Seminar on gestational trophoblastic disease (gtd) (f inal)
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Transcript of 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