1. GESTATIONAL
TROPHOBLASTIC DISEASE

2. INTRODUCTION
•GTD forms a spectrum of interrelated tumors which arise
in the epithelia of the trophoblast.
•Trophoblastic tumors are either benign, potentially
malignant or malignant tumors and they show various
grades of differentiation from recognizable chorionic villi
structure to highly virulent anaplastic masses of cells.

3. The malignant GTD’s whether locally
invasive or metastatic, even with wide
spread dissemination can be cured
completely, “Cure rate approaches
100% in most GTD’s

4. The tumors spectrum consist of:
•Hydatiform mole (molar pregnancy)
•Invasive mole
•Placental site trophoblastic tumor (PSTT)
•Choriocarcinoma

5. •The tumors elaborate a unique and
characteristic tumor marker, “human
chorionic gonadotropin (hCG)”
•Biological activity and clinical behavior of the
tumor are indication used to prognosticate the
patient

6. •Most of the GTD’s are non-cancerous (80%).
•The GTD’s arise from Trophoblastic tissues
which form the placenta and fetal membranes.
The tissues continue to grow but the fetus
doesn’t develop

7. EPIDEMIOLOGY
•Estimates of the incidence of GTD’s vary
dramatically in different regions of the world.
•They have been a striking geographical distribution
of GTD’s across the world.
•In Europe and North America are rare

8. • More common in Middle East and Asia, Malaysia, Singapore, Hong
Kong, Indonesia, Philippines and China.
• The incidence is also relatively high in Central Africa
• But they are found all around the world.

9. •Hydatiform mole (Molar pregnancy) is the most
common GTD encountered in clinical practice.
•It occurs in 1 out of 125 deliveries in Mexico, 1 out
of 1500 deliveries in US. The incidence also seems
to be higher among women who are under 20
and over 40

10. •Invasive mole is reported in 10 -15% of
patients who have had a primary molar
pregnancy.
•PSTT is a rare tumor that arises from the
placental site.

11. Choriocarcinoma are rare. Reported
in 2 – 5% of all cases of GTD’s. The
incidence in the US is about 1: 40,000
pregnancies but reported to be higher
in Asia

12. PATHOLOGY

13. HYDATIFORM MOLE
(MOLAR PREGNANCY)
Is an abnormal pregnancy
characterized grossly by multiple
grape vesicles filling and
distending the uterus

14. Molar pregnancy

15. •They are neoplasia of the trophoblast which
involves both the epithelial layers
(cytotrophoblast and syncytiotrophoblast) in
different proportions.
•The disease is usually benign and non-
metastatic in nature

16. •Molar pregnancies are categorized as
partial or complete in the basis of gross
morphology, histopathology and
karyotype.
•Most of the moles have been found to be
female.

17. COMPLETE MOLE
• Lack identifiable embryonic or fetal tissues and the
chorionic villi exhibit generalized hydatiform swelling
and diffuse trophoblastic hyperplasia
The molar chromosomes are entirely of paternal
origin.

18. COMPLETE MOLE
• Empty ovum + 23X sperm → 23X →duplicate → 46XX
• Empty ovum + 23X and 23X → 46XX
• Empty ovum + 23X and 23Y → 46XY

19. •The cysts vary in size from a pin-head to a
cherry. No fetal tissue can be identified.
•The molar chromosomes are entirely of
paternal origin.

20. PARTIAL MOLES
• 23X ovum +23X sperm = 69XXX
23X
• 23X ovum + 23Y sperm =69XYY
23Y sperm
• 23X ovum + 23X sperm =69XXY
23Y

21. PARTIAL MOLE
• Hydatiform change in the placenta may take place
without the death of the fetus (rare phenomenon).
• Generally partial moles have a triploid karyotype (69
x’somes), the extra haploid set of chromosomes from
the father

22. Partial mole

23. PARTIAL MOLE
•In twin pregnancy one of the conceptus may be a
partial mole and the other being a normal conceptus.
The normal conceptus develops normally to maturity.
•The disease usually arises in very early pregnancy so
that the fetus remains as only as a rudimentary
structure

24. PARTIAL MOLE
•Fetuses which survive exhibit a stigma of
triploidy like IUGR and congenital
malformations like hydrocephalus.
•Occasionally normal birth have however been
reported in partial moles.

25. RISK FACTORS
• Maternal age
• Previous molar pregnancy
• Parity
• Nutritional deficiencies of carotene, folate and proteins.
• Paternity
• ?Contraceptive use
• Life style-smoking and alcohol

26. CLINICAL FEATURES
Symptoms of complete mole are at
first those of early pregnancy but
with development of a mole

27. The general reactions to pregnancy are
exaggerated;
•Excessive nausea and vomiting
•Wt loss and ill feeling
-Pre-eclampsia in the first trimester in about
30% of cases

28. •Recurrent vaginal bleeding
associated with brown discharge in
more than 50% of cases.
•Passing vesicles per vaginum

29. The physical signs
• Uterus too large for gestation age in
50% of cases.
• Uterus is dough and doesn’t contract
• Fetal part cant be appreciated

30. • Fetal heart beets cant be heard
• No fetal movements
• Bilateral ovarian enlargement (Theca
Lutein cysts) in 25-50% of cases.
-Thyrotoxicosis

31. PARTIAL MOLES
•Clinical features not so drastic
•Vaginal bleeding is the symptom that is
usually seen.
•The rest of the symptoms are only seen
in 4% of cases

32. PARTIAL V/S COMPLETE MOLE
FEATURES COMPLETE PARTIAL
Fetal/embryonic tissue Absent present
Hydatidiform swelling of chorionic villi Diffuse Focal
Trophpblastic hyperplasia Diffuse Focal
Trophoblastic stromal inclussions Absent Present
Karyotype 46XX,46XY triploid
Fetal Rbcs Absent Present
B-hCG level in serum High/>50000 slight?/<50000
Classical symptoms Common Rare
Risk for development of persistent GTD 20-30% <5%

33. DIAGNOSIS OF MOLAR
PREGNANCY
• Clinical features
• USS
• The diffuse hydropic swelling of the chorionic villi produces a characteristic snow
storm appearance on USS throughout the uterine cavity.
• No gestation sac can be identified
• In partial moles; Focal cystic spaces are seen in the placental tissue and
transverse diameter of the gestation sacs is increased.
• B-hCG levels in the blood: Markedly elevated

34. Snow storm appearance on USS

35. TREATMENT
If the mole has expelled
itself, manage as incomplete
abortion

36. •If not expelled;
•I/V oxytocin in a drip
•cervical dilatation
•Evacuate the uterus by suction curate at any
gestation age
•Then do a gentle sharp curate after removing the
products by suction
•Rh negative women are given ant D antibody
injection.

37. HYSTERECTOMY
May be done with the mole insitu in women
who have completed their families or just
wish the operation
Also if bleeding is uncontrollable.

38. POST MOLAR PROPHYLAXIS
•Controversial issue
•Complete mole
•Patients are given either
Actinomycin-D or Methotrexate

39. POST MOLAR PROPHYLAXIS
•Criteria being;
•Age >35yrs
•Previous molar pregnancy
•Trophoblastic hyperplasia
•Anticipated persistent GTD

40. FURTHER MANAGEMENT
Material removed at
evacuation are always to
be examine microscopically

41. FOLLOW UP
•Clinical symptoms and signs of persistent GTD
should be asked at every visit
•Persistent vaginal bleeding post evacuation
•Cough
•Headache
•Jaundice and epigastric pain

42. FOLLOW UP
• B-hCG levels taken weekly till 3 consecutive normal
values then monthly for at least a year.
• Normal levels are expected 9-14 weeks post
evacuation.
• Plateauing or rising B-hCG levels calls for attention
(possibility of persistent molar pregnancy or
malignancy transformation).

43. MALIGNANT
GTD’s

44. PERSISTENT/MALIGNANT GTD
• INVASIVE MOLE
• PLACENTAL SITE
TROPHOBLASTIC TUMOR
• CHORIOCARCINOMA

45. INVASIVE MOLE
•Is a hydatiform mole that is locally
invasive
•It invades the myometrium or
adjacent structures
•It may totally penetrate the
myometrium and be associated with
uterine rupture and
haemoperitoneum

46. INVASIVE MOLE
• Microscopic findings are the same those of
hydatidiform mole.
• Develop in up to 15% of patients who have had molar
pregnancy though it may infrequently follow any
other type of gestation.
• The mole consists of cyto and syncytiotrophoblastic
cells

47. INVASIVE MOLE
•Syncytiotrophoblast produced
large amounts of B-hCG and
therefore patients present with
persistent elevation of B-hCG
•The patient presents with
persistent vaginal bleeding

48. PLACENTAL SITE TROPHBLASTIC TUMOR
•Is a very rare tumor
•Derived from the intermediate
trophoblast with minimal or absent
syncytiotrophoblastic tissue.
•Histologically, local invasion occurs
into the myometrium and
lymphatics

49. PLACENTAL SITE TROPHBLASTIC TUMOR
•Vascular invasion is a
rare phenomenon
•It may follow any type of
gestation

50. PLACENTAL SITE TROPHBLASTIC TUMOR
•It produces low levels of B-
hCG but relatively high
amounts of human
placental lactogen
compared to
Choriocarcinoma

51. PLACENTAL SITE TROPHBLASTIC TUMOR
•It shows a range of behavior from benign with
capacity to regress spontaneously to a highly
malignant form which can be highly resistant to
chemotherapy and therefore hysterectomy is
recommended route of treatment

52. CHORIOCARCINOMA
• Is a rare trophoblastic tumor
• Geographical distribution similar to that of
Hydatidiform mole.
• Pure epithelial tumor composed of cyto and
syncytiotrophoblastic cells

53. CHORIOCARCINOMA
• It may follow any type of gestation
• In 50% of cases it is preceded by a hydatidiform
mole,25% follow an abortion or ectopic pregnancy,
and 25% following normal pregnancy

54. CHORIOCARCINOMA
• The tumor is highly malignant with early local
invasion to the broad ligament,paracolpos and by
blood stream to;
• Lungs 80%
• Vagina 30%
• Pelvis 20%
• Brain 10%
• Liver 10%

55. PATHOLOGY
•Primary growth is usually in the uterine
wall though it may be in the cervix,
vagina, tubes or broad ligament
following an ectopic pregnant.
•The tumor is soft, necrotic and
hemorrhagic so it appears plum-colored
to the naked eye

56. PATHOLOGY
• On section the tumor shows cyto and
syncytiotrophoblastic tissues in varying proportions,
actively proliferating and assuming bizarre forms.
• There is also mononucleated and multinucleated
giant cells

57. PATHOLOGY
• Chorionic villi are characterically absent
• Choriocarcinoma is functional secreting large
quantities of B-hCG
• B-hcG causes luteinization of the ovaries.
• Choriocarcinoma also secretes some amounts of
human placental lactogen

58. CLINICAL FEATURES
•Irregular haemorrhage-characteristically
intermittent but alarming
•Metastatic features
• Dyspnoea
• Haemothorax
• Haemoptysis
-Neurological signs of headache, visual
disturbance, focal deficits

59. CLINICAL FEATURES
• CXR reveals cannon balls or snow storm appearance,
pleural effusion etc
• Hepatic metastasis
• Epigastric pain or right upper quadrant pain
• Acute emergency massive haemopertonial haemorrhage.
• Jaundice

60. ‘Cannon ball’ x ray appearance

61. CLINICAL FEATURES
• Vaginal metastasis
• Often enlarged uterus
• Palpable ovarian cysts

62. DIAGNOSIS
• Clinical features
• High levels of B-hCG in serum
• Diagnostic curate

63. METASTATIC WORK UP
• Abdominal/pelvic ultrasound
• CT scan
• MRI
• Lumbar puncture to demonstrate B-hCG in the CSF

64. • CLASSIFICATION OF MALIGNANT GTDs

65. CLASSIFICATION OF PERSISTENT/MALIGNANT
GTDs
• NATIONAL CANCER INSTITUTE (USA)
• WHO
• FIGO SYSTEM (STAGING

66. NATIONAL CANCER INSTITUTE
• Ultilized in the US to determine if the patient is in the
poor or good prognosis to respond well to single-
agent chemotherapy

67. NATIONAL CANCER INSTITUTE
• Non metastatic disease; no evidence of disease
outside the uterus.
• Metastatic diseases; evidence of disease outside
the uterus

68. Metastatic diseases
• Good prognosis
• Short duration (<4months)
• Serum B-hCG <40,000mIU/ml
• No metastasis to brain or liver
• No significant prior chemotherapy

69. Metastatic diseases
• Poor prognosis
• Long duration (>4months)
• Serum B-hCG >40,000mIU/ml
• Metastasis to brain or liver
• Unsuccessful prior chemotherapy
• GTN following a term pregnancy

70. RIVISED FIGO STAGING
I. Disease confined to the uterus
II. Disease extending outside the uterus but confined
to the genital structures(adenexa,vagina,broad
ligament)
III. Disease extending to the lungs with or without a
known genital tract involvement
IV. Disease at other metastatic sites

71. RIVISED FIGO STAGING
• A. No risk factor
• B.One risk factor
• C.Two risk factor

72. RIVISED FIGO STAGING
RISK FACTORS
• 1. B-hCG >100,000mIU/ml
• 2. Duration from termination of antecedent
pregnancy to diagnosis>6months

73. WHO PROGNOSTIC SCORING
parameter 0 1 2 3
Age <39 >39
Antecedent pregnancy Mole Abortion Term preg
Interval in months <4 4-6 7-12 >12
Pretreatment B-hCG 1000 1000-10000 10000-
100000 >100000
ABO (F/M) A*O,A*O B,AB
Largest tumor(cm) 3-5 >5
Sites of mets Spleen,kidne
y
GIT,liver Brain
Number of mets 1-4 4-8 >8
Prior chemotherapy failed single >2

74. WHO PROGNOSTIC SCORING
• Interval=time between termination of antecedent
pregnancy and initiation of chemotherapy.
• Score <5=low risk,5-7=medium risk,>7=high risk

75. TREATMENT OF MALIGNANT GTD
• CHEMOTHERAPY

76. PRE-TREATMENT WORK UP;
• FBP
• RFT
• LFT
• Bone marrow
• B-hCG levels

77. Non metastatic and low risk/good prognosis patients
• Methotraxate i/m .30-60mg/m2 once a week*
• Methotraxate i/v or i/m 0.4mg/kg/day for 5days. Repeated every
14days.
• Methotraxate i/m 1mg/kg/day on day 1, 3,5,7,9 and folinic acid
0.1mg/kg i/m on day 2,4,6,8 repeated every 15-18days

78. Non metastatic and low risk/good prognosis
patients
• Dactinomycin 1.25mg/m2 every 14days
• Dactinomycin 10-12ug/kg/day i/v for 5days repeat
every 14days

79. FOLLOW-UP
• Follow B-hcG weekly. Switch to alternative drug if levels rise 10 fold or
more or if plateau or new metastasis.
• Obtain weekly CBC. Hold chemotherapy if WBC<3000(Neut <1500),
platelets<100000

80. FOLLOW_UP
• Obtain weekly RFT/LFT. Hold chemotherapy when
elevation of BUN,Cr,AST,ALT Bilirubin or significant
side effects severe stomatitis,GIT ulceration of severe
anaemia or febrile course

81. FOLLOW_UP
• Oral contraceptives taken at least one yr after
remission.
• Chemotherapy cont for one or two causes after
negative B-hCG.
• Physical exam

82. *Follow up B hCG program
• B-hCG wkly until 3 consecutive negative titres, monthly for 12months,
then every 2months for 1additional yr.

83. Metastatic and poor prognosis
• MAC regimen

84. EMA/CO
• Etoposide, methotraxate, actinomycinD, cyclophosphamyde and
vincristine

85. EMA/CO REGIMEN
• Day 1 –etoposide i/v100mg/m2 slowly infused,actinomycynD
i/v0.5mg bolus,MTX i/v100mg/m2bolus then infuse 200mg/m2 over
12hrs

86. EMA/CO REGIMEN
• Day 2 Etoposide 100mg/m2 i/v slow over30minute, actinomycinD
0.5,gi/v bolus,folinic acid

87. EMA/CO REGIMEN
• Day 8 cyclophosphamide 600mg/m2 i/v infusion, vincristine 1mg/m2
i/v bolus
*EMA/CO is repeated every 2weeks.

88. SURGERY
• Stage I cases
• Future fertility not desired
• Resistant to chemotherapy
• PSTT normally resistant to chemotherapy

89. MODALITIES OF SURGERY
• Hysterectomy
• Thoracotomy
• Hepatic resection or hepatic artery embolization
• Craniotomy

90. RADIATION THERAPY
• Cerebral mets
• Liver mets

91. SUBSEQUENT PREGNANCIES
• No increased risk of complications like preterm labor,
anormalies or still birth.
• Pregnancies should be closely followed up with B-
hCG, USS

92. SUBSEQUENT PREGNANCIES
• After delivery placenta sent to pathologists and B-hCG followed up at
6weeks postpartum.
• Most pregnancies go uneventfully.

93. Thanks

94. REFERENCES
• Current diagnosis and treatment
• Jeffcoate’s principles of gynaecology.
• www.emedicine.com