Choriocarcinoma

Abstract

Choriocarcinoma is a form of malignant gestational trophoblastic disease. This can occur when there is evidence of persistent trophoblastic tissue after a pregnancy and is usually diagnosed after evacuation of a molar pregnancy and a persistently rising beta hCG. Choriocarcinoma can invade the vasculature, resulting in metastases to lung, vagina, brain, and liver most commonly. Before instituting therapy, a complete evaluation, including pelvic ultrasound, chest imaging, and brain MRI, are often ordered, with treatment based on FIGO or WHO staging.

Keywords

gestational trophoblastic neoplasia, choriocarcinoma, treatment, chemotherapy, prognosis, staging

Introduction

Malignant gestational trophoblastic disease (GTD) occurs when there is clinical, radiologic, pathologic, or hormonal evidence of persistent trophoblastic tissue, or abnormal growth of trophoblastic tissue. This is most commonly diagnosed after a molar pregnancy, but it can occur after any type of pregnancy.

Disease

Definition

Choriocarcinoma is a form of malignant GTD. It arises from cytotrophoblast as well as syncytiotrophoblasts without villi, and produces human chorionic gonadotropin (hCG).

Prevalence and Epidemiology

Choriocarcinoma develops in approximately 0.6 : 10,000 normal gestations, 0.7 : 10,000 abortions, and 250 : 10,000 complete molar pregnancies. It is the most aggressive form of gestational trophoblastic neoplasia (GTN), most commonly characterized by early vascular invasion and widespread metastases to the lungs, followed in frequency by the vagina, liver, and brain. The two factors consistently associated with increased risk of GTN are maternal age and history of hydatidiform mole.

Etiology and Pathophysiology

Gestational choriocarcinoma is comprised of both neoplastic syncytiotrophoblast and cytotrophoblast elements without chorionic villi. Choriocarcinoma is the most aggressive type of GTN, and often metastasizes hematogenously. Most choriocarcinomas have an aneuploidy karyotype, and approximately three-quarters contain a Y chromosome. Half of choriocarcinomas follow a molar pregnancy, and approximately one-fourth of choriocarcinomas are preceded by a full-term pregnancy.

Manifestations of Disease

Clinical Presentation

Following evacuation of a complete or partial molar pregnancy, the diagnosis of malignant trophoblastic disease, including choriocarcinoma, is usually made clinically based on a rising or stable serum beta hCG. However, women who develop malignant GTD after a nonmolar pregnancy usually undergo evaluation with ultrasound (US) and serum beta hCG only after they present with symptoms such as late postpartum bleeding.

According to the International Federation of Gynecology and Obstetrics (FIGO), the diagnosis can be made based on clinical or histopathologic criteria including:

1.

an hCG plateau for at least four values over 3 weeks
2.

an hCG increase of 10% or greater for at least three values over 2 weeks
3.

hCG persistence 6 months or more after molar pregnancy evacuation
4.

histopathologic diagnosis of choriocarcinoma
5.

presence of metastatic disease

Choriocarcinoma can metastasize due to its propensity for early vascular invasion. As the most common metastatic sites are lung (80%), vagina (30%), brain (10%), and liver (10%), disease can present with respiratory symptoms such as cough, chest pain, or hemoptysis or with gastrointestinal, urologic, or intracerebral bleeding.

Imaging Technique and Findings

Ultrasound.

Patients with suspected malignant GTD must undergo a thorough evaluation prior to institution of therapy. Patients should have pelvic ultrasonography with Doppler to look for retained trophoblastic tissue, measure the uterine size and volume, and evaluate the pelvis for local disease spread and disease vascularity. Choriocarcinomas appear as heterogeneous, echogenic uterine masses with areas of necrosis and hemorrhage. They are markedly hypervascular on Doppler interrogation.

Magnetic Resonance Imaging.

As pulmonary metastases are most common, chest imaging via chest radiograph or computed tomography (CT) are required to evaluate for lung metastases. If lesions are noted within the chest, whole body imaging with CT or 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) scan can be used to evaluate for more widespread disease. Brain magnetic resonance imaging (MRI), and in cases of equivocal findings, a lumbar puncture may be indicated to evaluate occult cerebral or meningeal disease. Choriocarcinomas typically present on MRI as heterogeneous endometrial or myometrial masses with necrosis, hemorrhage, and solid enhancing components. T2-weighted images are usually hyperintense, and MRI may also help to discern extrauterine invasion. Biopsies should not be performed because these lesions are highly vascular and may bleed heavily.

Synopsis of Treatment Options

Prenatal

Treatment recommendations will depend on a staging system that includes the International FIGO classification of disease stage, as well as the World Health Organization (WHO), which published a prognostic scoring system that assigned a weighted value to different individual clinical variables. Choriocarcinoma is staged similar to malignant GTN. The total prognostic index score used was a sum of the individual component scores to generate three risk categories. This scoring system was incorporated into the revised FIGO staging system ( Tables 100.1 and 100.2 ).

TABLE 100.1

FIGO STAGING OF GESTATIONAL TROPHOBLASTIC NEOPLASIA

Stage I	Disease confined to uterus
Stage II	Disease extending outside of uterus, but limited to genital structures
Stage III	Disease spread to lungs, with or without genital tract involvement
Stage IV	All other metastatic sites