Gestational Trophoblastic Disease

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On today’s podcast, we welcome Jenna Emerson, MD, the current 3rd year fellow in gynecologic oncology and alumnus of the residency at Brown University / Women and Infants! Jenna takes us today through the often confusing world of GTD (or GTN, or GTT).

GTD encompasses several distinct disease entities, including complete and partial molar pregnancy, invasive moles, gestational choriocarcinoma, and placental-site trophoblastic tumors (PSTT).

Molar Pregnancies are a form of non-invasive GTD, and will be encountered by the general OB/GYN. It’s estimated 1:600 TABs will pathologically be molar pregnancies. 20% will lead to malignant GTD and require treatment, with complete moles more often leading to malignancy than partial moles.

The distinction of complete versus partial moles make for great test questions, though the management is the same. There are two main distinctions:

  • Karyotype – partial is triploid, complete is diploid

  • Clinical features – complete is completely weird, while partial only partially weird. Though the ACOG PB 53 has since been retired, this table is helpful in going over the main differences:

ACOG PB 53

Moles generally present with first trimester bleeding or characteristic US findings (“snowstorm appearance”). Initial management requires a number of steps for evacuation or hysterectomy. Be sure to check out the NCCN guidelines (membership required, but free!) for review.

Malignant GTD occurs post-molar if bHCG plateaus, increases, or is persistently positive. This ultimately requires staging per FIGO criteria:

NCCN / FIGO

NCCN / FIGO

If disease is low risk and local disease only, management is hysterectomy vs repeat D&C. A second curettage for low risk cures 40% of patient, and avoids need for chemotherapy. This is a change from traditional teaching, based on a prospective trial published in 2016.

If this surgical management is unsuccessful while following bHCG, then it’s time to move to chemotherapy. Low risk disease is treated with single agent chemo (MTX or Actin-D). Per GOG174, Actin-D has a higher complete response rate, but is more toxic than MTX. High risk disease is treated with EMACO. Check out the NCCN guidelines for more information on these regimens. 

Choriocarcinoma and Placental Site Trophoblastic Tumor

  • Choriocarcinoma can follow term pregnancies (50%), moles (25%), or non-term histologically normal pregnancies (25%). They have early systemic mets, and require chemotherapy. The staging system is the same as above to decide single vs. multi-agent therapy. These are very vascular, so the classic CREOG answer is that you should not biopsy a suspected choriocarcinoma!

  • PSTT, epithelioid trophoblastic tumor – both of these are very rare and can follow any pregnancy. These should be referred to specialized centers, and are most commonly treated with hysterectomy.

Diagnostic Dilemmas

We reviewed a number of scenarios that can pose diagnostic challenges. In brief:

  • Malignant GTD following non-molar pregnancies

    • In the case of persistent AUB for > 6weeks after pregnancy, a bHCG should be checked to rule out new pregnancy or GTD

  • Choriocarcinoma as malignancy of unknown primary 

    • Mets have been reported in pretty much every body site.

    • Serum beta (which will almost certainly be above discriminatory zone) and pelvic US to r/o pregnancy allow for diagnosis.

  • Phantom hCG – heterophile antibodies

    • Positive serum hCG testing can result due to relatively non-specific circulating antibodies which bind to secondary antibody in a sandwich assay (antigen 🡪 primary antibody detects antigen-labeled secondary antibody, which detects primary antibody and has detectable indicator).

    • Several ways to identify: pos serum with neg urine (antibodies aren’t shed in the urine but bHCG glycoprotein is), value doesn’t decrease with serial dilutions, or can send to a separate lab which may use separate secondary assay.

  • Postmenopausal hCG

    • Baseline small amount of hCG produced by the pituitary – rises in peri- and post-menopausal, during chemo. Typically beta is 5 or less but can occasionally be higher. Confirm by checking LH – if LH is consistent with menopause, this confirms pituitary source.