Gestational Trophoblastic Disease: Epidemiology, Classification, Pathogenesis, Types, Symptoms, Diagnosis, Management and Prevention

Gestational Trophoblastic Disease (GTD)

~Introduction

Gestational Trophoblastic Disease (GTD) is a group of rare but important disorders that arise from abnormal proliferation of trophoblastic tissue, which normally forms the placenta during pregnancy. These conditions originate from pregnancy-related tissue and are characterized by excessive production of human chorionic gonadotropin (β-hCG). GTD ranges from benign conditions such as hydatidiform mole to malignant neoplasms collectively known as gestational trophoblastic neoplasia (GTN).

Although GTD is relatively uncommon, it is one of the most curable gynecological malignancies when diagnosed early and treated appropriately. Advances in chemotherapy and hCG monitoring have resulted in cure rates exceeding 90–95%, even in metastatic disease. GTD is therefore of great clinical importance due to its unique biology, high curability, and reproductive implications.

~Epidemiology

The incidence of GTD varies worldwide:

• Hydatidiform mole occurs in approximately:

  • 1 in 1000 pregnancies in North America and Europe

  • Higher incidence in Asia, Africa, and Latin America

• GTD is more common at the extremes of reproductive age

  • Teenagers (<20 years)

  • Women above 35–40 years

• Previous history of molar pregnancy increases the risk by 10–20 times

Nutritional deficiencies, particularly low dietary intake of carotene and vitamin A, have been suggested as contributing factors in high-incidence regions.

~Classification of Gestational Trophoblastic Disease

GTD is broadly classified into benign and malignant forms:

1. Hydatidiform Mole (Benign GTD)

• Complete hydatidiform mole

• Partial hydatidiform mole

2. Gestational Trophoblastic Neoplasia (Malignant GTD)

• Invasive mole

• Choriocarcinoma

• Placental site trophoblastic tumor (PSTT)

• Epithelioid trophoblastic tumor (ETT)

~Pathogenesis

GTD arises from abnormal fertilization and proliferation of trophoblastic tissue.

Complete Mole

• Results from fertilization of an empty ovum (no maternal chromosomes)

• Genetic material is entirely paternal (46,XX or 46,XY)

• No fetus or embryonic tissue present

• Diffuse swelling of chorionic villi

Partial Mole

• Results from fertilization of a normal ovum by two sperms (triploidy: 69,XXY or 69,XXX)

• Presence of abnormal fetus or fetal parts

• Focal trophoblastic proliferation

The malignant forms develop due to persistent trophoblastic tissue that invades locally or metastasizes.

~Types of Gestational Trophoblastic Disease

1. Hydatidiform Mole

a) Complete Hydatidiform Mole

Clinical Features

• Vaginal bleeding in early pregnancy

• Uterus larger than gestational age

• Severe nausea and vomiting (hyperemesis gravidarum)

• Early-onset preeclampsia (<20 weeks)

• Absence of fetal heart sounds

• High β-hCG levels

Ultrasound Findings

• “Snowstorm” or “cluster of grapes” appearance

• No fetus or amniotic sac

Complications

• Theca lutein ovarian cysts

• Progression to invasive mole or choriocarcinoma

b) Partial Hydatidiform Mole

Clinical Features

• Less severe symptoms than complete mole

• Vaginal bleeding

• Uterus may be small or appropriate for gestational age

• Fetal parts may be present

Ultrasound

• Abnormal placenta with cystic spaces

• Growth-restricted or malformed fetus

2. Invasive Mole

An invasive mole occurs when molar tissue invades the myometrium.

Features

• Persistent vaginal bleeding after evacuation of mole

• Elevated or plateauing β-hCG levels

• May cause uterine perforation and hemorrhage

• Can metastasize to lungs and vagina

3. Choriocarcinoma

Choriocarcinoma is a highly malignant GTD composed of cytotrophoblast and syncytiotrophoblast without chorionic villi.

Origin

• Can follow:

  • Molar pregnancy (most common)

  • Normal pregnancy

  • Abortion or ectopic pregnancy

Clinical Features

• Irregular vaginal bleeding

• Very high β-hCG levels

• Early hematogenous spread

Common Metastatic Sites

• Lungs (most common)

• Brain

• Liver

• Vagina

4. Placental Site Trophoblastic Tumor (PSTT)

• Rare variant

• Arises from intermediate trophoblast

• Produces low levels of β-hCG

• Slower growth but more resistant to chemotherapy

5. Epithelioid Trophoblastic Tumor (ETT)

• Very rare

• Resembles carcinoma histologically

• Occurs years after pregnancy

• Managed primarily by surgery

~Clinical Presentation

Common symptoms of GTD include:

• Abnormal vaginal bleeding

• Amenorrhea followed by bleeding

• Excessive nausea and vomiting

• Pelvic pain

• Symptoms due to metastasis:

  • Hemoptysis (lung metastasis)

  • Neurological symptoms (brain metastasis)

~Diagnosis

1. β-hCG Estimation

• Markedly elevated levels

• Used for diagnosis, follow-up, and monitoring response to therapy

2. Ultrasonography

• Transvaginal ultrasound is preferred

• Classic snowstorm appearance in complete mole

3. Histopathology

• Confirmation after evacuation

• Differentiates complete and partial mole

4. Chest X-ray / CT Scan

• To detect lung metastasis

5. FIGO Staging and WHO Risk Scoring

Used to guide treatment decisions.

~FIGO Staging of GTD

• Stage I: Disease confined to uterus

• Stage II: Extends to genital structures

• Stage III: Lung metastasis

• Stage IV: Other metastatic sites

~WHO Prognostic Risk Scoring System

Factors considered:

• Age

• Type of antecedent pregnancy

• Interval from pregnancy

• Pretreatment β-hCG level

• Tumor size

• Metastatic sites and number

• Previous chemotherapy

Score interpretation:

• Low-risk GTN: Score ≤6

• High-risk GTN: Score ≥7

~Management

Management of Hydatidiform Mole

1. Uterine Evacuation

   • Suction curettage is the treatment of choice

   • Oxytocin used after evacuation

2. Rh Immunoglobulin

   • Given to Rh-negative women

3. hCG Monitoring

   • Weekly until normal for 3 weeks

   • Monthly for 6–12 months

4. Contraception

   • Oral contraceptives recommended

   • Avoid pregnancy during follow-up

Management of Gestational Trophoblastic Neoplasia

Low-Risk GTN

• Single-agent chemotherapy:

  • Methotrexate or Actinomycin-D

• Cure rates >95%

High-Risk GTN

• Multi-agent chemotherapy:

  • EMA-CO regimen (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, Vincristine)

• Intensive monitoring required

Surgical Management

• Hysterectomy may be indicated in:

  • PSTT

  • ETT

  • Life-threatening hemorrhage

  • Women who have completed childbearing

~Follow-Up and Prognosis

• Serial β-hCG monitoring is crucial

• Early detection of recurrence is possible

• Fertility is usually preserved

• Subsequent pregnancies are generally normal

• Recurrence risk: 1–2%

~Complications

• Persistent GTD

• Malignant transformation

• Hemorrhage

• Metastatic disease

• Psychological distress due to prolonged follow-up

~Prevention and Counseling

• Early antenatal care

• Proper follow-up after molar evacuation

• Emotional support and counseling

• Education regarding contraception and compliance

~Conclusion

Gestational Trophoblastic Disease represents a unique spectrum of pregnancy-related disorders characterized by abnormal trophoblastic proliferation and elevated β-hCG levels. Despite its potentially malignant nature, GTD is one of the most curable gynecological conditions due to its high sensitivity to chemotherapy and reliable tumor markers. Early diagnosis, proper classification, appropriate treatment, and meticulous follow-up are essential for achieving excellent outcomes. With modern management, most women retain fertility and can expect normal future pregnancies, making GTD a success story in oncologic gynecology.