Gestational Trophoblastic Disease (GTD)

Summary

Gestational trophoblastic disease (GTD) is a rare pregnancy-related tumour spectrum, from benign moles to malignant neoplasia (invasive mole, choriocarcinoma, PSTT, ETT). It presents with vaginal bleeding or persistent symptoms post-pregnancy, diagnosed by β-hCG, ultrasound, and histology, and managed with evacuation, chemotherapy, or surgery, with high cure rates.

Definition

Gestational trophoblastic disease (GTD) refers to a heterogeneous group of rare pregnancy-related tumours arising from abnormal proliferation of trophoblastic tissue. GTD encompasses both benign (pre-malignant) and malignant conditions, with a spectrum ranging from molar pregnancies to highly aggressive neoplasms.

Classification

1. Pre-malignant GTD (Hydatidiform Mole)

• Complete molar pregnancy

• Results from fertilisation of an “empty” ovum by a single sperm that duplicates (most common) or two sperm.

• Karyotype: 46,XX (90%) or 46,XY (10%), entirely paternal in origin.

• No fetus, amniotic fluid, or placenta develops.

• Risk of malignant transformation: 15–20%

• Partial molar pregnancy

• Results from fertilisation of a normal ovum by two sperm.

• Karyotype: 69,XXY (70%), 69,XXX (27%), or 69,XYY (3%).

• May present with abnormal fetus/placenta (triploid or mosaic).

• Risk of malignant transformation: <5%.

2. Malignant GTD (Gestational Trophoblastic Neoplasia, GTN)

• Invasive mole – locally invasive form of molar pregnancy with myometrial infiltration, occasionally metastasising.

• Choriocarcinoma – highly malignant tumour composed of cytotrophoblasts and syncytiotrophoblasts, without villi; frequently metastasises (lungs, brain, liver, vagina).

• Placental site trophoblastic tumour (PSTT) – rare malignancy of intermediate trophoblasts; may follow normal pregnancy, miscarriage, or mole.

• Epithelioid trophoblastic tumour (ETT) – rare variant resembling squam*ous carcinoma, arising from chorionic-type intermediate trophoblasts.

Pathophysiology

GTD arises from abnormal fertilisation events leading to atypical chromosomal complements.

• Complete mole: paternal disomy, no embryonic development, diffuse villous oedema, circumferential trophoblastic proliferation.

• Partial mole: triploidy, with focal villous oedema and variable embryonic development.

• Neoplastic forms: malignant transformation of trophoblasts, with invasion, vascular dissemination, and metastatic potential.

Risk Factors

• Maternal age <20 or >35

• Prior molar pregnancy (highest risk, not reduced by partner change)

• History of miscarriage or infertility

• Oral contraceptive pill use

• Ethnic predisposition (higher in Asian and Indian populations)

• Extremes of parity and smoking

Clinical Features

Molar Pregnancy

• Vaginal bleeding (most common presenting symptom)

• Abdominal pain and uterine enlargement (uterus often “large for dates,” soft, boggy)

• Passage of vesicles (“grape-like”)

• β-hCG–mediated effects:

• Hyperemesis gravidarum

• Hyperthyroidism (gestational thyrotoxicosis)

• Early-onset preeclampsia (<20 weeks)

• Theca lutein ovarian cysts (30–60% of cases, regress post-evacuation)

Gestational Trophoblastic Neoplasia

• Persistent or heavy vaginal bleeding after pregnancy/miscarriage

• Enlarged uterus or inadequate involution postpartum

• Symptoms of metastasis:

• Lungs → cough, dyspnoea, haemoptysis (“cannonball metastases”)

• Brain → seizures, headaches

• Liver → abdominal pain, hepatomegaly

• Vagina → vascular nodules

Investigations

• Serum β-hCG – markedly elevated; cornerstone for diagnosis and follow-up

• Urinary pregnancy tests – persistently positive post-partum in GTD

• Pelvic ultrasound

• Complete mole: echogenic “snowstorm” or “bunch of grapes” appearance with cystic spaces

• Partial mole: thickened, cystic placenta with possible fetal parts (“Swiss cheese” appearance)

• Histopathology – definitive diagnosis; p57 immunostaining helps distinguish complete (negative) from partial (positive) moles

• Imaging for metastasis (if GTN suspected): chest X-ray, CT/MRI, pelvic ultrasound

Management

• Registration with a GTD referral centre is recommended in the UK and many countries for surveillance.

• Molar pregnancy

• Suction curettage is first-line for complete and non-viable partial moles.

• Anti-D prophylaxis for Rh-negative women.

• Serial β-hCG monitoring until undetectable (usually 8–12 weeks).

• Effective contraception recommended during surveillance.

• Gestational trophoblastic neoplasia

• Chemotherapy (methotrexate or actinomycin D; multi-agent for high-risk disease).

• Surgery (hysterectomy or excision of metastases) in selected cases.

• Cure rates >95% for good-prognosis GTN; ~65% for poor-prognosis metastatic disease.

Complications

• Haemorrhage and anaemia

• Uterine perforation, infection

• Thyrotoxicosis and preeclampsia

• Disseminated intravascular coagulation (rare)

• Malignant transformation: more common in complete mole

• Pulmonary trophoblastic embolisation during evacuation

Prognosis

• With early diagnosis and specialist care, most women achieve complete remission and retain fertility.

• Risk of recurrence:

• Complete mole → 15–20% risk of progression to GTN

• Partial mole → <5%

• Risk of repeat molar pregnancy in subsequent gestation: ~1–2%.

Summary Table – Overview of GTD