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

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Introduction0:00–0:55

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.

History and Physical0:55–3:01

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.

Suction D&C3:01–7:11

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.Okay, let’s go back to pathology and cytogenetic analysis.
If pathology identifies widespread villous edema with moderate to severe proliferation and marked atypia of trophoblasts; absent fetal tissue, and a diploid karyotype on cytogenetics, most commonly 46,XX, diagnose a complete molar pregnancy.
Similar to a partial mole, it’s important to trend quantitative hCG levels every 1 to 2 weeks until negative. But, because complete moles are at higher risk for GTN, after the hCG reaches negative it should be followed monthly for longer, usually 3 to 6 months, before you can be confident there is no GTN.
In this case, the patient will need additional monitoring in future pregnancies, which means obtaining an early ultrasound, sending the placenta to pathology after delivery, and checking an hCG 6 weeks postpartum.
As with partial moles, if at any point during monitoring after a complete molar pregnancy the hCG value plateaus or increases, you should diagnose GTN.
So, let’s talk about what to do when GTN develops. To begin, GTN is a malignancy, and while it most commonly follows cases of benign GTD, specifically hydatidiform moles, GTN can also occur after any miscarriage, ectopic pregnancy, or normal pregnancy.

Gestational Trophoblastic Neoplasia7:11–9:36

Once GTN is diagnosed, it’s important to do a thorough pelvic exam, paying careful attention to examining the vagina, which is the most common site of metastasis.
Obtain a pelvic ultrasound to look for tumors invading deeply into the uterus, and assess for spread to other pelvic organs outside the uterus.
Get a chest X-ray also because the lungs are the most common extrapelvic site of metastasis. A CT of the abdomen and pelvis and an MRI of the brain are only needed if the patient is symptomatic, or if there is evidence of metastatic disease on exam or chest X-ray.
Based on exam and imaging, assign a stage of GTN using the International Federation of Gynecology and Obstetrics, or FIGO, anatomical staging.
Additionally, you may apply a World Health Organization, or WHO, risk score depending on the subtype of GTN. The two most common types of GTN are postmolar GTN, also known as an invasive mole and choriocarcinoma.
Both of these can follow benign hydatidiform moles, and use WHO risk scores to guide management.For invasive moles and choriocarcinoma, low-risk disease confined to the uterus generally responds well to single-agent chemotherapy.
If the disease is more extensive, or if there’s an elevated WHO risk score, then multiagent chemotherapy is recommended.
If the disease is FIGO stage 4 or if the WHO risk score is very high, usually single-agent induction chemotherapy is used to decrease the tumor burden before multiagent chemotherapy, due to the risk of tumor lysis syndrome.There are less common forms of GTN called placental site trophoblastic tumor and epithelioid trophoblastic tumor, and treatment for these two subtypes is based on FIGO anatomic staging alone.
For these conditions, hysterectomy is the mainstay of treatment, unless it’s a later stage or more than 4 years from the preceding pregnancy, as these more complicated cases warrant multiagent chemotherapy.
Alright, as a quick recap… GTD refers to a group of disorders where the trophoblastic cells of pregnancy grow incorrectly.

Review9:36–10:18

Benign GTD includes partial and complete molar pregnancies, both of which are managed with a D&C.Following D&C, hCG levels must be monitored to ensure a malignant form of GTD, known as GTN, does not develop.
If hCG levels plateau or rise during postmolar surveillance, GTN is diagnosed. The most common forms of GTN are treated with either single or multiagent chemotherapy depending on the extensiveness of the disease, while the less common forms are usually treated with hysterectomy.
usually treated with hysterectomy