A mother developed multimetastatic gestational choriocarcinoma 13 months after delivery, and her infant died aged 11 months from the same tumor. The transplacental choriocarcinoma transmission was confirmed by genotyping. Henceforth, we recommend a 2-year maternal human chorionic gonadotropin follow-up after neonatal choriocarcinoma and extensive imaging if the human chorionic gonadotropin rises.
Choriocarcinoma following a live birth is a rare variant of gestational trophoblastic neoplasia and occurs in about 1 per 50,000 births. Typically, children with infantile choriocarcinoma become symptomatic at a median age of 1 month, whereas maternal disease commonly presents several months postterm with vaginal bleeding and multiple metastases. To date, transplacental choriocarcinoma transmission has already been suspected in several cases but never been confirmed by genotyping.
Case Report
In November 2008, a 5-month male infant was admitted to the hospital because of dyspnea and anemia (68 g/L). The clinical diagnosis of choriocarcinoma was established based on an elevated human chorionic gonadotropin (hCG) serum level of 27,860 IU/L, the presence of a liver mass, enlarged mediastinal lymph nodes, and pulmonary metastases. The placenta was no longer available for examination because it was macroscopically normal at the time of delivery.
Chemotherapy with etoposide, ifosfamide, and cisplatinum was initiated. After 3 courses, hCG decreased to 16 IU/L but then rose despite a second (1 course of bleomycin, vinblastine, and high-dose methotrexate) and a third line (2 courses of cisplatinium and liposomal doxorubicin) chemotherapy regimens. An extended hepatectomy was performed but hCG levels continued to increase. Histopathological examination revealed choriocarcinoma. Although a fourth line palliative chemotherapy (gemcitabine and oxaliplatinum) was given, the infant died aged 11 months.
The mother was 35 years old and had no previous history of molar pregnancy. Her hCG remained normal apart from a transient increase to 16 IU/L ( Figure ). However, a consistent increase to 107 IU/L was discovered 13 months after delivery when she also described intermittent headache and partial loss of vision. Whole-body computerized and 18 F-fluorodeoxyglucose-positron emission tomography showed a left occipital brain lesion, multiple pulmonary, and a left adrenal metastasis but normal pelvis. Magnetic resonance imaging of the pelvis was also normal.
The brain lesion was resected, and histology was consistent with necrotic metastasis of choriocarcinoma (International Federation Gynecology and Obstetrics stage IV score 14). Chemotherapy (combination of etoposide, actinomycin D, and cisplatinum) was initiated. Her hCG levels returned to normal after the first of 3 courses of chemotherapy, which were followed by stereotactic brain irradiation (39 Grays in 13 fractions). The lung nodules disappeared after chemotherapy but not the adrenal lesion, which persisted and was resected to avoid relapse. Histopathological examination found no viable cells in an adrenal metastasis from the choriocarcinoma. Three years after her diagnosis, hCG monitoring, magnetic resonance imaging, and positron emission tomography scan evaluations showed no evidence of relapse.
To determine the origin of the tumor in the mother, we genotyped with their agreement the patient and her partner (peripheral blood), tissue from the infant’s liver, and the mother’s brain metastases ( Table ). Deoxyribonucleic acid (DNA) was amplified using the AmpFlSTR Identifiler Plus kit (Applied Biosystems, Foster City, CA). Polymerase chain reaction products were separated by gel electrophoresis using the ABI 3100 and analyzed using GeneMapper Software (Applied Biosystems). This resulted in fluorescently labeled alleles for 15 autosomal loci on different chromosomes and a sex chromosome marker. The tumor in the infant’s liver showed loss of heterozygosity for a number of markers. However, there were no alleles present in the tumor that were not present in the child, confirming the tumor had originated in the same pregnancy as the infant. Genotyping confirmed the maternal brain metastasis was from a gestational trophoblastic tumor. Moreover, the liver metastases in the infant and the brain metastasis in the patient were derived from the same tumor.
