GESTATIONAL TROPHOBLASTIC DISEASE Flashcards
T/F: GTD can therefore occur with both intra-uterine and extra-uterine pregnancies
T
Definition of GTD
spectrum of proliferative abnormalities of the trophoblast associated with pregnancy.
These diseases are unique in that they secrete hCG which is the tumour marker
2 parts of the spectrum of GTD
- Hydatidiform mole
- Gestational trophoblastic neoplasia
The 2 types of hydatidiform mole
Partial and complete
The 4 forms of gestational trophoblastic neoplasia
- Invasive mole
- Placental site trophoblastic tumour
- Epitheloid trophoblastic tumour
- Choriocarcinoma
Risk factors for GTD
Age less than 15 and over 35 years
Previous molar pregnancy
Increased number of spontaneous abortion
Diet – low protein, low fat and vitamin A deficiency
3 morphologic characteristics of hydatidiform mole
- Mass of vesicles
- Loss of fetal blood vessels
- Hyperplasia of the trophoblast
T/F: There is fetal or embryonic tissue in complete hydatidiform mole
F
T/F: There is fetal or embryonic tissue in partial hydatidiform mole
T
Nature of hydatidiform swelling of chorionic villi complete mole
Diffuse
Nature of hydatidiform swelling of chorionic villi partial mole
Focal
Nature of trophoblastic hyperplasia in complete mole
Diffuse
Nature of trophoblastic hyperplasia in partial mole
Focal
Scalloping of chorionic villi is found in which type of mole
Partial
T/F: Both types of moles have trophoblastic stromal inclusions
F. Seen only in partial mole
What is the karyotype of complete mole
46XX; 46XY
All chromosomes are paternal in origin
What is the karyotype of partial mole
69XXX; 69XXY; 69XYY
Extra set of chromosomes is paternal in origin
Which type of mole is p57 negative
Complete mole
Why are the 2 types of hydatidiform mole not p57 positive
p57 is expressed only on the maternal allele therefore, the complete mole that is entirely composed of paternal chromosomes are negative for p57
What is the risk of gestational trophoblastic neoplasia with complete mole
15 - 20%
What is the risk of gestational trophoblastic neoplasia with partial mole
1 - 5%
List 7 clinical presentations of hydatidiform mole
- Abnormal bleeding in early pregnancy
- Hyperemesis gravidarum
- Preeclampsia before 20 weeks
- Lower abdominal pain
- Large-for-dates uterus
- Ovarian enlargement
- Expulsion of vesicles
With molar pregnancy, the uterus is larger than the period of amenorrhea in –% of cases
50%
With molar pregnancy, the uterus corresponds to the period of amenorrhea in –% of cases
25%
With molar pregnancy, the uterus is smaller than the period of amenorrhea in –% of cases
25% due to inactive or dead mole
2 reasons why the uterus is doughy in consistency in molar pregnancy
Absence of amniotic fluid and distension with vesicles
In which of the molar pregnancies are fetal parts seen with fetal heart sounds heard
Partial
Snowstorm appearance on USS is seen in which type of molar pregnancy
Complete
T/F: MRI can be useful in determining extent of trophoblastic disease
T
5 baseline workup in hydatidiform mole
hCG levels
Full blood count
Rhesus typing
Chest x-ray; any metastases?
Pelvic scan : Uterine size and ovarian enlargement
2 treatment modalities in molar pregnancy
- Suction curretage
2.Hysterectomy with Salpingectomy if patient has completed her family
T/F: Suction curretage is preferably done under USG guidance
T
T/F: Suction curretage is aided by oxytocic infusion started before the procedure.
F. oxytocin infusion after the start of the evacuation
serum HCG reach normal levels after — weeks post evacuation
8 – 12 weeks
T/F: 20% of patients with molar pregnancy will develop malignant sequelae (GTN).
T
Patient must be monitored for how long following evacuation or hysterectomy
6 months to 1yr
How is hCG monitored post evacuation in molar pregnancy
Weekly hCG till normal for 3 consecutive values, then monthly for 6-12 months
Frequency of CXR post evacuation in molar pregnancy
Chest x-ray initially and repeat if abnormal or if hCG rises or plateaus
Frequency of pelvic exam post evacuation in molar pregnancy
Pelvic exam every 2 weeks till normal then every 3 months
T/F: Normally the serum HCG is undetected after 3 months of evacuation
T
When is pregnancy allowed post evacuation in molar pregnancy
Pregnancy is allowed if the test remains negative for more than one year
How long should contraception last post evacuation in molar pregnancy
At least 1yr
Why is COC the preferred contraceptive post evacuation in molar pregnancy
COCs preferred because it suppresses endogenous LH/FSH, which may interfere with hCG measurement at low levels
5 reasons to consider chemotherapy in molar pregnancy
- Metastatic disease is present
- Choriocarcinoma is diagnosed on histology
- hCG level still elevated 6 months after molar evacuation
- hCG levels rise >10% for 3 values over2 weeks
- hCG levels plateaus for 4 consecutive values over 3 weeks
Definition of gestational trophoblastic neoplasia
A group of malignant neoplasms that consist of abnormal proliferation of trophoblastic tissue.
GTN may follow hydatidiform mole in –% of cases
50%
GTN may follow normal pregnancy in –% of cases
25%
GTN may follow ectopic pregnancy or incomplete abortion in –% of cases
25%
Pathologic features of invasive mole
- Trophoblastic hyperplasia
- Swollen villi
- Myometrial invasion
3 Clinical features of invasive mole
- Irregular postmolar vaginal bleeding
- Persistent hCG elevation
- <15% symptoms of lung/vaginal mets
3 Pathologic features of choriocarcinoma
- Mixture of cytotrophoblast and syncytiotrophoblast hyperplasia, no villi
- Myometrial invasion and metastatic potential
- Haemorrhage, Necrosis
Clinical features of choriocarcinoma
- Irregular postmolar vaginal bleeding
- Persistent hCG elevation
- Metastases and associated symptoms
Pathological features of placental site trophoblastic tumor
- Diploid, No villi, IT hyperplasia
- Less haemorrhage and necrosis
- High potential for lymphatic invasion and mets
- Focal hCG production
Clinical features of placental site trophoblastic tumor
- Low serum hCG
- Enlarged uterus
- hCG levels normal to 1,000 mIU/mL
- Metastases and associated symptoms
Pathological features of Epitheloid trophoblastic tumour
- IT nodules
- Extensive necrotic tissue,
Preserved blood vessel structure,
Hemorrhage and metastases rare
Which of the GTN has swollen villi as a pathologic feature
Invasive mole
Which GTN has mixture of trophoblast and syncytiotrophoblast hyperplasia as a pathological feature
Choriocarcinoma
The 2 types of GTN that has myometrial invasion as pathologic features
Invasive mole and choriocarcinoma
Which type of GTN has high potential for lymphatic invasion and mets
Placental site trophoblastic tumor
Which type of GTN has focal hCG production
Placental site trophoblastic tumor
Which type of GTN does not have necrosis as a pathologic feature
Invasive mole
Which of GTN has extensive necrotic tissue as a pathologic feature
Epitheloid trophoblastic tumor
Which type of GTN has preserved blood vessel structure as a pathologic feature
Epitheloid trophoblastic tumor
The two types of GTN that does not have villi as a pathological feature
Choriocarcinoma and placental site trophoblastic tumor
In which of the GTN is hCG normal to 1000mIU/mL
Placental site trophoblastic tumor
Which of the GTN has <15% of symptoms of lung/vaginal mets
Invasive mole
6 risk factors for GTN
Maternal age, <20 and >40
Recurrent abortions
Uterus larger than gestational age
hCG levels more than 100,000 IU/L after evacuation
Theca lutein cyst more than 6cm
?? C/S
A condition in which hydatidiform mole, with hydropic villi and proliferating trophoblast, has invaded the myometrium through the tissue or veins
Invasive mole
T/F: With invasive mole, molar villi may be observed on the uterine serosa and extrauterine tubal and ovarian moles can occur
T
T/F: Invasive moles are less hydropic, and trophoblastic proliferation is easily seen
T
– % of women with complete moles may develop choriocarcinoma
2%
Metastasis to the lungs, brain, liver, pelvis, vagina, kidney, intestines, and spleen seen in choriocarcinoma is due to
Direct invasion of the myometrium and vasculature
4 immunohistochemical markers for confirming histologic diagnosis of CCA
hCG, inhibin a, human placental lactogen (hPL) and cytokeratin
Staining pattern of immunohistochemical markers in choriocarcinoma
- hCG and inhibin a in the trophoblast
2.human placental lactogen (hPL) and inhibin a in intermediate trophoblast - cytokeratin in all trophoblast cells
In choricarcinoma histology, intermediate trophoblast stains strongly for – and –
human placental lactogen and inhibin A
In choriocarcinoma histology, trophoblast stains strongly for – and –
hCG and inhibin A
The immunhistochemical marker that stains strongly in all trophoblast cells of choriocarcinoma
Cytokeratin
T/F: PSTT lesions are usually diploid and monomorphic, developing from placental implantation site intermediate trophoblast after a normal or aborted uterine pregnancy
T
T/F: PSTT lesions contain primarily mononuclear intermediate trophoblast without chorionic villi that infiltrates the uterine wall in sheets or cords between myometrial fibres
T
PSTT contain –, –, – and – for immunohistochemical diagnosis
Cytokeran, hPL, inhibin A and Mel-CAM
Rare malignant tumour that arises from neoplastic transformation of chorion-type intermediate trophoblast
Epithelioid trophoblastic tumor
Lesions appear as nodules of mononuclear intermediate trophoblast, surrounded by hyalinized extracellular matrix within extensive necrotic tissue and with preserved blood vessel structure
Epithelioid trophoblastic tumor
Intra-tumour haemorrhage and metastases are rarely observed in which GTN
Epithelioid trophoblastic tumor
FIGO criteria for diagnosis of postmolar GTN
When the plateau of hCG lasts for four measurements over a period of 3 weeks or longer; that is, days 1, 7, 14, 21
When there is a rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; days 1, 7, 14
When the hCG level remains elevated for 6 months or more
If there is a histologic diagnosis of choriocarcinoma
T/F: hCG monitoring is not recommended for GTN after non molar pregnancy
T
Clinical presentations of GTN after non molar pregnancy
abnormal vaginal bleeding;
bleeding from metastatic sites in the abdomen, lung, or brain;
pulmonary symptoms; and
neurological signs from spine or brain metastasis
FIGO stage 1 of GTN
Gestational trophoblastic tumours strictly confined to the uterine corpus
FIGO stage 2 of GTN
Gestational trophoblastic tumours extending to the adnexa or to the vagina, but limited to the genital structures
FIGO stage 3 of GTN
Gestational trophoblastic tumours extending to the lungs, with or without genital tract involvement
FIGO stage 4 of GTN
All other metastatic sites
Low risk score for FIGO prognostic scoring of GTN
7
High risk score for FIGO prognostic scoring of GTN
> or = 7
T/F: Non metastatic and low risk metastatic GTN (Stage I and Stages II–III with scores <7) can be treated with single agent chemotherapy
T
T/F: High risk metastatic disease (Stage IV and Stages II–III with scores ≥7) should be treated with multi-agent chemotherapy
T
Patient workup for treatment of GTN
FBC including platelet count
Clotting studies
hCG level
Renal and liver function tests
Chest X-ray
T/F: Patients with low-risk GTN should be treated with one of the single agent methotrexate or actinomycin D protocols
T
T/F: The overall complete remission rate is close to 100% for low risk GTN
T
Chemotherapy should be changed to the alternative single agent in low risk GTN if
there has been a good response to the first agent but the hCG level plateaus above normal during treatment
if toxicity precludes an adequate dose or frequency of treatment
With low risk GTN multi-agent chemotherapy as for high-risk disease should be initiated
If
there is an inadequate response to the initial single agent
If there is significant elevation in hCG level
If there is development of metastasis
if there is resistance to sequential single-agent chemotherapy
With low risk GTN multi-agent chemotherapy as for high-risk disease should be initiated
If
there is an inadequate response to the initial single agent
If there is significant elevation in hCG level
If there is development of metastasis
if there is resistance to sequential single-agent chemotherapy
T/F: After the hCG level has returned to normal,
consolidation with 2–3 more cycles of chemotherapy to decrease the chance of recurrence
T
The 2 single agent chemotherapy regimen with methothrexate for low risk GTN
MTX-FA 8-day regimen (1mg/kg MTX intramuscularly on days 1,3,5,7 with Folinic acid 0.1mg/kg or 15 mg orally 24 h after MTX on days 2,4,6,8); repeat every 2 weeks.
MTX 0.3-0.5 mg/kg (max. 25 mg) intravenously or intramuscularly for 5 days every 2 weeks.
The single agent chemotherapy regimen with Actinomycin D for low risk GTN
Actinomycin D pulse 1.25 mg/m2 intravenously every 2 weeks.
Actinomycin D 0.5 mg intravenously for 5 days every 2 weeks
T/F: Etoposide and 5-fluorouracil can be used as single agents in low risk GTN
T
T/F: Single agent chemotherapy regimens can be used to treat high-risk GTN
F
Multiple agent chemotherapy regimens are used to treat high-risk GTN
The most commonly used multiple agent chemotherapy for high risk GTN is
EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine)
T/F: Ultra high risk (score greater than or equal to 12 ) as well as patients with liver, brain, or extensive metastases do poorly when treated with first-line multiple agent chemotherapy
T
For those with massive disease, starting with standard chemotherapy may cause severe marrow suppression leading to
bleeding, septicaemia and multiple organ failure
For those with massive disease,
starting with standard chemotherapy may cause severe marrow suppression leading to
bleeding,
Septicaemia
multiple organ failure
How do you avoid the severe marrow suppression observed with standard chemotherapy for those with massive disease
Start with INDUCTION chemotherapy
This may be avoided by starting with a lower dose and a less intensive regimen, such as etoposide 100 mg/m2 and cisplatin 20 mg/m2 on days 1 and 2, repeated weekly for 1–3 weeks, before starting the usual chemotherapy regimen (INDUCTION)
How do you give EMACO
Given in two regimens, regimen 1 and regimen 2. The two regimens alternate each week.
Regimen 1 for EMACO
Day 1
IV Etoposide 100 mg/m2 over 30 minutes
IV bolus Actinomycin-D 0.5 mg
IV bolus Methotrexate 100 mg/m2 followed by IV 200 mg/m2 over 12 hours
Day 2
IV Etoposide 100 mg/m2 over 30 minutes
IV bolus Actinomycin-D 0.5 mg
Folinic acid rescue 15 mg intramuscularly or orally every 12 hours for four doses (starting 24 hours after beginning the methotrexate infusion
Regimen 2 for EMACO
Day 8
IV bolus Vincristine 1 mg/m2 (maximum 2 mg)
IV Cyclophosphamide 600 mg/m2 over 30 minutes
T/F: Combination chemotherapy in high risk GTN should be given every 2 weeks or as often as toxicity permits until the patient achieves three consecutive normal hCG levels
T
T/F: In the treatment of high risk GTN, after normal hCG levels have been attained, an additional two to four cycles should be administered as consolidation therapy to reduce the risk of relapse.
T
Salvage/second line chemotherapy for high risk GTN
EP-EMA (etoposide, cisplatin, etoposide, methotrexate and actinomycin-D)
TP/TE (paclitaxel, cisplatin/paclitaxel, etoposide)
MBE (methotrexate, bleomycin and etoposide)
ICE (etoposide, ifosfamide, and cisplatin or carboplatin)
BEP (bleomycin, etoposide and cisplatin)
FA (5-fluorouracil, actinomycin-D)
FAEV (floxuridine, actinomycin-D, etoposide and vincristine)
Pembrolizumab (PD 1 inhibitor)
Avelumab(PD-L1 inhibitor)
Gemcitabine
Capecitabine
High-dose chemotherapy with autologous bone marrow or stem cell transplant(still under investigation)
T/F: Repeat dilatation and curretage is indicated for high risk GTN
Repeat dilatation and curettage is generally avoided to prevent morbidity and mortality caused by uterine perforation, haemorrhage, infection, uterine adhesions, and anaesthetic complications
T/F: Radiotherapy has a limited role in GTN
T. except in treatment of brain metastasis
What is the % of relapse in GTN after treatment
3 % of patients will relapse in 1st year, and less than 1 % in subsequent years
Duration of contraception after GTN treatment
Contraception in cases of GTN should continue for 12 months. (COCs preferred)
How is hCG monitored after treatment of GTN
In patients with GTN, after hCG is returned to normal, quantitative hCG levels should be evaluated monthly for 12 months.
T/F: Both PSTT and ETT are less chemo sensitive than choriocarcinoma.
T
T/F: Hysterectomy and salpingectomy is the primary mode of treatment in most cases of PSTT and ETT
T
The most commonly used chemotherapy for PSTT and ETT
EP-EMA
T/F: Fertility preservation is not suitable in diffuse lesions of PSTT and ETT
T
The most significant adverse prognostic factor in PSTT and ETT
Interval from antecedent pregnancy of more than 48 months
T/F: If fertility preservation is desired with PSTT and ETT, especially in a localized lesion, conservative management such as uterine curettage, hysteroscopic resection, and chemotherapy may be considered
T
Criteria for appropriate patient selection for surgical resection of isolated lung nodule
Good surgical candidate,
controlled primary malignancy,
no other evidence of metastatic disease,
pulmonary metastasis confined to one lung,
hCG <1,000.
T/F: With brain metastases, Whole brain irradiation performed, 3,000 cGy at 200 cGy fractions can achieve cure rates of 50–80 %
T
T/F: Cure rates for both low risk and non metastatic disease states approach 100 %.
T
—% of low risk patients with GTN will develop initial resistance, but will reach 90 % cure rate with single agent chemotherapy
20%
—% of low risk patients with GTN will require multi-agent chemotherapy.
10%
T/F: 80–90 % of high risk GTN patients will have curative therapy
T
—% of high risk GTN patients will relapse or fail first line therapy
30%
The metastasis in GTN with the lowest survival rate
Gastrointestinal tract metastasis has lowest survival rates at 50 %
With metastatic disease for PSTT, the curative rate is
50–60 %
Ideal time for USS in pregnancy after GTN
10 weeks
When is hCG measured after pregnancy following GTN and why
An hCG measurement 6 weeks after completion of the pregnancy to exclude occult trophoblastic neoplasia
T/F: Pregnancy during treatment should be monitored with USG at 6weeks and 10weeks
T
T/F: In pregnancy following GTN if placenta is fine at 10weeks there is little risk for recurrence
T
