What is the recommended diagnostic work‑up for suspected choriocarcinoma in a reproductive‑age woman?

Diagnostic Work-Up for Suspected Choriocarcinoma

In a reproductive-age woman with suspected choriocarcinoma, immediately obtain quantitative serum β-hCG, perform transvaginal pelvic ultrasound with Doppler, and obtain CT imaging of chest/abdomen/pelvis plus brain MRI to establish diagnosis and stage the disease before initiating treatment. 1

Initial Clinical Assessment

Key Historical Features to Elicit

• Antecedent pregnancy history: Approximately 50% of choriocarcinomas follow molar pregnancies, 25% follow term pregnancies, and 25% follow other gestational events (miscarriage, ectopic pregnancy, abortion) 2
• Time interval from last pregnancy: Choriocarcinoma can present weeks to years after any pregnancy event 3, 4
• Presenting symptoms: Vaginal bleeding (most common), symptoms of metastatic disease (hemoptysis, neurological symptoms, abdominal pain), or symptoms from markedly elevated β-hCG (hyperthyroidism) 1, 5, 3

Physical Examination Priorities

• Pelvic examination: Assess for uterine size, adnexal masses, and vaginal metastases (appear as purple/blue vascular lesions) 1
• Respiratory examination: Auscultate for signs of pulmonary metastases 1
• Neurological examination: Assess for signs of brain metastases, particularly in high-risk presentations 1

Essential Diagnostic Tests

Serum β-hCG Measurement

• Quantitative serum β-hCG is mandatory and serves as both a diagnostic marker and the primary tumor marker for monitoring treatment response 1, 5
• Use an assay that detects all forms of β-hCG to avoid false-negative results 5
• Markedly elevated levels (>100,000 mIU/mL) suggest either complete molar pregnancy or high-risk gestational trophoblastic neoplasia, though choriocarcinoma can occur at any β-hCG level 6, 5, 3
• Histological evidence of choriocarcinoma is an absolute indication for chemotherapy regardless of β-hCG level 1

Imaging Studies

Pelvic Imaging

• Transvaginal ultrasound with Doppler is the first-line imaging modality to evaluate the uterus and pelvis 1, 5
• Look for: Heterogeneous uterine mass, increased vascularity on Doppler (low pulsatility index predicts resistance to single-agent therapy), and absence of normal pregnancy structures 1, 5
• MRI pelvis provides additional detail for assessing myometrial invasion and pelvic spread 1

Metastatic Work-Up

• CT chest/abdomen/pelvis with contrast is mandatory for all patients to detect pulmonary, hepatic, and other visceral metastases 1
• Pulmonary metastases are the most common site of distant spread and appear as multiple nodules; lesions >2 cm are an indication for chemotherapy 1
• MRI brain is indicated in all poor-prognosis patients, particularly those with choriocarcinoma histology, high β-hCG (>50,000 IU/L), or multiple lung metastases 1
• CT-PET scan may be considered in select cases but is not routinely recommended 1

Histological Confirmation

• Tissue diagnosis is essential when possible but should not delay treatment in life-threatening presentations 1
• Suction curettage under ultrasound guidance is the preferred method for obtaining tissue from suspected uterine disease 1, 5
• All products of conception must undergo histological examination to avoid delayed diagnosis 6, 5
• Characteristic histology: Biphasic proliferation of cytotrophoblast and syncytiotrophoblast without chorionic villi, with abnormal trophoblast invasion 1

Additional Laboratory Tests

• Complete blood count: Assess for anemia from vaginal bleeding 5, 3
• Blood group determination: Required for anti-D immunization in Rh-negative women 5
• Thyroid function tests: If hyperthyroidism is suspected (β-hCG can cross-react with TSH receptor) 5
• Liver and renal function tests: Baseline assessment before chemotherapy 1

Risk Stratification Using FIGO Scoring

After diagnosis, apply the FIGO/WHO prognostic scoring system to determine low-risk (score 0-6) versus high-risk (score ≥7) disease, which dictates treatment approach 1, 2, 3

FIGO Scoring Factors

• Age: ≥40 years scores 1 point 1
• Antecedent pregnancy: Molar pregnancy scores 0, abortion scores 1, term pregnancy scores 2 1
• Interval from index pregnancy: <4 months scores 0,4-6 months scores 1,7-12 months scores 2, >12 months scores 4 1
• Pre-treatment β-hCG: <10³ scores 0,10³-10⁴ scores 1,10⁴-10⁵ scores 2, >10⁵ scores 4 1
• Largest tumor size: <3 cm scores 0,3-4 cm scores 1, ≥5 cm scores 2 1
• Sites of metastases: Lung scores 0, spleen/kidney scores 1, gastrointestinal tract scores 2, liver/brain scores 4 1
• Number of metastases: 0 scores 0,1-4 scores 1,5-8 scores 2, >8 scores 4 1
• Prior failed chemotherapy: None scores 0, single drug scores 2, ≥2 drugs scores 4 1

Critical Diagnostic Pitfalls

Do Not Delay Imaging Based on β-hCG Level

• Choriocarcinoma can present at any β-hCG level and imaging should never be deferred based on "low" values 7
• Approximately 22% of ectopic pregnancies occur with β-hCG <1,000 mIU/mL, and similar principles apply to choriocarcinoma 7

Recognize Atypical Presentations

• Choriocarcinoma can occur in ectopic locations including fallopian tube and ovary, separate from any intrauterine disease 4
• Gastrointestinal and brain metastases can present as acute surgical emergencies (bowel perforation, intracranial hemorrhage) before the primary diagnosis is established 8
• Postpartum choriocarcinoma may be mistaken for retained placenta when presenting with vaginal bleeding weeks after delivery 3

Distinguish Gestational from Non-Gestational Disease

• Gestational choriocarcinoma has a much better prognosis and responds better to chemotherapy than non-gestational disease 2, 4
• Genotyping can distinguish these subtypes when the diagnosis is uncertain, particularly for ovarian or pelvic tumors 4
• Most gestational choriocarcinomas are androgenetic/homozygous XX and often associated with prior complete molar pregnancy 4

Avoid Misdiagnosis in Post-Molar Surveillance

• Plateauing or rising β-hCG after molar evacuation indicates post-mole gestational trophoblastic neoplasia (which may be choriocarcinoma) and requires immediate evaluation 1, 7
• UK criteria: Four equivalent β-hCG values over 3 weeks OR two consecutive rises of ≥10% over 2 weeks 1
• Heavy vaginal bleeding, evidence of metastases, or β-hCG ≥20,000 IU/L at 4 weeks post-evacuation are all indications to begin treatment 1

Diagnostic Algorithm Summary

1. Obtain quantitative serum β-hCG immediately when choriocarcinoma is suspected 1, 5
2. Perform transvaginal ultrasound with Doppler to evaluate the uterus and pelvis 1, 5
3. Obtain CT chest/abdomen/pelvis to assess for metastatic disease 1
4. Add brain MRI if high-risk features present (choriocarcinoma histology, β-hCG >50,000 IU/L, multiple lung metastases, or neurological symptoms) 1
5. Obtain tissue diagnosis via suction curettage when feasible, but do not delay treatment in life-threatening presentations 1, 5
6. Calculate FIGO prognostic score to stratify risk and guide treatment selection 1, 2
7. Initiate chemotherapy promptly once diagnosis is established, as choriocarcinoma is highly aggressive but also highly chemosensitive 1, 2