3. Danforth's
Williams Obstetrics, 23e
B erek and Hacker's Gynecologic Oncology
Up To Dat
GESTATIONAL TROPHOBLASTIC DISEASE
PATHOGENESIS
DIAGNOSIS
MANAGEMENT
GESTATIONAL TROPHOBLASTIC NEOPLASIA
TREATMENT
SUBSEQUENT PREGNANCY
4. Gestational trophoblastic disease (GTD) is term
group of tumors with abnormal trophoblast
proliferation
produce human chorionic gonadotropin (hCG)
5. GTD histologically is divided into
benign
hydatidiform moles
( complete and partial)
Malignant
Invasive mole
6. Non -molar trophoblastic neoplasms
• Choriocarcinoma
• Placental site trophoblastic tumor
• Epithelioid trophoblastic tumor
7. Gestational trophoblastic neoplasia (GTN
)
Malignant forms of gestational trophoblastic
disease
GT N is all GTD except hydatidiform mole
Weeks or years following any type of pregnancy
But frequently occur after a hydatidiform mole
8. Hydatidiform mole
Microscopic (classic findings)
Absence embryonic elements
Trophoblastic proliferation
(cytotrophoblast and
syncytiotrophoblast)
Stromal edema and hydropic degeneration
Absence of blood vessels
10. Hydatidiform mole
Complete mole Partial mole Partial mole
Partial mol ( fetal tissue)
Grossly placenta a mixture of normal and
hydropic villi
Fetus Severe growth restriction
Multiple congenital anomalies
11. Risk Factors hydatidiform mole
Strongest risk factors are
Age and a
history of prior hydatidiform mole
Both extremes of reproductive age
adolescents twofold risk
Older than 40 tenfold risk
12. • history of Prior mole
• the risk of another mole
• Complete mole is 1.5 percent
• Partial mole is 2.7 percent
• Two prior molar pregnancies
• the risk is 23 percent
13. • An ethnic predisposition
• Diet (Deficiencies of protein or)
• (Vitamin A deficiency)
• animal fat
• Smoking
• Increased paternal age
14. Pathogenesis
Abnormal fertilization process
Normal ovum with a duplicated haploid sperm
Inactive ovum chromosomes
Karyotype 46, XX
diploid and result from androgenesis
Partial moles triploid karyotype
69, XXX, 69,XXY
15.
16. Clinical Findings
Because universal sonography in prenatal care
Typically diagnosed at a mean of 10 weeks
• Vaginal bleeding
• spotting to profuse hemorrhage
• Moderate iron-deficiency anemia
17. • Exaggerated early pregnancy symptoms
• Nausea and vomiting ( hyperemesis)
• Abdominal cramp
18. Abnormally enlarged and soft uterus uterine
growth
Theca-lutein cysts (hCG) 25 to 60%
(Torsion, infarction, rupture and hemorrhage)
Releases antiangiogenic factors that activate
endothelial damage
Severe preeclampsia
hypoxic trophoblastic mass
19. All hydatidiform moles secrete hCG
Thyrotrophic -like effects of hCG
hCG acts a thyrotrophic substance
Elevated serum free thyroxine (T4)
(TSH) levels to be decreased
thyroid hyper –function
“thyroid storm”
20. Diagnosis
Amenorrhea followed by irregular bleeding
Spontaneous passage of molar tissue
High values Serum β-HCG measurement
confirming the diagnosis
IHC stain positively for p57
24. • which of the following symptoms will a highly
intelligent physician assistant immediately
consider hydatidiform mole?
– pelvic pain at night during the first trimester
– significantly elevated BP in the first trimester
– significant bloody vaginal discharge in the first
trimester
– nausea and vomiting in the first trimester
26. Management
Termination of Molar Pregnancy
• Evacuation and Curettage
• Hysterectomy (rarely and select cases
• no desired future pregnancy )
• Chest radiograph
• Initiate effective contraception
• OCP or MPA } poor compliance}
27. Serum hCG levels:
48 hours of evacuation (baseline)
Weekly until undetectable Weekly until
normal for 3 consecutive weeks
monthly until normal for at least 6 consecutive
months
Median time for resolution is 9 weeks for
complete
7 weeks for partial
Hysterectomy reduces the incidence of malignant
sequelae
does not eliminate follow-up
28. hCG change
HM: 84-100 days
Spontaneous abortion: 19 days
Normal delivery: 12 days
Ectopic pregnancy 8-9 days
29. After molar evacuation
risk factors for malignant squeal
15 - 20 % complete moles
1 - 5 % partial moles
1 5% of HM become invasion moles
2.5% progress into choriocarcinoma
30. Twin Pregnancy (Normal Fetus
and Coexistent Complete Mole)
Diagnosis is difficult
(early pregnancy ultrasound)
A single partial molar pregnancy with
abnormal fetus Distinguished
31. A few cases the diagnosis is not suspected
until examination of the placenta
following delivery
32. Amniocentesis ( fetal karyotype )
diploid or triploid
If fetal karyotype is normal
Major fetal malformations are excluded by
ultrasound
Chest X-ray performed
Serum hCG values
If there is no evidence of metastatic disease
to allow the pregnancy
33. Possible risk for developing
• Subsequent GTN
• Preterm delivery
• Preeclampsia
• Sever hemorrhage
34. Persistent GTD :
Persistently elevated serum hCG level
Irregular vaginal bleeding
Persistent theca lute in cysts
(2 to 4 months regress spontaneously)
Uterine sub involution
Risk factors for GTN
35. Risk factors of GTN
Older age
β-hCG levels > 100,000 mIU/mL
Large uterine size for-gestational age
Theca-lutein cysts > 6 cm
Earlier recognition and evacuation of molar
pregnancies
not lower risk neoplasia
36. Criteria for Diagnosis of Gestational
Trophoblastic Neoplasia
Criteria for the diagnosis of postmolar GTN
1. Plateau or rise of serum β-hCG level
2. Detectable serum β-hCG level for
6 months or more
3. Histological criteria for choriocarcinoma
4-Irregular bleeding ,uterine sub involution
37. •
Plateau of serum β-hCG level (± 10 percent)
for four easurements during a period of
3 weeks or longer
days 1, 7, 14, 21
Rise of serum β-hCG level > 10 percent
during three weekly consecutive , during a
period of 2 weeks or more—days 1, 7, 14
39. SPESIAL
1-Selective angiography of abdominal and pelvic or
hepatic (if indicated )
2-Whole body PET Less commonly (occult disease )
3-Stool guaiac tests
If positive test is or if gastrointestinal symptoms
be routinely performed in persistent GTN
4- complete radiographic evaluation
of the gastrointestinal tract
40. GTN CLASSIFICATION
Invasive Mole
Almost all invasive moles arise from partial or
complete moles
Deep penetration into the myometrium
or peritoneum
Involvement of vaginal vault
48. Brain metastasis
• Plasma CSF /hCG level ratio is normally
• >60: 1
• In patients with CNS metastases <60: 1
•
• Falsely lowered plasma CSF /hCG level
• First -trimester abortions
In the absence of lung or vaginal metastasis
Risk of cerebral and hepatic spread
is exceedingly low
49. Generally in GTN
Serum hCG levels combined Clinical findings
Rather than a histological specimen
Diagnose and treat this malignancy
50. Follow-up of GTN
patients β-subunit until hCG
Weekly until normal for 3 consecutive
weeks
monthly until normal for at least 3
consecutive months
at 1-month interval for 1 year:
at 1- month interval for 2 years in high stage
at yearly interval for many years
(increased risk of late recurrence)
51. • Be careful :
• hCG
• Pelvic examination
• Chest X-ray
unusual rise of serum hCG
• Rule out Normal pregnancy
• Ectopic pregnancy
• False-Positive hCG
53. Quiescent GTN
Constant, low level of hCG <100 IU/L
Without evidence of a primary or metastatic
malignancy
Persisting for periods 3 months to 16 years
Slow-growing
Oral contraceptive pills
and avoid pregnancy until
hCG has been undetectable for six months
20 percent will eventually have recurrent
active
54. H CG variants
Hyperglycosylated hCG (H -hCG)
hCG produced by syncytiotrophoblasts
(H -hCG) synthesized by cytotrophoblast
(H -hCG) absolute marker of ongoing invasion
hCG-H is detectable >1 ng/ml: active GTN
To discriminate quiescent disease
55. Phantom hCG
False positive serum hCG
Send the serum to two laboratories
Using different commercial assays
If negative in one or both
false positive hCG
Presence of hCG in serum but not urine
56. Heterothallic antibodies may results
false-positive
False positive are at risk for recurrent
Risk for other false positives, such as
CA-125 and thyroid antibodies
57. Pituitary hCG
Secreted LH and hCG pulsatile and paralleled
Higher levels of h CG in postmenopausal
than premenopausal Cross-reactivity with LH
Pituitary production hCG ranges from
1 to 32 mIU/mL
HRT or BSO or OCP after 2–3 weeks
Suppress hCG Pituitary production
59. Staging
International staging of WHO may be
summarized as follows:
Ⅰ: lesion localized in uterus, no metastasis;
Ⅱ: lesion extends beyond uterus, but still
confined to internal genitalias;
Ⅲ: pulmonary lesion
Ⅳ: metastasis to other distant sites.
64. 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
drugs
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.
65. • According to the FIGO staging of gestational
trophoblastic tumors
• a lady with choriocarcinoma having
• lung metastasis will belong to which stage
66. protocol for treatment of GTD
Clinically staging( FIGO)
WHO scoring
Again, it is stressed that the diagnosis of
GTN made by persistently elevated serum
β-hCG without confirmation by pathological
tissue study
67. Choice of treatment
• Chemotherapy ( highly sensitive )
• Surgery ( unresponsive or drug fails )
• Irradiation (brain and liver )
68. Chemotherapy are best management
Protocols: Single-agent for
low-risk Methotrexate
Combination for high-risk disease
EMA-CO
Early-stage GTN is typically cured
Later -stage disease usually responds
to chemotherapy
69. Surgery in malignant GTN
• Hysterectomy
• Laparoscopy
• Craniotomy (brain hemorrhage)
• Thoracotomy
• (solitary nodules in drug-resistant disease )
• selective resection of lesion in uterus or liver
70. Main causes of death:
• Hemorrhage
• Infection
• Metastasis
71. Placental Site Trophoblastic Tumor
(PSST)
PSTT or non-trophoblastic malignancy
Uncommon tumor arises from implantation site-
intermediate trophoblast
Secrete (hPL) from intermediate cells
Relatively small amounts of hCG
hCG free β-subunit is more than one third of
hCG (30%)
72. Typically local myometrial invasion
Rare systemic metastases
Treatment of ( PSST) is preferred hysterectomy
Because resistant to chemotherapy
For higher-risk than stage I
combination chemotherapy given
73. Epithelioid Trophoblastic Tumor
This rare tumor
Intermediate trophoblast -type
Grossly a nodular fashion
Primary treatment is hysterectomy
Relatively resistant to chemotherapy
Approximately a fourth this neoplasm
will have metastatic disease,
combination chemotherapy
74. SUBSEQUENT PREGNANCY
Pregnancy outcomes are usually normal
May develop:
1-Repeat molar gestation 2-percent
2-Spontaneous abortions
3-Congenital anomalies
4-Ovarian failure (chemotherapy)
5-Secondary tumors including
leukemia
colon cancer, melanoma
and breast cancer
75.
76. After Termination of Subsequent
Pregnancy
Sonographic evaluation in early pregnancy
pathological evaluation placenta after delivery
serum β-hCG level is measured 6 weeks
postpartum
77. Conclusion
The possibility of metastatic GTN should be
considered
In any woman of the reproductive age
Presenting with metastatic disease
Or
an unknown primary site of malignancy
