Gestational Trophoblastic Disease

Question 1

Gestational Trophoblastic Disease

Answer 1

 Gestational Trophoblastic Dx (GTD) is a clinical spectrum encompassing all abnormal growth and
proliferation of placental (trophoblasts) that continue even beyond end of pregnancy
 Occurs when trophoblastic tissue proliferates abnormally and aggressively, producing human chorionic
gonadotropin (hCG), a serum peptide hormone, essential for GTD diagnosis, management, & surveillance
GTD arise from cells of conception and form a range of related conditions, from generally benign -partial
hydatidiform mole through to aggressive malignancies of choriocarcinoma, invasive moles and placental site
trophoblast tumours

Question 2

Risk factors for GTD

Answer 2

 Cause of GTD is unknown, but its associated with
a) Extremes of maternal age- younger than 20yrs & older than 40yrs of age.
b) Previous molar pregnancy.
c) Diet may play a causative role- less consumption of β-carotene (a retinoid) and folic acid (folate deficiency)
d) Ethnicity - Common in women of Asian origin
e) Blood group B is associated with recurrent GTD
f) Blood group-Type A women impregnated by type O men (AO) have 10 times the risk of choriocarcinoma
compared with AA coupling
g) Smoking

Question 3

Benign/premalignant GTD

Answer 3

ydatidiform molar pregnancy (most common). Arises from
villous trophoblast
 Complete mole
 Incomplete (partial) mole
NB: 20% of pts. with benign molar disease develop malignant dx

Question 4

Malignant disease/GTN

Answer 4

Invasive trophoblastic disease (“chorioadenoma destruens”).
 Persistent hydatidiform mole
 Choriocarcinoma- Arises from previllous trophoblast
 Placental site trophoblastic tumors- Arises from extravillous trophoblast
 Malignant GTN, may be
1. Non-metastatic
2. Metastatic GTN can be subdivided depending on sites of metastases into
i. Low risk / good prognosis
o Disease is present < 4 months duration
o Initial serum hCG level < 40,000 mlU/ml
o Metastasis limited to lung and vagina
o No prior chemotherapy
ii. High risk / poor prognosis groups
o Long duration of disease (> 4 months)
o Initial serum hcG > 40,000 miU/ml
o Brain / liver metastasis regardless of hcg titre
o Failure of prior chemo/to single-agent chemo
o Choriocarcinoma after a full-term delivery
o WHo score ≥ 7

Question 5

trophoblast

Answer 5

Trophoblats maintains implantation of blastocyst in endometrial stroma and establishes maternal-fetal circulation
 Inner layer – cytotrophoblast
 Outer layer – syncytiotrophoblast
 Intermediate layer – intermediate trophoblast
 Previllous trophoblast – early proliferation prior to development of chorionic villi
 Unique features
 Derived from fetal tissue - invades maternal tissue
 Elaborates steroid / protein hormones
3. Human Chorionic Gonadotropin (HCG)
4. Human Placental Lactogen (HPL)
 Spontaneous regression occurs in– 80%
 Persist or metastasize – 15-20% (require chemo)
 Cause choriocarcinoma, 1
st disseminated solid tumor cured with chemotherapy

Question 6

HYDATIDIFORM MOLE (Syn: Vesicular mole)

Answer 6

Hydatidiform Mole (Arises from villous trophoblast)
 Commonest type of GTD
 Latin word; “Hydatis” = watery vesicles - Moles = shapeless mass
 Abnormal proliferation of the syncytiotrophoblast and replacement of normal placental trophoblastic tissue by
hydropic placental villi
 Arise from fetal tissue at stage prior to formation of germ layers and is composed of both syncytiotrophoblast and
cytotrophoblast cell
 Trophoblastic tissue produces human chorionic gonadotropin (HCG),and amount produced correlates with
amount of tissue present
 Classified as complete or partial moles based on degree of histological changes, karyotypic differences, and
the absence or presence of embryonic elements
 Complete hydatidiform mole is a benign neoplasia of the chorion with malignant potential to GTN

Question 7

Partial mole

Answer 7

Partial mole is a triploid with one set of maternal and two sets of paternal
chromosomes, usually 69 XXY
 Dispermic fertilization of normal ovum
 These rarely metastasize & only rarely need chemotherapy because of plateaued or rising β-hCG levels
 Has identifiable fetal or embryonic structures
 Macroscopically often resembles the normal products of conception with an embryo initially present which
usually dies by week 8–9

Question 8

Histology of partial mole

Answer 8

Histology of partial mole shows less
swelling of chorionic villi (Hydropic villi)
than in a complete mole & there may be
only focal changes. Fetal vessels are present &
syncytiotrophoblastic tissue exhibits less striking
hyperplasia

Question 9

Clinical features of Partial mole

Answer 9

) Vaginal bleeding
2) Uterine size larger than expected
3) Lack of fetal heart tones
4) Excessive nausea/emesis
5) Marked gestational htn, proteinuria
6) Hyperthyroidism
7) Theca lutein cyst (enlarged adnexal masses)
8) Acute hypertensive crisis
9) β-hCG titre is not markedly raised.
10) Make diagnosis with ultrasonography

Question 10

Tx of Partial mole

Answer 10

Once the diagnosis is made and the fetus is not alive, termination of pregnancy is to be done.
 Obstetric mgt is by suction evacuation and histological review; all pts with partial mole shud be followed up by
registration and serial hCG measurement, for 3–6 months after hCG level returns to normal
 Rarely transforms into malignant disease, with an overall risk of 0.5–1% of pts requiring chemotherapy after a
partial mole
 Post-termination follow-up protocol should be same
as outlined in complete mole below

Question 11

Complete hydatidiform mole

Answer 11

‘Classical’ molar pregnancy.
 In general, complete moles have a 46, XX karyotype, the molar Chr are entirely derived partenally.
 Results from fertilization of an “empty ovum” (i.e., without Chr) by a haploid sperm (23X), which then
duplicates to restore diploid chromosomal complement (46, XX), a phenomenon known as androgenesis
 Chromosome complement is most commonly 46XX, resulting from one X chromosome-carrying sperm that
duplicates its DNA, or less frequently 46XY or 46XX from dispermic fertilization
 The higher the ratio of paternal: maternal Chr, the greater is the molar changes.
 Complete moles show 2:0 paternal/maternal ratio whereas partial mole shows 2: 1 ratio.
 H/O prior hydatidiform mole increases the chance of recurrence (1 to 4%)

Question 12

Pathology of hydatidiform mole

Answer 12

Classically complete hydatidiform mole is characterised by death of ovum or failure of embryo to grow
 Principally its a disease of the chorion

Question 13

Gross features of hydatidiform mole

Answer 13

Hydatidiform moles have multiple grape like vesicles filling the uterus.
 No faetal parts, or the amniotic sac are seen.
 Vesicle fluid is interstitial fluid and is almost similar to ascitic or edema
fluid, but rich in hCG
 Vesicle fluids are from secretion from hyperplastic cells and substances from
the maternal blood that accumulate in the stroma of the villi and are devoid of blood vessels

Question 14

Histologic features of hydatidiform mole

Answer 14

Trophoblastic proliferation of both cytotrophoblast ( Langhan’s cells) and syncytiotrophoblast (hyperplasia of
trophoblastic epithelium/tissue)
 Marked thinning of the stromal tissue due to hydropic degeneration
 Absence of fetal blood vessels in the villi

Question 15

Cytogenetic features of hydatidiform mole

Answer 15

In 90%, complete moles are 46, XX, from duplication of one haploid sperm (XX).
 And the rest are from two spermatozoa, i.e. dispermic (and usually XY).
 All chromosomal complements are paternaly derived

Question 16

Ovarian changes of hydatidiform mole

Answer 16

 Bilateral lutein cysts are present in about 50%- due to excessive production of
chorionic gonadotropin as observed in multiple pregn.
 Contained fluid is rich in chorionic gonadotropin as well as estrogen and progesterone.

Question 17

Clinical presentation of hydatidiform mole

Answer 17

 Irregular and abnormal vaginal Bleeding in 1st /early 2nd trimester of preg
 Absent H/O quickening
 Lower abdominal pain
 Pallor
 Constitutional symptoms:
(a) Pt is sick without any apparent reason
(b) Hyperemesis gravidarum- caused by markedly elevated beta-hCG
(c) Thyrotoxic features - Toxemia < 24 wks GA with tremors or tachycardia due to ↑chorionic thyrotropin.
(d) Breathlessness due to pulmonary embolization of trophoblastic cells
 Per abdomen:
 Uterus “large for dates”- not corresponding with period of amenorrhoea
 Uterus is firm, elastic (doughy)- due to the absence of the amniotic fluid sac
 No palpable fetal parts, nor any perception of fetal mvts and no external ballottement can be elicited.
 No fetal heart auscultated
 Per vaginum:
 Failure to elicit internal ballottement
 Vaginal expulsion of grape like vesicles is pathognomonic
 With open cervical os, blood clots or vesicles may be felt instead of membranes.
 Unilateral or bilateral enlargement of ovary (theca lutein cyst)- may be palpable
 Early features of preeclampsia < 20 weeks- due to hypoxic trophoblastic mass, which
releases antiangiogenic factors that activate endothelial damage
 Presence of gestational HTN during 1st
-half of pregnancy should alert the possibility of molar gestation.
NB: 1. Theca lutein cysts (due to increased serum levels of β-hCG & prolactin)
2.. Hyperthyroidism -from placental Thyrotropin like effects of hCG frequently cause serum free thyroxine
(fT4) levels to be elevated and TSH levels to be decreased

Question 18

Investigations and diagnosis of hydatidiform mole

Answer 18

Typical pt is one with H/O amenorrhoea, large for dates uterus with marked
early features of pregnancy and with PVB
1. Full blood count- exclude anaemia
2. ABO and Rh grouping.
3. Clotting profile- platelet count, PT, aPTT, and fibrinogen level, to exclude DIC
4. LFT, U/E + Crea
5. Thyroid function- fT4,fT3 and TSH
6. Ultrasonography- mainstay of trophoblastic disease diagnosis
 Show numerous anechoic cystic spaces described as ‘snowstorm’ appearance - that is diagnostic.
 No fetus or amnionic sac.
 Unilateral or bilateral ovary enlargement due to Theca lutein cysts
7. Quantitative serum β- hCG: Rapidly rising serum hCG (hCG > 100,000
mIU/mL), is suggestive of molar preg.
8. Radiologically:
 Plain X-ray abdomen: For uterine size > 16 wks, there is a neg fetal shadow
 Straight CXR- carried out as routine for evidence of pulmonary embolization
in all forms of GTD.
9. Electrocardiogram if tachycardia is present or if pt is older than 40 yrs
10. Histological of products of conception- for definitive diagnosis

Question 19

Differential diagnosis of hydatidiform mole

Answer 19

Some conditions may be confused with molar pregnancy but estimation of serum hCG and
ultrasonography clarify the conundrum and are diagnostic
1. Threatened abortion.
2. Fibroid or uterine leiomyoma with cystic degeneration.
3. Ovarian tumor with pregnancy.
4. Multiple pregnancy: presence of PE in early months, disproportionally enlarged uterus & ↑hCG titre in urine

Question 20

Complications of molar pregnancy

Answer 20

mmediate:
1. Hemorrhage (concealed or revealed) and shock- due to;
 Separation of vesicles from its attachment to decidua
 Perforating mole causing massive intraperitoneal hemorrhage
 Atonic uterus or uterine injury post evacuation
2. Sepsis: due to lack of amnionitic sac, vesicle degeneration, sloughing decidua and old blood favors nidation of
bacterial growth and operative interference.
3. Perforation of the uterus: due to perforating mole and during vaginal evacuation
4. Pre-eclampsia
5. Acute pulmonary insufficiency due to pulmonary embolization of trophoblastic cells, 4–6hrs post evacuation.
6. Coagulation failure
Late:
1) Malignant transformation to choriocarcinoma- risk ranges betwn 2 to 10% following hydatidiform mole
2) Risk factors for malignant change
a. Patient’s age ≥ 40 or < 20 years irrespective of parity
b. Parity ≥ 3. Age is more important than the parity
c. Serum hCG > 100,000 mIU/mL
d. Uterine size > 20 weeks
e. Previous history of molar pregnancy
f. Thecaleutin cysts: large (> 6 cm diameter)

Question 21

Management of molar pregnancy

Answer 21

 Management principles are:
1. Uterine evacuation of the mole soon after diagnosing.
2. Supportive therapy: correction of anemia and infection, if there is any.
3. Counseling for regular follow-up
 Supportive therapy- pt may be anemic and associated with infection.
1. IVF with R/L is started while waiting for BT
2. BT if the pt is anemic or due to excessive blood loss.
3. Parenteral antibiotic
4. Keep blood for use during evacuation as there is risk of hemorrhage
5. Treat abnormal coagulopathy with FFP and platelet transfusions, as indicated
6. Rarely, for ARDS from trophoblastic embolization or fluid overload- need respiratory support via a
ventilator & careful cardiopulmonary monitoring
 Definitive management: main stay treatment is suction evacuation (SE), up to uterine size of 28 weeks
gestation, under diazepam sedation or general anesthesia
 Alternatively, cervical dilatation and evacuation is done and ideally monitor oxygen saturation
 If cervix is tubular and closed- slow dilatation of the cervix is done with laminaria tent followed by suction and
evacuation or vaginal misoprostol (PGE1) 400 µg, 3 hours before surgery
 Oxytocin is given IV to contract the uterus after evacuation and close blood supply to the molar tissue

Question 22

Complications of vaginal evacuation

Answer 22

1. Injury to the uterusuterine perforation
2. hemorrhage and shock
3. Acute pulmonary insufficiency
4. Thyroid storm- if hyperthyroid state is present during evacuation is done under GA, acute features such as
   hyperthermia, delirium, convulsions, coma & cardiovascular collapse develop. Treat with β-adrenergic
   blocking agents.

Question 23

Hysterectomy in molar preg is indicated in

Answer 23

Hysterectomy is indicated in:
a) Pts aged over 35
b) Satified parity irrespective of age
c) Uncontrolled hemorrhage or uterine perforation during surgical evacuation

Question 24

Follow- up protocol for molar preg

Answer 24

Routine follow-up is mandatory for all cases for at least 1 year as occurance of choriocarcinoma is mostly
confined to this period
 hCG levels post evacuation regresses to normal within 3 months if disease is not persistent GTD that is
considered malignant.
 Obtain weekly β- HCG titers until its negative for atleast 3 consecutive test
 After titre is neg, obtain monthly β-hCG titers for 12 months
 And then 3-monthly for 2nd year.
 Post uterine evacuation, β-hCG levels steadily decline to undetectable levels, usually within 12 to 16 wks.
 Following a complete mole, pt must wait at least 6 months from hCG returning to 0 (or for 1 year following
chemotherapy) before trying for a further pregnancy to minimize risks of recurrence.
 Use contraception in follow up period to prevent confusion of recurrent disease with rising titers from pregnancy

Question 24

Prophylactic Chemotherapy for molar preg

Answer 24

Not indicated in pts, with molar pregnancy, because 90% of them have spontaneous remissions post evacuation.  But if β-hCG levels plateau or continue to rise after uterine evacuation, chemotherapy can be initiated.  Methotrexate 1 mg/kg/day IV or IM is given on days 1, 3, 5 & 7 with Folinic acid 0.1 mg/kg IM on days 2, 4, 6 and 8. Repeated every 7 days & give a total of 3 courses. β-hCG level decreases by at least 15%, 4-7 days after methotrexate. Monitor FBC, platelet count daily  Alternatively,IV actinomycin D 12 µg/kg daily for 5 days may be given. It is less toxic than methotrexate. Monitor FBC, platelet count, Liver biochem daily  Combination therapy is employed in high-risk situation with agents such as actinomycin, cyclophosphamide and vincristine

Question 25

Persistent gestational Trophoblastic disease

Answer 25

Persistent GTD is evidenced by persistence of trophoblastic activity following evacuation of molar pregnancy.  Evidenced by clinical, imaging, pathological and or hormonal study following initial treatment.  May follow treatment of hydatidiform mole, invasive mole, choriocarcinoma or placental site trophoblastic tumor, abortion or ectopic pregnancy and another 25% following normal pregnancy After molar evacuation serum β-hCG becomes normal in about 12–16 wks.  Serious postmolar GTN may be either invasive mole or choriocarcinoma but GTN after non-molar preg is always a choriocarcinoma.

Question 26

Persistent gestational Trophoblastic disease is Clinically diagnosed when...

Answer 26

) Irregular vaginal bleeding. b) Subinvolution of uterus. c) Persistence of theca lutein cysts and d) Level of hCG either plateaus or re-elevates after an initial fall post-molar evacuation e) Pathologically may be; invasive mole, choriocarcinoma or placental site trophoblastic tumor

Question 27

Tx of Persistent gestational Trophoblastic disease

Answer 27

Treatment: classified into low or high risk categories, Regardless of histological dsis, therapeutic approach is almost the same a) Low risk group receive single agent chemotherapy (usually methotrexate). b) High risk group receive combination chemotherapy (usually EMA-CO). c) Hysterectomy- justified in those approaching 40 and/or with satisfied parity.  Following hysterectomy or chemotherapy, regular follow-up is essential

Question 28

Gestational trophoblastic neoplasia

Answer 28

Group includes; invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor  Almost always develop with or follow some form of recognized pregnancy; hydatidiform mole, miscarriage or ectopic pregnancy, and or develop after a preterm or term pregnancy.  Although the 4 tumor types are histologically distinct, diagnosing is usually solely by persistently elevated serum β-hCG levels because tissue is frequently not available for pathological study

Question 29

Placental site trophoblastic tumour

Answer 29

Tumor arises predominantly from intermediate trophoblast of placental bed and a few syncytial elements  Composed mainly of cytotrophoblastic cells.  Rare histological diagnosis with generally absent syncytiotrophoblast cells.  Incidence is < 1% of all pts with GTN, 15–20% of these pts develop metastases.  Presents with abnormal vaginal bleeding.  Invasion occurs locally into the myometrium and lymphatics  Since its largely composed of cytotrophoblasts, β hCG secretion is low  But human placental lactogen (hPL) is secreted & monitored during follow up.  Serial serum hPL may be a reliable marker & useful for immunohistochemical staining to confirm diagnosis  Treatment: Not responsive to chemotherapy. Hysterectomy is the preferred treatment

Question 30

Invasive Mole (Chorioadenoma Destruens)

Answer 30

An invasive mole is usually a locally invasive tumor.  It comprises about 15% of all GTN.  Prominent features are invasive& destructive potentialities  Lesion may abnormally penetrate entire myometrium, rupture through the uterus, and result in massive hemorrhage into broad ligament or peritoneal cavity.  Uterine perforation maybe on multiple areas showing purple, fungating growth.  Rarely it may invade pelvic bld vessels& metastasizes to vagina or distant sites as like a choriocarcinoma.

Question 31

Dx of Invasive Mole (Chorioadenoma Destruens)

Answer 31

 Histologic confirmation of an invasive mole is almost always made at time of hysterectomy 1. On Laparotomy: in those with persistent β-hCG levels post molar evacuation or those with persistent titers despite chemotherapy, with no evidence of metastatic disease. Uterus will show; a) Perforation of uterus through which purple fungating growth is visible. b) Hemoperitoneum. 2. Histology- penetration of uterine wall by hyperplastic trophoblastic cells with retained villus structures. No evidence of muscle necrosis. Uterine curettage is often deceptive as lesion may be deep inside myometrium. 3. Persistent high level of urinary or serum hCG

Question 32

Gestational choriocarcinoma

Answer 32

 Highly malignant tumor arising from chorionic epithelium & secondarily involves the uterus.  Pleomorphic histologically having both; syncytiotrophoblast & cytotrophoblast without villi- different from a hydatidiform mole  Lesion has a pattern that recapitulates growth of early previllous trophoblast but may display a variety of patterns  Contains both maternal and paternal chromosomes, unlike choriocarcinoma of ovarian origin (non gestational choriocarcinoma)  Genetic analysis of choriocarcinomas usually reveals aneuploidy or polyploidy, typical for anaplastic carcinoma  About 50% of cases preceed molar pregnancy or follow a normal term pregnancy, stillbirth, spontaneous or induced abortion, or ectopic pregnancy de novo.  Trophoblastic disease following a normal pregnancy is always choriocarcinoma or PSTT (rare) but not a benign or invasive mole.  Choriocarcinoma commonly accompanied by bilateral lutein cysts in about 30% due to excessive production of chorionic gonadotropin.

Question 33

Gestational choriocarcinoma disseminates to

Answer 33

Has a tendency to disseminate hematogenously, particularly to; a) Lungs (80%)- causing haemoptysis b) Vagina, (30%)- lead to abnormal pv bleeding c) Brain, (10%), leading to neurological abnormalities d) Liver, (10%)- leading to jaundice e) Kidneys, leading to haematuria and f) Gastrointestinal tract- causing chronic bld loss / melaena

Question 34

Spread of GTN

Answer 34

Local infiltration to uterine walls and surrounding structures  Vascular erosion takes place early and hence rapid occurrance of distant metastases to lungs, liver, brain etc

Question 35

Pathology of gestational choriocarcirnoma

Answer 35

Primary site:  Anywhere in uterus.  Rarely, starts in fallopian tubes or ovary.  Ovarian choriocarcinoma (non-gestational) may be associated with malignant teratoma or dysgerminoma. Gross  Usually localized nodular lesion with red, hemorrhagic and necrotic appearance.  Nodular lesion may be deep in myometrium with intact overlying endometrium, often giving false -ve diagnosis on uterine curettage.  At times, lesion is diffuse involving entire endometrium Histology  Anaplastic sheets/columns of trophoblastic cells invading uterine musculature  Consists of malignant sheets of syncytiotrophoblast or cytotrophoblast cells, haemorrhage, necrosis & intravascular growth with no identifiable villi  Tumor is characterized by masses & sheets of cells that invade surrounding tissue and permeates vascular spaces.

Question 36

Clinical features of choriocarcinoma

Answer 36

Clinical presentation range from disease locally in the uterus leading to PV bleeding, or from distant metastases e.g., lungs, CNS, liver, kidney etc.  Depend on location of primary growth and on its secondary deposits.  Usually follow a H/O molar pregnancy in recent past but rarely is related to term pregnancy, abortion or ectopic pregnancy  GTN after a non-molar pregnancy = choriocarcinoma. Symptoms:  Persistent ill health.  Irregular vaginal bleeding, at times brisk.  Continued amenorrhea due to gonadotropin secretion Symptoms due to metastatic lesions are:  Lung: Cough, breathlessness, hemoptysis.  Vaginal: Irregular and at times brisk hemorrhage.  Cerebral: Headache, dizzy spells, convulsion, paralysis or coma  Liver: Epigastric pain, jaundice.  GIT- Rectal bleeding or “dark stools”  Occasionally, presents with an acute abdomen because of rupture of uterus, liver, or theca lutein cyst. Signs due to metastatic disease  Ill-looking pt.  Pallor of varying degrees  Jaundice  Pulmonary signs: of consolidation/Pleural effusion  Neurological features: partial weakness/paralysis, or features of SOL- dysphasia, aphasia, or unreactive pupil etc

Question 37

Bimanual examination of choriocarcinoma

Answer 37

 Uterus subinvolution/enlargement  Firm, purplish red nodular mass in lower-third of anterior vaginal wall  Unilateral or bilateral ovarian enlargement which may be palpable through lateral fornices  Speculum exam; blood coming through the os

Question 38

Investigations and diagnosis of choriocarcinoma

Answer 38

 Choriocarcinoma is a great imitator of other diseases, so unless it follows a molar preg, it may not be suspected  In females of reproductive age, do β-hCG to screen for choriocarcinoma in pts with unusual clinical features a) Routine Blood investigation: FBC/DC, LFT, U/E+ Creat, urinalysis, stool for occult blood b) Serum quantitative β- hCG – usually elevated > 100 000 c) Urine β-hCG – not routinely done d) Chest X-ray: shows ‘cannon ball’ shadow or ‘snowstorm’ appearance due to numerous tumor emboli  Pleural effusion may be present. e) Pelvic ultrasonography: localize the lesion and help to differentiate GTN from a normal pregnancy f) Diagnostic uterine curettage: not routinely done for histological purpose as it may be inconclusive due to deeply located lesion or uterus not being the primary site * Pretherapy D and C reduces the intrauterine tumor bulk but one has to take meticulous care and be alert as brisk hemorrhage may occur for which a life saving hysterectomy may have to be done. g) Lumbar puncture- done if CT scan of brain is normal, to evaluate β-hCG in CSF and serum to allow detection of early cerebral metastases- because β-subunit does not readily cross the blood–brain barrier * Metastatic brain lesion is suspected when the ratio of β- hCG in spinal fluid/in serum is more than 1: 60. * Suggests CNS involvement, with secretion of β-hCG directly into cerebrospinal fluid h) CT scan or MRI - To r/o liver, kidney, lung and brain metastases  NB: Excision biopsy or biopsy of vaginal nodules should not be done due to massive hemorrhage

Question 39

FIGO staging of gestational trophoblastic neoplasia

Question 40

Drawbacks of FIGO staging of GTT

Question 41

Management of GTN

Answer 41

Can be preventive or Curative  Curative approach can be for both non-metastatic (good prognosis) and metastatic (poor prognosis) disease  Prophylactic chemotherapy may be considered in ‘at risk’ women post molar evacuation to prevents uterine invasion or metastasis Meticulous follow up post molar evacuation is essential for at least 6 months to detect early evidence of trophoblastic reactivation.  A single agent chemotherapy is effective in non-metastatic & low-risk metastatic GTN  Selective hysterectomy in hydatidiform mole over 35 years. There is 4 fold reduction in the risks of choriocarcinoma. Do diagnostic uterine curettage in unexplained abnormal bleeding, 8 weeks following term delivery or abortion. Curative modalities: Chemotherapy ♦ Surgery ♦ Radiation  Chemotherapy regimen is decided on the consideration of anatomic staging, risk factor assessment and WHO prognostic scoring a) Chemotherapy- In general, those with non-metastatic (low risk) and good prognosis disease are treated effectively with single agent therapy (Methotrexate or Actinomycin). Pts with poor prognosis metastatic disease should be treated with combination drug regimen (EMACO regimen) Radiation: For brain and Liver metastasis

Question 42

Women at risk of GTN post molar evacuation

Answer 42

At risk’ women are: a) Patient age of > 35 years. b) Initial levels of serum hCG >100,000 IU/mL. c) hCG level fails to become normal by 7–9 wks time or there is re-elevation d) Histologically diagnosed as infiltrative mole. e) Evidence of metastases irrespective of the level of hCG. f) Previous H/O a molar pregnancy. g) Woman who is unreliable for follow up

Question 43

outline the chemotherapy regimen for GTN

Answer 43

i) Stage I - Low risk GTN, (single agent chemotherapy) Methotrexate 1–1.5 mg/kg IM/IV Days 1, 3, 5 & 7 with folinic acid 0.1–0.15 mg/kg IM Days 2, 4, 6 & 8. Courses are to be repeated at interval of 7 days - High risk or Resistant – use combination therapy. MAC protocol in low-risk cases (INSERT TABLE) Repeat courses at 2 wkly interval, 3 to 6 cycle’s initially plus 1 to 3 cycles consolidation - If satisfied parity→ hysterectomy (ii) Stage II and III - low risk GTN- Single agent chemotherapy. - With satisfied parity do Hysterectomy to reduce tumor mass - High risk or Resistant- combination therapy. Hysterectomy- to reduce (trophoblastic) tumor mass. (iii) Stage IV - combination chemotherapy. - Surgery (hepatic resection, craniotomy). - Radiation (cerebral metastasis) [INSERT TABLE]

Question 44

investigations to be done during chemotherapy of GTN

Answer 44

During treatment do the following investigations; a) Daily do FBC/DC, LFT and RFT b) Chest x-ray- repeat only if hCG titer plateaus or rises c) Weekly serum/urine hCG

Question 45

Avoid repeat chemotherapy treatment course in GTN if

Answer 45

Avoid repeat treatment course if :  WBC < 3000 cu mm  Polymorphonuclear leucocytes < 1500 cu mm  Platelet counts < 100,000 cu mm  Significant elevation of BUN, SGPT  Continue treatment at 1–3 weekly interval until 3 consecutive negative weekly hCG titers

Question 46

Primary hysterectomy in GTN

Answer 46

Not routinely done as chemotherapy alone is successful in 85% of pts with non-metastatic and good prognosis metastatic GTN but decreases the number of courses of chemotherapy.  Indications of hysterectomy a) Lesions confined to uterus in those aged > 35 years, not desirous of fertility b) Placental site trophoblastic tumor c) Intractable vaginal bleeding Course will restart after 7–14 days, if possible. Generally 2 additional courses are given after the hCG levels become normal. d) Localized uterine lesion resistant to chemotherapy e) Accidental uterine perforation during uterine curettage.  Other surgeries: total hysterectomy, Lung resection (thoracotomy) in pulmonary metastasis in drug resistant cases and craniotomy for control of bleeding

Question 47

hCG follow up after GTN treatment

Answer 47

CG follow up after GTN treatment  During and after treatment of GTN, serum hCG surveillance, should be every week until neg for 3 consective wks → once negative → every 2 weeks for 3 months → then every month for 1 year →finally every 6–12 months for life or at least 3–5 years