Post on 29-Dec-2015
Epidemiology Complete versus partial
mole Clinical picture Natural history Diagnosis Treatment Follow up
INTRODUCTION
GTD is among the rare tumors that can be cured even if metastasizedTypes:
Complete mole Partial mole Placental site mole Choriocarcinoma
Persistent GTT:Most commonly follow molar pregnancyMay also follow: abortion, ectopic or term
pregnancy
EPIDEMIOLOGY
%varies in different sites:Japan = 2 : 1000 pregnanciesUSA = 0.6 – 1.1 : 1000 pregnanciesIn pathological studies:
Complete mole 1 : 945 Partial mole 1 : 695
Risk factors in complete mole: 1 – nutritional :
↓carotene ↓vit A
2 – Age: > 35 years = X 2 > 40 years = X 7.5
Risk factors in partial mole: 1 - OCCP
2 - H/O irregular menstruation
COMPLETE VERSUS PARTIAL MOLE
Complete molePathology:
No fetal or embryonic tissue Villi show:
Diffuse hydropic swelling Diffuse trophoblastic hyperplasia
Chromosome: 90% 46XX
10% 46XY
Chromosomes are entirely paternal Mitochondria DNA is maternal in origin
1 - Absent or inactivated ovum nucleus + 1 haploid sperm
endoredublication homozygous mole
2 –Absent or inactivated ovum nucleus + 2 haploid sperms
heterozygous mole
Partial moleVilli vary in size and show:
Focal hydropic swelling Focal trophoblastic hyperplasia Focal cavitation Stromal trophoblastic inclusion Scalloping
Fetal or embryonic tissues
Chromosomes:Absent or inactivated ovum nucleus
+3 haploid sperms triploid in 90% =69XXX, 69XXY, 69XYY
The fetus shows triploidy stigmata:
GR Multiple congenital anomalies as:
Syndactyly - Hydrocephalus
Complete PartialFetus absent presentKaryotype 46XX(90%) 69XXX
46XY (90%)Hydropic swelling diffuse focalTrophoblastic diffuse focal hyperpleasiaScalloping no presentStromal inclusions no present
CLINICAL PICTURE
Complete Partial
past nowVaginal bleeding 97% 84% 74%Anemia 50% 5%Excessive uterine size 50% 28% 4%
Preeclampsia 50% 1.5% Hyperemesis 27% 8%
Hyperthyroidism 7% 0% Trophoblastic embolism 2% 0%Theca lutein cysts 50%HCG > 100,000mIU/mL 6%
Excessive uterine size: = ↑trophoblastic tissue
↑ hCG ↑ preeclampsia
↑ hyperthyroidism ↑ hyperemesis gravidarum
↑ trophoblastic embolization ↑ theca lutein cyst size
Preeclampsia:Early preeclampsia = hydatidiform moleHyperthyroidism:
Due to ↑ free T3, T4
C/P : tachycardia warm skin tremor
Thyroid storms: Give β–blockers before anesthesia
to avoid thyroid stormsC/P:
↑pulse, ↑ temp, ↑ COP + delirium + convulsions
may HF
Chest examination diffuse ralesChest X ray bilateral infiltratesCauses of respiratory distress: Trophoblastion embolization Complications of: • preeclampsia • thyroid storm • excessive fluid intake
Theca lutein ovarian cysts Due to ovarian overstimulation by ↑
hCG May not be felt with oversized uterus May pressure symptoms treated by decompression by laparoscopic or U/S guided aspiration If ruptured or torsion occur acute pain laparoscope
NATURAL HISTORY
Complete mole Invasive = 15% Metastatic = 4%
Risk factors: hCG > 100,000 mIU/mL Excessive uterine size Theca lutein cysts = 6 cm
Low risk = 60% 3.4% persistent mole
0.6% metastaticHigh risk = 40%
31% persistent mole 9% metastatic
Age: > 40 years = 37%
> 50 years = 56%
DIAGNOSIS
Complete moleU/S vesicular patternPartial moleU/S focal cystic spaces in placenta
+ ↑transverse diameter of GSBoth together 90% +ve predictive
value
TREATMENT
I – Hystrectomy + aspiration of CL cyst
+ follow up as usual2 - Suction evacuation
Preferred ttt for hydatidiform mole Give oxytocine before anesthesia
Use 12 canula If > 14 weeks support the fundus
+ do fundal massage
Dilatation ↑ bleeding Suction evacuation ↓ bleeding
If RH –ve give Anti RH Ig3 - Prophylactic chemotherapy
↓invasive mole to 4% after 1st course ”””””””””””””””””“ ↓0% after 2nd
course Controversial : Why to expose all
patients to chemotherapy while only 20% will need it ?
Useful if follow up is: Unreliable
Unavailable Study:
Prophylactic chemotherapy in high risk patients ↓ persistent
mole from 47% to 14%
FOLLOW UP
1 - HCG Average time needed to return to
normal values = 9 weeks Measure hCG/week
3 consecutive normal results /month 6 consecutive normal R
2 - Contraception: OCCP or barrier methods
IUD is C/I perforation
Nonmetastatic disease Placental-site TT Metastatic D Staging Prognostic scoring systems Diagnostic evaluation Management
NONMETASTATIC DISEASE
Invasive mole = 15% after evacuationC/P:
Irregular vaginal bleeding Uterine subinvolution Theca lutein cysts ↑hCG Perforation of myometrium internal Hg Perforation of uterine vessels vaginal Hg Infection acute pain purulent discharge
Histology : After molar pregnancy hydatidiform mole or choriocarcinoma After nonmolar pregnancy choriocarcinoma = sheets of anaplastic cytotrophoblast and syncytiotrophoblast + no villi
PLACENTAL-SITE TT
UncommonVariant of choriocarcinomaConsists of intermediate trophoblastProduce small amounts of hCG & hPLTends to be confined to the uterusMetastasize lateResistant to chemotherapy
METASTATIC DISEASE
=4% after molar pregnancyMore often after nonmolar pregnancyUsually associated with choriocarcinomaHighly vascular spontaneous bleedingEarly vascular spreading Sites:
Pulmonary 80% Hepatic 10% Vaginal 30% Brain 10%
Pelvic 20%
1 –Pulmonary metastases: Symptoms :
dyspnea cough
hemoptysis chest pain
asymptomatic May be acute of chronic
Chest X ray: Snowstorm pattern Discrete rounded densities Pleural effusion Pulmonary artery embolism
May be misdiagnosed as 1ry pulmonarydisease and only recognized as GTD after thoracotomy
Pulmonary embolism may pulmonary HTN
Early RF + intubation = bad prognosis 2 – Vaginal metastasis
highly vascular biopsy may excessive bleeding
Symptoms: Vaginal bleeding Purulent discharge Site: fornices/suburethral
3 – Hepatic metastasis Usually in advanced cases
Symptoms: Epigastric or upper RT ¼ pain due to
stretching subcapsular hematoma Rupture internal Hg4 – Brain metastasis
Usually in advanced cases Spontaneous bleeding acute focal
neurological defects
STAGING
Stage I confined to uterusStage II confined to genital structuresStage III pulmonary metastasisStage IV other metastasisAt any stage:
A = no risk factors B = 1 risk factor
C = 2 risk factors
PROGNOSTIC SCORING SYSTEMS
0 1 2 4Age ≤39 >39Pregnancy mole abortion termDuration <4m 4-6 7-12 >12
hCG <1000 <10000 <100000> Largest size <3cm 3-5 >5Site of met 0 kidney/spleen GIT/liver brainNumber <3 1-3 4-8 >8ABO group 0 A/O B/ABChemotherapy 1 ≥2
DIAGNOSTIC EVALUATION
H/O Examination hCG Liver function tests Kidney function tests Thyroid function tests WBCs Platelet count
IMAGING
Chest X-ray -- CTAbd & pelvis U/S -- CTBrain MRI -- CTIf no pulmonary or vaginal metastasis metastasis are rareChest CT for micrometastasisLiver CT for abnormal LFTsBrain CT for asymptomatic lesions
If brain CT is normalmeasure CSF hCGIf serum hCG/CSF hCG = < 60% then there is brain metastasisPelvic U/S for:
Extent of uterine lesion Localization of resistant lesions Identifying patients who will benefit from hystrectomy
STAGE I
If the patient does not wish to preserve fertility Hystrectomy + Chemotherapy to:
↓ dissemination of GTD Treat dissemination of GTD Treat occult metastasis ↓ bleeding ↓ sepsis
If the patient wish to preserve fertility:Low risk Single agent High risk Combined chemotherapyResistant Local uterine resection
after localization of resistant sites by U/S, MRI, or arteriography
Placental site GTD: -Only curative ttt for nonmetastatic
cases is hystrectomy -Resistant to chemotherapy few
metastatic cases reported complete remission after chemotherapy
STAGE II & III
Pulmonary metastasisLow risk single agent 82% CRHigh risk combined chemotherapyResistant thoracotomy after
localization of and exclusion of other
resistant sites
Vaginal metastasisLow risk single agent 84% CRHigh risk combined chemotherapyResistant wide local excisionVaginal bleeding:
Packing of the vagina Wide local excision Embolization of hypogastric arteries
Hystrectomy -In metastatic disease
- to control Hg - to control sepsis
-In extensive uterine disease - to ↓ GTT burden
- to ↓ chemotherapy courses
Follow up of stage I, II, III:hCG/week
3 consecutive normal results hCG/month
12 consecutive normal results +effective contraception
STAGE IV
Should be referred to specialized centersMay be unresponsive or rapidly progress All should receive intensive combined chemotherapy ± irradiation / surgeryHepatic metastasis:
Resistant cases intrahepatic infusion of chemotherapy
Hemorrhage local excision or arterial embolization
Brain metastasis:All cases receive:
Whole brain irradiation by 3000 cGy in 10 fractions Combined chemotherapy + intrathecal MTX 86% CRResistant local excisionHemorrhage craniotomy50%CRNo residual neurologic deficits
SINGLE AGENT CHEMOTHERAPY
Used in nonmetastatic and low risk mmMTX&Act-D are used/other week X5days
1964 :MTX-FA well tolerated ↓ toxicity
MTX-FA the preferred ttt for GTDMTX-FA 88% CR
81% by single course 90% CR in stage I 68% CR in stage II
Complications: Thrombocytopenia 1.6% Agranulocytopenia 6% Hepatotoxicity 14%
Resistant cases: Choriocarcinoma Metastasis Initial hCG > 50,000 mIU/mL
Technique: Measure hCG after each course Draw a curve Stop MTX if the curve is progressively ↓ Do not give MTX at any predetermined or fixed interval Give another course if:
hCG is ↑ or plateaus for > 3 weeks hCG ↓ < 1 log at day 18 post ttt
If the response to the 1st course is adequate give the same dose If the response to the 1st course is inadequate ↑ the dose to 1.5 mg/Kg body weight/day X 4 days Adequate response = ↓ hCG by 1 log If the response to the 2nd & 3rd courses is inadequate give ACT-D If the response to ACT-D is inadequate give combined chemotherapy
COMBINED CHEMOTHERAPY
Triple therapy ( MTX + ACT-D + cyclophosphamide ) is inadequate in ttt of high risk cases 50% CR only Etoposide 95% CR in nonmetastatic and low risk metastatic cases 1984: triple therapy + Etoposide + Vincristine ( EMA-CO )
83% CR in high risk patients
EMA-CO is well tolerated and is the preferred 1ry ttt for patients with metastasis and high risk score
76% CR when used as 1ry ttt 86% CR in brain metastasis If resistant to EMA-CO give EMA-EP (cisplatin) on day
8 76% CR in resistant patients
Duration of Therapy: Give combined chemotherapy 3 consecutive normal results Add at least 2 additional courses to ↓ risk of relapse
SUBSEQUENT PREGNANCIES
Complete/Partial mole Persistent GTTTerm 70% 70%PTL 7% 6%Ectopic 1% 1%SB ½% 11/2%
Recurrence 11/2% 1%1st T abortion 16% 15%2nd T abortion 1.6% 1.5%Congenital anom 4% 2.5%CS 16% 19%