Melody Smith and David M. Hyman
Definition
• Heterogeneous group of proliferative disorders of trophoblastic cells arising from the placenta
• Maternal tumor arises from gestational as opposed to maternal tumor
• Generally characterized by elevation of the beta subunit of hCG
Epidemiology
• Complete & partial hydatidiform moles comprise 90% of GTD cases
• Incidence of hydatidiform mole ranges from 23–1299 per 100000 pregnancies
• Malignant GTD is less common
Risk Factors
• Extremes of maternal age (>35 y old), h/o previous GTD, cigarette smoking, nulliparity, h/o infertility, use of oral contraceptives
Clinical Subtypes
• Hydatidiform mole (complete or partial)
• Partial hydatidiform mole: Triploid karyotype, generally dispermic, arising from fertilization of a haploid egg by 2 sperm, only type of GTD a/w a fetus, embryo survives until 8th wk of gestation
• Early presentation: Absence of p57 (KIP2) immunostaining
• Late presentation: Uterus large for date, U/S (hydropic changes, no embryo), vaginal bleeding, theca lutein cysts, preeclampsia, hyperemesis, hyperthyroidism
• Complete hydatidiform mole: Common in woman <20 & >40 y, diploid but androgenic, usu arise by fertilization of an enucleate egg by two sperm or by a single sperm that duplicates, less likely to become malignant
• Persistent/invasive GTN: May present after a molar pregnancy, most common sx is vaginal bleeding
• RF: Large theca lutein cysts (≥6 cm), age >40, previous GTD, initial hCG >100000 mlU/mL, excessively enlarged uterus for date
• Choriocarcinoma: Most aggressive GTN, arise from villous trophoblasts, early vascular invasion, widespread mets, often presents as late postpartum bleeding, malignant transformation of molar tissues or de novo lesion arising spontaneously
• Surgical evacuation: D&C, hysterectomy
• Close monitoring of postevacuation hCG levels (baseline w/in 48 h of evacuation, weekly until nl)
• Placental site trophoblastic tumor: Rare (<0.2% of all GTD), slow-growing malignant tumors, arise from intermediate cytotrophoblast cells that are present in the placenta (Lancet 2009;374:48). Generally resistant to chemo-Tx & early-stage disease mandates hysterectomy.
Diagnosis
• Obtain an hCG level &, if elevated, then perform an U/S
• Always send a urine pregnancy test
• FP hCG may occur due to heterophile Ab or nonspecific protein interference
• Criteria for dx of GTN
• 4 values or more of plateau of hCG over at least 3 wk
• Rise of hCG of 10% or greater for 3 values or longer over at least 2 wks
• Persistence of hCG 6 mos after mole evacuation (Lancet 2012;379:130)
• Presence of histologic choriocarcinoma
FIGO Anatomic Staging
• Based on extent of GTD
• Stage I: Tumor confined to the uterus
• Stage II: Tumor extension outside the uterus but confined to the pelvis
• Stage III: Tumor extension to the lungs
• Stage IV: All other met sites
Prognostic Scoring System (GOG)
International Federation of Gynecology & Obstetrics (2000) scoring system for GTN, by prognostic factor
• Low risk: Score of 6 or less, tend to respond well to chemo-tx: Typically treated w/single-agent chemo-tx
• High risk: Score of 7 or greater, tend to respond less well to chemo-tx: Typically treated w/multiagent chemo-tx
Management
• Single-agent Rx
• MTX is the recommended Rx
• Dactinomycin has activity in pts w/low-risk GTD who develop MTX resistance & whose hCG is low (JCO 2002;20:1838)
• Combination chemo-tx
• EMA-CO, w/c is etoposide, MTX, & actinomycin (JCO 2013;31:280)
• If resistance to EMA-CO develops, consider EMA-EP; etoposide, MTX, actinomycin, etoposide, & CIS