Gestational trophoblastic disease (GTD) and neoplasia (GTN): Clinical sciences

Gestational trophoblastic disease, or GTD, is a group of conditions where trophoblastic cells of pregnancy grow improperly. The most common type of GTD is benign hydatidiform mole, which includes complete molar pregnancies and partial molar pregnancies that arise from abnormal fertilization.

Diagnosis and treatment of GTD is important because early recognition and proper management reduces the risk of gestational trophoblastic neoplasia, or GTN, which is a malignant type of GTD. While GTN can arise from pregnancies that aren’t GTD, such as miscarriages or viable pregnancies, GTN is most common after a molar pregnancy and therefore, close surveillance is warranted in all cases of GTD.

When a patient presents with a chief concern suggesting gestational trophoblastic disease, perform a focused history and physical exam, order a quantitative human chorionic gonadotropin, or hCG, test, and obtain a pelvic ultrasound. Your patient will usually report amenorrhea and present for care thinking they are pregnant. But unlike a normal pregnancy, the patient might report pelvic pain or pressure from early uterine enlargement, or vaginal bleeding with possible passage of “grape-like” vesicles. The patient may also report symptoms specific to high hCG levels often seen with GTD, such as tremors or heat intolerance which are due to hCG stimulation of the thyroid. Or the patient might experience hyperemesis and weight loss. Risk factors for GTD include a prior molar pregnancy; extremes of maternal age including those older than 40 years and those younger than 20 years; and individuals of Asian ancestry.

On examination, you might see signs of preeclampsia like new blood pressure elevations and protein in the urine. You may also find that the uterus is larger or smaller than you would expect for the estimated gestational age. You might also feel an adnexal mass on a bimanual exam because high hCG levels can stimulate the formation of large theca lutein cysts. Finally, you may also note that the hCG level is higher than you'd expect for the anticipated gestational age.

On pelvic ultrasound, you might see a heterogeneous intrauterine mass with diffuse anechoic spaces, with a characteristic “bunch of grapes” or “snowstorm appearance” and peripheral vascularity that is highly suggestive of a complete molar pregnancy. On the other hand, a partial molar pregnancy can look very similar to a normal pregnancy or spontaneous abortion, so you might see an empty gestational sac or even fetal tissue. If the placenta is identified, it might be enlarged and cystic. Make sure to also look at the ovaries, which often reveal large theca lutein cysts.

Based on these findings, suspect a molar pregnancy, and proceed with a suction dilatation and curettage, or D&C, which serves as both diagnosis and treatment.

Here’s a clinical pearl! There’s a high risk of hemorrhage at the time of D&C in cases of molar pregnancy. Make sure to order a type and cross before going to the operating room in case a transfusion is needed, and have medications readily available to treat uterine atony, such as methylergonovine, carboprost, or oxytocin. Additionally, order CBC, CMP, and thyroid function tests preoperatively; and get a serum quantitative hCG level to serve as a reference point against future values. Also, remember to get a chest X-ray for future comparison since the lungs are the most common extrapelvic metastatic site for GTN. Spread to the lungs may appear as discrete rounded opacities classically described as “cannonball” metastases.

Now, some patients who have completed childbearing may request a hysterectomy rather than D&C. While this isn’t common, it’s a reasonable choice. However, patients must be warned that they’ll require postsurgical monitoring because a hysterectomy doesn’t exclude potential metastatic GTN developing in the future.

Alright, back to our treatment. After D&C, send the products of conception for pathology and cytogenetic analysis to confirm the diagnosis. If the analysis reveals focal villous edema with slight to moderate proliferation and mild atypia of trophoblasts, fetal tissue, and a triploid karyotype on cytogenetics, most frequently 69,XXY, then you can diagnose a partial molar pregnancy.

Now, while it’s accepted that hCG levels need to be monitored after a molar pregnancy, there’s no hard and fast rule of how often to monitor. Many chose to do a quantitative hCG every 1 to 2 weeks until the value is negative. Once a negative hCG is reached, a repeat is usually done one month later. As long as the hCG remains negative twice over the span of a month, no additional testing is needed to rule out GTN. But, because there is a higher chance of a subsequent molar pregnancy, you’ll want an early ultrasound for all future pregnancies. Even if future pregnancies are normal, send the placenta for examination after delivery and order a quantitative hCG 6 weeks postpartum, because there’s also an elevated risk of GTN in the future. However, if at any point during monitoring after the D&C, the hCG value plateaus or increases, you should diagnose GTN.

Here’s another clinical pearl! While your patient’s hCG levels are monitored, you should counsel them to use reliable contraception to avoid pregnancy, since the rise in hCG from a new pregnancy can’t be distinguished from an hCG rise caused by GTN.