Choriocarcinoma: Epidemiology, Etiology, Pathology, Symptoms, Diagnosis, Staging, Treatment and Prevention

Choriocarcinoma

~Introduction

Choriocarcinoma is a rare, highly malignant tumor that arises from trophoblastic tissue, the cells that normally form the placenta during pregnancy. It belongs to the group of gestational trophoblastic neoplasms (GTNs) and is characterized by aggressive growth, early hematogenous spread, and markedly elevated levels of human chorionic gonadotropin (hCG). Despite its malignant nature, choriocarcinoma is one of the most curable cancers, even in the presence of widespread metastases, due to its remarkable sensitivity to chemotherapy.

Choriocarcinoma can be classified as gestational or non-gestational, with the former being more common and associated with pregnancy-related events such as hydatidiform mole, normal pregnancy, ectopic pregnancy, or abortion. Non-gestational choriocarcinoma arises from germ cells and may occur in the ovaries, testes, or extragonadal sites.

~Historical Background

The term “choriocarcinoma” originates from the Greek words chorion (fetal membrane) and carcinoma (cancer). It was first recognized as a distinct pathological entity in the late 19th century. Before the advent of chemotherapy, choriocarcinoma was almost universally fatal. The introduction of methotrexate therapy in the 1950s revolutionized treatment and transformed this once-deadly disease into one with cure rates exceeding 90%.

~Epidemiology

Choriocarcinoma is rare, with incidence varying by geographic region:

• Gestational choriocarcinoma occurs in approximately:

  • 1 in 20,000–40,000 pregnancies in Western countries

  • Higher incidence in Asia, Africa, and Latin America

• Non-gestational choriocarcinoma is extremely rare and usually occurs as part of mixed germ cell tumors.

Risk Factors

• Previous hydatidiform mole (most common)

• Extremes of maternal age (<20 or >35 years)

• Prior history of gestational trophoblastic disease

• Short interval between pregnancies

~Etiology and Pathogenesis

Gestational Choriocarcinoma

Gestational choriocarcinoma develops from abnormal proliferation of trophoblastic tissue following:

• Complete hydatidiform mole (most common)

• Partial mole

• Normal pregnancy

• Spontaneous or induced abortion

• Ectopic pregnancy

The tumor is composed of malignant cytotrophoblasts and syncytiotrophoblasts without formation of chorionic villi. These cells invade the myometrium and blood vessels, leading to early metastasis.

Non-Gestational Choriocarcinoma

This form arises from germ cells and is genetically unrelated to pregnancy. It may occur in:

• Ovaries

• Testes

• Mediastinum

• Retroperitoneum

~Pathology

Gross Appearance

• Soft, hemorrhagic, necrotic mass

• Poorly circumscribed

• Extensive areas of hemorrhage due to vascular invasion

Microscopic Features

• Absence of chorionic villi

• Biphasic population of cells:

  • Cytotrophoblasts: mononuclear, polygonal cells

  • Syncytiotrophoblasts: multinucleated giant cells

• Extensive hemorrhage and necrosis

• High mitotic activity

Immunohistochemistry

• Strong positivity for β-hCG

• Positive for placental alkaline phosphatase (PLAP)

• Cytokeratin-positive

~Clinical Features

Choriocarcinoma typically presents weeks to months after a pregnancy-related event.

Gynecological Symptoms

• Persistent or irregular vaginal bleeding

• Enlarged uterus inconsistent with gestational age

• Amenorrhea or secondary postpartum hemorrhage

Systemic Symptoms

Due to early metastasis:

• Lungs: cough, hemoptysis, dyspnea

• Brain: headaches, seizures, focal neurological deficits

• Liver: abdominal pain, jaundice

• Vagina: bluish hemorrhagic nodules

~Metastasis

Choriocarcinoma spreads hematogenously, often early in the disease.

Common Sites

1. Lungs (most common)

2. Vagina

3. Brain

4. Liver

5. Kidneys

6. Gastrointestinal tract

~Diagnosis

Laboratory Investigations

• Markedly elevated serum β-hCG (often >100,000 IU/L)

• Serial hCG monitoring is crucial for diagnosis and follow-up

Imaging Studies

• Pelvic ultrasound: intrauterine mass

• Chest X-ray/CT scan: pulmonary metastases

• CT/MRI brain: suspected CNS involvement

• CT abdomen: liver metastases

Histopathological Confirmation

Biopsy is usually avoided due to the risk of severe hemorrhage. Diagnosis is often clinical, based on:

• Elevated hCG

• History of recent pregnancy

• Radiologic findings

~Staging and Risk Assessment

The FIGO staging system combined with the WHO prognostic scoring system is used.

FIGO Staging

• Stage I: confined to uterus

• Stage II: extends to genital structures

• Stage III: lung metastases

• Stage IV: metastases to other organs

WHO Risk Score

Factors include:

• Age

• Type of antecedent pregnancy

• Interval since pregnancy

• Pretreatment hCG level

• Size and site of metastases

• Previous chemotherapy

Patients are classified as:

• Low-risk (score ≤6)

• High-risk (score ≥7)

~Treatment

Choriocarcinoma is highly chemosensitive, making chemotherapy the cornerstone of treatment.

Low-Risk Disease

• Single-agent chemotherapy:

  • Methotrexate

  • Actinomycin D

• Cure rates exceed 95%

High-Risk Disease

• Combination chemotherapy:

  • EMA-CO regimen

    • Etoposide

    • Methotrexate

    • Actinomycin D

    • Cyclophosphamide

    • Vincristine

• Requires intensive monitoring

Surgical Management

• Hysterectomy in selected cases (e.g., uncontrolled bleeding)

• Resection of isolated resistant metastases

Radiotherapy

• Used for brain metastases or uncontrolled hemorrhage

~Follow-Up and Monitoring

• Serial serum β-hCG measurements:

  • Weekly until normalization

  • Monthly for 6–12 months

• Effective contraception during follow-up

• Pregnancy should be avoided for at least one year

~Prognosis

The prognosis of choriocarcinoma is excellent with appropriate treatment.

• Low-risk disease: >98% survival

• High-risk disease: 80–90% survival

• Poor prognostic factors:

  • Liver or brain metastases

  • Very high hCG levels

  • Delayed diagnosis

~Complications

• Severe hemorrhage

• Chemotherapy-related toxicity

• Tumor lysis syndrome (rare)

• Psychological impact and fertility concerns

~Prevention and Screening

• Early detection and proper management of hydatidiform mole

• Regular hCG follow-up after molar pregnancy

• Patient education regarding symptoms

~Choriocarcinoma in Males and Children

Non-gestational choriocarcinoma can occur in males as part of testicular germ cell tumors. It is aggressive and associated with:

• Gynecomastia

• High β-hCG

• Poor prognosis compared to gestational type

~Conclusion

Choriocarcinoma is a rare but aggressive malignancy originating from trophoblastic tissue. Despite its rapid growth and early metastasis, it stands out as one of the most treatable and curable cancers in modern medicine. Early diagnosis through hCG monitoring, accurate staging, and prompt initiation of chemotherapy are essential for favorable outcomes. Advances in chemotherapy regimens and follow-up strategies have significantly improved survival rates, preserving fertility and quality of life in most patients.