GTD
 Heterogenous group of inter-related lesions that arise from
abnormal proliferation of placental trophoblasts
 Histologically distinct and can be benign or malignant
 BENIGN lesions- Hydatidiform moles ,
Complete mole ,
Partial mole
 MALIGNANT lesions(GTN)- Invasive mole,
Placental site trophoblastic tumor(PSTT),
Epitheloid trophoblastic tumors(ETT),
Choriocarcinoma.
 Malignant lesions are locally invasive and metastatic in
nature
 GTNs are among the rare human tumors that can be
cured even in the presence of widespread
dissemination
 Although GTNs commonly follow a molar pregnancy,
they can occur after any gestational event, including
induced or spontaneous abortion/ ectopic
pregnancy/term pregnancy.
HYDATIDIFORM MOLES
 INCIDENCE- higher in Eastern countries than in the
West.
 India and Middle East- 1:160 and 1:500
 Malignant potential is higher in South East Asia(10-
15%) compared to western countries(2-4%).
 Geographical and environmental factors plays a major
role.
Risk factors
 Age –adolescents (7%)and women over 40 years (2-
10%)
 Ova from adolescents and older women may be more
susceptible to abnormal fertilization
 Diet deficiency- vitamin A, b- carotene, folic acid
 Maternal age and nutrition influences the incidence of
complete mole than partial mole
Risk factors
 Blood group A or AB are at slightly higher risk than
those with type B or O
 Smoking
 Previous h/o GTD-
-If one previous mole, 1% chance of
recurrence(vs. 0.1% in general population)
-if 2 previous moles, risk of recurrence increases
to 16-28%
 Oral contraceptive use & h/o irregular menstruation
increases the risk for partial mole
Pathology
 Based on morphology, histopathology and karyotype,
Hydatidiform mole
Complete mole Partial mole
Complete mole
 Arise from an ovum fertilised by an haploid sperm,
which duplicates its own chromosomes.
 Ovum nucleus may be absent or inactivated.
sperm empty egg 46,XX
23x 23X 23X
.
sperm empty egg 46,XY
 They usually have 46,XX karyotype, but about 10% have
46,XY karyotype.
 Molar chromosomes are entirely of paternal origin, with
mitochondrial DNA of maternal origin
23Y 23 X 23 X 23Y
Partial mole
 They usually have triploid karyotype (69
chromosomes),the extra haploid set of chromosome is
derived from the father.
sperm normal egg 69,XXY
(69,XXX)
23Y 23 X 23X 23Y 23X
23 X 23X 23X 23X 23X
Recurrent molar pregnancy
 Due to dysregulation of normal parental imprinting of
genes, with loss of maternally transcribed genes.
 Recurrent complete molar pregnancy is due to
biparental origin, rather than the more usual
androgenetic origin.
 Mutations in NLRP7 gene is responsible for abnormal
development of embryonic and extra embryonic
tissue.
Complete vs. partial mole
Complete mole Partial mole
Based on clinical findings
1. Fetus
2. Fetal vessels
ABSENT PRESENT( malformed/
IUGR)
Histologically
1) hydropic changes
2) trophoblastic
hyperplasia
Diffuse & placenta not
present
Marked
Focal
Mild to moderate
b- HCG VERY HIGH Comparatively low
Karyotype 46 XX ( paternally
derived)
69 XXY
MALIGNANT
POTENTIAL
15-20% rare
Clinical features
 Vaginal bleeding – most common
-H/o passage of vesicles
- due to separation of molar tissues from decidua and
disruption of maternal vessels, and large volumes of
retained blood may distend the endometrial cavity
 Uterine enlargement-
-doughy in consistency
-trophoblastic overgrowth and usually associated
with high levels of HCG
- External & internal ballotment cannot be elicited
and FHR cannot be heard in Doppler.
Clinical features
 Theca lutein cysts ( 50%)- due to high level HCG
which cause ovarian hyperstimulation.
 It regresses spontaneously after molar evacuation
usually within 2-4 months.
 Partial mole have the signs & symptoms of missed/
incomplete abortion.
 Asymptomatic (<1%)
Complications
 Anaemia (5%) – due to prolonged bleeding
 Pre eclampsia (27%)- before 24 weeks
 Hyperemesis (8%)- may lead to electrolyte disturbances
 Hyperthyroidism (7%)
 Trophoblastic embolization-
-occurs after molar evacuation and they may
present with chest pain, dyspnea, tachycardia but within 72
hrs it can be resolved with cardiopulmonary support .
Differential diagnosis
 Mistaken date
 Multiple pregnancy
 Acute hydraminos
 Fibroid in pregnancy
 Threatened abortion
Diagnosis
 Ultrasonography – most sensitive, quick & safe
1) Complete mole :
- characteristic vesicular pattern( SNOW STORM
) is seen as early as the first trimester.
-absence of fetal shadow
2) Partial mole :
-focal cystic spaces in placental tissues and there is
an increase in the transverse diameter of gestational sac.
-Malformed fetus / IUGR fetus and placenta are
visualised
Diagnosis
 HORMONAL assays-
are mainly confined to post molar & post
chemotherapy follow up
 Serum b- HCG level is very high in complete mole
than partial mole.
 Human placental lactogen- low in C. Mole but raised
in P.mole, Pulmonary metastasis, PSTT.
 Chest X- ray – to rule out pulmonary metastasis
 CT scan- for liver / brain metastasis
 Histopathology – for partial mole
Treatment
 Evaluate for co existing conditions:
- history & physical
- CBC, coagulation profile, serum chemistry
- thyroid function
-blood type and cross match( trophoblast cells
express RhD factor, for RH-ve patients should receive
Rh immune globulin)
- pelvic USG and
- Chest X ray
Treatment
 Suction & curettage : preferred method, regardless
of uterine size
 Indications-
i)who desire to preserve fertility
ii)haemodynamically stable Procedure –
Oxytocin infusion>>>>> dilatation & curettage
Treatment
 Hysterectomy – may be performed with the mole in
situ and for those who are willing for surgical
sterilization.
 Ovaries may be preserved at the time of surgery, even
in presence of theca lutein cysts.
 It does not prevent metastasis ; patients still require
follow up with assessment of HCG levels.
Follow up
After evacuation
weekly monitoring of HCG until normal for 3 consecutive
weeks
Monthly monitoring until normal for 6 consecutive months
& 3 monthly in first year / 6 monthly in second year.
 Average time to achieve the first normal HCG after
evacuation is about 9 weeks.
Follow up
 After achieving non detectable levels, the risk of
developing GTN approaches to be 0.
 Encourage patients to use effective contraception
during HCG follow up and preferably pregnancy
should be avoided for 1 year.
 Oral contraceptives are safe during follow up.
 Incomplete evacuation will cause HCG levels to
remain elevated and interfere with proper follow up.
Follow up
 Follow up for 2 years remains the only option for
detecting early choriocarcinoma .
 Pelvic examination – to r/o vulval / vaginal metastasis.
 USG abdomen – for theca lutein cysts
 Chest X ray
,

Gestational Trophoblastic Diseases (GTD).pptx

  • 2.
    GTD  Heterogenous groupof inter-related lesions that arise from abnormal proliferation of placental trophoblasts  Histologically distinct and can be benign or malignant  BENIGN lesions- Hydatidiform moles , Complete mole , Partial mole  MALIGNANT lesions(GTN)- Invasive mole, Placental site trophoblastic tumor(PSTT), Epitheloid trophoblastic tumors(ETT), Choriocarcinoma.
  • 3.
     Malignant lesionsare locally invasive and metastatic in nature  GTNs are among the rare human tumors that can be cured even in the presence of widespread dissemination  Although GTNs commonly follow a molar pregnancy, they can occur after any gestational event, including induced or spontaneous abortion/ ectopic pregnancy/term pregnancy.
  • 4.
    HYDATIDIFORM MOLES  INCIDENCE-higher in Eastern countries than in the West.  India and Middle East- 1:160 and 1:500  Malignant potential is higher in South East Asia(10- 15%) compared to western countries(2-4%).  Geographical and environmental factors plays a major role.
  • 5.
    Risk factors  Age–adolescents (7%)and women over 40 years (2- 10%)  Ova from adolescents and older women may be more susceptible to abnormal fertilization  Diet deficiency- vitamin A, b- carotene, folic acid  Maternal age and nutrition influences the incidence of complete mole than partial mole
  • 6.
    Risk factors  Bloodgroup A or AB are at slightly higher risk than those with type B or O  Smoking  Previous h/o GTD- -If one previous mole, 1% chance of recurrence(vs. 0.1% in general population) -if 2 previous moles, risk of recurrence increases to 16-28%  Oral contraceptive use & h/o irregular menstruation increases the risk for partial mole
  • 7.
    Pathology  Based onmorphology, histopathology and karyotype, Hydatidiform mole Complete mole Partial mole
  • 8.
    Complete mole  Arisefrom an ovum fertilised by an haploid sperm, which duplicates its own chromosomes.  Ovum nucleus may be absent or inactivated. sperm empty egg 46,XX 23x 23X 23X
  • 9.
    . sperm empty egg46,XY  They usually have 46,XX karyotype, but about 10% have 46,XY karyotype.  Molar chromosomes are entirely of paternal origin, with mitochondrial DNA of maternal origin 23Y 23 X 23 X 23Y
  • 10.
    Partial mole  Theyusually have triploid karyotype (69 chromosomes),the extra haploid set of chromosome is derived from the father. sperm normal egg 69,XXY (69,XXX) 23Y 23 X 23X 23Y 23X 23 X 23X 23X 23X 23X
  • 11.
    Recurrent molar pregnancy Due to dysregulation of normal parental imprinting of genes, with loss of maternally transcribed genes.  Recurrent complete molar pregnancy is due to biparental origin, rather than the more usual androgenetic origin.  Mutations in NLRP7 gene is responsible for abnormal development of embryonic and extra embryonic tissue.
  • 12.
    Complete vs. partialmole Complete mole Partial mole Based on clinical findings 1. Fetus 2. Fetal vessels ABSENT PRESENT( malformed/ IUGR) Histologically 1) hydropic changes 2) trophoblastic hyperplasia Diffuse & placenta not present Marked Focal Mild to moderate b- HCG VERY HIGH Comparatively low Karyotype 46 XX ( paternally derived) 69 XXY MALIGNANT POTENTIAL 15-20% rare
  • 13.
    Clinical features  Vaginalbleeding – most common -H/o passage of vesicles - due to separation of molar tissues from decidua and disruption of maternal vessels, and large volumes of retained blood may distend the endometrial cavity  Uterine enlargement- -doughy in consistency -trophoblastic overgrowth and usually associated with high levels of HCG - External & internal ballotment cannot be elicited and FHR cannot be heard in Doppler.
  • 14.
    Clinical features  Thecalutein cysts ( 50%)- due to high level HCG which cause ovarian hyperstimulation.  It regresses spontaneously after molar evacuation usually within 2-4 months.  Partial mole have the signs & symptoms of missed/ incomplete abortion.  Asymptomatic (<1%)
  • 15.
    Complications  Anaemia (5%)– due to prolonged bleeding  Pre eclampsia (27%)- before 24 weeks  Hyperemesis (8%)- may lead to electrolyte disturbances  Hyperthyroidism (7%)  Trophoblastic embolization- -occurs after molar evacuation and they may present with chest pain, dyspnea, tachycardia but within 72 hrs it can be resolved with cardiopulmonary support .
  • 16.
    Differential diagnosis  Mistakendate  Multiple pregnancy  Acute hydraminos  Fibroid in pregnancy  Threatened abortion
  • 17.
    Diagnosis  Ultrasonography –most sensitive, quick & safe 1) Complete mole : - characteristic vesicular pattern( SNOW STORM ) is seen as early as the first trimester. -absence of fetal shadow 2) Partial mole : -focal cystic spaces in placental tissues and there is an increase in the transverse diameter of gestational sac. -Malformed fetus / IUGR fetus and placenta are visualised
  • 18.
    Diagnosis  HORMONAL assays- aremainly confined to post molar & post chemotherapy follow up  Serum b- HCG level is very high in complete mole than partial mole.  Human placental lactogen- low in C. Mole but raised in P.mole, Pulmonary metastasis, PSTT.  Chest X- ray – to rule out pulmonary metastasis  CT scan- for liver / brain metastasis  Histopathology – for partial mole
  • 19.
    Treatment  Evaluate forco existing conditions: - history & physical - CBC, coagulation profile, serum chemistry - thyroid function -blood type and cross match( trophoblast cells express RhD factor, for RH-ve patients should receive Rh immune globulin) - pelvic USG and - Chest X ray
  • 20.
    Treatment  Suction &curettage : preferred method, regardless of uterine size  Indications- i)who desire to preserve fertility ii)haemodynamically stable Procedure – Oxytocin infusion>>>>> dilatation & curettage
  • 21.
    Treatment  Hysterectomy –may be performed with the mole in situ and for those who are willing for surgical sterilization.  Ovaries may be preserved at the time of surgery, even in presence of theca lutein cysts.  It does not prevent metastasis ; patients still require follow up with assessment of HCG levels.
  • 22.
    Follow up After evacuation weeklymonitoring of HCG until normal for 3 consecutive weeks Monthly monitoring until normal for 6 consecutive months & 3 monthly in first year / 6 monthly in second year.  Average time to achieve the first normal HCG after evacuation is about 9 weeks.
  • 23.
    Follow up  Afterachieving non detectable levels, the risk of developing GTN approaches to be 0.  Encourage patients to use effective contraception during HCG follow up and preferably pregnancy should be avoided for 1 year.  Oral contraceptives are safe during follow up.  Incomplete evacuation will cause HCG levels to remain elevated and interfere with proper follow up.
  • 24.
    Follow up  Followup for 2 years remains the only option for detecting early choriocarcinoma .  Pelvic examination – to r/o vulval / vaginal metastasis.  USG abdomen – for theca lutein cysts  Chest X ray
  • 25.