Gestational Trophoblastic Disease

Question 1

What are the different classifications of GTD? How do they differ in:

• Aetiology
• Pathological features
• Clinical Features
• Management

Answer 1

Classification

Usual karyotype

Originates from (cell type)

Pathology (macro)

Clinical Features

Management.

Premalignant

Partial hydatidiform mole

69XXY

Focal hyperplasia + swelling of the villi.

Fetal material present (also seen on an US).

Vaginal bleeding

Vaginal discharge

Abdo pain

Excessive morning sickness.

Risk of malignant change = 1%. - Chemo not usually required.

Complete hydatidiform mole

46XX (both paternal - “androgenically diploid”)

Fetal material absent.

Marked hyperplasia

Gross vesicular swelling of villi.

“bunch of small grapes”

Later presentation

Large-for-dates uterus (from the bulk of the tumour)

Hyperemesis

Thyrotoxicosis (bHCG mimics actions of TSH).

10-15% become malignant - require chemo after evacuation.

Malignant

Invasive

• Formed from molar tissue
• Tissue invades (predominantly) into myometrium.

Almost always androgenically diploid

Trophoblastic cells +++ Synctiotrophoblasts

Similar to CHM (above)

Uterine mass

Elevated hCG.

Uterine rupture + abdo pain + bleeding (invaded through wall –> uterine rupture).

Chemotherapy (good response)

Choriocarcinoma

• Highly malignant
• Arises from malignant transformation of hydatidiform mole.

NB - NO RF!!!! - random occurrence.

Maternal + paternal

Trophoblastic cells Synctiotrophoblasts +++

Haemorrhage

Necrosis

Intravascular growth.

Lacks villous structure (highly dysplastic)

• Right after pregnancy

OR

• Up to 20 years after the causative pregnancy
• Usually following a live birth/still birth/miscarriage/ectopic pregnancy.
• Vaginal bleeding
• Markedly raised hCG level.
• Presentation of mets in
  
  • Lung (haemoptysis/dyspnoea)
  • Brain (neurological abnormalities)
  • Gastro tract (chronic blood loss/malaena)
  • Liver (jaundice)
  • Kidney (hamaturia).
• Elevated hCG + advanced cancer = choriocarcinoma (highly suggestive).

Chemotherapy (good response).

Placental Site Trophoblastic Tumour

• Slow growing malignancy
• Invades the myometrium

Maternal + paternal

Trophoblastic cells only.

• Lower capacity to invade
• Makes less hCG

Elevated hCG (less elevated than choriocarcinoma)

Vaginal bleeding.

Surgery, chemotherapy.

Question 2

How is GTD investigated?

Answer 2

1. BLOODS:
   - bHCG - elevated, often > 100 000 IU/L.
   - FBC: possible anemia from blood loss.
   - Blood group + Rh factor.
   - TSH (hCG + TSH crossreactivity may cause thyrotoxicosis, in absence of elevated TSH).
2. IMAGING
   - Pelvic US: abnormal uterine enlargement, “snow storm appearance” (abnormal vesicles), +/- foetal parts.

NB - early/partial: difficult to see on US.

• CXR: exclude mets to lungs.
  3. POST EVACUATION
• Histo + cytogenetics if abnormalities found.
• BhCG levels until -ve for 3 weeks.

Question 3

What are the generalised clinical features of GTD?

Answer 3

History

1. Vaginal bleeding (spotting–> heavy) = most predominant feature.

2. Pelvic pain/pressure.
3. 1st trimester pregnancy w missed menstrual period + positive urine pregnancy test / positive bHCG on lab test.

Rare:

• hyperemesis gravidarum
• hyperthyroidism
• vaginal passage of vesicles
• pre eclampsia

Examination

1. Uterus size larger than dates (common)

2. Theca lutein cyst of ovaries

Pelvic exam + speculum:

• uterine bleeding through external cervical os (uncommon).

Question 4

What are the DD of GTD?

Answer 4

• Spontaneous abortion (differentiated on US)
• Multiple gestation (larger than normal uterus + elevated hcg)
• pelvic tumour (enlarged uterus, painless bleeding, adnexal mass).

Question 5

What is the prognosis of treatment in GTD?

Answer 5

Chemo = 95% cure.

Question 6

What is the management of GTD?

Answer 6

A. Molar pregnancy, fertility-preservation desired

- dilation and evacuation (medical termination avoided: mets risk)

B. Molar pregnancy: fertility-preservation not desired:

- hysterectomy.

C. Persistent GTN after molar pregnancy (bHCG plateaus/ > over 10 weeks; persistent detectable bHCG > 6months after evacuation).

Low risk: methotrexate (single dose)

High risk: Combination chemotherapy

Select cases: hysterectomy.

D. Mets

- D+E + Chemotherapy.

MANAGEMENT AFTER EVACUATION:

-

Bhcg: weekly until normal for 3 consecutive weeks –> monthly until normal for 6 months.

(typically become normal after 2-4 weeks).

Avoid pregnancy until normal for 6 months (pregnancy can mask GTD –> later dx and mx).

OCP is fine to use.

After further pregnancies: placenta should always be sent to histopathology and cytogenetics.

Question 7

What are possible complications of GTD and how are they managed?

Answer 7

Hyperemesis Gravidarum

• fluid replacement + antiemetic/ H2 antagonist.

Active bleeding

• oxytocin IM + blood products.

Thyrotoxicosis

• beta blockers, thyroid management protocols.

Pre eclampsia

• Magnesium sulfate/anti hypertensives

Theca lutein cyst

• involutes over time (expectant) + drainage/

Question 8

What is the definition of trophoblastic neoplasia?

Answer 8

• requirement of chemotherapy/excisional surgery due to persistence of bHCG after hytidaform evacuation.

OR

• presence of trophoblastic metastases.

Criteria (Gestational trophoblastic neoplasia after molar pregnancy):

• Serum bHCG which plateus after molar pregnancy
• Serum bHCG which rises after molar pregnancy (>10% over 2 weeks)
• Persistence of detectable bHCG > 6months after evacuation

Question 9

What is the epidemiology/RF of GTD?

Answer 9

• previous molar disase
• SE Asian communities
• extremes of maternal age.