Gestational Trophoblast Disease

Question 1

Abnormal Placental Implantation - Ectopic Pregnancy

Answer 1

• 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.

Question 2

Gestational Trophoblastic Disease

Answer 2

• 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

Question 3

The Moles

Answer 3

• 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

Question 4

Complete Hydatidiform Mole (CHM)

Answer 4

• Most common type of GTD
• Presenting symptoms include

– rapidly enlarging uterus

– vomiting,

– hypertension,

– hyperthyroidism,

– extreme elevation of beta-hCG

– “snowstorm” on ultrasound

Question 5

Answer 5

• CHM
• Abundant tissue
• Grossly identifiable, grape-like “vesicles”, up to 2 cm in diameter = hydropic villi

Question 6

Answer 6

• 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)

Question 7

Genetic Composition of CHM

Answer 7

• 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

Question 8

Clinical Behavior of CHM

Answer 8

• 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

Question 9

Partial Hydatidiform Mole (PHM)

Answer 9

• 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

Question 10

Answer 10

• PHM
• Not as much tissue as a CHM
• Normal and hydropic appearing villi
• May have recognizable embryo/fetus

Question 11

Answer 11

• 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

Question 12

Genetic Composition of PHM

Answer 12

• • 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

Question 13

Clinical Behavior of PHM

Answer 13

• 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

Question 14

Complete vs. Partial Mole

Answer 14

• 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

Question 15

Invasive Mole

Answer 15

• 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

Question 16

Choriocarcinoma

Answer 16

• 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)

Question 17

Answer 17

• choriocarcinoma
• Variable size
• Very friable (crumbly), hemorrhagic, necrotic
• Infiltrating borders

Question 18

Answer 18

• choriocarcinoma
• Solid sheets of cytotrophoblast admixed with syncytiotrophoblast infiltrate myometrium
• Extensive vascular invasion (the cause of the hemorrhagic appearance)
• No villi

Question 19

Clinical Features of Choriocarcinoma

Answer 19

• 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