obstetrics & gynecology,

2. Gestational Trophoblastic
Disease (GTD)
WAQAR ULLAH
08-207

3. Introduction
What is GTD ?
 It is a clinical term used to indicate closely
related conditions characterized by active
abnormal proliferation of trophoblastic cells
It is too among the rare human
malignancies that can be cured
even in the presence of widespread
metastases

4. Which does it include?
It includes a spectrum of interrelated
tumors, including
hydatidiform mole (HM) 80 % of cases
invasive mole (IM) 12-15%
Choriocarcinoma (CH) 5-8%
Placental-site trophoblastic tumor
(PSTT, borderline, very rare)

5. Relationship of HM. IM. CH
hydatidiform therapeutic or
mole spontaneous abortion
term pregnancy
ectopic
invasion mole choriocarcinoma.

6. Hydatidiform mole

7. Hydatidiform mole

8. Hydatidiform mole
It is a neoplastic
proliferation of
the trophoblast
in which the
terminal villi
are
transformed
into vesicles
filled with clear
viscid material.

9.  It is usually benign but has
malignant potentiality.
 Incidence:
 south east Asia is 1/500-600
 the US and Europe:1/500-2000
 China:1/1238

10. Classification
It is divided into two classification
complete hydatidiform mole
partial hydatidiform mole

11. complete hydatidiform mole(CHM):
 the entire
uterus
filled with
abnormal
vesicles,
no signs of
fetus.

12. partial hydatidiform mole
 partial
hydatidiform
mole with
evidence of
a conceptus.

13. Etiology
Though it is not known a number of
associated factors have been noted:
age:>45 years women are 10 times
more likely to develop HM than
those younger.
Previous hx of HM
Previous misscarriage
Excessive smoking

14. abnormal fertilization process:
the fertilization of a normal ovum
with a duplicated haploid
sperm:46XX
the fertilization of an empty egg by
two sperms(dispermy):46XY

15. Complete Mole, Pathogenesis
Duplication 46XX
Empty ovum
23X
Diandric diploidy
Androgenesis
Paternal
chromosomes only

16. Complete Mole, Pathogenesis
46XX
Empty ovum
23X
Dispermic diploidy
Paternal
chromosomes only
23X 23X
23X

17. Partial Mole, Pathogenesis
69XXY
Normal ovum
23X
Dispermic triploidy
Paternal extra set
23Y 23X
23Y 23X
23X

18. Pathologic findings

19. complete hydatidiform mole
pathology
Complete moles lack identifiable
embryonic or fetal tissues, and
the chorionic villi exhibit
generalized hydatidiform swelling
and diffuse trophoblastic
hyperplasia.

20. Gross
we see a mass of
vesicles, vary in
size, grape-like
with stems, blood
and clot filling the
inter-vesicle space

21. Microscopic(complete mole)
Cytotrophoblast &
syncytiotrophoblast
hyperplasia(variable)
Avascularity
No fetal parts

22. partial hydatidiform mole
It are characterized by the following
pathologic features :
Chorionic villi if varying size with
focal hydatidiform swelling and
cavitation.
It contain identifiable embryonic or
fetal tissues.

23. Gross
we see a
mass of
vesicles,
vary in size,
grape-like
and
identifiable
embryonic
or fetal
tissues.

24. Microscopic(partial mole)
Vesicles have certain degree
of vascularity till fetal death
Fetal parts
Syncytiotrophoblast
hyperplasia

25. Fetal hand demonstrating syndactyly. The fetus had a triploid karyotype, and the chorionic
tissues were a partial mole

27. Feature Partial mole Complete mole
Karyotype
Most commonly
69, XXX or - XXY
Most commonly
46, XX or -,XY
Pathology
Fetus Often present Absent
Amnion, fetal RBC Usually present Absent
Villous edema Variable, focal Diffuse
Trophoblastic proliferation Focal, slight-moderate Diffuse, slight-severe
Clinical presentation
Diagnosis Missed abortion Molar gestation
Uterine size Small for dates 50% large for dates
Theca lutein cysts Rare 25-30%
Medical complications Rare 10-25%
Features Of Partial And Complete Hydatidiform Moles

28. 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)

29. signs
1) abnormally
enlarged and
soft uterus
2) absence of
braxton hicks
contractions

30. 3) Bilateral ovarian
enlargement
4) Absence of fetal
parts on palpation
5) Pre eclampsia
6) Hyperthyrodism

31. Diagnosis
suspicion:
abnormal bleeding after amenorrhea
inappropriately enlarged uterus;
absence of fetal heart sounds or
could not feel fetal parts by palpation
between 16-20th week
hyperemesis gravidarum
bilateral ovarian cysts

32. Hydatidiform Mole
 Diagnosis:
• Serum hCG levels:
 Serum hCG levels of greater than 92 000
IU/l associated with absent fetal heart beat
indicate a diagnosis of complete
hydatidiform moles (Romero et al, 1985)
 Serum hCG level decreases quickly if the
patient has an abortion, but it does not in
molar pregnancy

33. Ultrasonography:
 It is a reliable and sensitive technique for the
diagnosis of complete molar pregnancy. Because
the chorionic villi exhibit diffuse hydatidiform
swelling. Complete moles produce a characteristic
vesicular sonographic pattern, usually referred to
as a “snowstorm” pattern.

34.  Ultrasonography may also
contribute to the diagnosis of
partial molar pregnancy by
demonstrating focal cystic spaces
in the placental tissues and an
increase in the transverse
diameter of the gestational sac.

35. Differential diagnosis
abortion;
multiple pregnancy;
polyhydramnios

36. Hydatidiform Mole
 Management:
Complete history and physical examination
Investigations
Medical and surgical care
1
3
2

37. Hydatidiform Mole
 Management:
• History and physcal examination:
 Should aim to rule out the classic
symptoms and signs that would lead to a
diagnosis of:
• severe anemia
• dehydration
• preeclampsia
• thyrotoxicosis
The patient should be stabilized
hemodynamically 

38. Hydatidiform Mole
 Management:
• Investigations:
 Laboratory:
 Pre-evacuation hCG
 Complete blood count
 Electrolytes, BUN, creatinine
 Liver function tests
 Thyroid function tests
 Imaging:
 Pelvic ultrasound
 Chest x-ray

39. Hydatidiform Mole
 Management:
• Medical care:
 Correction of:
 Anemia
 Dehydration
 Hyperthyroidism
 hypertension

40. Hydatidiform Mole
 Management: Surgical care:
Suction curettage (with
oxytocin or prostaglandin
infusion)
Hysterectomy
•The method of choice
•Increased risk of medical
complications
•Associated with a markedly
decreased rate of malignant
sequelae (3.5%) when compared
with suction evacuation.

41. Mangement
suction & curretage
 Under GA.
 Cervix dilation till 12mm.and S&C induced
to the uterine cavity.
 I.V oxytocin infusion is started .
 S&C started by negative pressure of about
60 to 70cmHg.
 The curette is genteelly rotated to ovoid
perforation of the soft uterus, and the
majority of the molar tissue is evacuated
rapidly ,and the uterine size decreases

43. F0llow-up
 After the uterus has been evacuated :
 About 90% of cases ,the trophoblastic tissue
die out completely.
 About 10% of cases the trophoblastic tissue
does not die out completely and may persist
or recur as : invasive mole or
choriocarcinoma.

44. Follow-up
 So it is important that women who
have had a hydatidiform mole:
 should have close follow-up by serum
hCG levels after the evacuation of the
uterus,
To ensure early recognition of persistent
trophoblastic tissue .

45. F0llow-up
 After a molar pregnancy ,the hCG
levels will usually have returned to non
pregnant levels by 4 to 6 weeks after
evacuation.
 The follow-up is recommended for 2
years in cases of complete moles, and 6
months of cases of partial moles after
the evacuation of uterus.

46. F0llow-up
 Serial quantitative measurement of
serum hCG level at weekly
intervals, after evacuation of moles
till 4 to 5 weeks when the hCG
become normal. Then every other
week .When the titer gets negative
the measurements are done every
month fore 1 year.

47. chemotherapy
 Indication of chemotherapy after
the evacuation of the hydatidiform
mole in:
 Serum hCG >20000 i.u/L , at any
time after evacuation of mole.
 Raised hCG at 4 to 6 weeks after
evacuation of mole.

48. F0llow-up
 Evidence of metastases
,hepatic,brain,and pulmonary.
 Persistent uterine hemorrhage
after evacuation of mole with
raised hCG levels.

49. pregnancy
 To achieve effective follow-up ,the
pregnancy is better to be avoided ,and also
the use of oral contraceptive pills until the
hCG levels returns to normal after the
evacuation of the mole.
 Early diagnosis of persistent trophoblastic
disease ensures a good prognosis and an
effective system of follow-up.

50. Invasion Mole

51. Introduction
 Invasion Mole arises from HM
 it has malignant potentialities,
invades the myometrium and
penetrates the uterine wall,
extends into the broad ligament
or peritoneal cavity.

52.  in half or more of all cases
invasive mole metastasizes
through the peripheral
circulation to distant sites,
mostly to the lung.

53. Pathologic findings
 excessive trophoblastic
proliferation and
invasiveness
 the degree of anaplasia is
variable: completely benign-
--highly malignant

54. differentiation between invasive
mole and choriocarcinoma lies in
whether the villous pattern is
preserved:
if we see villi, it must be
invasion mole;
if we can’t see villi, it is
choriocarcinoma.

55. Clinical course
Symptoms caused by primary lesions
vaginal bleeding
pelvic examination reveals delayed
involution of the uterus, persisting
cyst .
abdominal pain
intra-abdominal hemorrhage,
penetration of the uterus .

56.  Metastatic symptoms
• cough, hemoptysis---positive X-ray
signs
• profuse vaginal bleeding---vaginal
or cervical metastasis, we can see
bluish nodule in vaginal
• headache, nausea, vomit, paralysis
or coma—it is caused by cerebral
lesion.

57. Diagnosis
history and clinical manifestation
hCG assay:
diagnosis suspected if hCG titers
persist to be high 12 weeks after
evacuation of a HM, or once
regress to normal range but rise
rapidly.

58. possible reasons : retained HM
pregnancy
huge theca-lutein cyst persist
when we remove these reasons
we can diagnosis invasive mole
other measurement
ultrasound
X-ray

59. Prophylaxis
 respond well to chemotherapeutic
agents
 main causes of death:
hemorrhage, metastasis and
infection

60. Treatment:
Identical to that for
choriocarcinoma

61. Choriocarcinoma
It is highly malignant GTT
It may follow HM,
invasion mole, abortion,
normal pregnancy, ectopic
pregnancy.

62. Pathologic findings
Gross inspection
 irregular or circumscribed
hemorrhagic growth in the uterine
wall
ulcerating surface opens into the
endometrial cavity (rarely
embedded in myometrium)
penetration into broad ligament or
the peritoneal cavity
dark red blood:.it is filled
metastatic nodules

63. ulcerating
surface opens
into the
endometrial
cavity (rarely
embedded in
myometrium)

64. Histologic findings
 we see masses of anaplastic
trophblastic cells in microscopy;
 invasion into the uterine wall,
destroying vessels, muscle tissue
 prominent necrosis and
hemorrhage
 villi can not be recognized
 spread through circulation

65. Clinical Manifestations
 irregular bleeding after
preceding gestation;
 malignant tumor cells enter the
circulation through the open
blood vessels and are
transported to lungs, brain or to
other distant sites.

66.  metastatic symptoms
 pulmonary lesions
 cerebral lesions
 metastatic nodule in the vagina,
vulva or cervix ,it is bluish
nodule filled dark red blood.

67. Diagnosis
 Diagnosis must be suspected as
a possible reason for continued
(irregular) bleeding after any
form of pregnancy.
 we assay hCG , the time of hCG
change into normal is different in
various diseases.

69. FIGO Staging
 STAGE
I. Confined to the uterus
II. Outside of uterus, limited to genital structures
III. Extends to lungs +- genital tract involvement
IV. All other metastatic sites

70. Who Orgnaization prognostic scoring system for gestational trophoblastic neoplasia
Prognostic factor 0 1 2 4
Age <39 >39 _ -
Antecedent pregnancy Hydatidiform Abortion , ectipic Term pregnancy -
Interval (months) <4 4-6 7-12 >12
hCG level (IU/liter) <10 10-10 10-10 >10
ABO blood groups
(female/male)
O/A B A/O AB
Largest tumor (cm) <3 3-5 >5 _
Site of metastasis _ Spleen, kidney Gastrointestinal tract, liver Brain
Number of metastases _ 1-3 4-8 >8
Prior chemotherapy _ _ Single drug Multiple
druge
The total score is obtained by adding the individual scores for each prognostic factor . Total score
:<4 , low risk ; 5-7 , intermediate risk ;>8 , high risk .
Interval :between antecedent pregnancy and start of chemotherapy.

71. Treatment
highly sensitive to chemotherapy,
which is invariably the treatment
choice.
surgery has little place (because of
the high vascularity and the
effectiveness of chemotherapy). it is
indicated for tumor resistant to
chemotherapy and single metastases
persisting despite chemotherapy.

72. Chemotherapy
most often used drugs
 methotrexate (MTX)
 actinomycin D (Act-D)
 5-fluorouracil (5-Fu)
 vincristine (VCR)
 cyclophosphamide (CTX)
 chlo-ranbucil, etc

73. principles
 low-risk patients are usually treated with a
single agent
 medium-risk patients are usually treated
with ABACA regimen with 80-90% survival
rate. (Etoposide,
Methotrexate,Hydroxyurea,6-
mercaptopurine,Actinomycin-d,Folinic acid)
 High-risk No. of regimens are used.most
common
EMA/CO(etoposide,methotrexate,actinomy
cin-d,cyclophosphamide,vincristine)

74. Operation
unresponsive or drug fails to
reach the tumor;
if the tumor can be eradicated
by drug therapy, esp.in young
women, there is no reason to
remove the uterus;
the ovaries need not be
removed.

75. Follow-up examinations
 at 1-month interval for 1 year:
at 3-month interval for 2 years
 at 1-year interval for 3 years
 at 2-year interval afterwards.
pelvic examination
chest X-ray film
hCG

76. Placental-Site Trophoblastic Tumor
(PSTT)
 Originate from intermediate cytotrophoblast
cells
 Secrete human placental lactogen (hPL)
 B-hCG often normal
 Less vascular invasion, necrosis and
hemorrhage than choriocarcinoma
 Lymphatic spread
 Arise months to years after term pregnancy
but can occur after spontaneous abortion or
molar pregnancy

77. Placental-Site Trophoblastic Tumor
(PSTT)
 Most common symptom is vaginal bleeding
 Tend to:
- Remain in uterus
- Disseminate late
- Produce low levels of B-hCG compared to
other GTN
- Be resistant to chemotherapy (treat with
surgery)