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Gestational Trophoblastic
     Disease (GTD)
Part I : Molar Pregnancy
     • Dr. Mohamed El Sherbiny
       MD Ob.& Gyn. Senior Consultant
           • Damietta, Egypt
Part I: Molar Pregnancy
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. 38 .2010
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
Classifications
Gestational Trophoblastic Disease (GTD)
I-Pathologic Partial mole    Invasive Chorio                      Placental site
                                                                  trophoblastic
Classification Complete mole mole                                 tumour
                                      carcinoma
                           Pe
                              rsi
                                  st   en
                                         tG           G.T. Neoplasia
II-Clinical       Benign                      TD

Classification    G.T.D.                            Malignant G.T.D.
βhCG based:
WHO, FIGO,
ACOG 2004 &                                                    Metastatic
                     Non metastatic
RCOG 2010

                                                   Low risk       High risk
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 .
Hydatidiform Mole

         (H. MOLE)
-
              =
       Vesicular Mole
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.
Features Of Partial And Complete Hydatidiform Moles
Feature                      Partial mole              Complete mole
                             Most commonly             Most commonly
                             69, XXX or - XXY          46, XX or -,XY
Karyotype
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%
Postmolar CTN                2.5-7.5%                  6.8-20%
        Disaia &Creasman Clinical Gynecological Oncology 2007
                                               rd
Epidemiology& Risk Factors
Incidence:USA 1/1000 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
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
Karyotype
Homozygous 90%


Pathogenesis of complete H. Mole
Heterozygous 10%

Pathogenesis of complete H. Mole
Pathogenesis of Partial H. Mole
Pathology of
   Molar
 Pregnancy
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%
1-Trophoblastic proliferation




                                        2-Hydropic Degeneration




Complete hydatidiform mole: Microscopically Enlarged,
edematous villi and abnormal trophoblastic proliferation that
diffusely involve the entire placenta
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"
Complete Hydatiform Mole




Uterine wall
Pathogenesis of
      Choriocarcinoma
–Aneuploidy
–(Not a multiplication of 23
 chromosome )
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
Partial Hydatidiform Mole




     Scalloping of chorionic villi



Trophoblastic proliferation are slight and focal
Vesicles




Maternal side
                       Partial Hydatiform Mole
Fetal hand demonstrating syndactyly. The fetus had a triploid karyotype, and the chorionic
tissues were a partial mole
Partial H. mole.
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
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
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
What Is The Most Common Presenting
Symptom Of A Complete Molar Pregnancy?

A. Hyperemesis                             10%

B. Bilateral enlarged theca lutein cysts   30%

C. Vaginal bleeding                        85%

D. Uterine enlargement> than expected for GA 40%

E. Pregnancy-induced hypertension          1%
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
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
TVS “Milestones” Versus βhCG
β hCG mIU/mL  Weeks

Detection Level              >5                3-4
Choriodecidual thickening    100               4
Gestational sac (D Zone) 1000 -1500            4-5
Yolk sac                      7000                 5- 6
Heart motion                10,000                 6
Embryonic Movem. > 10.000                      6- 7
Maximum level               50,000to 100,000   8-10
Molar pregnancy
Complete Molar Pregnancy
Complete hydatidiform mole. The classic "snowstorm"
appearance is created by the multiple placental vesicles.
Complete H.Mole
(High-resolution) U/S
Complex intrauterine
mass containing many
small cysts.



Complete H.Mole
Associated theca-lutein
cysts. U/S Power Doppler
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
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
Partial Molar Pregnancies
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?
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.
Which Diagnostic Test Would Be
Most Useful?

The most useful diagnostic
 test is :
            U/S
Complex intrauterine mass containing many small cysts
(Snowstorm appearance)
 What is the most likely diagnosis?

 Hydatidiform (Vesicular) mole
 What Would One Expect To See At 
 Scan If Her Pregnancy Is Normal?

                    Gestational (Chorionic) Sac
Molar pregnancy
 What Is The Ultrasonogaphic 
 Differential Diagnosis For  This Case?


U/S DD :
1-Missed 
  abortion
2-Degenerated 
  fibroid
Differential Diagnosis:
      Long standing missed abortion
 with cystic degeneration of the placenta
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?
Molar pregnancy
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 
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.  
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.
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
C. Single suction evacuation
D. Medical trial with misoprostol &oxytocine before
  suction
               C.
 What Is The Evidence ?
What Is The 
Evidence ?
The Management Of 
 Gestational Trophoblastic 
 Disease
RCOG Guideline  No. 38 ; 
 2010
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
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 0.1- 
  0.5%.

    RCOG Guideline  No. 38 ; 2010
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
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/SCOG Guideline  No. 38 ; 2010
    R
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.
Other seats of suction curettage
Suction curettage has been performed
using 10mm canula under U/S guidance :
  El SHERBINY HOSP




                     Canula
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
The Molar Content For Histopathological Examination
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
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.
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
Complete H. Mole with
large for date uterus&
Theca-lutein cyst        Complete H. Mole
                         After Hysterectomy
Patient was 42 years
5th G P5 initial
BhCG:195,000mIU/mL
Theca-lutein cyst associated with a complete H. mole in >30%
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*
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
Post-evacuation
       Surveillance
Why?
To determine when pregnancy
 can be allowed
To detect persistent
 trophoblastic disease (i.e. GTN)
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
Cunningham et al,Williams Obstetrics,23 ed ,2010
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
What Is The Optimum Follow-up Period
Following Normalization of β hCG?
A. For 6 months from the date of uterine
  evacuation.
B. For 6 months from normalization of the β hCG
  level.
C. For 12 months from the date of uterine
  evacuation.
                B
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
     6 months from the date of uterine evacuation.
 >56 days of the pregnancy event :Follow up is
   6 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.
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
Case Scenario 2

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
US scanning revealed




What Is The U/S Differential Diagnosis?
What Is The U/S Differential Diagnosis?

 Complete mole with a coexisting
 normal twin
 Partial mole
 Other placental abnormalities
 Rtroplacental hematoma
 Degenerating myoma
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.
β hCG :80,000 mµ/ml
  Free T4 : 2µg/ml (N 0.3-1.7µg/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 .
Molar pregnancy
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
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
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
Thank You


Egypt

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Molar pregnancy

  • 1. Gestational Trophoblastic Disease (GTD) Part I : Molar Pregnancy • Dr. Mohamed El Sherbiny MD Ob.& Gyn. Senior Consultant • Damietta, Egypt
  • 2. Part I: Molar Pregnancy
  • 3. 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. 38 .2010
  • 4. 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) I-Pathologic Partial mole Invasive Chorio Placental site trophoblastic Classification Complete mole mole tumour carcinoma Pe rsi st en tG G.T. Neoplasia II-Clinical Benign TD Classification G.T.D. Malignant G.T.D. βhCG based: WHO, FIGO, ACOG 2004 & Metastatic Non metastatic RCOG 2010 Low risk High risk
  • 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 .
  • 7. Hydatidiform Mole (H. MOLE) - = Vesicular Mole
  • 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 Feature Partial mole Complete mole Most commonly Most commonly 69, XXX or - XXY 46, XX or -,XY Karyotype 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% Postmolar CTN 2.5-7.5% 6.8-20% Disaia &Creasman Clinical Gynecological Oncology 2007 rd
  • 10. Epidemiology& Risk Factors Incidence:USA 1/1000 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
  • 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
  • 13. Homozygous 90% Pathogenesis of complete 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"
  • 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
  • 24. Vesicles Maternal side Partial Hydatiform Mole
  • 25. Fetal hand demonstrating syndactyly. The fetus had a triploid karyotype, and the chorionic tissues were a partial 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
  • 30. What Is The Most Common Presenting Symptom Of A Complete Molar Pregnancy? A. Hyperemesis 10% B. Bilateral enlarged theca lutein cysts 30% C. Vaginal bleeding 85% D. Uterine enlargement> than expected for GA 40% E. Pregnancy-induced hypertension 1%
  • 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 β hCG mIU/mL Weeks Detection Level >5 3-4 Choriodecidual thickening 100 4 Gestational sac (D Zone) 1000 -1500 4-5 Yolk sac 7000 5- 6 Heart motion 10,000 6 Embryonic Movem. > 10.000 6- 7 Maximum level 50,000to 100,000 8-10
  • 36. 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. Complete H.Mole 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
  • 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. Which Diagnostic Test Would Be Most Useful? The most useful diagnostic test is : U/S
  • 44. Complex intrauterine mass containing many small cysts (Snowstorm appearance) What is the most likely diagnosis? Hydatidiform (Vesicular) mole
  • 48. Differential Diagnosis:  Long standing missed abortion  with cystic degeneration of the placenta
  • 49. 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?
  • 51. 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 
  • 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 C. Single suction evacuation D. Medical trial with misoprostol &oxytocine before suction C. What Is The Evidence ?
  • 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 0.1-  0.5%. 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/SCOG Guideline  No. 38 ; 2010 R
  • 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 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. 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.
  • 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
  • 68. Complete H. Mole with large for date uterus& Theca-lutein cyst Complete H. Mole After Hysterectomy Patient was 42 years 5th G P5 initial BhCG:195,000mIU/mL
  • 69. Theca-lutein cyst associated with a complete H. mole in >30%
  • 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*
  • 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. 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? A. For 6 months from the date of uterine evacuation. B. For 6 months from normalization of the β hCG level. C. 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 6 months from the date of uterine evacuation.  >56 days of the pregnancy event :Follow up is 6 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 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. 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. β hCG :80,000 mµ/ml Free T4 : 2µg/ml (N 0.3-1.7µg/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