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Chapter 17: Gestational Trophoblastic Neoplasia

John R. Lurain

INTRODUCTION

Epidemiology

Gestational trophoblastic disease (GTD) is a spectrum of inter-related abnormal proliferations of the placental trophoblast, encompassing benign hydatidiform mole (complete and partial) as well as malignant gestational trophoblastic neoplasia (GTN), which includes invasive mole (IM), choriocarcinoma (CC), placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT)

Complete Hydatidiform Mole (CHM)

  • Incidence: 1 in 1000–2000 pregnancies in the United States and Europe, but higher in Asia and Latin America

  • Risk Factors: extremes of reproductive age (<20 and >40), prior molar pregnancy

  • GTN: develops in about 15–20% (12–18% IM and 2–3% CC) after molar evacuation

Partial Hydatidiform Mole (PHM)

  • Incidence: 3 in 1000 pregnancies

  • Risk Factors: possible history of irregular menses and prolonged oral contraceptive use

  • GTN: develops in 1–5% after molar evacuation (almost all IM)

Choriocarcinoma

  • Incidence: 1 in 40,000 pregnancies

  • Risk Factors: history of complete hydatidiform mole (1000× more likely to arise from a CHM, although one-half of cases develop from other pregnancy events)

  • Common sites of metastasis: lungs (80%), brain (10%), liver (10%), vagina (~5%)

PSTT/ETT

  • Incidence: <0.2% of all cases of GTD

  • Risk Factors: insufficient data exist to adequately characterize any risk factors; however, 95% develop following a term pregnancy or nonmolar abortion and may present many months or years later

 

Lurain JR. Am J Obstet Gynecol 2010;203:531–539

Clinicopathology

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Clinicopathology
Disease Pathologic Features Clinical Factors
Complete mole

  • Diploid (46,XX, rarely 46,XY)

  • Absent fetus/embryo

  • Diffuse swelling of villi

  • Diffuse trophoblastic hyperplasia

  • Vaginal bleeding

  • Large for dates uterine size

  • Bilateral theca-lutein cysts

  • Medical complications

  • hCG often >100,000 mIU/mL

  • 15–20% postmolar GTN
Partial mole

  • Triploid

  • Abnormal fetus/embryo

  • Focal swelling of villi

  • Focal trophoblastic hyperplasia

  • Pre-D&C diagnosis usually incomplete or missed abortion

  • Medical complications rare

  • hCG rarely >100,000 mIU/mL

  • <5% postmolar GTN
Invasive mole

  • Swollen villi

  • Hyperplastic trophoblast

  • Myometrial invasion

  • Irregular postmolar vaginal bleeding

  • Persistent hCG elevation

  • Most often diagnosed clinically rather than pathologically

  • 15% metastatic—lung/vagina
Choriocarcinoma

  • Abnormal trophoblastic hyperplasia

  • Absent villi

  • Hemorrhage

  • Necrosis

  • Irregular vaginal bleeding after any pregnancy event

  • hCG elevation

  • Symptoms associated with vascular spread to distant sites
PSTT

  • Intermediate trophoblastic hyperplasia

  • Absent villi

  • Less hemorrhage and necrosis

  • Vascular and lymphatic invasion

  • Tumor cells stain positive for hPL

  • Enlarged uterus

  • Total hCG low

  • Free beta subunit of hCG elevated

  • Relatively chemoresistant

  • Mainly surgical treatment
ETT

  • Chorionic-type intermediate trophoblast

  • Extensive necrosis

  • Rare hemorrhage

  • Tumor cells stain positive for p63

  • Enlarged uterus; cervical tumor

  • Metastases with associated symptoms

  • No or very low elevation of hCG

  • Relatively chemoresistant

hCG, human chorionic gonadotropin; hPL, human placental lactogen; PSTT, placental site trophoblastic tumor; ETT, epithelioid trophoblastic tumor

Modified from Lurain JR. Am J Obstet Gynecol 2010;203:531–539

Staging

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Staging
FIGO Anatomic Staging System for GTN
Stage Extent of GTN
I Confined to the uterus
II Extends outside the uterus but is limited to the genital structures (adnexa, vagina, broad ligament)
III Extends to the lungs, with or without known ...

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