Gestational Trophoblastic Disease Flashcards
What is the definition of gestational trophoblastic neoplasia?
GTD that requires chemotherapy
List the 4 types of GTN
Invasive mole
Choriocarcinoma
placental site trophoblastic tumour
epithelioid trophoblastic tumour
What are the management steps for GTN?
refer to MDT Investigations - baseline bloods FBC, TFTs, U&Es, COags Imaging - CXR, Pelvic USS, consider MRI FIGO risk assessment Chemotherap
What types of chemotherapy are used for GTN treatment
Single agent if low risk
- Methotrexate + folic acid
- continue until hCG is normal for 3 cycles
Multiple agents if high risk of resistant to methotrexate
- Methotrexate, Etoposide, Actinomysin
How do you follow up GTN depending on Low/High risk
Low risk - Monthly HCG for 12 months
High risk - monthly hCG for 2 years
PSTT or ETT - monthly hCG for 5 years
what is the karyotype of complete molar pregnancies and what percentage persist?
46 XX 26% persist
What is the karyotype of a partial molar pregnancy and what percentage persist?
69XXY or 69XYY
5% persist
How does a complete molar pregnancy form?
usually occurs when the ovum contains no genetic material and is fertilised by one sperm that replicates (75%) or by 2 sperm (25%)
How does a partial molar pregnancy form?
when an egg is fertilised by two or more sperm (triploid)
how does persistent GTD present?
PV bleeding, abdominal pain, swelling
persistent hCG rise
what clinical scenarios does gestational choriocarcinoma occur after?
after a complete molar pregnancy (25-50%)
within 12 months of a non molar abortion (25%)
after a term pregnancy (25-50%)
What are the symptoms of gestational choriocarcinoma?
abdominal pain and swelling
PV bleeding
symptoms from a distant metastasis; liver, lung, brain
when should you suspect molar pregnancy?
early pregnancy: - USS features - PV bleeding - Hyperemesis - abnormally high HCG levels midtrimester: - hyperthyroidism - PET - pulmonary or neurological symptoms
what investigations do you need to prepare for suction D&C for molar pregnancy?
TFTs
G&H (partial moles can contain fetal RBCs)
LFT, COag, CXR
baseline serum bHCG
What extra tests can be performed to assess partial vs complete molar pregnancies?
p57
karyotype
how long do you have to keep testing BHCG for partial vs complete molar pregnancies?
partial - after 3 consecutive normal results
complete - monthly for 6 months after a negative result following evacuation
how long do you have to keep testing BHCG for partial vs complete molar pregnancies?
partial - after 3 consecutive normal results
complete - monthly for 6 months after a negative result following evacuation
what counselling should you give once bhCG have normalised to patients who have had molar pregnancies?
Can now try for another pregnancy (given the hCG F/U has been appropriate for the type of molar pregnancy)
Fertility rate is not affected
1:70 risk of a repeat molar pregnancy (recommend early USS, bhCG 6/52 following the completion of any future pregnancy normal or not)
what counselling should you give once bhCG have normalised to patients who have had molar pregnancies?
Can now try for another pregnancy (given the hCG F/U has been appropriate for the type of molar pregnancy)
Fertility rate is not affected
1:70 risk of a repeat molar pregnancy (recommend early USS, bhCG 6/52 following the completion of any future pregnancy normal or not)
what pattern of bHCG would indicate persistent disease?
Rise - greater than 10% rise in bHCG levels over 2 weeks (3 consecutive hCG)
plateau - less than 10% fall in bHCG over 3 weeks (4 consecutive hCG)
elevated levels at 6/12
in some cases a second D&C may be requiring after D&C for molar pregnancy, what should you consider?
Still a 70% chance of requiring chemotherapy
8% chance of uterine perforation
2nd D&C not recommended if bHCG >5000
What medications should be considered for a evacuation?
Prostaglandin to ripen cervix (misoprostol pre op)
Avoid oxytocinon until after evacuation
Anti D if Rh Negative mother
Are mirenas recommended after molar pregnancy?
No, to reduce perforation risk
what time frame should women wait after receiving chemo for invasive molar pregnancy?
12 months due to increased risk of early pregnancy otherwise
when and why would a hysterectomy be considered for a woman who has had a molar pregnancy?
If family is complete
if GTN confined to the uterus
note chances of needing chemotherapy after a hysterectomy are 3-10% so reduced but not eliminated
How is it decided whether patients need 1 or 2 agents for treatment of persistent GTD?
FIGO scoring
Score of <6 = methotrexate only/single agent
Score of >7 = Multiple agents - EMA-Co
How is it decided whether patients need 1 or 2 agents for treatment of persistent GTD?
FIGO scoring
Score of <6 = methotrexate only/single agent
Score of >7 = Multiple agents - EMA-Co
describe the methotrexate regimen required for persistent GTD
Methotrexate 1mg/kg given on D1,3,5,7
Folic acid 15mg given D2,4,6,8
Cycles given 2 weekly
Treat until tHCG undetectable +2-3 cycles
What drugs make up EMA-Co?
Etoposide Methotrexate Actinomycin cyclophosphamide vincristine
What are 3 side effects of methotrexate treatment?
mild allergy
minor mucositis
rarely - pleuritis, hepatitis, serositis
List 5 side effects of EMA-Co
Myelosupression Hepatic dysfunction Neuropathy, constipation Bladder irritation Risk of secondary malignancy
Generally, what is the prognosis for persistent GTD?
Prognosis worse after term pregnancy
prognosis depends on sites of metastases if present
Low risk
- 99% cure rate
High risk
- 80% ish cure rate
- mortality related to initial complications - cerebral bleeding
What is the risk of relapse following chemotherapy treatment for persistent GTD?
3.5%
of this, 75% occur in first year, 85% within 2 years
For the first 2 years following chemotherapy for persistent GTD how frequently does hCG levels need to be checked?
Q1 monthly
change to Q2 monthly after 3 years, Q3 monthly at 5 years
What are the characteristic histopathological features of a molar pregnancy?
p57 stain negative
hydropic chorionic villi
hyperplastic trophoblastic tissue
What is the risk of recurrence of complete molar pregnancy?
1:70
How would you describe the genetics of a molar pregnancy to a patient?
Molar pregnancies have an imbalance, or excess of paternal to maternal genetics.
In the case of complete molar pregnancy - there is no maternal DNA as the oocyte is empty of DNA
The oocyte is then fertilised by one or two sperm. This makes a 46XX or 46XY (less commonly) karyotype
How would you describe the genetics of a molar pregnancy to a patient?
Molar pregnancies have an imbalance, or excess of paternal to maternal genetics.
In the case of complete molar pregnancy - there is no maternal DNA as the oocyte is empty of DNA
The oocyte is then fertilised by one or two sperm. This makes a 46XX or 46XY (less commonly) karyotype
How would you describe the genetics of a molar pregnancy to a patient?
Molar pregnancies have an imbalance, or excess of paternal to maternal genetics.
In the case of complete molar pregnancy - there is no maternal DNA as the oocyte is empty of DNA
The oocyte is then fertilised by one or two sperm. This makes a 46XX or 46XY (less commonly) karyotype
Whereas a partial molar pregnancy has 2:1 ratio of paternal to maternal genetic information due to the fertilisation of one oocyte by two sperm
What are the USS features of a complete molar pregnancy?
polypoid mass between 5 and 7 weeks gestation
thickened cystic appearance to villous tissue with no identifiable gestational sac after 8/40
What is the USS appearance of a partial molar pregnancy?
an enlarged placenta
cystic changes within the decidual reaction
empty sac
What does ‘imprinting’ refer to in genetics and what role does this have in GTD?
- imprinting (parent of origin effect) refers to expression of genetic trait based on whether the gene is inherited from one parent or other
- paternal genes have more of an impact on placental growth, while maternal genes have more control over fetal growth
- in GTD the excess paternal genes result in abnormal placentation
Is anti D required fro all molar pregnancies?
No just partial molar pregnancies
But if at D&C the diagnosis is not established then give Anti D anyway
Is anti D required for all molar pregnancies?
No just partial molar pregnancies - complete moles do not contain any fetal tissue therefore do not express Rh antigen
But if at D&C the diagnosis is not established then give Anti D anyway
What is the theoretical issue with using oxytocic agents in molar pregnancies?
The contraction of the myometrium may force tissue into the venous spaces at the site of the placental bed, this may result in dissemination or embolisation of the placental tissue. In theory this could increase the risk of metastatic disease
In the event of life threatening bleeding oxytocinon can be used
What is the incidence of GTD unrecognised prior to removal of tissue?
2.7%
What is the follow up for complete molar pregnancy?
tumour hCG weekly until 2 normal levels, then monthly thereafter
if tHCG normal within 56 days of D&C then for a total of 6 months from D&C
if tHCG NOT normal within 56 days then 6 months from normal result
What is PSTT?
Placental site trophoblastic tumour
Very rare
1/3 present with metastases
can present with nephrotic syndrome and hyperprolactinaemia
PSTT and ETT make up 0.2% of all GTD
What is ETT?
Epithelioid trophoblastic tumour - extremely rare form of GTN
1/3 present with metastases
PSTT and ETT make up 0.2% of all GTD
What is the follow up for partial molar pregnancy?
once tHCG has returned to normal on two samples at least 4 weeks apart (so monthly tHCG until 2 negative)
