gestational trophoblastic disease
DESCRIPTION
Lecture for undergraduate medical studentTRANSCRIPT
![Page 1: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/1.jpg)
Gestational Trophoblastic
Disease (GTD)
• Dr. Swati Singh• Department of Obs and Gyn
• UDUTH
![Page 2: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/2.jpg)
Molar Pregnancy
![Page 3: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/3.jpg)
It is a spectrum of trophoblastic diseases that includes:
Complete molar pregnancy
Partial molar pregnancies
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy.
DefinitionsGestational Trophoblastic Disease (GTD)
![Page 4: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/4.jpg)
Chorio
carcinoma
I-Pathologic Classification
II-Clinical ClassificationβhCG based: WHO, FIGO, ACOG 2004 & RCOG 2010
Benign G.T.D.
G.T. Neoplasia
Malignant G.T.D.
Partial moleComplete mole
Invasivemole
MetastaticNon metastatic
Low risk High risk
Gestational Trophoblastic Disease (GTD)
Placental site trophoblastic tumour
Persistent GTD
Classifications
![Page 5: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/5.jpg)
-
Hydatidiform Mole
(H. MOLE)=
Vesicular Mole
![Page 6: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/6.jpg)
Hydatidiform Moles (H.M.)Hydatidiform moles are abnormal pregnancies
characterized histologically by :
Trophoblastic proliferation (Both syncitiotrophoblast & cytotrophoblast)
Edema of the villous stroma (Hydropic) .
Based on the degree and extent of these tissue changes, hydatidiform moles are categorized as either
Complete hydatidiform mole.
Partial hydatidiform mole.
![Page 7: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/7.jpg)
Feature Partial mole Complete mole
Karyotype
Most commonly69, XXX or - XXY
Most commonly46, XX or -,XY
Pathology
Fetus Often present Absent
Amnion, fetal RBC Usually present Absent
Villous edema Variable, focal Diffuse
Trophoblastic proliferation Focal, slight-moderate Diffuse, slight-severe
Clinical presentation
Diagnosis Missed abortion Molar gestation
Uterine size Small for dates 50% large for dates
Theca lutein cysts Rare 25-30%
Medical complications Rare 10-25%
Postmolar CTN 2.5-7.5% 6.8-20%
Features Of Partial And Complete Hydatidiform Moles
![Page 8: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/8.jpg)
Epidemiology& Risk FactorsIncidence:USA 1/1000 South East 1/500 (Hospital) and in Nigeria 1/379.
Risk Factors:
Age: <20y (2fold) , > 40y(10 fold) & >50y (50% V.mole)
Prior Molar Pregnancy
Second molar: 1% - Third molar : 20%!
Diet:↑ in low fat Vit. A or carotene diet (complete mole)
Contraception :COC double the incidence
Previous spontaneous abortion: double the incidence
Repetitive H. moles in women with different partners
![Page 9: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/9.jpg)
Partial moles have been linked to:Higher educational levels
Smoking
Irregular menstrual cycles
Only male infants are among the prior live births
Epidemiology & Risk Factors
![Page 10: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/10.jpg)
Homozygous 90%
Pathogenesis of complete H. Mole
Karyotype
![Page 11: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/11.jpg)
Pathogenesis of complete H. Mole
Heterozygous 10%
Karyotype
![Page 12: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/12.jpg)
Pathogenesis of Partial H. Mole
Karyotype
![Page 13: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/13.jpg)
Complete H. MoleMicroscopically Enlarged, edematous villi and abnormal trophoblastic proliferation that diffusely involve the entire villiNo fetal tissue, RBCs or amnion are produced
Macroscopically, these microscopic changes transform the chorionic villi into clusters of vesicles with variable dimensions “ like bunch of grapes" No fetal or embryonic tissue are producedUterine enlargement in excess of gestational age .Theca-lutein cyst associated in 30%
![Page 14: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/14.jpg)
Complete hydatidiform mole: Macroscopically, these microscopic changes transform the chorionic villi into clusters of vesicles with variable dimensions the name hydatidiform mole stems from this "bunch of grapes"
![Page 15: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/15.jpg)
Partial H. MoleMicroscopically: The enlarged, edematous villi and abnormal trophoblastic proliferation are slight and focal and did not involve the entire villi.There is a scalloping of chorionic villi Fetal or embryonic or fetal RBCs
Macroscopically: The molar pattern did not involve the entire placenta.Uterine enlargement in excess of gestational age is uncommon. Theca-lutein cysts are rare Fetal or embryonic tissue or amnion
![Page 16: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/16.jpg)
Partial Hydatiform Mole
Vesicles
Maternal side
![Page 17: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/17.jpg)
Partial H. mole.
![Page 18: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/18.jpg)
The classic features are
Irregular vaginal bleeding
Hyperemesis
Excessive uterine enlargement &
Early failed pregnancy.
Breathlessness due to anaemia
Abdominal pain
Presentation
Some women will present early with passage of molar tissue
![Page 19: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/19.jpg)
Rarer presentations include:
Hyperthyroidism
Early onset pre-eclampsia
Abdominal distension due to theca lutein cysts
Very rarely
Acute respiratory failure
Neurological symptoms such as seizures (?metastatic disease).
![Page 20: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/20.jpg)
Clinical FindingsAnemia
Breathlessness
Pseudo- Toxemia which consist of Systolic hypertension edema and proteinuria
The Uterus is doughy in consistence
Absence of fetal part
Enlarged Cystic Ovaries
![Page 21: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/21.jpg)
Complete Molar Pregnancy
![Page 22: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/22.jpg)
Complete hydatidiform mole. The classic "snowstorm" appearance is created by the multiple placental vesicles.
![Page 23: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/23.jpg)
Complete H.Mole (High-resolution) U/S Complex intrauterine mass containing many small cysts.
Complete H.Mole Associated theca-lutein cysts. U/S Power Doppler
![Page 24: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/24.jpg)
In most patients with a partial mole,
the clinical and U/S diagnosis is
Usually missed or incomplete abortion.
This emphasizes the need for a
thorough histopathologic evaluation of
all missed or incomplete abortions
![Page 25: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/25.jpg)
Classically: A thickened, hydropic placenta with fetal or embryonic tissue
Multiple soft markers, including:
Cystic spaces in the placenta and
Transverse to AP dimension a ratio of the gestation sac of > 1.5, is required for the reliable diagnosis of a partial molar pregnancy
![Page 26: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/26.jpg)
Differential diagnosis
• Multiple pregnancy.
• Hydatidiform mole.
• Threatened abortion.
• Ectopic pregnancy.
![Page 27: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/27.jpg)
Partial Molar Pregnancies
![Page 28: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/28.jpg)
There are 2 important basic lines :
1-Evacuation of the mole
2-Regular follow-up to detect persistent
trophoblastic disease
If both basic lines are done
appropriately, mortality rates can be
reduced to zero.
Management
![Page 29: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/29.jpg)
For Partial mole: It depends on the fetal parts
Small fetal parts :Suction curettage
Large fetal parts: Medical (oxytocics)
In partial mole the oxytocics is safe ,as the hazard to embolise and disseminate trophoblastic tissue is very low
Also, the needing for chemotherapy is 0.1- 0.5%.
Is That The Same For Partial Mole?
![Page 30: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/30.jpg)
Post-evacuation Surveillance
Why?
To determine when pregnancy
can be allowed
To detect persistent
trophoblastic disease (i.e. GTN)
![Page 31: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/31.jpg)
The Post-evacuation Surveillance. How?
A baseline serum β -hCG level is obtained within 48 hours after evacuation.
Levels are monitored every 1 to 2 weeks
while still elevated to detect persistent trophoblastic disease (GTN).
These levels should progressively fall to an undetectable level (<5 mu/ml).
If symptoms are persistent, more frequent β hCG estimation and U/S examination ± D&C are advised
![Page 32: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/32.jpg)
What Is The Optimum Follow-up Period Following Normalization of β
hCG?A. For 6 months from the date of uterine
evacuation.
B. For 6 months from normalization of the β
hCG level. B
C. For 12 months from the date of uterine
evacuation. (For Nigeria)
![Page 33: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/33.jpg)
Barrier methods until normal β hCG level.
Once βhCG level have normalized:Combined
oral contraceptive (COC ) pill may be used.
If oral COC was started before the diagnosis of
GTD ,COC can be continue as its potential to
increase risk of GTN is very low
IUCD should not be used until β hCG levels are
normal to reduce uterine perforation.
What Is Safe Contraception Following GTD?
![Page 34: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/34.jpg)
Part II: Gestational Trophoblastic Neoplasia (GTN)
![Page 35: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/35.jpg)
Nonmetastatic disease Locally invasive GTT develops in about
15%
Patient usually present with Irregular vaginal bleedingTheca lutein cystsUterine subinvolution or asymptomatic
enlargement Persistently elevated serum hCG level
Persistent GTTAfter hydatiaiform mole
![Page 36: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/36.jpg)
Invasive Mole Villus formation preserved
Trophoblast cells invade myometrium and blood vessels
Myometrium invaded
Myometrium
Villus
![Page 37: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/37.jpg)
Invasive H. Mole
Myometrial invasion
Sometimes involving the peritoneum, parametrium, or vaginal vault. Originate almost always from H. mole
Vesicles
![Page 38: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/38.jpg)
Placental-site trophoblastic tumor
Uncommon but important variant of choriocarcinoma
Characteristic Produce small amount of hCG and
hPLRemain confined to the uterusMetastasizing late in their course
Relatively insensitive to chemotherapy
![Page 39: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/39.jpg)
Gestational Choriocarcinoma
Aneuploidy (not multiplication of 23 )
1 in 30,000 pregnancies in western world
1 in 300 to 1000 in Nigeria
40% after molar pregnancy: Easily Diagnosed
60% non-molar pregnancy: Difficult Diagnosis
The main presentations are often non-
gynecologic including hemoptysis or pulmonary
embolism, cerebral hemorrhage, gastrointestinal
or urologic hemorrhage.
![Page 40: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/40.jpg)
Gestational ChoriocarcinomaSheets of anaplastic cytotrophoblast and
syncytiotrophoblast cells with hemorrhage &
necrosis.
Myometrial & B. vessels invasion and early metastases
No Villus formation
Cytotrophoblast
Syncytiotrophoblast
![Page 41: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/41.jpg)
Metastatic disease Metastatic GTT occur in about 4%
after complete mole
Symptom of metastases may result from spontaneous bleeding at metastatic foci
The common site of metastases areLung(80%)vagina(30%) pelvis(20%) liver(10%) brain(10%)
![Page 42: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/42.jpg)
GTN Vaginal Metastasis
![Page 43: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/43.jpg)
Cranial MRI scan: Large metastasis on the left (black arrows)
Brain MRI of a patient with a solitary brain metastasis in remission
![Page 44: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/44.jpg)
Autopsy specimen Multiple hemorrhagic hepatic metastasis
CT Scan: Liver metastsis
![Page 45: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/45.jpg)
Stage I Disease confined to the uterus
Stage II GTN extends outside of the uterus but is limited to the genital structures (adnexa, vagina, broad ligament)
Stage III GTN extends to the lungs, with or without known genital tract involvement
Stage IV
All other metastatic sites (brain, liver)
FIGO Anatomic Staging Of GTN
![Page 46: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/46.jpg)
Staging : FIGO
Risk factor affecting staging hCG level > 100,000 mIU/mlDuration of disease longer than 6
months from termination of pregnancy
Stage 1-4Without risk factors a 1 risk factor bWith 2 risk factors c
![Page 47: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/47.jpg)
FIGO SCORING 0 1 2 4
Age (years) <40 >40
Antecedent pregnancy Mole Abortion Term --
Pregnancy to treatmentInterval (months)
<4 4to <7 7to <13 ≥13
Pretreatment serum hCG (iu/l)
<1000 1000-10,000 10,000-100,000 > 100,000
Largest tumour size, including uterus (cm)
< 3 3 to<5 ≥5 --
Site of metastases Lung Spleen & Kidney
Gastro-intestinal
Liver & brain
Number of metastases -- 1-4 5-8 >8
Previous failed chemotherapy
-- -- Single drug ≥2 Drugs
FIGO Prognostic Scoring For GTN (2000(
Total Score Survival : ≤ 6 = Low risk (100%) ≥7 = High risk. (95%)
![Page 48: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/48.jpg)
Non metastatic GTD Metastatic
Single agent Chemotherapy
Methotrexate or Actinomycen D
Multi-agent
Chemotherapy
Low Risk ( ≤ 6) High Risk (≥7)
What Is The Optimum Treatment For GTN?
GTN
![Page 49: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/49.jpg)
What is the best methotrexate regimen? MTX:1mg/kg IM D:1, 3 ,5 ,7 alternating with
Folinic acid 0.1mg/kg IM D 2 , 4 , 6 , 8
followed by 6 rest days
Treatment is continued, until the hCG level
has returned to normal and then for a further
6 consecutive weeks.
As any chemotherapy treatment is reevaluated if FBC,
liver or kidney FT are affected or at drug resistance
![Page 50: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/50.jpg)
Chemotherapy Combination chemotherapy
Triple therapy : MTX, Act-D, cyclophosphamide
EMA-CO : etoposide, MTX, Act-D, cyclophosphamide, vincristine
EMA-EP : etoposide and cisplatin on day 8
Duration of therapy Until 3 normal hCG level
After that, at least 2 additional course are administered
![Page 51: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/51.jpg)
Follow UpStage 1-3 receive follow-up with
Weekly hCG level until normal for 3 wks
Monthly hCG level until normal for 12 months
Effective contraception during the entire interval of hormonal follow-up
Stage 4 receive follow-up with Weekly hCG level until normal for 3 wksMonthly hCG level until normal for 24
months
![Page 52: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/52.jpg)
Stage Survival Percent %
I 424/424 100
II 27/27 100
III 130/131 99
IV 14/18 78
What Is The Survival of GTN By FIGO Stage?
Disaia &Creasman Clinical Gynecological Oncology 2007
![Page 53: Gestational Trophoblastic disease](https://reader033.vdocuments.mx/reader033/viewer/2022061116/5465ff75af7959642f8b517a/html5/thumbnails/53.jpg)