutive months.

3.3. Effective contraception during the entire Effective contraception during the entire

interval of hormonal follow up. interval of hormonal follow up.

ChemotherapyChemotherapy

Single agent chemotherapy with either actinomycin D Single agent chemotherapy with either actinomycin D

or methotrexate has achieved comparable and excellent or methotrexate has achieved comparable and excellent

remission rates in both non metastatic and low risk remission rates in both non metastatic and low risk

metastatic GTN. metastatic GTN.

single drug regimen in low rate case –single drug regimen in low rate case –

Drug Dosage Route Days

Methotrexate 1-15 mg/kg IM/IV 1,3,5,7.

Folonic acid 1-015 mg/kg IM 2,4,6,8.

Actinomycin D 12 g/kg IV 1-5

Cyclophosphamide

3mg/kg IV 1-5

EMA- CO protocol in poor prognosis EMA- CO protocol in poor prognosis metastatic disease metastatic disease

The course will restart after 7-14 days. If possible, Generally 2 The course will restart after 7-14 days. If possible, Generally 2 additional courses are given after the hCG levels become normal.additional courses are given after the hCG levels become normal.

Days Drug Dose

Day-1 Etoposide 100mg /m2in 200 ml saline infused over 30 minutes.

Actinomycin D 0.5 mg IV bolus

Methotrexate 100mg /m2 bolus folllowed by 200mg /m2 IV infusion over 12 hours.

Day -2 Etoposide 100mg /m2in 200 ml saline infused over 30 minutes.

Actinomycin D 0.5 mg IV bolus

Folinic acid 15mg IM every 12 hrs for 4 doses begnning 24 hours after starting methotrexate.

Day-8 Cycolphosphamide

600mg/m2 IV in saline over 30 min.

Vincristine (oncovin)

1mg/m2 bolus

PROGNOSISPROGNOSIS

Cure rates should approach 100% in Cure rates should approach 100% in

nonmetastatic and low-risk metastatic nonmetastatic and low-risk metastatic

GTDGTD

Intensive multimodality therapy has Intensive multimodality therapy has

resulted in cure rates of 80-90% in resulted in cure rates of 80-90% in

patients with high-risk metastatic GTDpatients with high-risk metastatic GTD

FOLLOW-UP AFTER SUCCESSFUL FOLLOW-UP AFTER SUCCESSFUL TREATMENTTREATMENT

Quantitative serum hCG levels should be Quantitative serum hCG levels should be obtained monthly for 6 months, every obtained monthly for 6 months, every two months for remainder of the first two months for remainder of the first year, every 3 months during the second year, every 3 months during the second yearyear

Contraception should be maintained for Contraception should be maintained for at least 1 year after the completion of at least 1 year after the completion of chemotherapy. Condom is the choice.chemotherapy. Condom is the choice.

Placenta Site Placenta Site Trophoblastic Trophoblastic Tumor (PSTT)Tumor (PSTT)

Placenta Site Trophoblastic Tumor is an Placenta Site Trophoblastic Tumor is an

extremely rare tumor that arised from the extremely rare tumor that arised from the

placental implantation siteplacental implantation site

Tumor cells infiltrate the myometrium Tumor cells infiltrate the myometrium

and grow between smooth-muscle cellsand grow between smooth-muscle cells

DEFINITION DEFINITION

Serum hCG levels are relatively low compared Serum hCG levels are relatively low compared to those seen with choriocarcinoma. to those seen with choriocarcinoma.

Several reports have noted a benign behavior Several reports have noted a benign behavior of this disease. They are relatively of this disease. They are relatively chemotherapy-resistant, and deaths from chemotherapy-resistant, and deaths from metastasis have occurred. metastasis have occurred.

Surgery has been the mainstay of treatmentSurgery has been the mainstay of treatment

DIAGNOSIS AND TREATMENT DIAGNOSIS AND TREATMENT