Gestational Trophoblastic Disease Ermos Nicolaou Fetal Medicine Centre Chris Hani Baragwanath Hospital University of the Witwatersrand
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.
Hydatidiform mole is subdivided into complete and partial mole
based on genetic and histo-pathological features.
Complete moles are
andro-genetic in origin
no evidence of fetal tissue.
Arise as a consequence of
duplication of the haploid sperm following fertilisation of an ‘empty’ ovum ( diandry)
Some complete moles arise after dispermic fertilisation of an
“ empty’ ovum. (dispermy)
Molar Pregnancy Complete Mole
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
Triploid in origin with usually two sets of paternal haploid genes and
one set of maternal haploid genes.
They occur, in almost all cases, following dispermic fertilisation of an ovum. There is usually evidence of a fetus or fetal red blood cells.
In some cases failure of meiosis I or II in the ovum leads to Triploidy with 46 maternally derived chromosomes and 23 paternal
Partial Molar Pregnancy
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
When extra set of chromosomes is paternally derived , is associated with a molar placenta and the pregnancy rarely persists beyond 20 weeks. When there is a double maternal chromosome contribution, the pregnancy may persist into the third trimester. The placenta may be of normal consistency and the fetus demonstrates severe asymmetrical growth retardation
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
Trophoblast cells appear to evade the attack by the NK cells via
interactions with “killer inhibitory receptor molecules” on CD56+ve
Choriocarcinoma Hydatidiform Mole Normal Pregnancy
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
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
Diagnosis of Gestational Trophoblastic Disease
Increasing use of ultrasound in early pregnancy has led to the
earlier diagnosis of molar pregnancy.
The majority of histologically proven complete moles however are
associated with an ultrasound diagnosis of delayed miscarriage or
The ultrasound features of a complete mole are reliable but the
ultrasound diagnosis of a partial molar pregnancy is more complex.
RCOG, February 2004
‘ 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
Sebire NJ et al . Ultra sound Obste t Gynecol 2001 Dec; 18 ( 6 ): 662
retrospective review ( 6-month period )
194 cases referred to the National Trophoblastic Disease Surveillance Centre (Charing Cross Hospital) with suspected molar pregnancies
The successful outcome in patients with GTT depends on several factors:-
(i) Need for a national registration scheme of patients at risk of developing a GTT (ii) The ability to monitor the disease and its response to treatment with serial hCG estimations. (iii) The intrinsic biological property of GTT in being inherently very sensitive to a range of chemotherapeutic agents.