Gestational Trophoblast Disease Flashcards
Abnormal Placental Implantation - Ectopic Pregnancy
- The most important predisposing factor is pelvic inflammatory disease with chronic salpingitis (35% to 50% of cases).
- Additional factors include peritubal adhesions (due to endometriosis, appendicitis, or previous surgery) and intrauterine devices.
- Interestingly, up to 50% of the cases of ectopic pregnancy occur in apparently normal tubes.
Gestational Trophoblastic Disease
- Gestational Trophoblastic Disease comprises a group of diseases which all have in common an abnormal proliferation of trophoblast.
- Included under this designation are the following entities:
- hydatidiform mole (complete and partial)
- invasive mole
- choriocarcinoma
The Moles
- Abnormal fertilizations with an excess of paternal genes, not neoplasms
- Derived from villous trophoblast
- Occur in ~1/1000-2000 pregnancies in the U.S., incidence higher in parts of Asia
- More common at extremes of childbearing age
Complete Hydatidiform Mole (CHM)
- Most common type of GTD
- Presenting symptoms include
– rapidly enlarging uterus
– vomiting,
– hypertension,
– hyperthyroidism,
– extreme elevation of beta-hCG
– “snowstorm” on ultrasound
- CHM
- Abundant tissue
- Grossly identifiable, grape-like “vesicles”, up to 2 cm in diameter = hydropic villi
- CHM
- Diffusely hydropic villi
– ALL of the villi are hydropic
– Central “cisterns”= acellular spaces
• Trophoblastic hyperplasia and severe atypia
– Circumferential (as opposed to polar)
• No embryo/fetus (usually)
Genetic Composition of CHM
• Fertilization of an anucleate egg
– 90%: homozygous 46 XX
result from duplication of a single haploid sperm
– 10%: heterozygous, predominantly 46 XY
result from dispermic fertilization
Clinical Behavior of CHM
• 10-30% of patients will develop persistent disease
– Residual tissue in uterus
– Invasive mole (10%)
– Malignant transformation (2-3%): choriocarcinoma
- Increased risk for repeat mole
- Prognosis is excellent!
- Treatment
– Follow beta-hCG levels to normal
– 6 months to a year of contraception
– If beta-hCG rises, treat with chemo
Partial Hydatidiform Mole (PHM)
- Incidence is uncertain, probably less common than CHM
- Risk factors are similar to CHM, but maternal age does not seem to have an influence
- Presenting symptoms include: spontaneous or missed abortion, without abnormally accelerated increase in uterine size or beta-hCG level
- PHM
- Not as much tissue as a CHM
- Normal and hydropic appearing villi
- May have recognizable embryo/fetus
- PHM
- Two kinds of villi
– Fairly normal villi
– Hydropic villi
- Scalloped borders
- Trophoblastic “pseudoinclusions” (tangential cuts)
- Some cisterns, usually scarce
– Less trophoblastic proliferation than CHM
Genetic Composition of PHM
- • Abnormal fertilization of a normal egg by two sperm or a diploid sperm (diandric triploidy)
- NOTE: Digynic triploidy (two copies of maternal chromosomes) is only 15-20% of triploidy cases and is NOT molar- it causes triploid fetus that aborts
Clinical Behavior of PHM
• 4-11% of patients will develop persistent disease
– Rarely invasive
– Very rarely (probably never) malignant transformation
- Prognosis is extremely good!
- Treatment is the same as CHM
Complete vs. Partial Mole
- Histologic and clinical features
- P57 immunohistochemistry is useful
– A paternally imprinted gene, expressed only if maternal gene is present
– Absent in CHM, which have only paternal genes
• Ploidy analysis, other genetic studies
Invasive Mole
- Rare
- Molar villous tissue invades myometrium, blood vessels
- Can perforate uterus
- Can embolize, but not true metastases
- Usually detected after prior diagnosis of mole by rising beta-hCG
- Treated with chemotherapy (like choriocarcinoma), without acquiring tissue
Choriocarcinoma
- Rare in U.S.
- Usually presents within months of a known gestation, but can be years later
- Usually follows a molar gestation (50%), but can follow any type of normal or abnormal gestation, including ectopic (rarely)
- Usually is derived from the most recent gestation, but occasionally normal pregnancies have intervened (!!!)
- Derived from villous trophoblast (gestational tissue)
NOTE: GESTATIONAL CHORIOCARCINOMA is NOT THE SAME as CHORIOCARCINOMA OF GERM CELL ORIGIN.
Despite having the same name and identical morphology, CCA of gestational origin differs from CCA of germ cell origin:
– Genetically distinct from patient
– Prognosis is very different (gestational tumors are extremely chemosensitive)
- choriocarcinoma
- Variable size
- Very friable (crumbly), hemorrhagic, necrotic
- Infiltrating borders
- choriocarcinoma
- Solid sheets of cytotrophoblast admixed with syncytiotrophoblast infiltrate myometrium
- Extensive vascular invasion (the cause of the hemorrhagic appearance)
- No villi
Clinical Features of Choriocarcinoma
- Extreme elevations of b-hCG levels
- Presenting symptoms include abnormal uterine bleeding, hemorrhage from metastases – Common sites of mets include lung, vagina, brain, liver, kidney
- Overall prognosis is very good, with >90% remission with current chemo regimen
