Trophoblastic Neoplasm

Gestational trophoblastic neoplasia (GTN) is a group of rare diseases related to pregnancy, characterised by abnormal trophoblast cells growing in the uterus.

Micrograph of intermediate trophoblast and a hydatidiform mole

Gestational trophoblastic neoplasia (GTN) is a subset of gestational trophoblastic disease (GTD). It can be classified into benign lesions, such as placental site nodule and hydatidiform moles, and malignant lesions, which include invasive mole, gestational choriocarcinoma, placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumour (ETT). Choriocarcinoma has two significant subtypes: gestational and non-gestational, differentiated by biological features and prognosis.

Signs and symptoms vary among individuals and disease types. Common symptoms include uterine bleeding, pelvic pain or pressure, an enlarged uterus, and high blood pressure during pregnancy. The exact cause of GTN is unknown, but diagnosis is often based on elevated total beta-human chorionic gonadotropin (β-hCG) levels in the serum.

Cause and Risk Factors

The cause of GTN is unknown, though it often arises after molar pregnancies, miscarriages, or term pregnancies. Risk factors do not directly cause the disease but can impact its development. Studies indicate that the risk of complete molar pregnancy is highest in women under 20 and over 35, and even higher for those over 45.

Signs and Symptoms

• Vaginal bleeding, often with mild elevation of serum β-hCG (< 2,500 IU/L)
• Uterus larger than expected during pregnancy
• Pelvic pain or pressure
• Severe nausea and vomiting during pregnancy
• High blood pressure, headache, and swelling of feet and hands early in pregnancy
• Fatigue, shortness of breath, dizziness, and fast or irregular heartbeat caused by anaemia
• Symptoms associated with metastatic disease if present

Diagnosis

Screening tests for GTN include:

• Internal Pelvic Exam: To check for lumps or unusual changes.
• Ultrasound Exam of the Pelvis: Creates a picture of the internal organs. Transvaginal ultrasound involves inserting an ultrasound wand into the vagina to take pictures of the uterus.
• Blood Chemistry Studies: To check hormone levels and other substances affected by GTN.
• Serum Tumour Marker Test: Checks blood for β-hCG levels, which may indicate GTN if elevated in a non-pregnant woman.
• Urinalysis: Tests urine for β-hCG and other abnormalities.
• Spinal Tap: Tests cerebrospinal fluid for β-hCG if GTN has spread to the brain or spinal cord.
• Computed Tomography (CT): Measures tumour size.
• Chest X-Ray: Checks for tumour spread outside the uterus.

Tumour Staging

• Stage I: Disease confined to the uterus.
• Stage II: GTN extends outside the uterus but is limited to genital structures (adnexa, vagina, broad ligament).
• Stage III: GTN extends to the lungs, with or without genital tract involvement.
• Stage IV: All other metastatic sites.

Pathophysiology

High magnification micrograph of choriocarcinoma

GTNs originate from the placenta, which develops in the uterus during pregnancy. Choriocarcinoma's pathogenesis is not fully understood, but cytotrophoblast cells may transform into malignant forms.

Treatment

Treatment options include surgery, chemotherapy, or a combination of both. Surgical methods such as dilation and curettage or hysterectomy are common initial treatments, depending on the tumour stage.

Prognosis

The FIGO modified Prognostic Scoring System evaluates patients with GTN as low-risk or high-risk based on several factors, including age, pregnancy interval, tumour size or metastases, and prior chemotherapy. Scores range from 0-4 for each factor, and the total score determines risk level:

• Low-risk (Score ≤ 6): Good prognosis, usually responds well to chemotherapy.
• High-risk (Score ≥ 7): Less responsive to chemotherapy, may require intensive treatment.

Epidemiology

GTN is more frequent in Asia compared to North America or Europe. As of 2020, choriocarcinoma incidence ranges from 1 in 40,000 pregnancies in North America and Europe to higher rates in Southeast Asia and Japan. Hydatidiform mole appears more frequently at the extremes of reproductive age (under 15 and over 45), with increased risk after age 35.

Research

Advances in epigenetic modifications and molecular biology techniques aim to improve GTN diagnosis, management, and treatment. Anti-angiogenesis therapy and molecular targeted cancer therapies show promise, particularly for patients with drug resistance. Emerging treatments include genetically engineered neural stem cells, anti-body, and gene therapy, demonstrating significant inhibitory effects on tumour growth.

Self-assessment MCQs (single best answer)

Which of the following is NOT a common symptom of Gestational Trophoblastic Neoplasia (GTN)?

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What is the primary hormone used to diagnose GTN?

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Which of the following is a malignant lesion associated with GTN?

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What is the most common initial treatment method for GTN?

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Which of the following stages of GTN indicates the disease is confined to the uterus?

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Which imaging technique is commonly used to evaluate the spread of GTN to the lungs?

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What type of GTN is characterised by an abnormal proliferation of trophoblast cells following a molar pregnancy?

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According to the FIGO modified Prognostic Scoring System, what score range indicates a low-risk GTN?

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What is a common risk factor for developing a hydatidiform mole?

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Which emerging treatment shows promise for patients with drug-resistant GTN?

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