Chapter 13. Gestational Trophoblastic Diseases
BS. Nguyễn Hồng Anh
Gestational trophoblastic disease (GTD) is the term used to
encompass a group o tumors typied by abnormal trophoblast prolieration. rophoblast produces human chorionic
gonadotropin (hCG). Tus, the measurement o this peptide
hormone in serum is essential or GD diagnosis, management, and surveillance. GD histologically is divided into
hydatidiorm moles, which are characterized by the presence
o villi, and nonmolar trophoblastic malignant neoplasms,
which lack villi.
Hydatidiorm moles are excessively edematous immature
placentas (Benirschke, 2012). Tese include the benign complete
hydatidiorm mole and partial hydatidiorm mole (Table 13-1).
Te third member is the malignant invasive mole (Hui, 2014b).
Invasive mole is deemed malignant because o its marked
penetration into and destruction o the myometrium and its
ability to metastasize.
Nonmolar trophoblastic neoplasms include choriocarcinoma,
placental site trophoblastic tumor, and epithelioid trophoblastic
tumor (Hui, 2014a). Tese three are dierentiated by the
trophoblast type that they contain.
Under the GD umbrella term, the malignant orms o
GD are termed gestational trophoblastic neoplasia (GTN).
Tese include invasive mole, choriocarcinoma, placental site
trophoblastic tumor, and epithelioid trophoblastic tumor.
Tese malignancies develop weeks or years ollowing any type
o pregnancy, but more requently ollow hydatidiorm mole.
Each GN malignancy type is histologically distinct and
varies in its propensity to invade and metastasize. However,
these diagnoses are inrequently identied rom an actual
histological specimen. Instead, measurement o serum hCG
levels and clinical ndings are more oten used to diagnose and
treat this malignancy. Accordingly, GN is oten managed as
a single composite clinical entity. With chemotherapy, most
tumors currently are highly curable.
HYDATIDIFORM MOLE
Classic histological ndings o molar pregnancy include trophoblast prolieration and villi with stromal edema (Fig. 13-1).
Te degree o histological changes, karyotype and immunostaining dierences, and the absence or presence o embryonic elements are used to classiy them as either complete or
partial hydatidiorm moles (Table 13-2). Tese two also vary
in their associated risks or developing medical comorbidities
and postevacuation GN. O the two, GN more requently
ollows complete hydatidiorm mole.
Grossly, complete moles have abnormal chorionic villi that
appear as a mass o clear vesicles. Tese vary in size and oten
hang in clusters rom thin pedicles. In contrast, partial molar
pregnancies have ocal and less advanced hydatidiorm changes
and contain some etal tissue. Both orms o moles usually ll
the uterine cavity, but they rarely may be ectopic (Sebire, 2005;
Yamada, 2016).
FIGURE 13-1 Complete hydatidiform mole. A. Gross specimen with characteristic vesicles of variable size. (Photograph contributed by
Dr. Sasha Andrews. Reproduced with permission from Patel S, Roberts S, Rogers V, et al [eds]: Williams Obstetrics Study Guide, 25th ed.
New York, NY: McGraw Hill; 2019.) B. Low-magnification photomicrograph shows generalized edema and cistern formation (black asterisks)
within avascular villi. Haphazard trophoblastic hyperplasia is marked by a yellow asterisk on the right. (Reproduced with permission from
Dr. Erika Fong.)
TABLE 13-2. Features of Partial and Complete Hydatidiform Moles
Te strongest risk actors are age and a prior hydatidiorm
mole. Women at both extremes o reproductive age are most
vulnerable (Savage, 2013; Sebire, 2002a). With a prior complete mole, the risk o another mole is 0.9 percent, and with a
previous partial mole, the rate is 0.3 percent. Ater two prior
complete moles, approximately 20 percent o women have a
third mole (Eagles, 2015).
■ Pathogenesis
Molar pregnancies typically arise rom chromosomally abnormal ertilizations. Complete moles most oten have a diploid
chromosomal composition. Tese usually are 46,XX and result
rom androgenesis, meaning both sets o chromosomes are
paternal. Te chromosomes o the ovum are either absent or
inactivated. As shown in Figure 13-2A, an ovum is ertilized
by a haploid sperm, which then duplicates its own chromosomes ater meiosis. Less commonly, the chromosomal pattern may be 46,XY or 46,XX and due to ertilization by two
sperm, that is, dispermic ertilization or dispermy (Lawler, 1991;
Ohama, 1981).
Partial moles have a triploid karyotype, which is 69,XXX,
69,XXY, or much less commonly, 69,XYY. Tese are each composed o two paternal haploid sets o chromosomes contributed
by dispermy and one maternal haploid set (see Fig. 13-2B).
Less requently, a similar haploid egg may be ertilized by an
unreduced diploid 46,XY sperm. Tese triploid zygotes result
in some embryonic development, however, it ultimately is a
lethal etal condition (Joergensen, 2014; Lakovschek, 2011).
Fetuses that reach advanced ages have severe growth restriction,
multiple congenital anomalies, or both.
Twin Pregnancy
Rarely, in some twin pregnancies, one chromosomally normal
etus is paired with a complete diploid molar pregnancy. Importantly, these cases must be distinguished rom a single partial
molar pregnancy with its associated abnormal etus. Other
potential diagnoses include placental mesenchymal dysplasia,
subchorionic hematoma, or chorioangioma (Chap. 6, p. 112)
(Cavoretto, 2020). o help distinguish among these, chorionic
villus sampling, amniocentesis, or etal cord blood sampling
coupled with etal karyotyping aid conrmation (Lee, 2010).
Several unique pregnancy problems complicate such twin
pregnancies. Tyrotoxicosis is common, but the most worrisome
are preeclampsia or hemorrhage. Tese requently necessitate
preterm delivery. Tus, many women may choose to terminate
the gestation, i diagnosed early. In those with continuing pregnancy, survival o the normal etus varies and depends on associated comorbidity rom the molar component. Wee and Jauniaux
(2005) reviewed outcomes in 174 women, o whom 82 chose
termination. O the remaining 92 pregnancies, 42 percent either
miscarried or had a perinatal death; approximately 60 percent
delivered preterm; and 40 percent delivered at term.
Another concern or those continuing their pregnancy is
the risk or developing subsequent GN. Most evidence indicates no signicant dierence between women who continue or
terminate their pregnancy (Lin, 2017; Sebire 2002b).
■ Clinical Findings
Molar pregnancy is diagnosed sooner than in the past because
prenatal care is sought much earlier and sonography is virtually universal. For example, in 194 women with a complete
mole, evacuation was completed at a median gestational age o
9 weeks and at 12 weeks or 172 patients with a partial mole
(Sun, 2015). As a result, most molar pregnancies are treated
beore complications ensue.
ypically, 1 to 2 months o amenorrhea precede the diagnosis.
As gestation advances, symptoms tend to be more pronounced
with complete compared with partial moles (Niemann, 2007).
Untreated molar pregnancies will almost always cause uterine bleeding that varies rom spotting to prouse hemorrhage.
Bleeding may presage spontaneous molar abortion, but more
oten, it ollows an intermittent course or weeks to months.
In more advanced moles with considerable concealed uterine
hemorrhage, moderate iron-deciency anemia develops. Nausea and vomiting also may be signicant. O physical ndings,
many women have uterine growth exceeding that expected, and
the enlarged uterus is comparatively soter. Fetal heart motion is
absent with complete moles. Te ovaries can be uller and cystic
FIGURE 13-2 Typical pathogenesis of complete and partial moles.
A. A 46,XX complete mole may be formed if a 23,X-bearing haploid
sperm penetrates a 23,X-containing haploid egg whose genes
have been “inactivated.” Paternal chromosomes then duplicate
to create a 46,XX diploid complement solely of paternal origin.
B. A partial mole may be formed if two sperm—either 23,X- or
23,Y-bearing—both fertilize (dispermy) a 23,X-containing haploid
egg whose genes have not been inactivated. The resulting fertilized egg is triploid with two chromosome sets being donated by
the father (diandry).238 First- and Second-Trimester Pregnancy Loss
Section 5
rom multiple theca-lutein cysts (Fig. 13-3). Tese are more
common with a complete mole and likely result rom ovarian
overstimulation by excessive hCG levels. Remember that hCG
and luteinizing hormone share the same receptor, and both can
stimulate the theca layer that surrounds ollicles. Because thecalutein cysts regress ollowing pregnancy evacuation and subsequent hCG level decline, expectant management is preerred.
Occasionally, a larger cyst may undergo torsion, inarction, and
hemorrhage. However, oophorectomy is not perormed unless
extensive inarction persists ater untwisting.
Te thyrotropin-like eects o hCG requently cause serum
ree thyroxine (4) levels to be elevated and thyroid-stimulating
hormone (SH) levels to be decreased (Chap. 61, p. 1089).
Despite this, clinically apparent thyrotoxicosis is unusual and
in our experience can be mimicked by bleeding and sepsis rom
inected products. Moreover, the serum ree 4 levels rapidly normalize ater uterine evacuation. Despite this, cases o presumed
“thyroid storm” have been reported (Konas, 2015).
Severe preeclampsia and eclampsia are relatively common
with advanced molar pregnancies. However, these are seldom
seen today because o early diagnosis and evacuation. An exception is the case o a normal etus coexisting with a complete
mole, described earlier. In continuing twin gestations, severe
preeclampsia requently mandates preterm delivery.
■ Diagnosis
Serum β-HCG Measurements
Most women initially have irregular bleeding that almost always
prompts pregnancy testing and sonography. Less oten, women
will spontaneously pass molar tissue.
With a complete molar pregnancy, serum β-hCG levels
are commonly elevated above those expected or gestational
age. With more advanced moles, values in the millions are not
unusual. Importantly, these high values can lead to erroneous
alse-negative urine pregnancy test results. ermed a hook efect,
excessive β-hCG hormone levels oversaturate the assay’s targeting
antibody and create a alse-negative reading (Cormano, 2016). In
these cases, serum β-hCG determinations with or without sample
dilution will yield a positive result. With a partial mole, β-hCG
levels may also be signicantly elevated, but more commonly
concentrations are in ranges expected or gestational age.
Sonography
Although this is the mainstay o trophoblastic disease diagnosis,
not all cases are conrmed initially. In a large series o more
than 1000 patients with molar pregnancy, sonography’s sensitivity was 44 percent, and its specicity was 74 percent (Fowler,
2006). With grayscale sonography, a complete mole appears as
an echogenic uterine mass lling the endometrial cavity and is
surrounded by normal myometrium. Te mass is composed o
numerous anechoic cystic spaces o dierent sizes and shapes,
but without a etus or amnionic sac. Te appearance is oten
described as a “snowstorm” (Fig. 13-4). Application o color
Doppler displays marked surrounding myometrial vascularity.
FIGURE 13-3 Sonogram of an ovary with multiple theca-lutein cysts in a woman with a complete hydatidiform mole.
FIGURE 13-4 Sonograms of hydatidiform moles. A. Transverse view of a uterus with a complete hydatidiform mole. The characteristic “snowstorm” appearance reflects an echogenic uterine mass, marked by calipers, that has numerous anechoic cystic spaces. Notably, a fetus or amnionic
sac is absent. B. In this sagittal image of a partial hydatidiform mole, the fetal head (arrow) lies adjacent to an enlarged, multicystic placenta.Gestational Trophoblastic Disease 239
CHAPTER 13
However, absent internal ow reects the avascular villi o
complete moles.
A partial mole has eatures that include a thick, multicystic
placenta plus a etus or etal tissue. Tin septa can be ound
within the gestational sac (Savage, 2017). Aected etuses usually die in the rst trimester. Tose advancing urther oten
show growth restriction, oligohydramnios, and limb or CNS
deects (Cavoretto, 2020).
In early pregnancy, however, these sonographic characteristics are seen in ewer than hal o hydatidiorm moles. At
earlier gestations, a complete mole may appear as a polypoid
hyperechoic mass that lacks internal cysts and is surrounded by
anechoic uid (Jauniaux, 2018).
Te most common mimics are incomplete or missed abortion. In these cases, histological evaluation, described next,
ultimately is diagnostic. Occasionally, molar pregnancy may be
conused or a multietal pregnancy or a uterine leiomyoma
with cystic degeneration.
Pathology
Because o the risk or subsequent GN ollowing molar pregnancy, postevacuation surveillance is indicated. Tus, moles must
be distinguished rom other pregnancy types that are not molar
but that have hydropic placental degeneration. Most oten, these
are hydropic abortuses ormed by the traditional union o one
haploid egg and one haploid sperm but are pregnancies that have
ailed. Teir placentas display hydropic degeneration, in which
villi are edematous and swollen, and thus mimic some villous
eatures o hydatidiorm moles. Tese mimics do not require
postevacuation surveillance. Some distinguishing histological
characteristics are shown in able 13-2.
In pregnancies beore 10 weeks, classic molar histological
changes may not be apparent. Villi may not be enlarged, and
molar stroma may not yet be edematous and avascular. Histopathologic evaluation can be enhanced by immunohistochemical staining or p57 expression and by molecular genotyping
(Banet, 2014). p57KIP2 is a nuclear protein whose gene is paternally imprinted and maternally expressed. Tis means that the
gene product is produced only in tissues containing a maternal
allele. Because complete moles contain only paternal genes, the
p57KIP2 protein is absent in complete moles, and tissues do not
pick up this stain (Merchant, 2005). In contrast, this nuclear
protein is strongly expressed in normal placentas, in spontaneous pregnancy losses with hydropic degeneration, and in partial
hydatidiorm moles (Castrillon, 2001). Accordingly, immunostaining or p57KIP2 is an eective means to isolate complete mole
rom the diagnostic list. For distinction o a partial mole rom
a nonmolar hydropic abortus, both o which express p57KIP2,
molecular genotyping can be used (Ronnett, 2018). Molecular
genotyping determines the parental source o alleles. Tereby,
it can distinguish among a diploid diandric genome (complete
mole), a triploid diandric-monogynic genome (partial mole), or
biparental diploidy (nonmolar abortus) (Xing, 2021).
■ Management
Maternal deaths rom molar pregnancies are rare because o
early diagnosis, timely evacuation, and vigilant postevacuation
surveillance or GN (Sun, 2016). Preoperative evaluation
strives to identiy potential complications, such as preeclampsia, hyperthyroidism, anemia, electrolyte depletions rom
hyperemesis, and metastatic disease (Table 13-3). Most recommend chest radiography, whereas computed tomography (C)
and magnetic resonance (MR) imaging are not routinely done
unless a chest radiograph shows lung lesions or unless other
extrauterine disease is suspected.
Molar Pregnancy Termination
Regardless o uterine size, molar evacuation by suction curettage
usually is the preerred treatment. Preoperative cervical dilation
with an osmotic dilator is recommended i the cervix is minimally
dilated. Intraoperative bleeding can be greater with molar pregnancy than with a comparably sized uterus containing nonmolar
products. Tus with large moles, adequate anesthesia, sufcient
intravenous access, and blood-banking support is imperative.
A step by step description o dilation and curettage is ound
in Chapter 11 (p. 213). For molar evacuation, the cervix is
mechanically dilated to preerably allow insertion o a large
Karman suction cannula. Depending on uterine size, a 10- to
14-mm diameter is typical. As evacuation is begun, oxytocin
is inused to limit bleeding. Intraoperative sonography is oten
recommended to help ensure complete uterine cavity emptying and minimize peroration risk. When the myometrium has
contracted, a thorough but gentle curettage with a sharp largeloop Sims curette may be perormed. I bleeding continues
despite uterine evacuation and oxytocin inusion, other uterotonic agents are given (see able 13-3). Uncommonly, pelvic
arterial embolization, uterine packing, or hysterectomy may be
necessary (Chap. 44, p. 779) (se, 2007).
Some volume o trophoblast is deported into the pelvic
venous system during molar evacuation (Hankins, 1987). With
large moles, the amount o tissue may be sufcient to produce
clinically apparent respiratory insufciency, pulmonary edema,
or even embolism (Delmis, 2000). In our earlier experiences
with substantial moles, these and their chest radiographic maniestations clear rapidly without specic treatment.
Following curettage, anti-D immunoglobulin (Rhogam) is
given to Rh D-negative women because etal tissues with a partial
mole may include red cells with D-antigen (Chap. 18, p. 356).
Tose with suspected complete mole are similarly treated because
a denitive diagnosis o complete versus partial mole may not be
conrmed until histological evaluation o the evacuated products.
Following evacuation, the long-term prognosis or women
with a hydatidiorm mole is not improved with prophylactic
chemotherapy. Moreover, chemotherapy toxicity can be signi-
cant, and thus it is not recommended routinely (Gueye, 2014;
Wang, 2017).
Methods other than suction curettage can be considered or
select cases. Hysterectomy with ovarian preservation may be
preerable or women who have nished childbearing and who
carry complete moles with high-risk eatures. O women aged 40
to 49 years, up to 50 percent will subsequently develop GN,
and hysterectomy markedly reduces this likelihood (Elias, 2012;
Zhao, 2019). During hysterectomy, theca-lutein cysts do not
require removal, and they spontaneously regress ollowing molar
termination. Last, labor induction or hysterotomy is seldom240 First- and Second-Trimester Pregnancy Loss
Section 5
used or molar evacuation in the United States. Both will likely
increase blood loss and theoretically may raise the incidence o
persistent trophoblastic disease (idy, 2000).
Postevacuation Surveillance
Close biochemical surveillance or persistent gestational neoplasia ollows each hydatidiorm mole evacuation. Serial measurement o serum β-hCG levels aim to detect persistent or renewed
trophoblastic prolieration. As a glycoprotein, hCG shows structural heterogeneity and exists in dierent isoorms. Tus, or
surveillance, an hCG assay that can detect all orms o hCG
should be used (Harvey, 2010; Ngan, 2018). Tese are dierent rom those used or routine pregnancy testing (de Medeiros,
2009). Te initial β-hCG level is obtained within 48 hours ater
evacuation. Tis serves as the baseline, which is compared with
β-hCG quantication done thereater every 1 to 2 weeks. Levels
are ollowed until they become undetectable.
Te median time or such resolution is 6 weeks or partial
moles and 7 weeks or complete moles. O patients, 95 percent have normal β-hCG levels by 14 weeks postevacuation
and 99 percent by 25 weeks (Eysbouts, 2017a). Once β-hCG
is undetectable, this is conrmed with monthly determinations
or another 6 months (Lurain, 2010; Sebire, 2007).
Concurrently, reliable contraception is imperative to avoid
conusion caused by rising β-hCG levels rom a new pregnancy.
Most recommend combination hormonal contraception, injectable depot medroxyprogesterone acetate, or progestin implant.
Te latter two are particularly useul i poor patient compliance
is anticipated. Intrauterine devices are not used until β-hCG levels are undetectable because o the risk o uterine peroration i
an invasive mole is present. Ater these 6 months, monitoring
is discontinued and pregnancy allowed. Although not recommended, i a woman conceives during surveillance, live-birth and
congenital anomalies rates appear to mirror general population
rates (uncer, 1999b).
During β-hCG levels surveillance, increasing or persistently
plateaued levels mandate evaluation or GN. I the woman has
not become pregnant, these levels signiy trophoblast prolieration that is most likely malignant. Several actors predispose a
patient to GN ollowing molar evacuation. Complete moles
have a 15 to 20 percent incidence o malignant sequelae, compared with 1 to 5 percent ollowing partial moles. Surprisingly,
with much earlier recognition and evacuation o molar pregnancies, the risk or GN has not dropped (Sun, 2015). Other GN
risk actors are older maternal age, preevacuation β-hCG levels
>100,000 mIU/mL, uterine size that is large-or-gestational age,
theca-lutein cysts >6 cm, and a slow decline in β-hCG levels
(Berkowitz, 2009; Kang, 2012; Wolberg, 2005).
GESTATIONAL TROPHOBLASTIC NEOPLASIA
Tis group includes invasive mole, choriocarcinoma, placental
site trophoblastic tumor, and epithelioid trophoblastic tumor.
Tese tumors almost always develop with or ater some orm
o recognized pregnancy. Hal ollow hydatidiorm mole,
a ourth ollow miscarriage or tubal pregnancy, and another
ourth develop ater a preterm or term pregnancy (Goldstein,
2012). Tese our tumor types are histologically distinct but are
usually diagnosed solely by persistently elevated serum β-hCG
levels because tissue is inrequently available or study. Criteria
to diagnose postmolar GN are shown in Table 13-4.
■ Diagnosis, Staging, and Prognostic Scoring
Clinically, these placental tumors are characterized by their
aggressive invasion into the myometrium and propensity to
metastasize. Te most common nding with GN is irregular
bleeding associated with uterine subinvolution. Te bleeding
may be continuous or intermittent and sometimes may be sudden and massive. Myometrial peroration rom trophoblastic
growth can cause intraperitoneal hemorrhage. In some women,
lower genital tract metastases are evident. In others, only distant
metastases, with no trace o uterine tumor, are ound.
Consideration or the possibility o GN is the most important actor in its recognition. Unusually persistent bleeding
ater any type o pregnancy should prompt serum β-hCG level
measurement. Uterine size is assessed, and careul examination
seeks lower genital tract metastases, which usually are bluish
vascular masses (Cagayan, 2010). issue biopsy o such masses
is unnecessary and may cause signicant bleeding.
Once the diagnosis is veried, a baseline serum β-hCG level and
hemogram are obtained. A search or local disease and metastases
includes tests o liver and renal unction, transvaginal sonography,
chest C or radiography, and brain and abdominopelvic C scan
or MR imaging. Less oten, positron-emission tomographic (PE)
scanning and cerebrospinal uid β-hCG level determination are
used to identiy metastases (Lurain, 2011).
I no extrauterine disease is ound, a second curettage or hysterectomy may be considered. Ater either, β-hCG levels are then
measured every 2 weeks until three consecutively lie in undetectable range. Levels are subsequently repeated monthly or 6 months.
In contrast, i β-hCG levels persist ater curettage or hysterectomy
or i initial extrauterine disease is ound, patients undergo staging
and chemotherapy is instituted (Koh, 2018; Osborne, 2016).
GN is staged clinically using the system o the International
Federation o Gynecology and Obstetrics (FIGO) (2009). Tis
includes a modication o the World Health Organization
(WHO) (1983) prognostic index score, with which scores o
0 to 4 are given or each o the categories shown in Table 13-5.
Women with WHO scores o 0 to 6 are considered to have
TABLE 13-4. Criteria for Diagnosis of Gestational Trophoblastic Neoplasia
1. Plateau of β-hCG level (± 10 percent) for four measurements during a period of 3 weeks or longer—days 1, 7, 14, 21
2. Rise of serum β-hCG level >10 percent during three weekly consecutive measurements or longer, during a period of
2 weeks or more—days 1, 7, 14
3. Serum β-hCG level remains detectable for 6 months or more
4. Histological criteria for choriocarcinoma
TABLE 13-5. International Federation of Gynecology and Obstetrics (FIGO) Staging and Diagnostic Scoring System for
Gestational Trophoblastic Neoplasia
low-risk disease, whereas those with scores ≥7 are considered
in the high-risk group.
■ Histological Classification
Clinical staging is assigned without regard to histological
ndings, even i available. Still, distinct histological types are
recognized.
Invasive Mole
Tese are a common trophoblastic neoplasm, and almost all
invasive moles arise rom partial or complete moles. Previously
known as chorioadenoma destruens, invasive mole is characterized by extensive tissue invasion by trophoblast and whole villi.
rophoblastic cells penetrate deep into the myometrium and
sometimes involve the peritoneum, adjacent parametrium, or
vaginal vault. Although locally aggressive, invasive moles are
less prone to metastasize.
Gestational Choriocarcinoma
Tis is the most common trophoblastic neoplasm to ollow a term
pregnancy or a miscarriage, and only a ourth o cases ollow a
molar gestation (Soper, 2021). Choriocarcinoma is composed
o cells reminiscent o early cytotrophoblast and syncytiotrophoblast, however, it contains no villi. Tis rapidly growing tumor
invades both myometrium and blood vessels to create hemorrhage
and necrosis. Myometrial tumor may spread outward and become
visible on the uterine surace as dark, irregular nodules. Metastases
oten develop early and are generally blood-borne. Te most common sites are the lungs and vagina, but tumor may travel to the
vulva, kidneys, liver, brain, ovaries, and bowel. With choriocarcinomas, ovarian theca-lutein cysts commonly coexist.
Placental Site Trophoblastic Tumor
Tis uncommon tumor arises rom intermediate trophoblasts at
the placental site. Tese tumors have associated serum β-hCG
levels that may be only modestly elevated (Gadducci, 2019).
However, they produce variant orms o hCG, and identiying a
high proportion o ree β-hCG avors this diagnosis (Horowitz,
2017). reatment o placental site trophoblastic tumor by hysterectomy is preerred because these locally invasive tumors are
usually resistant to chemotherapy. For higher-risk stage I and
or later stages, adjuvant multidrug chemotherapy also is given
(Koh, 2018; Schmid, 2009).
Epithelioid Trophoblastic Tumor
Tis rare tumor develops rom chorionic-type intermediate trophoblast. Te uterus is mainly involved, and bleeding but low
hCG levels are typical ndings (Gadducci, 2019). Primary treatment is hysterectomy because this tumor is relatively resistant to
chemotherapy. Metastatic disease is common, and combination
chemotherapy is employed (Frijstein, 2019; Koh, 2018).
■ Treatment
Women with GN are best managed by oncologists, and some
evidence supports treatment in centers specializing in GN
(Kohorn, 2014). Chemotherapy alone is usually the primary
treatment. In some GN cases without extrauterine disease,
a second uterine evacuation may be an adjuvant therapeutic
option to avoid or minimize chemotherapy (Hemida, 2019;
Koh, 2018; Pezeshki, 2004). In other cases, suction curettage
may inrequently be needed to resolve bleeding or remove a
substantial amount o retained molar tissue. In specic cases,
hysterectomy may be primary or adjuvant treatment (Bolze,
2018; Eysbouts, 2017b).
Single-agent chemotherapy protocols are usually sufcient
or nonmetastatic or low-risk metastatic neoplasia (Lawrie,
2016; Koh, 2018). In their review o 108 women with low-risk
disease, Abrão and colleagues (2008) reported that monotherapy protocols with either methotrexate or actinomycin D were
equally eective compared with a regimen containing both. In
general, methotrexate is less toxic than actinomycin D (Chan,
2006; Seckl, 2010). Regimens are repeated until serum β-hCG
levels are undetectable.
Combination chemotherapy is given or high-risk disease, and reported cure rates approximate 90 percent (Lurain,
2011). Several regimens are successul. One is EMA-CO, which
includes etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (Oncovin). In selected cases, adjuvant surgical and radiotherapy also may be employed (Hanna,
2010). Despite chemotherapy successes in general, requent
causes o death include hemorrhage rom metastatic sites, respiratory ailure, sepsis, and multiorgan ailure due to widespread
chemoresistant disease (Lybol, 2012; Neubauer, 2015).
With either low- or high-risk disease, once serum β-hCG
levels are undetectable, serosurveillance is continued or 1 year.
During this time, eective contraception is crucial to avoid
teratogenic eects o chemotherapy to the etus and to mitigate
conusion rom rising β-hCG levels caused by superimposed
pregnancy.
A ew women during surveillance, despite no evidence o
metastases, will be ound to have very low β-hCG levels that
plateau. Tis phenomenon is called quiescent hCG and presumably stems rom dormant trophoblast. Close observation without therapy is recommended, but 20 percent will eventually
have recurrent active and progressive GN (Ngu, 2014).
SUBSEQUENT PREGNANCY
Women with prior hydatidiorm mole generally do not have
impaired ertility, and their pregnancy outcomes are usually
normal (Joneborg, 2014; Matsui, 2001; Sebire, 2003). One
concern is the 1-percent risk or developing trophoblastic disease
in a subsequent pregnancy (p. 237). Sonographic evaluation is
recommended in early pregnancy, and subsequently as needed.
Women with GTN who have successully completed chemotherapy are advised to delay pregnancy or 1 year. Most
relapses develop within this time period (ranoulis, 2019).
Also, methotrexate may persist in human tissues or months
(Hackmon, 2011). Despite this, women who become pregnant
within 1 year postchemotherapy or GN can be reassured o
a likely avorable outcome (Woolas, 1998). Risk o miscarriage or GN relapse is not increased compared with women
conceiving ater the suggested 1-year surveillance (Williams,
2014). However, these gravidas are advised that the diagnosisGestational Trophoblastic Disease 243
CHAPTER 13
o a tumor relapse may be delayed during pregnancy (Blagden,
2002; uncer, 1999a).
In general, ertility and pregnancy outcomes ollowing GN
treatment are typically normal, and congenital anomaly rates are
not increased (Berkowitz, 2000; se, 2012). One exception is a
higher stillbirth rate o 1.5 percent compared with a background
rate o 0.8 percent (Vargas, 2014).
For those with prior hydatidiorm mole or GN treatment,
the placenta or products o conception in a subsequent pregnancy are sent or pathological evaluation at delivery. A serum
β-hCG level also is measured 6 weeks postpartum (Lurain,
2010; Royal College o Obstetricians and Gynaecologists,
2010). Tis assay may be less valuable or those solely with a
prior mole compared with those previously treated or GN
(Earp, 2019).
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