1. Gestational Trophoblastic Disease (GTD) Part I : Molar Pregnancy
Dr. Mohamed El Sherbiny MD Ob.& Gyn. Senior Consultant
Damietta, Egypt 1

2. Part I: Molar Pregnancy

3. Gestational Trophoblastic Disease (GTD)
Definitions
Gestational Trophoblastic Disease (GTD)
It is a spectrum of trophoblastic diseases that includes:
Complete molar pregnancy
Partial molar pregnancies
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy.
RCOG Guideline No

4. Gestational Trophoblastic Neoplasia (GTN)
Definitions
Gestational Trophoblastic Neoplasia (GTN)
=Malignant Gestational Trophoblastic Disease
It is a spectrum of trophoblastic diseases that develops malignant sequelae. GTN includes:
Persistent post molar GTD
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
The last 2 may follow abortion, ectopic or normal pregnancy.
Disaia &Creasman Clinical Gynecological Oncology 2007 Cunningham et al Williams Obsterics 23rd , 2010

5. Classifications Gestational Trophoblastic Disease (GTD) II-Clinical
Invasive
mole
I-Pathologic
Classification
Partial mole
Complete mole
Chorio
carcinoma
Placental site trophoblastic tumour
II-Clinical
Classification
βhCG based: WHO, FIGO, ACOG 2004 & RCOG 2010
G.T. Neoplasia
Malignant G.T.D.
Persistent GTD
Benign
G.T.D.
Metastatic
Non metastatic
Low risk
High risk 5

6. Gestational Trophoblastic Disease
Over the last 30 years major advances have taken place in our understanding and management of gestational trophoblastic disease.
1- It is now possible to diagnose a mole by
ultrasonography in minutes .
2-It became the most curable gynec. malignancy.
3-βhCG has very important role in the diagnosis, evaluation and follow up of GTN
4- The cytogenetic profile has thrown
light on the etiology of the disease . 6

7. (H. MOLE) = Vesicular Mole
Hydatidiform Mole
(H. MOLE) = Vesicular Mole - 7

8. Hydatidiform Moles (H.M.)
Hydatidiform moles are abnormal pregnancies characterized histologically by :
Trophoblastic proliferation &
Edema of the villous stroma (Hydropic) .
Based on the degree and extent of these tissue changes, hydatidiform moles are categorized as either
Complete hydatidiform mole.
Partial hydatidiform mole.

9. Features Of Partial And Complete Hydatidiform Moles
Partial mole
Complete mole
Karyotype
Most commonly
69, XXX or - XXY
46, XX or -,XY
Pathology
Fetus
Often present
Absent
Amnion, fetal RBC
Usually present
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
10-25%
Postmolar CTN %
6.8-20%
Disaia &Creasman Clinical Gynecological Oncology 2007 Cunningham et al Williams Obsterics 23rd , 2010

10. Epidemiology& Risk Factors
Incidence:USA 1/ South East 1/100 (Hospital)
Risk Factors:
Age: <20y (2fold) , > 40y(10 fold) & >50y (50% V.mole)
Prior Molar Pregnancy
Second molar: 1% Third molar : 20%!
Diet:↑ in low fat Vit. A or carotene diet (complete mole)
Contraception :COC double the incidence
Previous spontaneous abortion: double the incidence
Repetitive H. moles in women with different partners
Cunningham et al,Williams Obstetrics,23 ed ,2010 10

11. Epidemiology & Risk Factors
Partial moles have been linked to:
Higher educational levels
Smoking
Irregular menstrual cycles
Only male infants are among the prior live births

12. Karyotype

13. Pathogenesis of complete H. Mole
Homozygous 90%
Pathogenesis of complete H. Mole

14. Pathogenesis of complete H. Mole
Heterozygous 10%
Pathogenesis of complete H. Mole

15. Pathogenesis of Partial H. Mole

16. Pathology of
Molar Pregnancy

17. Complete H. Mole
Microscopically Enlarged, edematous villi and abnormal trophoblastic proliferation that diffusely involve the entire villi
No fetal tissue, RBCs or amnion are produced
Macroscopically, these microscopic changes transform the chorionic villi into clusters of vesicles with variable dimensions “ like bunch of grapes"
No fetal or embryonic tissue are produced
Uterine enlargement in excess of gestational age .
Theca-lutein cyst associated in 30%

18. 1-Trophoblastic proliferation
2-Hydropic Degeneration
Complete hydatidiform mole: Microscopically Enlarged, edematous villi and abnormal trophoblastic proliferation that diffusely involve the entire placenta

19. Complete hydatidiform mole: Macroscopically, these microscopic changes transform the chorionic villi into clusters of vesicles with variable dimensions the name hydatidiform mole stems from this "bunch of grapes"

20. Complete Hydatiform Mole
Uterine wall 20

21. Pathogenesis of Choriocarcinoma
Aneuploidy
(Not a multiplication of 23 chromosome )

22. Partial H. Mole
Microscopically: The enlarged, edematous villi and abnormal trophoblastic proliferation are slight and focal and did not involve the entire villi.
There is a scalloping of chorionic villi
Fetal or embryonic or fetal RBCs
Macroscopically: The molar pattern did not involve the entire placenta.
Uterine enlargement in excess of gestational age is uncommon.
Theca-lutein cysts are rare
Fetal or embryonic tissue or amnion

23. Partial Hydatidiform Mole
Scalloping of chorionic villi
Trophoblastic proliferation are slight and focal 23

24. Vesicles
Maternal side
Partial Hydatiform Mole 24

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

26. Partial H. mole.

27. How Do Molar Pregnancies Present To The Clinician?
The classic features are
Irregular vaginal bleeding
Hyperemesis
Excessive uterine enlargement &
Early failed pregnancy.
Clinicians should check a urine pregnancy test in women presenting with such symptoms.
RCOG Guideline No. 38 ; 2010
Some women will present early with passage of molar tissue

28. How Do Molar Pregnancies Present To The Clinician?
Rarer presentations include:
Hyperthyroidism
Early onset pre-eclampsia
Abdominal distension due to theca lutein cysts
Very rarely
Acute respiratory failure
Neurological symptoms such as seizures (?metastatic disease).
RCOG Guideline No. 38 ; 2010

29. What Is The Most Common Presenting Symptom Of A Complete Molar Pregnancy?
A. Hyperemesis
B. Bilateral enlarged theca lutein cysts
C. Vaginal bleeding
D. Uterine enlargement> than expected for GA
E. Pregnancy-induced hypertension 29

30. What Is The Most Common Presenting Symptom Of A Complete Molar Pregnancy?
A. Hyperemesis %
B. Bilateral enlarged theca lutein cysts %
C. Vaginal bleeding %
D. Uterine enlargement> than expected for GA 40%
E. Pregnancy-induced hypertension % 30

31. How Is Complete Mole Diagnosed?
U/S is helpful in making a pre-evacuation diagnosis but the definitive diagnosis is made by histological examination.
U/S: Early detection reduced from 16 weeks (passage of vesicles) to 12 ws
βhCG levels > 2 multiples of the median may be of value in the diagnosis
RCOG Guideline No. 38 ; 2010

32. U/S& βhCG Definite diagnosis on first U/S examination U/S alone: 68%
U/S + βhCG > threshold of 82,350 mIU/mL: 89%
Disaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007

33. TVS “Milestones” Versus βhCG
 hCG mIU/mL Weeks
Detection Level >
Choriodecidual thickening
Gestational sac (D Zone)
Yolk sac
Heart motion ,
Embryonic Movem. > Maximum level ,000to 100, 33

35. Complete Molar Pregnancy35 35

36. Complete hydatidiform mole
Complete hydatidiform mole. The classic "snowstorm" appearance is created by the multiple placental vesicles.

37. Complete H.Mole (High-resolution) U/S Complex intrauterine mass containing many small cysts.
Associated theca-lutein cysts. U/S Power Doppler

38. How Is Partial H .Mole Diagnosed?
In most patients with a partial mole, the clinical and U/S diagnosis is Usually missed or incomplete abortion. This emphasizes the need for a thorough histopathologic evaluation of all missed or incomplete abortions
Disaia &Creasman Clinical Gynecological Oncologym 7th edd. 2007

39. How Is Partial H .Mole Diagnosed?
Classically: A thickened, hydropic placenta with fetal or embryonic tissue
Multiple soft markers, including:
Cystic spaces in the placenta and
Transverse to AP dimension a ratio of the gestation sac of > 1.5, is required for the reliable diagnosis of a partial molar pregnancy
RCOG Guideline No. 38 ; 2010

40. Partial Molar Pregnancies

41. Case Scenario 1
A 24-year-old 2nd Gravida ,Para 1 woman at 8 Ws GA (Blood group: O, negative) complains of: 1-Worsening nausea, and vomiting over the last 2 weeks which is unlike her prior pregnancy . 2-Irregular vaginal bleeding over the last 7 days She denies any abdominal or back cramps. What does the differential diagnosis include for this patient?

42. What Does The Differential Diagnosis Include For This Patient?
The differential diagnosis of bleeding with early pregnancy and progressive vomiting are: Multiple pregnancy. Hydatidiform mole. Threatened abortion. Ectopic pregnancy.

43. U/S Which Diagnostic Test Would Be Most Useful?
The most useful diagnostic test is :
U/S

44. Hydatidiform (Vesicular) mole
Complex intrauterine mass containing many small cysts (Snowstorm appearance)
 What is the most likely diagnosis?
Hydatidiform (Vesicular) mole

45. Gestational (Chorionic) Sac
 What Would One Expect To See At Scan If Her Pregnancy Is Normal?
Gestational (Chorionic) Sac

47.  What Is The Ultrasonogaphic Differential Diagnosis For This Case?
U/S DD :
1-Missed abortion
2-Degenerated fibroid

48. Differential Diagnosis: Long standing missed abortion with cystic degeneration of the placenta

49. The B subunit hCG assay: 195,000 mlU/mL
What Is The Recommended Subsequent Test ?
β subunit hCG
The B subunit hCG assay:
195,000 mlU/mL
Then
1-What is the most likely diagnosis?
2-How can the patient be managed? 49

51. Probably complete V. mole
1-What Is The Most Likely Diagnosis?
The snowstorm pattern on U/S&
The abnormally high hCG level
are diagnostic of
Vesicular Mole
Probably complete V. mole 51

52. Why It Is Probably Complete V. Mole?
It demonstrates the typical U/S appearance of complete V. mole : a complex, echogenic intrauterine mass containing many small cystic spaces. Fetal tissues and amnionic sac are absent However the final differentiation is after histopathology.

53. What Is The Plan of Management?
There are 2 important basic lines : 1-Evacuation of the mole 2-Regular follow-up to detect persistent trophoblastic disease If both basic lines are done appropriately, mortality rates can be reduced to zero.

54. What Is The Best Method Of Evacuating This Molar Pregnancy?
A. Cervical priming with misoprostol then suction evacuation
B. Suction evacuation to be repeated 1-2 weeks later
Single suction evacuation
D. Medical trial with misoprostol &oxytocine before suction C.
What Is The Evidence ? 54

55. What Is The Evidence ?
The Management Of Gestational Trophoblastic Disease
RCOG Guideline No. 38 ; 2010

56. What Is The Best Method Of Evacuating A Molar Pregnancy?
For Complete mole is:
Suction curettage
Cervical preparation with prostaglandins or misoprostol , should be avoided to reduce the risk of embolisation (No sufficient studies)
RCOG Guideline No. 38 ; 2010

57. Is That The Same For Partial Mole?
For Partial mole: It depends on the fetal parts
Small fetal parts :Suction curettage
Large fetal parts: Medical (oxytocics)
In partial mole the oxytocics is safe ,as the hazard to embolise and disseminate trophoblastic tissue is very low
Also, the needing for chemotherapy is %.
RCOG Guideline No. 38 ; 2010

58. Can Oxytocic Infusions Be Used During Surgical Evacuation?
The use of oxytocic infusion prior to completion of the evacuation is not recommended (fear of embolisation).
If the woman is experiencing significant haemorrhage prior to evacuation, surgical evacuation should be expedited and the need for oxytocin infusion weighed up against the risk of tumour embolisation.
RCOG Guideline No. 38 ; 2010

59. Should Products Of Conception Be Examined Histologically?
Histological examination is indicated in:
Failed pregnancies (missed or molar) :All medically or surgical managed cases
Products of conception, obtained after all repeat evacuations (post abortive or p.partum)
There is no need after therapeutic termination : provided that fetal parts is identified on U/S
RCOG Guideline No. 38 ; 2010

60. Return to Case Scenario 1
Suction curettage has been performed using 10mm canula under U/S guidance
10mm
Canula up to a maximum of 12 mm, is usually sufficient to evacuate all complete molar pregnancies.

61. Other seats of suction curettage

62. Suction curettage has been performed using 10mm canula under U/S guidance :
El SHERBINY HOSP
El SHERBINY HOSP
Canula

63. U/S Guided Suction Curettage
Suction curettage can be performed under U/S guidance to:
Facilitate the procedure
Confirm complete evacuation of contents.
Garner UpToDate 2010

64. The Molar Content For Histopathological Examination

65. These findings are diagnostic of:
Meticulous histopathological examination revealed:
Villi have extensive stromal edema
Abnormal trophoblastic proliferation
No embryonic or fetal tissue or RBCs
These findings are diagnostic of:
Complete Hydatidiform Mole

66. The Case is Now Confirmed Histopathological As A Complete H. Mole
What Is The Most Appropriate Management?
A- Surveillance :Weekly then monthly βhCG
B-Hysterectomy
C-Transvaginal U/S examination
D-Repeated curettage &Biopsy
E-Prompt chemotherapy A. 66

67. Hysterectomy may be preferred to suction curettage at age ≥ 40 with no desire for further pregnancies especially with other risk factors for GTN as :
Large theca lutein cysts( >6 cm)
Significant uterine enlargement
Pretreatment βhCG ≥ 105.
Although hysterectomy does not eliminate possibility of GTN this, it markedly reduces its likelihood.
Soper. Obstet Gynecol 108:176, 2006
Garner UpToDate 2010
Cunningham et al,Williams Obstetrics,23 ed ,2010 67

68. Complete H. Mole with large for date uterus& Theca-lutein cyst
Patient was 42 years 5th G P5 initial BhCG:195,000mIU/mL
Complete H. Mole with large for date uterus& Theca-lutein cyst
Patient was 42 years 5th G P5 initial BhCG:195,000mIU/mL
Complete H. Mole After Hysterectomy
Complete H. Mole After Hysterectomy

69. Theca-lutein cyst associated with a complete H. mole in >30%69

70. Second Uterine Evacuation :There is no clinical indication for the routine use of second uterine evacuation
RCOG Guideline No. 38 ; 2010
Prophylactic Chemotherapy: The long-term prognosis for women with a H. mole is not improved with prophylactic chemotherapy. Because toxicity—including death—may be significant, it is not recommended routinely *
It may be useful in the high-risk cases when follow-up are unavailable or unreliable. * *
American College of Obstetricians and Gynecologists, 2004* 70

71. Is Anti-D Prophylaxis Required For This Case?No
When Anti-D Is Required?
It is required in partial due to the presence of fetal RBCs
In complete mole: if diagnosis is not confirmed histopathologically
RCOG Guideline No. 38 ; 2010

72. Post-evacuation Surveillance
Why?
To determine when pregnancy can be allowed
To detect persistent trophoblastic disease (i.e. GTN)

73. The Post-evacuation Surveillance. How?
A baseline serum β -hCG level is obtained within 48 hours after evacuation.
Levels are monitored every 1 to 2 weeks
while still elevated to detect persistent
trophoblastic disease (GTN).
These levels should progressively fall to an undetectable level (<5 mu/ml).
If symptoms are persistent, more frequent β hCG estimation and U/S examination ± D&C are advised
RCOG Guideline No. 38 ; 2010

74. Cunningham et al,Williams Obstetrics,23 ed ,2010

75. No At the 9 week follow up the β hCG level : 2u/L
Is this level sufficient to stop follow up ? No 4-
The Scenario case
Cunningham et al,Williams Obstetrics,23 ed ,2010

76. What Is The Optimum Follow-up Period Following Normalization of β hCG?
For 6 months from the date of uterine evacuation.
For 6 months from normalization of the β hCG level.
For 12 months from the date of uterine evacuation. B

77. What Is The Optimum Follow-up Period After Which Pregnancy Is Allowed?
It depends upon when hCG has reverted to normal
≤ 56 days of the pregnancy event: Follow up is months from the date of uterine evacuation.
>56 days of the pregnancy event :Follow up is months from normalization of the hCG level.
RCOG Guideline No. 38 ; 2010
At this period levels of βhCG are monitored every month
Practically once βhCG has normalized after molar evacuation, the possibility of GTN developing is very low.

78. What Is Safe Contraception Following GTD?
Barrier methods until normal β hCG level.
Once βhCG level have normalized:Combined oral contraceptive (COC ) pill may be used.
If oral COC was started before the diagnosis of GTD ,COC can be continue as its potential to increase risk of GTN is very low
IUCD should not be used until β hCG levels are normal to reduce uterine perforation.
RCOG Guideline No. 38 ; 2010

79. Case Scenario 2 She complains of:
A 34-year-old woman, married for 7 years 3rd Gravida ,Para 0 at 14 Ws GA.
The previous abortions were at 7&8 weeks.
She complains of:
1-Mild vaginal bleeding for 4 days
2-Nausea, and moderate vomiting
Pulse 95/m, Bp 140/85

80. What Is The U/S Differential Diagnosis?
US scanning revealed
What Is The U/S Differential Diagnosis?

81. What Is The U/S Differential Diagnosis?
Complete mole with a coexisting normal twin
Partial mole
Other placental abnormalities
Rtroplacental hematoma
Degenerating myoma

82. What Are The Required Investigations?
Quantities serum β hCG
Free T4
Protein in urine
Rescanning after one week in a tertiary or fetal medicine center for diagnosis & screening.

83. U/S Tertiary center report:
β hCG :80,000 mµ/ml
Free T4 : 2µg/ml (N µg/ml)
Protein in urine: Negative
U/S Tertiary center report:
Molar pregnancy with a coexisting normal twin
The mole is mostly complete ,to be confirmed histopathologicaly (After termination).
U/S Fetal screening: No detectable anomalies
Follow up is recommended .

85. How Cane We Council The Couple?
1-Counseling for the increased risk of perinatal morbidity :
Bleeding
Pre-eclampsia5-20%
Hyperthyrodism 5%
premature labor 35%
Early fetal loss 40%
Live birth only :25%.
2-Counseling for the increased risk of GTN outcome and need of serial surveillance .
RCOG Guideline No. 38 ; 2010

86. The Patients Elects To Continue The Pregnancy. How Can We Manage?
Close maternal surveillance for development of preeclampsia or hyperthyroidism.
Fetal karyotype may be considered if follow up screening is not assuring
Serial hCG level for detection of GTN.
A chest x-ray to exclude pulmonary metastases (choriocarcinoma)
Postpartum: the placenta should be sent for evaluation by a pathologist
Garner UpToDate ,2010

87. When Must Pregnancy Be Terminated ?
Development of preeclampsia or hyperthyroidism.
Fetal karyotype is not normal dioploidy
β hCG level levels consistent with GTN.
Evidence of metastases (choriocarcinoma)
Accidental hemorrhage
Garner UpToDate ,2010

88. Thank You
Egypt