Gestational Trophoblastic Disease - www.jinekolojivegebelik.com

1. Gestational Trophoblastic Disease Ermos Nicolaou Fetal Medicine Centre Chris Hani Baragwanath Hospital University of the Witwatersrand

2. Gestational Trophoblastic Disease (GTD) is a relatively rare event with a calculated incidence of 1/714 live births. There is evidence of ethnic variation in the incidence of GTD in the UK, with women from Asia having a higher incidence compared with non-Asian women (1/387 versus 1/752 live births). This may under-represent the true incidence of the disease because of problems with reporting, particularly with regard to partial moles.

6. North America and Europe: Partial mole 1/700 Complete mole 1/1500-2000 Asian Countries: Partial mole 1/120 Complete mole 1/350-500 HYDATIDIFORM MOLE Incidence

7. 1. Maternal age > 40 years < 15 years 2. Paternal age > 45 years 3. Previous hydatidiform mole 1 st 1-2% 2 nd 15-28% 4. Vitamin A deficiency HYDATIDIFORM MOLE Risk factors

9. Empty ovum Empty ovum 46XX 46XX or 46XY 23X or Y 23X 23X Complete Mole (46XX diploid) Complete Mole (46XX or 46XY, diploid) A single sperm fertilizes an empty ovum, with duplication of the 23X haploid set of chromosomes, giving rise to a homozygous diploid complete mole. Two sperms with two independent haploid sets of chromosomes fertilize an empty ovum, producing a dyspermic complete mole with either 46XX or 46XY karyotype. COMPLETE MOLE Modified from Cheung, 1995

11. Father F

18. 23X 23X Dyspermy 23X/23Y or 23X/23X 23Y Partial Mole (69XXY, or 69XXX, or 69XYY triploid) PARTIAL MOLE 23X 23X 23Y 69XXY Fertilization of a normal 23X haploid ovum by two sperms, producing a triploid partial mole with either 69XXY, 69XXX or 69XYY karyotype Modified from Cheung, 1995

20. Fetal or embryonic tissue absent present Hydatiform swelling of chorionic villi extensive focal Trophoblastic hyperplasia extensive focal Scalloping of chorionic villi absent present Trophoblastic stromal inclusions absent present Karyotype 46XX (90%); Triploid (69 XXY) 46XY (10%) Complete mole Partial mole Cohn DE, Herzog TJ. Curr Opin Oncol 2000 Sep; 12(5):492-6 FEATURES OF PARTIAL AND COMPLETE MOLE

29. A–C depicts staining against cytokeratin-positive cells,which identify trophoblast / tumor cells, marked by brown staining. D–F shows representative examples of the distribution and density of CD8+ cells, which are present as clusters in CC (D) and HM (E). S. Knoeller, E. Lim, L. Aleta, et al AJRI 2003; 50: 41–47 Choriocarcinoma Hydatidiform Mole Normal Pregnancy

39. COMPLETE HYDATIFORM MOLE CLINICAL FEATURES Vaginal bleeding (anemia) 97% Excessive uterine size 50% Theco-lutein ovarian cysts 50% Preeclampsia 27% Hyperemesis 25% Hyperthyroidism 7% Trophoblastic embolization 2% (respiratory distress)

40. The increasing performance of ultrasound examination, either routinely in the first trimester or for management of early pregnancy complications, allows evacuation of most pregnancies affected by hydatiform mole prior to development of the classic sonographic and pathological features. ULTRASOUND FINDINGS

41. Multiple hypoechoic areas extensive focal Increased echogenicity extensive focal Enlarged uterine volume present absent Theca-lutein cysts present absent > Ø gestational sac - present < Uterine artery PI present - Complete mole Partial mole ULTRASOUND FINDINGS

42. COMPLETE MOLE “ snow storm”

43. PARTIAL MOLE “ Swiss cheese”

45. ‘ T he diagnostic implications of routine ultrasound examination in histologically confirmed early molar pregnancies ‘ OBJECTIVE : to determine the sonographic findings of routine ultrasound examinations in patients with a proven histological diagnosis of complete or partial hydati f orm mole. Sebire NJ et al . Ultra sound Obste t Gynecol 2001 Dec; 18 ( 6 ): 662

47. 194 63 (33%) hydatiform mole 155 131 (67%) missed misc./anembryonic pregn. Ultrasonographic diagnosis Histological diagnosis 53 (84%) hydatiform mole 64 compl mole 91 partial mole 37 (58%) mole 16 (17%) mole Sebire NJ et al . Ultra sound Obste t Gynecol 2001 Dec; 18 ( 6 ): 662

49. DIAGNOSTIC ACCURACY OF ULTRASONOGRAPHY IN COMPLETE MOLAR PREGNANCY Sebire et al. (2000) 58% Lazarus et al. (1999) 57% Benson et al. (2000) 79% Lindholm et al. (1999) 80%

51. DIFFERENTIAL DIAGNOSIS partial mole hydatiform mole + viable fetus mesenchymal dysplasia Fetus absent complete mole Fetus present

52. PARTIAL MOLE More than 90% of partial moles are found in triploid fetuses. Feto-placental ultrasound findings n % Fetal anatomic defects 65 92.9 1 10 14.3 2 23 32.9 >2 32 45.7 Asymmetrical growth restriction 45 64.2 Placental molar changes 20 28.6 Amniotic fluid changes 33 47.1 Olygohydramnios 31 44.2 Polyhydramnios 2 2.9 Jauniaux E, Nicolaides KH: Placenta 1997, 18; 701-6

53. Ultrasound abnormalities in triploid fetuses Malformed hands 34 52.3 Ventriculomegaly 24 36.9 Heart abnormalities 22 33.9 Micrognathia 17 26.2 Hyperechogenic bowel 10 15.4 Renal malformations 8 12.3 Increased nuchal thickness 8 12.3 Spina bifida 5 7.7 Talipes equinovarous 5 7.7 Dandy-Walker malformation 5 7.7 Collapsed stomach 5 7.7 Single umbilical artery 4 6.2 Omphalocele 4 6.2 Holoprosencephaly 2 3.1 Hydrops 2 3.1 Bilateral pleural effusion 2 3.1 Ascites 2 3.1 Diaphragmatic hernia 1 1.5 Kyphoscoliosis 1 1.5 Cleft lip and palate 1 1.5 Variables n = 65 % Jauniaux E, Nicolaides KH: Placenta 1997, 18; 701-6

55. GTD and Twin Pregnancy

56. Incidence 1:22.000 – 1:100.000 Variants viable fetus with partial hydatiform mole viable fetus with complete hydatiform mole GTD and Twin Pregnancy

58. Prognosis Miscarriage 50% Stillbirth <32 wks 30% Preterm delivery <32 wks 30% Pre-eclampsia > 50% COMPLETE HYDATIFORM MOLE AND COEXISTING VIABLE FETUS

67. FIGO score Low Score <6 High Score > 7 >100.000 >10.000-100.000 1.000- 10.000 <1.000 Pretreat. hCG 12 7-12 4-6 <4 Interval (months) Term pregnancy abortion Hydat Mole Antecedent pregnancy 4 2 1 >39 0 <39 Age Combined Single drug Previous failed chemo >8 4-8 1-4 0 No of metastasis Brain, Liver GI tract Spleen, kidney Site of metastasis 5cm 3-4cm Largest tumour size