gestational trophoblastic disease (gtd) by ahmed refaat abd elzaher assistant lecturer of medical...
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Gestational Trophoblastic Disease
(GTD)
ByAhmed Refaat Abd ELzaher
Assistant Lecturer of Medical Oncology
South Egypt Cancer Institute2015
GTD Overview• Heterogeneous group of related lesions• Arise from abnormal proliferation of trophoblast of
the placenta• Can follow any gestational event – abortion,
miscarriage, ectopic, normal pregnancy• Unique because the maternal lesions arise from
fetal (not maternal) tissue• Most GTD lesions produce (B-hCG)• Can be cured even in the presence of widespread
metastases
OverviewHydatidiform Mole:• Complete • Partial** BenignGestational Trophoblastic Neoplasia (GTN):• Persistent/Invasive Mole• Choriocarcinoma• Placental-Site Trophoblastic Tumor (PSTT)** Malignant
Relationship of HM. IM. CH
hydatidiform therapeutic or
mole spontaneous abortion term pregnancy
ectopic
invasion mole choriocarcinoma.
Hydatidiform mole
Hydatidiform Mole
• North America: 0.6-1.1 per 1000 pregnancies• Asia: 2-10 per 1000 (3x Western countries)• Difference possibly related low dietary intake
of carotene (vitamin A deficiency) and animal fat
• More common at reproductive extremes in age (>35y or <20y)
Hydatidiform MoleRisk Factors:• History of previous GTD
– If one previous mole, 1% chance of recurrence (vs. 0.1% in general population)
– If 2 previous moles, risk of recurrence increases to 16-28%
• Smoking• Vitamin A deficiency• Blood type:
– A or AB are at slightly higher risk than those with type B or O
Hydatidiform mole
1. Complete mole
23X
sperm empty egg
23X 23X
46,XX
23X
sperm empty egg
23Y 23X
46,XY
23Y
sperm
Hydatidiform mole
2. Partial mole
23X
sperm normal egg23Y 23X
69,XXY
23Y
sperm
23X23X
23X
sperm Normal egg23X 23X
69,XXX
23X
sperm
23X23X
Hydatidiform MoleClinical Manifestations:• Vaginal bleeding (97%) /anemia• Enlarged uterus (size > dates)• Pelvic pain• Theca lutein cysts• Hyperemesis gravidarum• Hyperthyroidism• Preeclampsia <20 weeks gestation• Vaginal passage of hydropic vesicles• Partial mole usually presented as incomplete or missed
abortion
Diagnosis
• Complete : U/S usually very sensitive – generalized
swelling (snow-storm )
• partial mole U/S may detect focal cystic spaces of varying
diameter Diagnosis on histology of curettings
Complete vs. partial moleFeature Complete Partial
Karyotype Diploid(usually 46,xx or rarely
46,xy)
Triploid
(69,xxx or 69, xxy)
Swelling of chorionic villi diffuse focal
Trophoblastic hyperplasia diffuse focal
Embryonic tissue absent Present
hCG Often > 100,000 usually< 100,000
Trophoblastic sequelae 15 - 20% <5%
Theca lutein cysts Up to 25% Rare
Medical complications Up to 25% Rare
Uterine size 50% large for dates Small for dates
Hydatidiform Mole Treatment • Evaluate for coexisting conditions:
- History and physical- CBC, coagulation profile, serum chemistry- thyroid function- blood type and cross match- chest radiography- pelvic ultrasonography
• Evacuation of mole- Suction curettage- Hysterectomy if completed childbearing
• If Rh negative, give rhogham
Hydatidiform Mole Treatment
chemotherapy
HM don’t need usually chemotherapy because HM is benign disease.
Follow-Up Care – Molar Pregnancy• 80% of patients cured by evacuation• Follow B-hCG levels every two weeks until 3 consecutive tests
negative• Then monthly B-hCG every month for 6-12 months• More than half of patients will have complete regression of
hCG to normal within 2 months of evacuation.• Avoid pregnancy for at least 6 months after first normal B-hCG
(oral contraceptive pills is preferable)• Subsequent Pregnancies:
– Send placenta for pathology– Check B- hCG 6 weeks postpartum
Prognosis• Complete mole has the latent risk of local
invasion or telemetastasis• The high-risk factors includes
– β-HCG>100000IU/L– uterine size is > 20 weeks size.– the luteinizing cyst is >6cm– If >40 years old,the risk of invasion and metastasis
may be 37%, If >50 years old,the risk of invasion and metastasis may be 56%.
– repeated mole: the morbidity of invasion and metastasis increase 3~4 times
Gestational Trophoblastic Neoplasia (GTN)
• Persistent/Invasive Mole• Choriocarcinoma• Placental-Site Trophoblastic Tumor (PSTT)** Malignant
Risk Factors for GTN After Mole
• Preevacuation uterine size greater than gestationl age or larger than 20 weeks gestation
• Theca-lutein cysts larger than 6 cm• Age > 40 years• Serum hCG levels > 100,000 mIU/mL• Previous hydatidiform mole
Invasive Mole
• Myometrial invasion by hydatidiform mole• Formerly known as chorioadenoma destruens• 1 in 15,000 pregnancies• 10-17% of hydatidiform moles will progress to
invasive moles
Persistent Mole
Definition of persistent molar disease and need for chemotherapy (at least one of the following):– B-hCG plateau for ≥ 4 values for ≥ 3 weeks– B-hCG increase of ≥ 10% for ≥ 3 values for ≥ 2
weeks– B-hCG persistence 6 months after molar
evacuation– Histopathologic diagnosis of choriocarcinoma– Presence of metastatic disease
Choriocarcinoma• Most aggressive type of GTN• Abnormal trophoblastic hyperplasia• Absence of chorionic villi• Direct invasion of myometrium• Most often develops from a complete
hydatidiform mole• Vascular spread to distant sites:
– Lungs – Brain – Liver– Pelvis and vagina– Spleen, intestines, and kidney
Choriocarcinoma• May come from any type of pregnancy
- 25% follow abortion or tubal pregnancy- 25% with term gestation- 50% from hydatidiform moles
• 2-3% of moles progress to choriocarcinoma• Incidence 1 in 40,000 pregnancies
– Rarely, choriocarcinomas can develop in other parts of the body in both men and women. These are not related to pregnancy as ovaries and testicles
• Nongestational choriocarcinoma tends to be less responsive to chemotherapy and has a less favorable prognosis than the gestational variant
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
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)
Signs & Symptoms GTN
• Continued uterine bleeding, uterine perforation, enlarged irregular uterus, persistent bilateral ovarian enlargement
• From metastatic lesions: abdominal pain, hemoptysis, melena, increased intracranial pressure (headaches, seizures, hemiplegia), dyspnea, cough, chest pain
Diagnosis of GTN
• Increase or plateau in B-hCG after molar pregnancy
• Pathologic diagnosis by D&C or biopsy of metastatic lesions
• WARNING: biopsy of metastatic lesions can result in massive hemorrhage
• Metastatic workup: CXR (or CT chest), CT abdomen/pelvis +/- CT/MR of brain
Classification & Staging of GTD
• FIGO Staging– Describes anatomic distribution of disease
• World Health Organization (WHO) Scoring Index– Describes prognosis
FIGO Staging
Stage Description
I Disease confined to the uterus
II Disease extends outside the uterus but limited to genital structures (adnexa, vagina, and broad ligament)
III Disease extends to the lungs with or without genital tract involvement
IV Disease involves any other metastatic sites
The World Health Organization (WHO) scoring system for GTD
WHO Prognostic Score IndexScore
Characteristic 0 1 2 4
Age <40 ≥40 - -
Antecedent preg Mole Abortion Term -
Pregnancy to treatmentInterval (months)
<4 months
4-6 months
7-12 months >12 months
Pretreatment hCG <103 103- 104 104-105 >105
Largest tumor size (including uterus)
< 3cm 3-4 cm ≥5cm -
Site of metastases Lung Spleen, kidney
GI tract Liver, brain
Number of metastases - 1-4 5-8 >8
Previous failed chemotherapy
- - Single drug ≥2 drugs
Therapy for GTN
• Single agent therapy for nonmetastatic (stage I) or low-risk metastatic (stage II and III) with score <7 survival rates ~ 100%
• Combination chemotherapy +/- radiation and/or surgery for high-risk metastatic disease with score ≥7
Therapy: Nonmetastatic GTN• Single-agent with either methotrexate or
dactinomycin• Chemotherapy continued until hCG values normal
and then 2-3 cycles beyond• Change to alternative single-agent for hCG plateaus
above normal or toxicities• If significant elevation of hCG or new metastases,
switch to multiagent• 85-90% cured with initial regimen, <5% will require
hysterectomy for cure
Therapy: Low-risk Metastatic GTN
• Low-risk metastatic disease can be treated with single-agent therapy with 5-day regimens
• Cure rates ~100% but 30-50% will be develop resistance to first agent
• If resistance to sequential single-agent chemotherapy (5-10% of patients), switch to multiagent chemotherapy
Therapy: High-risk Metastatic GTN• Stage IV • Stage II/III with score > 7• Disease refractory to single-agent chemotherapy
Combination Chemotherapy:• EMACO:
– Day 1: Etoposide, Methotrexate and Dactinomycin – Day 8: Cyclophosphamide and Vincristine
(Oncovorin)– Repeat q2 weeks until remission– Continue for at least 2-3 cycles beyond first normal
hCG• MAC (Methotrexate, Dactinomycin, Cyclophosphamide)• EMA/EP – EMA + Etoposide and Cisplatin
Metastatic Gestational Trophoblastic Tumors
• Surgery – It is indicated for tumor resistant to
chemotherapy and single metastases persisting despite chemotherapy.
• RT – RT, in combination with chemotherapy, is clearly
indicated for the primary management of patients with brain metastases.
PSTT Therapy
• Hysterectomy• Chemotherapy for metastatic disease or
nonmetastatic disease with poor prognosis:- Interval from index pregnancy > 2 years- Deep myometrial invasion- Tumor necrosis- Mitotic count > 6 per 10 high-power fields
• Survival rates:– ~100% for nonmetastatic disease– 50-60% for metastatic disease
Follow-up Care
• After completion of chemotherapy, follow serial hCG every 2 weeks for three months, then monthly for one year
• Physical examinations every 6-12 months and imaging as indicated
Reproductive Performance
• Most women resume normal ovarian function
• Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment
• No increase risk of stillbirths, abortions, congenital anomalies, prematurity, or major obstetric complications
False Positive Serum hCG
• Phantom hCG syndrome/ phantom choriocarcinoma
• 3-4% of healthy individuals have human-antimouse antibodies that can mimic hCG immunoreactivity
• To verify:– Urine hCG should be negative– Should not show parallel decrease with serial dilutions– Test at national B-hCG reference lab
Summary
• Hydatidiform mole is a benign condition, 80% cured with suction D&C
• Malignant GTN:– Persistent or invasive mole– Choriocarcinoma– PSTT
• WHO score > 7 represents high-risk disease• GTN very sensitive to chemotherapy
Thank You Thank You For Your For Your TimeTime