Gestational trophoblastic disease should be suspected if a pregnant woman experiences unexplained vaginal bleeding or if bleeding after miscarriage or delivery (lochia) persists for an abnormally long time.
The diagnosis is based on an ultrasound examination of the uterus and on a serum human chorionic gonadotrophin (hCG) assay.
Definitions
Hydatidiform mole (molar pregnancy) is a disease of the placenta characterised by trophoblastic hyperplasia and chorionic villi with grapelike (hydatidiform) swelling.
Hydatidiform mole may be subdivided into complete and partial mole based on histopathological features. Their caryotype and clinical features differ from each other (table T1).
If left untreated, hydatidiform mole may penetrate the myometrium (invasive mole).
Choriocarcinoma, epithelioid trophoblastic tumour and placental site trophoblastic tumour are malignant trophoblastic neoplasms.
Approximately half of all choriocarcinomas occur after complete hydatidiform mole, the rest occur after partial hydatidiform mole, full term pregnancy, miscarriage or ectopic pregnancy.
Comparison of complete and partial hydatidiform mole
There is significant variability in the incidence of gestational trophoblastic disease between different regions of the world. The incidence is lower in western industrialized countries than in Africa or in Southeast Asia http://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.13877.
The risk is increased in women aged either less than 20 years or more then 40 years. A history of previous hydatidiform mole is a risk factor predisposing to another molar pregnancy.
Signs and symptoms
Vaginal bleeding is the most common presenting symptom (over 90% of cases).
Unexplained and prolonged bleeding after miscarriage or delivery (lochia) warrants an hCG test in order to exclude gestational trophoblastic disease.
High hCG concentrations may be associated with hyperemesis gravidarum or ovarian theca lutein cysts.
In complete hydatidiform mole the serum hCG concentration may be significantly higher than in normal pregnancy. In partial hydatidiform mole, the concentration is often within the reference range for a normal singleton pregnancy (< 200 000 IU/l).
In complete mole, an ultrasound examination will typically reveal a ”snow storm” pattern (picture) with no evidence of fetal tissue. The findings of an ultrasound examination of partial mole will be similar to miscarriage or missed abortion.
Metastases may occur both in hydatidiform mole and malignant trophoblastic diseases.
The lungs are the most common site of metastasis, and the patient may present with dyspnoea and haemoptysis.
Metastases may also develop in the vagina, liver and brain.
In hydatidiform mole, a plain chest x-ray is used as a staging investigation. In malignant trophoblastic neoplasms, a whole body CT scan as well as an MRI scan of the lower abdomen and the brain are performed.
Treatment
Suction curettage is the method of choice for evacuation of hydatidiform mole. Anti-D prophylaxis is given to RhD-negative patients. Hysterectomy may be considered if the patient does not wish to become pregnant again.
Postmolar GTN (gestational trophoblastic neoplasia) denotes a situation where serum hCG concentration does not decrease as expected after the treatment of hydatidiform mole or the patient is found to have an invasive mole, choriocarcinoma or metastases.
Divided into low and high risk subtypes based on, for example, serum hCG concentration as well as the location and number of metastases.
Treatment is carried out with cytostatic drugs. Hysterectomy is indicated when the largest tumour mass is in the uterus.
The treatment of epithelioid trophoblastic tumour and of placental site trophoblastic tumour is primarily surgical.
Follow-up
Determination of serum hCG concentration is an essential follow-up method.
Complete hydatidiform mole
Serum hCG concentration is determined 2 days after suction curretage and then monitored every 2 weeks until it is normal in 3 consecutive tests. After that, serum hCG concentration is continued at 1-month intervals for a period of 6 months.
Partial hydatidiform mole
Serum hCG concentration is monitored after suction curretage every 2 weeks until it is normal in 2 consecutive tests.
During the follow-up period, reliable contraception has to be ensured. Oral conctraceptives may be started right away after suction curretage.
Ultrasonography of the uterus should be performed at the beginning of subsequent pregnancies (recurrence risk after one hydatidiform mole is 1.3% and after two moles 15%. After delivery, the placenta is histologically examined and the serum hCG concentration of the mother is determined after 6 weeks.
Postmolar GTN, epithelioid trophoblastic tumour and placental site trophoblastic tumour
After serum hCG has become normal, follow-up is continued for a year in low-risk postmolar GTN and for 5 years in high-risk postmolar GTN. In epithelioid trophoblastic tumour and placental site trophoblastic tumour, the follow-up is continued for 10 years.
Pregnancy is not recommended within one year from the end of cytostatic therapy.
Prognosis
The prognosis is good; after 5 years 85-100% of the patients are alive.
References
Brown J, Naumann RW, Seckl MJ et al. 15 years of progress in gestational trophoblastic disease: Scoring, standardization, and salvage. Gynecol Oncol 2017;144(1):200-207. [PubMed]
Lok C, van Trommel N, Massuger L et al. Practical clinical guidelines of the EOTTD for treatment and referral of gestational trophoblastic disease. Eur J Cancer 2020;130:228-240. [PubMed]
Soper JT. Gestational Trophoblastic Disease: Current Evaluation and Management. Obstet Gynecol 2021;137(2):355-370. [PubMed]