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46 Cards in this Set

  • Front
  • Back
What is the common cell/tissue of origin for all GTD?
Trophoblast
List the non-malignant GTDs
Hydatidiform Mole
Partial
Complete
Placental nodule
Exaggerated Placental site
List the malignant GTDs (GTN)
Invasive Mole
Choriocarcinoma
Placental site trophoblastic tumour
Epithelioid trophoblastic tumour
What is the incidence of GTD?
0.1% (1/1000 pregnancies)

(may be higher in NA indians and hispanics)
1) List the two main RFs for GTD

2) List other RFs for GTD
1)
Maternal age (old>>young>neither)
(>35a, >45a=1%, >50a=15-30%)
Previous molar pregnancy
(x1=1%, x2=25%)

2)
Paternal age
Smoking (15 cigs / d)
Non- "O" bloodtype
Infertility
Nulliparity
?ART
?vitamin A
True or False:
Complete or partial moles:

1) Are non-invasive, localized tumours that develop from aberrant fertilization
1) True
What percentage of GTD is due to hydatidiform mole?
90%
True or False:
1) GTN (malignant GTD) develops primarily from/following molar pregnancies

2) GTN can develop following a normal pregnancy
1) True (90%)

2) True (PSTT, ETT, choriocarcinoma)
Approximately what percentage of GTN, including metastatic GTN, is curable?
85-100%
In general, in the zygote, maternal DNA contributes more to the formation of:
a) fetus or placenta

and paternal DNA contributes more to the formation of
b) fetus or placenta
a) fetus
b) placenta
What percentage of hydatidiform moles are:

a) complete
b) partial

c) Malignant GTN is more likely to occur following what type of molar pregnancy?
a) 90%
b) 10%

c) complete (15-20%);
List histopathological attribues of:

a) complete mole

b) partial mole
a)
no fetal tissue
diffuse hydropic villi
variable/increased trophoblastic proliferation
p57kip2 negative

b)
fetal tissue present
focal trophoblastic edema
focal/minimal trophoblastic proliferation
p57kip2 positive
Discuss the cytogenetics of

a) Complete Mole

b) Partial Mole
a)
90% XX, 10% XY, (YY is lethal)
all DNA is paternal (imprinted)
result from dispermy or duplication

b)
90% are triploid (XXX, XXY, XYY)
mixture of maternal and paternal DNA - thought to arise from haploid egg with dispermy or duplication of paternal haploid complement
True or false:
a) Nuclear DNA from complete moles is always of paternal origin?

b) describe the rare situation when nuclear DNA is of biparental origin in a complete mole
a) False

b)
familial mole
rare autosomal recessive disorder
(women with this disorder have a very high rate of recurrence and development of persistent GTN)
What does the presence of Y-chromatin mean with regards to the prognosis of a molar pregnancy?
More likely to be malignant (invasive mole, choriocarcinoma)
a) What are other medical conditions/diagnoses can be associated with a molar pregnancy?

b) What is the average gestation that complete moles are now diagnosed?
a)
Hyperemesis gravidarum
Large for dates
Hyperthyroidism
Theca lutein cysts
Pre-eclampsia

b) 12 weeks
How are partial moles typically diagnosed?
Pathology review of products obtained from D&C for miscarriage
What can early molar pregnancies be confused with?
Hydropic abortuses
Should Rh- women be given WinRho following evacuation of a molar pregnancy?
Yes - in case it is a partial mole and there is fetal tissue present.
a) What is the treatment for molar pregnancy?

b) A patient undergoes suction D&C and anesthesia tells you they are having problems with ventilation and mantaining O2 saturation - what has happened?
a) Suction D&C
(rarely primary hysterectomy)

b) Trophoblastic embolization
a) What percentage of patients with complete moles will be diagnosed eventually with GTN?

b) What percentage will have metastatic disease?
a) 15%

b) 75% local, 25% mets
a) How are patients monitored for development of invasive disease (i.e. GTN) following molar evacuation?

b) When is persistant (malignant) disease diagnosed?
a)
Weekly bhCG until undetectable x 3.
Monthly for 6 months
Avoid pregnancy for 6 months after negative bhCG (time limit depends on source)

b)
1. Plateau of β-hCG lasts for four measurements over a period of 3 weeks or longer (days 1, 7, 14, and 21).
2. Ri se of β-hCG of 3 weekly consecutive measurements or longer, over a period of 2 weeks or more (days 1, 7, and 14).
3. β-hCG remains elevated for 6 months or more.
4. Histologic diagnosis of choriocarcinoma.
What has prophylactic chemotherapy (1 dose actinomycin D given at time of suction curettage) for molar pregnancy been shown to do?
Reduce locally invasive and metastatic disease (5% versus 20%)

[the use of prophylactic chemo in this situation is controversial]
List high-risk features of a molar pregnancy that may indicate prophylactic chemotherapy following suction D&C
bhCG > 100,000
Theca Lutein cysts > 6cm
Enlarged uterus
What contraceptive methods for post-molar women are:

a) recommended
b) not recommended
a)
hormonal
COCP, DMPA

b) IUD (copper or Mirena) - can perf with invasive disease
A D&C is done and pathology reports a molar pregnancy. bhCG has plateaued and ultrasound indicates an endometrial mass ?retained products. Is D&C indicated?
Controversial. Repeat D&C for post-molar GTN is not standard practice but may be considered in some circumstances.
Describe the spectrum of malignant GTN
Post-molar:
Invasive mole (chorionic villi), Choriocarcinoma (no villi)
PSTT, ETT (more rare)
Post-non molar:
Choriocarcinoma
PSTT, ETT
When considering choriocarcinoma versus invasive mole, what are relevant differences?
choriocarcinoma is highly malignant and often presents with mets already established
still amenable to chemotherapy
a) Where are the most common sites for mets for GTN?

b) Is biopsy of suspected GTN-mets not recommended?
Lung (70%), Vagina (30%), pelvis, brain, liver, GI

b) No - highly vascular
How is GTN treated?
Chemotherapy - single versus multi-agent based on risk factor score (WHO scoring system)

[Hysterectomy for invasive mole/choriocarcinoma is controversial... if childbearing complete, can consider.]
How is GTN staged?
Stage I
Disease confined to uterine corpus
Stage II
GTN outside of uterus but confined to genital structures
Stage III
Lung mets
Stage IV
All other mets
List factors in the WHO scoring system that are used to differentiate low from high risk GTN
Age
Antecendant gestation (normal preg, mole, ectopic)
Previously failed chemo?
Time since preg (months)
Mets: site
Mets: number
bhCG value
Size of tumour
If GTN is suspected, what investigations should be ordered?
CT chest/abdo/pelvis
CT brain
True or False: Choriocarcinoma following a term pregnancy has a higher mortality rate?
True - delay in diagnosis, more likely to have mets (e.g. brain mets)
a) What are first-line agents for low-risk GTN?

b) What is given with methotrexate to rescue hematopoetic cells?
a)
Methotrexate (IM better than IV)
q7d 50mg/m2 until bhCG negative
Actinomycin D

b) Folinic acid
What is given for low-risk GTN that fails first line therapy?
Actinomycin D (if MTX was used, otherwise MTX if acintomycin D was given)
What is the therapy for high-risk GTN?
EMA/CO
etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine (oncovin)
a) What percentage of post-pregnancy GTN is PSTT?

b) When are they typically diagnosed?

c) what is the treatment?
a) 0.2% (very rare)

b) Months to years after the antecedent pregnancy

c) Hysterectomy
Histology of Invasive Mole
whole chorionic villi with excessive trophoblastic overgrowth and invasion.
Histology of Gestational Choriocarcinoma
Sheets of anaplastic cytotrophoblast cells and syncytiotrophoblasts with prominent hemorrhage, necrosis and vascular invasion.

No formed chorionic villi (different than in molar pregnancy)
Histology for placental site trophoblastic tumor
intermediate trophoblasts at the placental site
Histology for epithelial trophoblastic tumor
neoplastic transformation of chorionic type intermediate trophoblasts.
Treatment for low risk (WHO score <7) GTN
Single-agent methotrexate is the most common treatment, and complete response rates ranging from 67 to 81 % have been reported.
Side effects of methotrexate treatment
methotrexate is a folic acid antagonist that inhibits DNA synthesis. Mild stomatitis is the most common side effect, but other serosal symptoms, especially pleurisy, develop in up to one quarter of patients treated with low-dose methotrexate. Pericarditis, peritonitis, and pneumonitis are infrequent.
Chemo for high risk GTN (WHO Score >=7)
Etoposide, methotrexate, and dactinomycin (actinomycin D) alternating with cyclophosphamide and vincristine (Oncovin) (EMA/CO)

chemotherapy is a well-tolerated and highly effective regimen for high-risk GTN.
What is the risk of a mole in a subsequent pregnancy
Women having a pregnancy affected by a histologically
confirmed complete or partial mole may be counseled that the risk of a repeat mole in a subsequent pregnancy approximates 1 %

Most will be of the same type of mole as the preceding pregnancy.

Although chemotherapy for GTN induces menopause on average 3 years earlier, fertility is not thought to be greatly affected