Gestational trophoblastic neoplasm (ORPHA:59305)
A rare, malignant group of gestational trophoblastic diseases always following pregnancy, most often molar pregnancy (hydatidiform mole). Four histological forms are described: invasive mole, gestational choriocarcinoma, placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT).
Epidemiology
Gestational choriocarcinoma is the most frequent form of gestational trophoblastic neoplasia (GTN); whilst epidemiological data is limited, in the Netherland incidence is estimated at 1/33,000 deliveries and in the USA 1/41,000 pregnancies. This disease appears to be more frequent amongst the Asian population. The PSTT and ETT occur less frequently, with a reported incidence in the Netherlands of approximately 1/100,000 and 1/1,000,000, respectively.
Clinical description
Indicative signs of GTN are an absence of normalization or a secondary elevation of total serum chorionic gonadotropin (hCG) levels after evacuation of a hydatidiform mole (more than 60% of cases), persistent unexplained metrorrhagia following spontaneous miscarriage or voluntary termination of pregnancy (about 30% of cases) and very occasionally, unexplained metrorrhagia in the weeks or months following normal childbirth or ectopic pregnancy (about 10% of cases). Exceptionally, metastasis may be a sign of the disease in women of childbearing age.
Etiology
The etiology of GTN is not known. Identification of a GTN is based on a total serum hCG assay, which is recommended following hydatidiform moles in patients with metrorrhagia persisting for more than six weeks after pregnancy, and in any patient of childbearing age who has metastasis (lung, liver, brain, kidney, vagina) with no known primary tumor.
Diagnostic methods
Diagnosis of a post-molar GTN relies on one of the following four criteria: stable hCG levels (variation of less than 10%) with at least four weekly assays over a period of at least three weeks (days 1, 7, 14, 21), increase of at least 10% in hCG with at least three weekly assays over at least two weeks (days 1, 7, 14), persistence of detectable hCG values for more than six months following mole evacuation or based on histological diagnosis of a choriocarcinoma.
Differential diagnosis
GTNs must not be confused with hydatidiform moles and, for choriocarcinomas, with non-gestational choriocarcinomas, which are most often ovarian.
Antenatal diagnosis
Diagnosis of hydatidiform mole is often by ultrasound and hCG concentration.
Genetic counseling
In extremely rare cases, recurrent molar pregnancy with or without post-molar GTN can have a genetic cause (NLRP7 mutation) with an autosomal recessive pattern of inheritance (familial recurrent hydatidiform mole).
Management and treatment
As soon as the diagnosis is made, staging must be performed to identify frequent metastases. Staging involves pelvic ultrasound, pelvic and cerebral MRI, and abdominal/chest CT. A lung X-ray must be performed to calculate the FIGO 2000 score (International Federation of Obstetrics and Gynecology). This score makes it possible to distinguish between low-risk GTNs (score of 6 or lower) and high-risk GTNs (score of 7 or higher). Management should be multidisciplinary and must be discussed by a panel of physicians, preferably in a specialized center. Low-risk tumors are treated by systemic single-agent chemotherapy, e.g. methotrexate or dactinomycin. High-risk tumors are treated first line with systemic multi-agent chemotherapy. Hysterectomy can of course not be considered for first-line treatment in women who wish to become pregnant, unless there is no other option, but can be considered for older women or women who do not wish to bear children. Placental site trophoblastic tumors and epithelioid trophoblastic tumors are special cases: the FIGO score is not appropriate and total hysterectomy is the standard treatment as these tumors are usually chemo-resistant. For advanced stage disease, multi-agent chemotherapy is indicated. hCG levels should be surveyed during and following treatment.
Prognosis
The overall recovery rate for low-risk GTN is around 99%. The prognosis is very closely related to the FIGO score and, in case of PSTT and ETT, FIGO stage.

                            Last update: 
                            May 2022


                            - Expert reviewer(s): 
                            Dr Baljeet KAUR | EURACAN* - Dr Christianne LOK 


                                * European Reference Network