Definition/General
Introduction:
Placental choriocarcinoma is a highly malignant trophoblastic tumor composed of both syncytiotrophoblast and cytotrophoblast without chorionic villi
It represents the most aggressive form of gestational trophoblastic disease
The tumor has high metastatic potential
It occurs in 1 in 20,000-40,000 pregnancies
Excellent response to chemotherapy when diagnosed early.
Origin:
Arises from abnormal trophoblastic proliferation
May develop after any gestational event (normal pregnancy, abortion, molar pregnancy)
Malignant transformation of trophoblastic tissue
Loss of normal growth controls
Invasive and metastatic from onset.
Classification:
Part of gestational trophoblastic neoplasia: Invasive mole
Choriocarcinoma
Placental site trophoblastic tumor
Epithelioid trophoblastic tumor
By origin: Post-molar (50%)
Post-abortion (25%)
Post-term pregnancy (25%).
Epidemiology:
Incidence: 1:20,000-40,000 pregnancies
Higher in Asian countries
Risk after complete mole: 15-20%
Risk after partial mole: <2%
Bimodal age distribution
More common at extremes of age.
Clinical Features
Presentation:
Irregular vaginal bleeding
Persistently elevated β-hCG
Uterine enlargement
Theca lutein cysts
Pulmonary symptoms (metastases)
Neurological symptoms (brain metastases)
Abdominal pain.
Symptoms:
Abnormal bleeding (90% cases)
Amenorrhea followed by bleeding
Pelvic pain
Cough, hemoptysis (lung metastases)
Headache, seizures (brain metastases)
Abdominal distension.
Risk Factors:
Previous molar pregnancy (major risk)
Extremes of age (<20, >40 years)
Asian ethnicity
ABO blood group incompatibility
Previous miscarriages
Oral contraceptive use
Dietary factors (low carotene).
Screening:
Serial β-hCG monitoring
Pelvic ultrasound
Chest X-ray (lung metastases)
CT/MRI (staging)
Complete blood count
Liver function tests.
Master Choriocarcinoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Hemorrhagic, friable mass
Dark red to purple color
Soft, necrotic areas
No identifiable chorionic villi
Extensively necrotic and hemorrhagic
Infiltrative growth pattern.
Characteristics:
Bulky, irregular masses
Areas of necrosis and hemorrhage
Myometrial invasion
Vascular invasion prominent
Absence of villous structures.
Size Location:
Variable size: few cm to large masses
Uterine corpus most common
Cervical involvement possible
Extrauterine sites: lungs, brain, liver
Metastatic deposits.
Multifocality:
Multifocal growth common
Extensive metastases
Hematogenous spread
Pulmonary nodules
CNS involvement.
Microscopic Description
Histological Features:
Biphasic pattern: syncytiotrophoblast and cytotrophoblast
Absence of chorionic villi
Extensive necrosis
Hemorrhage
Vascular invasion
High mitotic activity.
Cellular Characteristics:
Syncytiotrophoblast: multinucleated giant cells
Cytotrophoblast: mononuclear cells
Marked pleomorphism
Prominent nucleoli
Atypical mitoses
Extensive necrosis.
Architectural Patterns:
Sheets and nests of trophoblast
No villous architecture
Hemorrhage and necrosis
Vascular space invasion
Invasive growth pattern.
Grading Criteria:
WHO classification: Low-risk vs high-risk
FIGO staging
Prognostic scoring: age, β-hCG level, size, sites of metastases
Risk stratification guides therapy.
Immunohistochemistry
Positive Markers:
β-hCG (syncytiotrophoblast)
hPL (human placental lactogen)
Cytokeratin (trophoblast)
Inhibin-α
CD68 (occasional)
Ki-67 (high proliferation).
Negative Markers:
p63 (usually negative in syncytiotrophoblast)
Mel-CAM (extravillous trophoblast)
EMA (variable)
CD10 (stromal marker).
Diagnostic Utility:
Confirms trophoblastic origin
Distinguishes from other tumors
β-hCG essential for diagnosis
Proliferation markers assess aggressiveness.
Molecular Subtypes:
Post-molar choriocarcinoma
Post-gestational choriocarcinoma
Primary ovarian choriocarcinoma
Non-gestational choriocarcinoma.
Molecular/Genetic
Genetic Mutations:
p53 mutations
PTEN alterations
PIK3CA mutations
Beta-catenin pathway
Chromosomal instability.
Molecular Markers:
High β-hCG production
Increased VEGF
Matrix metalloproteinases
Angiogenic factors
Drug resistance markers.
Prognostic Significance:
β-hCG level most important
Site of metastases
Time from pregnancy
Prior chemotherapy
Histological features.
Therapeutic Targets:
Methotrexate (single agent)
Combination chemotherapy (EMA/CO)
High-dose therapy (resistant cases)
Surgery (selected cases)
Immunotherapy (experimental).
Differential Diagnosis
Similar Entities:
Invasive mole
Placental site trophoblastic tumor
Epithelioid trophoblastic tumor
Carcinoma (poorly differentiated)
Melanoma
Sarcoma.
Distinguishing Features:
Choriocarcinoma: No chorionic villi
Biphasic pattern
High β-hCG
Invasive mole: Villi present
Intact basement membrane
PSTT: Intermediate trophoblast
Lower β-hCG.
Diagnostic Challenges:
Extensive necrosis obscures morphology
Small biopsy samples
Distinguishing from other poorly differentiated tumors
Clinical correlation essential.
Rare Variants:
Choriocarcinoma syndrome
Intraplacental choriocarcinoma
Choriocarcinoma in teratoma
Primary extragonadal choriocarcinoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[Curettage/Hysterectomy] specimen with choriocarcinoma
Diagnosis
Choriocarcinoma
Clinical Correlation
Elevated β-hCG: [X] mIU/mL, [clinical presentation]
Gross Findings
Hemorrhagic, friable tissue, no identifiable chorionic villi
Microscopic Findings
Biphasic trophoblast population, no villi, extensive necrosis
Immunohistochemistry
β-hCG: positive (syncytiotrophoblast), Ki-67: [X]%
Staging
FIGO Stage [I-IV], WHO Risk Score: [low/high]
Risk Assessment
[Low/High] risk based on prognostic factors
Treatment Recommendation
[Single agent/Combination] chemotherapy indicated
Final Diagnosis
Choriocarcinoma, [risk category]