Coupon Accepted Successfully!


Definition & Classification

Gestational Trophoblastic Disease (GTD) encompasses a spectrum of proliferative abnormalities of trophoblasts associated with pregnancy. Persistent GTD (persistently raised ~-hCG) is referred as gestational trophoblastic neoplasia (GTN).






- Hydatidiform mole


- Invasive mole


- Choriocarcinoma


- Placental dite trophoblastic tumor (PSTT).

Modified WHO classification (1998)


Classification of GTD

  1. Hydatidiform mole: - Complete - Partial
  2. Invasive mole
  3. Placental site trophoblastic tumor
  4. Choriocarcinoma

Non metastatic disease (confined to the uterus)


Metastatic disease:

  1. Low risk (good prognosis)
    1. Disease is present < 4 months duration
    2. Initial serum hCG level < 40,000 mIU/ml
    3. Metastasis limited to lung and vagina
    4. No prior chemotherapy
    5. No preceding term delivery
  2. High risk (poor prognosis)
    1. Long duration of disease (> 4 months)
    2. Initial serum hCG > 40,000 mlU/ml
    3. Brain or liver metastasis
    4. Failure of prior chemotherapy
    5. Following term pregnancy
    6. WHO score ≥ 8

Hydatidiform mole (molar pregnancy): Molar pregnancy is characterized histologically by abnormalities of the chorionic villi that consist of trophoblastic proliferation and edema of villus stroma (hydropic degeneration).

Incidence and risk factors

  1. ​Incidence is maximum in Asia and South America and least in U.S.
  2. Maximum incidence is in Philippines (1 in 80). In India it is 1 in 400 pregnancies.
  3. Risk is more in women too elderly (> 35) or too younger (< 18 years).
  4. Low socioeconomic status.
  5. History of molar pregnancy.
  6. Diet deficient in protein, folic acid and vitamin A.
  7. Blood group A women married to group O men.

Note: Maternal age> 35 years and dietary deficiencies are risk factors for complete mole whereas partial mole is linked to the use of oral contraceptive pills and history of irregular menstruation.

Also know

Familial repetitive hydatidiform mole has been linked to a missense mutation in the NLRP710cus on chromosome 19; in one report, this mutation was present in 60% of patients who had two molar pregnancies.

Features of Partial and Complete Hydatidiform Moles


Partial Mole

Complete Mole


Usually 69,XXX or 69,XXY

Partial moles generally have a triploid karyotype; the extra haploid set of chromosomes usually is derived from the father.

Fetus exhibits stigmata of triploidy including growth retardation and multiple congenital malformations such as syndactyly & hydrocephaly.

46,XX (90%) or 46,XY (10%)

The molar chromosomes are entirely of paternal origin, although mitochondrial DNA is of maternal origin.

The complete moles arises from an ovum that has been fertilized by a haploid sperm, which then duplicates its own chromosomes called as Androgenesis. The ovum nucleus may be either absent or inactivated.



Often Present


Amnion, fetal red blood cells

Often Present


Villus edema

Variable, focal


Uterine size

Small for dates

50% large for dates

Theca-lutein cysts



Medical complications



Gestational trophoblastic neoplasia




  1. Amenorrhea of varying duration followed by continuous or intermittent brown or bloody discharge (usually not profuse) evident by - 12 weeks. Uterine bleeding is a" most universal (it is the most common presenting feature).
  2. Passage of vesicles per vaginum
  3. Hyperemesis (due to the high levels of circulating HCG).


  1. Uterus:
    1. The fundal height of uterus is more than the period of amenorrhea in 50% cases. In 35% it corresponds to the gestational period and in the rest it may be smaller.
    2. Uterus is doughy in consistency (due to absence of amniotic fluid).
    3. Fetal parts will not be felt.
    4. Fetal heart sounds will not be heard (even on doppler).
    5. External and internal ballottement cannot be elicited.
  2. Theca lutein cysts:
    1. May be felt in the ovaries in about 25 to 60%.
    2. Due to overstimulation of the luteal elements by the large amounts of circulating HCG.
    3. Persistent trophoblastic disease is more likely in women with theca lutein cysts >6 cms.
  3. Early onset preeclampsia:
    - When hypertension appears before 24 weeks, it is important to rule out hydatidiform mole.
  4. Thyrotoxicosis seen due to the thyrotrophin-like effect of HCG.
  5. Spontaneous expulsion occurs at around 16 weeks and rarely delayed beyond 28 weeks,"
    1. Past history of hydatidiform mole increases the chance of recurrence (1-4%).
    2. Theca-lutein cysts: In many cases of hydatidiform mole, the ovaries contain multiple theca-lutein cysts. Theses may vary from microscopic size to 10 cm or more diameters. Their surfaces are smooth, often yellowish and lined with lutein cells. The incidence of obvious cysts in association with a mole is reported to be from 25% to 60%. They are thought to result from overstimulation of lutein elements by large amounts of hCG secreted by proliferating trophoblastic cells.
    3. Incidence of molar pregnancy is highest in women aged 15 years or younger and those aged 45 years or older. In the latter group, the relative frequency of the lesion is at least 10 times greater than that at ages 20-40 years.
    4. Uterine bleeding is almost universal and may vary from spotting to profuse hemorrhage. It is the MC presenting feature. The discharge has "white currant in red currant juice" appearance.
    5. Uterine size: The growing uterus often enlarges more rapidly than usual, exceeding in about half of cases that expected from the gestational age.
    6. Gestational hypertension: Because hypertension caused by pregnancy is rarely seen before 24 weeks, preeclampsia that develops before this gestational age may be from hydatidiform mole or extensive molar degeneration. Thyrotoxicosis (alpha component of hCG is similar to TSH): Plasma thyroxine levels in women with molar pregnancy are often elevated.

Diagnosis of H. mole

  1. Ultrasound shows “Snow storm” appearance in the uterus.
  2. In case of complete molar pregnancy:
    - Chorionic villi exhibit diffuse hydropic swelling
    - Absence of fetal shadow.
  3. In case of partial molar pregnancy:
    - Focal cystic spaces are seen in placental tissue
    - Increase in transverse diameter of the gestation.
    - Some fetal tissue is identifiable.

Note: For diagnostic purpose USG alone is adequate, quick and a sale procedure. Hormonal assay are now limited to post molar and post chemotherapy follow-up.

Serum β HCG

  1. Serum beta HCG levels are very high in case of molar pregnancy.
  2. Levels more than 40,000 as detected by radio immunoassay are seen in trophoblastic diseases.
  3. Rapidly increasing serum values of HCG are also suggestive of molar pregnancy.

Chest X-ray


Done to rule out lung metastasis

Note: Straight X ray of chest should be carried out as a routine, for evidence of pulmonary embolization even in benign moles.

CT scan

  1. Done to rule out brain and liver metastasis.
  2. Definitive diagnosis is done by histological examination of products of conception.

Management of H. mole

  1. TOC in H. mole
    1. Suction curettage (It is the treatment of choice irrespective of uterine size)
    2. Suction evacuation is done first. After most of the molar tissue has been removed by aspiration, oxytocin is given.
      Once the myometrium has contracted, thorough but gentle curettage with a large sharp curette is performed.
      Intraoperative ultrasonography examination may help document that the uterine cavity has been emptied.
  2. Hysterectomy: It is indicated only in case of:
    1. Female has completed her family irrespective of age
    2. Age of patient - >35 years (as chances of malignancy are more).
    3. Uncontrolled haemarrhage during scutum evacuation

Hysterotoy: Indicated in cases complicated by haemorrhage.

Follow-up Evaluation of molar pregnancy:


Routine follow up is mandatory for all cases for atleast 6 months following molar pregnancy. Doing hysterectomy dose not negate the need for followup.

  1. Monitor serum hCG levels every 2 weeks.
  2. Chemotherapy is not indicated as long as these serum levels continue to regress. A rise or persistent plateau in the level demands evaluation for gestational trophoblastic neoplasia and usually treatment. Prevent pregnancy for a minimum of 6 months using hormonal contraception.
  3. Once the hCG level falls to a normal level, test the patient monthly for 6 months; then follow-up is discontinued and pregnancy allowed.

Prophylactic Chemotherapy


Routine prophylactic chemotherapy is not advocated, because 80% molar pregnancies resolve following evacuation. If chemotherapy is prescribed for all molar pregnancies, 80% patients would be exposed to unnecessary morbidity and toxicity of the Chemotherapeutic drugs.


  1. Initial high levels of β HCG (> 100,000 mlU/ml)
  2. If hCG fails to becomes normal by stipulated time (10-12 weeks).
  3. Reelevation of serum HCG after reaching normal levels
  4. Evidence of metastasis irrespective of HCG levels.
  5. Post evacuation hemorrhage.
  6. Age patient >35 years.
  7. Theca lutein cysts ≥ 6 cms.

Contraceptive Advice


Estrogen-progestin contraceptives or depot medroxyprogesterone is usually used to prevent a subsequent pregnancy during the period of surveillance. Contraceptive of choice being combined oral pills. Note- Earlier the contraceptive of choice was Barrier method.

Theca Lutein Cyst

  1. Theca lutein cysts are seen in H. mole due to high circulating levels of hCG.
  2. They vary in size from microscopic to 10 cms size.
  3. Yellow coloured.
  4. They are the result of overstimulation of lutein cysts by large amount of HCG.
  5. Theca lutein cyst are also seen in case of : - Fetal hydrops
    - Placental hypertrophy
    - Multifetal pregnancy.


  1. It may undergo torsion, infarction and hemorrhage and then may require surgical treatment.
  2. Patients with theca lutein cysts (> 6 cms) have high risk of developing choriocarcinoma.

Persistent Gestational Trophoblastic Disease

Definition: Persistent GTD is defined where there is persistence of trophoblastic activity as evidenced by clinical, imaging, pathological and or hormonal study following initial treatment. This may be following treatment of hydatidiform mole, invasive mole, choriocarcinoma or placental site trophoblastic tumor.

A postmolar GTD may be benign or malignant. But a GTD after non-molar pregnancy is always a choriocarcinoma.

Overall incidence of persistent GTN after complete hydatidiform moles is 15-20%.


Approximately, 50% of the cases of persistent GID develop following a hydatidiform mole, 25% following an abortion or ectopic pregnancy and another 25% following normal pregnancy.

Gestational Trophoblastic Neoplasia

  1. Gestational trophoblastic neoplasia almost always develops with or follows some form of pregnancy.
  2. Among all the cases of choriocarcinoma:
    1. 50% develop following a hydatidiform mole
    2. 25% develop following an abortion
    3. 20% develop following a full-term pregnancy
    4. 5% develop following an ectopic pregnancy.

Histological features

  1. Choriocarcinoma
    1. Absence of villous pattern?
    2. Columns and sheets of trophoblastic cells penetrating the muscle and blood vessels
    3. Cellular atypia
  2. Invasive mole
    1. Excessive trophoblastic over growth and extensive penetration by the trophoblastic cells including the villi.
    2. Invasive moles penetrate into the myometrium and sometimes the peritoneum, parametrium and vaginal vault but lack the tendency to widespread metastasis typical of choriocarcinoma
  3. Placental site trophoblastic tumor
    1. It arises at the placental implantation site
    2. Characteristic features:
      - Absent syncytiotrophoblast
      - Many prolactin producing cells and a few gonadotropin producing cells are seen
      Local invasion occurs into the myometrium and lymphatics and less commonly into the vasculature (different from choriocarcinoma)
Tumor marker for Gestational Trophoblastic Neoplasia is BhCG
Tumor marker for Placental site Trophoblastic tumor is hPL.


  1. Most malignant tumor of uterus.
  2. MC mode of spread is hematogenous
  3. Most common sites of metastases in choriocarcinoma are:

Lung (80%) > Vagina (30%) > Pelvis (20%) > Liver (10%) and Brain (10%)


Symptoms: Mostly presents as irregular bleeding or uterine hemorrhage following an abortion, a molar pregnancy or a normal delivery.

Lung Metastasis

  1. It is seen in 80% cases
  2. Patient presents with respiratory symptoms like dyspnoea, hemoptysis, chest pain etc.
  3. On X-ray it may produce the following four patterns
    1. An alveolar snow storm pattern (Remember snowstorm appearance on USG- means H mole; snowstorm appearance on chest X-ray- means choriocarcinoma)
    2. Discrete rounded densities or canon ball appearance
    3. Pleural effusion
    4. An embolic pattern caused by pulmonary arterial occlusion.

Vaginal Metastasis

  1. It is seen in 30% cases
  2. Metastasis occurs in suburethra or in fornices
  3. Metastasis appears as purple hemorrhagic projections which are highly vascular and bleed on touch (pathognomic of choriocarcinoma).


FIGO anatomic staging for GTT



Stage I     The lesion is confined to the uterus.


Stage II    The lesion spreads outside the uterus but is confined to the genital organs.


Stage III   The lesion metastasizes to the lungs.


Stage IV   The lesion metastasizes to sites such as brain, liver or gastrointestinal tract.


WHO prognostic scoring system for gestational trophoblastic disease








Age (y)





Antecedent pregnancy





Interval in months from index pregnancy & chemotherapy started within

<4 months

4-6 months

7-12 months

>12 months

Pretreatment b-hCG level





ABO group (female x male)


O or A

A or AB


Largest tumor (cm)





Site of metastases


Spleen, kidney

Gastrointestinal, liver


Number of metastases





Prior chemotherapy





Total score:

<4-low risk

≥ 8 – high risk




Patients having a score of 6 or less are considered as having low risk or good prognosis and patient having a score of ≥6 are considered as having high risk or good prognosis.

In general a patient belonging to good prognosis or low risk group (score 0-6) means that they can be treated by a single agent chemotherapy which is usually successful in them, whereas a patient belonging to poor prognosis/ high risk group (score > 7) respond badly to chemotherapy and require prolonged hospitalization with multiple courses of chemotherapy.


  1. Chemotherapy is the treatment of choice for choriocarcinoma
  2. Methotrexate is the drug of choice.
  3. If the patient has jaundice then actinomycin D should be given.
  4. Multidrug therapy used most commonly is Bagshaw regime consisting of-

E = etoposide


M = methotrexate


A = actinomycin D


C = cyclophosphamide


O = vincristine (oncovin)

High risk patients and patients with stage 4 are to be treated with combination chemotherapy- EMACO

EMA-CO regimen results in response rates of about 90% and survival rates of 80-100%.


Management of GTN

A. Stage I

Low risk GTN

High risk or Resistant


B. Stage II and III

Low risk GTN

High risk or Resistant



C. Stage IV

• Single agent chemotherapy.

• Combination therapy

• Family completed hysterectomy.


• Single agent chemotherapy.

• Hysterectomy (family completed) to reduce tumor mass.

• Combination therapy

• Hysterectomy - to reduce (trophoblastic) tumor mass.


• Combination chemotherapy.

• Surgery (hepatic resection, craniotomy).

• Radiation (cerebral metastasis).

Single Drug Regimen 'In Low-Risk Cases


Methotrexate    1-1.5 mg/kg        IM/IV     Days 1,3, 5 and 7


Folinic acid       0.1-0.15 mg/kg   1M          Days 2, 4, 6 and 8


The courses are to be repeated at interval of 7 days

Role of Surgery


Total hysterectomy is done if required in choriocarcinoma. The ovaries are usually not involved and if involved, can be effectively cured with postoperative chemotherapy, hence bilateral salpingo-oophorectomy is not done.

Test Your Skills Now!
Take a Quiz now
Reviewer Name