Gestational trophoblastic diseases

[Subject]

Gestational trophoblastic diseasesGestational
trophoblastic diseases
DEFINITION 3. By a diploid sperm produced by failure of
 Encompasses a heterogeneous group of either the first or second meiotic division
diseases form the benign to malignant type
 It arises from the placental trophoblastic Partial Mole
epithelium after a normal or abnormal  Derived from one maternal and two paternal
fertilization chromosomes, resulting to triploid genotype

MODIFIED WHO CLASSIFICATION Fertilization of Haploid Egg (23X)
Molar Lesions Non-Molar Lesions 1. By two haploid sperms (dispermy)
Hydatidiform Choriocarcinoma 2. By single diploid sperm which then
Mole Placental site trophoblastic replicates (monogenic diandric triploidy)
Complete, tumor 3. By a diploid sperm produced by failure of
Partial Epithelioid trophoblastic tumor either 1st or 2nd meiotic division
Invasive mole Miscellaneous trophoblastic
lesions Fetuses affected by triploidy in atrial moles gave
 Exaggerated placental multiple congenital anomalies and mental
site retardation.
 Placental site nodule
Clinicopathologic Features
HYDATIDIFORM MOLE Feature Partial Complete
 An abnormal placenta characterized by Karyotype 69 XXX/69 46,X or 46,
edematous and vesicular chorionic villi XXY XY
accompanied by variable amount of Fetus Often present Absent
proliferative trophoblasts Amnion, RBC Usually Absent
 Subtypes: present
o Complete Villous edema Variable Focal, diffuse
o Partial Trophoblastic Focal, slight Diffuse, slight
proliferation to moderate to severe
Risk factors Diagnosis Missed Molar
 Age abortion gestation
o Extremes of age (<15 and >40 yo) Uterine size Small for Large for
 Reproductive history dates dates
o H mole – risk of repeat Hmole is 1- Theca lutein cyst Rare 25-30% of
1.5% cases
o After 2nd molar pregnancy – 18% risk Medical Rare Less than
of recurrence complications 25%
 Diet Postmolar <5% 6-32%
o Low animal fat and beta-carotene malignant
diet sequelae

Pathogenesis Diagnosis
 Role of oncogenes  Clinical presentation
 Complete moles  Sonographic picture
 Overexpression of p53, cfms, c-myc, c-er  Beta hCG titer
B2, bcl-2, p21, Rb, and MdM2  Histopathologic examination
 Epidermal growth factor receptor (EGFR)
higher in molar pregnancies
Complete Mole
 Derived from the paternal or androgenetic
origin Clinical Presentation
 No maternal chromosomes  Confirmed pregnancy
 Classic “snowstorm” pattern  Uterine size and date discrepancy
 Exaggerated subjective symptoms of
Fertilization of an empty ovum pregnancy (nausea, vomiting)
1. By a SINGLE HAPLOID SPERM (23X)  Painless second trimester bleeding
which duplicates itself to restore 46XX o With prevalence of early ultrasound,
karyotype called diandric diploidy moles are now diagnosed in the first

, 1. Anemia Discriminatory level of BHCG
2. Pre-eclampsia  In normal pregnancy, GS visible
3. Hyperthyroidism o TVS at HCG 1000-2000 mIu/ml
4. Electrolyte imbalance o TAS at HCG 2400-3600 mIu/ml
5. Hyperemesis gravidarum o 90% of early moles correctly
6. Pulmonary insufficiency diagnoses when HCG level >
7. Disseminated Intravascular Coagulopathy 82,360mIu/ml and no FHT seen

Vaginal Bleeding Normal Pregnancy
 Occurs in 89-97% of cases  Serum HCG = 20000 to 100000 at 7-10
 Occurs when molar chorionic villi disrupts weeks followed by gradual decline
maternal vessels by separating from the
deciduas GTD
 Prune juice in character, and in some  Any HCG level >1000000 at any time in
cases, vesicles are passed out pregnancy OR
 >320000 miu/ml after 100 days of
Excessive Uterine Enlargement amenorrhea
 Discrepancy between uterine size and AOG
 Seen in 40-50% of patients with complete Immunostaining
mole  The use of p57KIP2 during the early first
 Due to retained blood and hydropic villi trimester
 P57KIP2 is paternally derived and
Pre-eclampsia maternally expressed so that its absence
 12-27% of patients on nuclear staining establishes the
 Limited almost exclusively to patients with didagnosis of CHM;
markedly elevated hCG values  A positive staining is seen in PHM and
 Rare if the molar pregnancy is diagnosed hydropic abortus
before 10-12 weeks
 Management: Familial recurrent molar pregnancy
o Control of hypertension  Rare occurrence
o Prevention of convulsions  Characterized by recurrent complete
o Prevention of end organ damage hydatidiform mole of biparental origin rather
than the more usual androgenetic origin
Hyperthyroidism  Evaluation of families with recurrent molar
 Clinically evident hyperthyroidism is seen in pregnancy suggests that dysregulation of
2-7% of patients normal parental imprinting of genes
 Laboratory evidence of hyperthyroidism is  Genetic mapping shows that in most
more common families the gene responsible is located in
 Presenting symptoms include thyroid 1.1mb region on chromosome 19q13.4
enlargement, tachycardia  Mutations in the gene result in dysregulation
 Due to cross-stimulation of TSH receptor of normal parental imprinting of genes
with HCG
 PTU and Propranolol given to inhibit Diagnostic CHM PHM Hydropic
peripheral conversion of thyroxine to test abortus
triiodothyronine Ultrasound Snowstor Cystic Cystic
 Propranolol also blocks sympathetic m pattern spaces spaces
response to thyroid hormones – to prevent within within
thyroid storm placenta, placenta,
feuts, GS fetus, GS
Pulmonary Insufficiency Serial HCG Sustained, Sustained, Elevated,
 Occurs in 2% of cases markedly markedly decline
 Observed after molar evacuation in patients elevated elevated
with high βhCG levels, excessive uterine Karyotyping 46xx 69xxx, 69xxx
size and very large theca lutein cysts 69xxy oor
 May result from pulmonary embolism, 69xyy
congestive heart failure due to
preeclampsia, severe anemia,
hyperthyroidism, and intravenous fluid Histopathologic examination
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Sonographic Picture
Theca Lutein Cysts
 Multicystic, anechoic cysts