Evaluation and Diagnosis of Choriocarcinoma
Immediately obtain quantitative serum β-hCG, perform transvaginal Doppler pelvic ultrasound, and acquire chest imaging when choriocarcinoma is suspected—these three tests establish baseline disease burden and identify the most common metastatic site (lung). 1
Initial Diagnostic Workup
Mandatory Baseline Tests
- Quantitative serum β-hCG is required for baseline risk stratification and subsequent monitoring of treatment response 1
- Transvaginal Doppler pelvic ultrasound evaluates uterine size, vascularity, and identifies characteristic findings including abnormal trophoblastic proliferation without chorionic villi, accompanied by hemorrhage and necrosis 2, 1
- Chest X-ray serves as the initial screen for pulmonary metastases, which represent the most frequent site of spread 1
- Measure β-hCG and α-fetoprotein (AFP) when evaluating mediastinal or retroperitoneal masses, as these suggest possible germ cell tumor origin 2
Clinical Presentation Patterns
Choriocarcinoma arises from different antecedent pregnancies with distinct frequencies 2:
- 50% follow hydatidiform mole (complete or partial)
- 25% occur after term or preterm gestation
- 25% develop after tubal pregnancy or abortion
Patients typically present with persistent vaginal bleeding, markedly elevated hCG (often >100,000 IU/L), and may have symptoms related to metastatic disease 2, 3
Extended Staging for Metastatic Disease
When to Obtain Advanced Imaging
If pulmonary lesions larger than 1 cm are seen on chest X-ray or if the patient has symptoms suggesting advanced disease, obtain contrast-enhanced CT of the chest, abdomen, and pelvis to delineate thoracic and abdominal tumor extent 1
Brain Metastasis Screening
- Perform brain MRI to detect cerebral metastases, which occur in roughly 20% of patients and necessitate additional therapeutic considerations 1
- Brain involvement is associated with poorer prognosis and requires intensified systemic chemotherapy plus consideration of intrathecal methotrexate and/or whole-brain radiotherapy 2, 1
Additional Imaging Considerations
- CT-PET may be employed in complex cases or when conventional imaging is equivocal 1
- For patients with mediastinal involvement, testicular ultrasound should be considered if β-hCG and AFP levels are elevated in men 2
Histopathologic Confirmation
Histological confirmation of choriocarcinoma mandates immediate initiation of chemotherapy, irrespective of the serum hCG level or its trend 1
Characteristic tissue findings include 2:
- Abnormal trophoblastic hyperplasia and anaplasia
- hCG production
- Absence of chorionic villi (distinguishes from invasive mole)
- Hemorrhage and necrosis
FIGO Risk Stratification
All patients must be scored using the FIGO prognostic system (maximum 24 points) to determine whether single-agent or multi-agent chemotherapy is indicated 1
Risk Categories
- Low-risk disease: FIGO score 0-6 1, 3
- High-risk disease: FIGO score ≥7 1, 3
- Ultra-high-risk disease: FIGO score ≥13, requiring a modified initial approach 1
The FIGO scoring incorporates age, antecedent pregnancy type, interval from index pregnancy, pretreatment hCG level, largest tumor size, sites of metastases, number of metastases, and prior failed chemotherapy 2
Post-Molar Pregnancy Surveillance
Monitoring Protocol After Molar Evacuation
- Measure serum hCG at least once every 2 weeks until normalization after diagnosis of hydatidiform mole 2
- For complete hydatidiform mole, continue monthly hCG monitoring for up to 6 months after normalization 2
- Plateauing or rising hCG levels after molar pregnancy treatment suggests development of gestational trophoblastic neoplasia 2, 4
Diagnostic Criteria for Post-Molar GTN
Post-molar GTN develops in approximately 15-20% of complete moles but only 1-5% of partial moles 2. Diagnosis is made when:
- hCG plateaus over 3 consecutive cycles (four equivalent values over at least 3 weeks) 2
- hCG rises over 2 consecutive cycles 2
- Histologic diagnosis of choriocarcinoma is confirmed 2
Critical Diagnostic Pitfalls
Do Not Delay Treatment
Do not postpone chemotherapy while awaiting hCG trends when histology confirms choriocarcinoma; tissue diagnosis alone obligates immediate treatment 1. Choriocarcinoma grows rapidly and may progress if there is treatment delay 2
Do Not Rely Solely on hCG
Do not rely solely on hCG to rule out metastases; imaging is mandatory for accurate staging 1. Approximately 2-3% of hydatidiform moles progress to choriocarcinoma, and early detection through imaging improves outcomes 2
Recognize Choriocarcinoma Syndrome
Be aware of choriocarcinoma syndrome, characterized by bleeding from metastatic sites, which represents a medical emergency associated with high morbidity and mortality 5, 6. This occurs predominantly in patients with extensive lung metastases and can manifest as acute respiratory distress syndrome following chemotherapy initiation 6
Assay Interference
When hCG results do not fit the clinical picture, measure hCG on a different assay, as different assays have varying sensitivities and may detect different forms of hCG 7. Cross-reactive molecules in blood that cause false positives rarely get into urine, so urine hCG can help confirm true elevation 7, 8
Special Diagnostic Considerations
Testicular Choriocarcinoma
In young men presenting with testicular mass and markedly elevated hCG, consider testicular choriocarcinoma—an aggressive subtype with 5-year survival less than 80% compared to >95% for other germ cell tumors 5. Testicular ultrasound should be performed if β-hCG and AFP are elevated in men with mediastinal or retroperitoneal masses 2
Intracranial Germ Cell Tumors
Most (93.3%) intracranial germ cell tumors show elevated hCGβ expression compared to normal brain tissue, with the highest expression in tumors harboring choriocarcinoma or syncytiotrophoblastic giant cell components 9. However, hCG levels may need to be interpreted with caution as most germ cell tumors have the capacity to produce hCG irrespective of histology 9