AssessmentsGestational trophoblastic disease: Clinical practice
USMLE® Step 2 style questions USMLE
A 32-year-old, nulliparous woman comes to the obstetrics clinic for her first prenatal visit at 14 weeks. Ultrasound examination shows a molar pregnancy. She is scheduled for a dilatation and curettage. A pre-operative chest X-ray is normal. Which of the following is the most appropriate follow-up for this patient after surgical management?
Content Reviewers:Rishi Desai, MD, MPH
Gestational trophoblastic disease includes both benign and malignant proliferations of placental cells.
At the benign end of the spectrum, there’s moles - and no, we’re not talking about the cute little brown ones above the upper lip. In this case, moles refer to a molar pregnancy, and they are also called hydatidiform moles.
Risk factors for molar pregnancies include maternal age extremes - like younger than 20, or older than 35, and a previous molar pregnancy.
Moles result from errors in normal fertilization.
Normally, at fertilization, a single egg with 23 chromosomes fuses with a single sperm with 23 chromosomes, resulting in a new organism with 46 chromosomes. This can go wrong in two ways, so we have two kinds of moles - complete, or classic, and incomplete, or partial mole. Both lead to an abnormal proliferation of placental cells, and an abnormal placenta.
The difference is that a complete mole appears when a chromosomally empty egg fuses with a normal sperm, and the sperm genetic material duplicates to form a 46 chromosome organism. However, this organism doesn’t have both maternal and paternal chromosomes, so the mole develops into a mass rather than developing into a fetus.
With a complete mole, the placenta secretes a huge amount of HCG. So affected females present with signs of pregnancy, like missed periods, and a positive urine pregnancy test.
Interestingly, HCG has a subunit that’s similar to TSH, FSH, and LH. This causes symptoms of hyperthyroidism - like insomnia, anxiety, tachycardia, and palpitations, as well as the formation of theca lutein cysts on the ovaries, which can cause adnexal mass symptoms like pain or pressure on the affected side.
So while missed periods and vaginal bleeding may be present, the uterus is not larger than expected for gestational age, and there aren’t symptoms of HCG hyperstimulation like hyperemesis gravidarum, hyperthyroidism, or ovarian cysts.
Sometimes, however, the HCG levels may not reach that threshold and so it can also be diagnosed when a transvaginal ultrasound shows a “snowstorm”, or “swiss cheese” pattern. This is a diffuse echogenic pattern resulting from the presence of abnormal placental villi and blood clots.
If hyperthyroid symptoms are present, serum TSH will be low and serum free T4 will be high.
Suction curettage per se involves three main steps - first, the cervix is mechanically dilated, then the uterine contents are suctioned out, and finally curettage is done to scrape any remaining tissue from the uterine walls.
The uterine evacuation contents should always be examined histologically, for a definitive diagnosis.
The typical approach is to measure serum HCG weekly, until it’s undetectable for three consecutive weeks, and then once a month for 6 months. This should be done while the female is on reliable contraception - like the barrier method or oral contraception.
Both these malignant tumors arise from the abnormal proliferation of trophoblast cells.
Also, an invasive mole always follows a molar pregnancy, whereas choriocarcinoma can also develop after a non-molar pregnancy - meaning a normal or ectopic pregnancy, or an abortion done for other reasons.
A persistent, invasive mole is more common after a complete mole - especially when the mole caused the uterus to enlarge, when the serum HCG level was over 100,000 milli international units per milliliter, or when there were theca lutein cysts on the ovaries.
The diagnosis is made when HCG levels plateau, meaning they remain within 10% of the previous result, over a three week period, or when HCG levels increase more than 10% across three values recorded over two weeks, or when there is still detectable serum HCG up to 6 months after evacuation of a molar pregnancy.
Choriocarcinoma accounts for a minority of the cases of gestational trophoblastic neoplasia that follow a molar pregnancy, but the diagnosis is the same - it’s identified when HCG levels plateau or rise.
An ultrasound should be done to rule out pregnancy - even if the female is on reliable contraception.
On ultrasound, an invasive mole looks like one or more poorly defined mass in the uterus with anechoic areas, which invade into the myometrium.
And on Doppler ultrasound, an invasive mole has anechoic areas with high vascular flow.
And on Doppler ultrasound, a choriocarcinoma also has high vascular flow.
One unique situation is when a choriocarcinoma develops in the first year after a non-molar pregnancy. In this case, it may be trickier to diagnose, because the serum HCG is not routinely being measured.
So these females often develop symptoms, like abnormal uterine bleeding or unexplained amenorrhea weeks to months after pregnancy.