Pocket Oncology (Pocket Notebook Series), 1st Ed.

GESTATIONAL TROPHOBLASTIC DISEASE

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