Overview and Pathophysiology of Gestational Trophoblastic Disease

DR Rehana PerveenAssociate ProfessorDept of Obs/GynaeShaheed Suhrawardi Medical College

Overview and Pathophysiology of Gestational Trophoblastic Disease1Gestational Trophoblastic Disease(GTD) is a spectrum of interrelated pregnancy disorders arising from the placental trophoblastic tissueDefinition2Overview on GTD

HistoryHippocrates was probably the 1st to describe GTD around 400 BCMarchard 1st associated hydatidiform mole with pregnancy in 1895Prior to the development of early diagnosis & effective evacuation in 1970s mole was associated with serious bleeding & its consequences History cont..Choriocarcinoma had a mortality rate - 100% with metastastatic disease - 60% with non-metastetic disease 50 yrs ago prior to the introduction of Methotrexate in 1956 GTN are now the most curable tumors with cure rate of >98% even with widespread metastases -early detection -individualization of treatment -effective chemotherapeutic agent -centralization of care NomenclatureGestational Trophoblastic disease(GTD) includes

Benign or potentially malignant variantHydatidiform mole - Complete hydatidiform mole(CHM) - Partial hydatidiform mole(PHM)Malignant variantGestational Trophoblastic Neoplasia(GTN) or (GTT) - Invasive mole(IM) - Choriocarcinoma(CC) - Placental site trophpblastic disease(PSTT) - Epitheloid trophoblastic tumor(ETT)

Nomenclature cont..Persistent Gestational Trophoblastic Disease/ postmolar GTN - Serum -HCG plateus or rises - Level persists >20,000 mIU/ml following evacuation of mole

IncidenceIncidence of Hydatidiform mole Europe & North America 1/1000 births Malaysia 2.8/1000 Japan 2/1000 Taiwan 1/125 South Korea 4.4/1000 births in 1960 1.6/1000 in 1990 Incidence cont..Incidence of ChoriocarcinomaEurope & North America 1 in 40,000pregnanSouth East Asia 9.2/40,000Japan 3.3/40,000

Incidence of choriocarcinoma has declined over the past 30yrs in all population

Risk Factors in molar pregnancyExtremes of maternal age -1.9 times higher if maternal age is >35yr & 40yrs

Prior molar pregnancy One molar pregnancy 1% - 2% Two 15% - 20%

Dietary deficiency of -carotene & animal fat Oral contraceptive pills Blood group ARisk factors for persistent GTD Advanced maternal age Uterine size > 20 weeks Pre-evacuation HCG > 100000U/L Theca lutein cysts > 6cm Preeclampsia Uterine sub-involution with haemorrhageClassification of GTN Clinical classification by Hammond in 1973 Non-metastatic GTT Metastatic GTTLow-risk group/Good prognosisHigh-risk group/Bad prognosis

Prognostic Risk Scoring modified by WHO

Anatomical staging system adopted by FIGO

Prophylactic ChemotherapyUse of chemotherapy following evacuation of mole to prevent malignant sequelae

15 20% of hydatidiform mole will develop malignant GTD 80% will be subjected to a toxic drug There are risk factors that predisposes to malignant GTD Incidence of postmolar GTN reduced from 47.4% to 14.3% with Methotrexate & Patient who are unable to come, poor, HCG monitoring is not available or having high risk factors - prophylaxis can be considered Problem in Diagnosis of Mole during 1st trimeClassic clinical features are becoming less commonSonographic classical features are largely absent during the 1st trimester -only 40 -50% of CHM & 15 20% of PHM are diagnosed & rest are missed as a case of missed abortion or blighted ovum , so escape regular HCG monitoring & present late as persistent GTD

Difficulty in Histological diagnosis in 1st trimesterClassical histological features are absent Abnormal budding villous structure with trophoblastic hyperplasiaStromal karyorrectic debrisCollapsed villous blood vesselsEstimation of HCG 4 weeks after termination of pregnancy

Recurrent Disease Re-elevation of normalized HCG values Appearances of new metastases after primary remission 5% of low risk GTN recurs 20% of high risk GTN recur Recurrence occurs usually within the 1st yr of follow up Risk factors for recurrence are large-volume disseminated disease & inappropriate initial therapy ConclusionGTN are highly curable diseaseTreatment is to be individualized based upon risk factors , single agent therapy for low risk cases but multidrug therapy for high risk cases must be started from the beginningHigh risk cases should be managed in specialized centers by experts

THANK YOUTHANK YOURecurrent Disease Re-elevation of normalized HCG values Appearances of new metastases after primary remission 5% of low risk GTN recurs 20% of high risk GTN recur Recurrence occurs usually within the 1st yr of follow up

Pathophysiology

Placental Trophoblast -Cytotrophoblast -Syncytotrophoblast -Intermediate trophoblastPath contHydatidiform mole -complete hydatidiform mole(CHM) -partial hydatidiform mole(PHM)Path contHydatidiform mole -complete hydatidiform mole(CHM) -partial hydatidiform mole(PHM)CHM Morphology -uniform vesicular enlargement of villi -uniform cellular hyperplasia with atypia -avascular villous -absent fetal tissueCytogenetic analysis -46XX karyotype with both sets of chromosomes being of paternal originMalignant potential -15- 20% will be followed by persistent GTD PHMMorphology -focal vesicular enlargement of villi -focal cellular hyperplasia with mild atypia -villous vascular pattern preserved -fetal tissue presentCytogenetic analysis -karyotyping reveals triploidy 69XXX, 69XXYMalignant potential