index of suspicion

Case 1 Presentation
A baby boy is born by vaginal delivery after a 35-week gestation. During
the week prior to delivery, his mother
experienced low-grade fever, coryza,
diarrhea, abdominal cramping, and
mild vaginal bleeding. A small placental abruption was diagnosed, and
labor was induced. In the first few
hours after birth, the baby develops
poor perfusion and tachypnea. Blood
cultures are drawn, and he is treated
with ampicillin and gentamicin for
5 days and improves. The cultures
show no growth.
On the fifth day of life, just prior
to discharge, the infant suddenly becomes apneic and again demonstrates poor perfusion. He is intubated, stabilized, and again evaluated
for sepsis, including lumbar puncture. Antibiotics are changed to vancomycin and cefotaxime. Acyclovir is
added.
His white blood cell (WBC)
count is 14.1103/mcL (14.1
109/L), with an absolute neutrophil
count of 13.1103/mcL (13.1
109/L) and bands noted on smear.
Cerebrospinal fluid (CSF) results reveal 15103/mcL (15109/L)
WBC, 3,920103/mcL (3,920
109/L) erythrocytes (believed to be
due to a traumatic puncture), a normal glucose level, and an elevated
protein level. Bacterial cultures of
CSF, blood, and urine are negative.
Polymerase chain reaction (PCR)
testing of CSF also is negative for
herpes simplex.
For 24 hours the baby is stable,
then quickly deteriorates. He rapidly
develops hypotension, severe coagulopathy (with an international normalized ratio [INR] of 10 and partial
thromboplastin time [PTT] of
150 sec), renal failure, liver failure,
and acute respiratory distress syndrome.
Supportive care is initiated, including intravenous fluid, inotropic

drugs, fresh frozen plasma, platelet

transfusions, and eventually peritoneal dialysis. He develops a massive
left intracerebral hemorrhage, resulting in brainstem herniation, with loss
of brainstem reflexes. With parental
approval, support is withdrawn on
the eighth day after birth.
A test result reported after death
confirms the diagnosis.

Case 2 Presentation
An 8-year-old boy is brought to the
hospital having a 3-month history of
cough and occasional fever. The
cough is intermittent, is nonproductive, and lacks diurnal fluctuation.
He has had no chest pain, hemoptysis, anorexia, weight loss, or headache, nor any history of asthma, allergy, sinusitis, or exposure to
tuberculosis. His initial chest radiograph shows normal findings, and results of a tuberculin test with purified
protein derivative are negative.
On physical examination, the
boys weight is 55 lb (25 kg) (50th
percentile), temperature is 99.2F
(37.3C), pulse is 86 beats/min, respiratory rate is 20 breaths/min, and
oxygen saturation is 97% in room air.
He has no pallor, lymphadenopathy,
clubbing, or sinus tenderness. Ear,
nose, and throat findings are normal.
His trachea is midline, and the apex
beat is in the left fifth intercostal
space at the midclavicular line. The
chest is symmetric with normal
movement. Percussion reveals normal resonant notes bilaterally. Breath
sounds and vocal resonance are completely absent in the entire left hemithorax. Breath sounds in the right
hemithorax are normal. Cardiovascular and abdominal findings are
normal. Complete blood count, repeat chest radiographs (inspiratory
and expiratory), and sinus radiographs show normal findings. A diagnostic intervention is performed.
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index of suspicion

Case 3 Presentation
A 2-month-old infant is brought to
the emergency department because
of progressive respiratory distress.
Cough, rhinorrhea, and fever started
1 week ago. As the respiratory distress has worsened, she has displayed
acute episodes of agitation with feedings and has had decreased oral intake over the preceding 24 hours.
A term infant, she has been well
previously.
Physical examination reveals a
lethargic, pale infant in moderate respiratory distress. Her rectal temperature is 99F (37.2C), blood pressure is 83/44 mm Hg, pulse is
190 beats/min, respiratory rate is 60
breaths/min, pulse oximetry saturation is 100%, height is 56 cm (25th
percentile), weight is 4 kg (45th percentile), and head circumference is
38 cm (40th percentile). She is
breathing with nasal flaring and subcostal and suprasternal retractions.
Mild expiratory wheezing is audible.
The cardiac examination reveals no
murmurs, but a laterally displaced
cardiac point of maximal impulse,
thready pulses, cool extremities, and
a capillary refill of 4 sec are noted.
The liver edge is measured 3 to 4 cm
below the costal margin.
A rapid antigen test for respiratory
syncytial virus (RSV) is positive. A radiograph of the chest shows a large
cardiac silhouette with streaky perihilar markings. A 12-lead electrocardiogram (ECG) shows deep Q waves
in leads 1, aVL, and V6 and ST segment elevation in leads V4 to V6.
Further testing confirms the diagnosis.

Case 4 Presentation
A 16-year-old African-American girl
comes to the emergency department
because of 1 week of painless, intermittent vaginal spotting without
nausea, vomiting, vaginal discharge,

or previous bleeding. The patient is

sexually active, has multiple sexual
partners, and uses condoms occasionally. Her last menstrual period
was 3 months ago, and a urine pregnancy test was positive 2 months ago.
She underwent an abortion at age 14
years and a miscarriage at age 15
years. Her menarche was at age 11
years, and her menstrual pattern has
been regular. There have been no
prior medical problems, including
sexually transmitted diseases.
Physical examination reveals an
obese girl in no distress. Her pulse is
83 beats/min, blood pressure is
100/70 mm Hg, respiratory rate is
16 breaths/min, and temperature is
98.7F (36.7C). The abdomen is
soft, nonrigid, nontender, and free of
palpable masses. The vagina shows
no discharge or bleeding. A speculum examination reveals some
bloody discharge, but no clots or fetal parts. The cervix is closed and has
no erosions. A bimanual examination
shows no cervical or adnexal tenderness or fullness in the adnexal area.
The uterus is large; the examiner
could not get around it with his fingers. Laboratory tests lead to the diagnosis.

Case 1 Discussion
The CSF viral culture grew echovirus
type 11, the infectious agent that
caused this babys illness and death

Epidemiology
Enteroviruses are members of a large
group of viruses that includes polioviruses, coxsackieviruses, and echoviruses. Enteroviral infections occur
worldwide and have a seasonal peak
from May through September in
Canada and the United States.
Transmission occurs through fecaloral or respiratory routes. The incubation period is 2 to 6 days. Viral
replication occurs initially in the

pharynx and gastrointestinal tract.

Subsequently, viremia and dissemination of the virus occur. Most infections are asymptomatic or cause a
nonspecific febrile illness.
Hematogenous
dissemination
across the placenta or perinatal ingestion or aspiration of infectious vaginal or fecal matter can result in infection in the first week after birth.

Clinical Picture
Neonates are very susceptible to enteroviral disease. Many serotypes
cause self-limited syndromes in newborns similar to those in adults.
However, some serotypes can cause
fulminant disease that often is fatal.
In general, signs develop between
3 and 7 days after birth. Early in the
course, the manifestations are mild
and nonspecific and include poor
feeding, lethargy, transient respiratory distress, and increasing jaundice.
About 30% of infants have a biphasic
illness, with a period of 1 to 7 days of
well-being between the initial phase
of mild signs and the development of
a more severe illness.
Serious neonatal disease often
manifests as myocarditis, fulminant
hepatitis, or meningoencephalitis.
Myocarditis usually is due to coxsackie group B viral infections.
Fulminant hepatitis is characterized by hypotension, disseminated
intravascular coagulation, jaundice,
and multisystem failure. Echovirus
11 is the most common isolate from
cases of fulminant hepatitis. In the
second phase of the illness, significant jaundice, bleeding from puncture sites, and petechiae often are
seen. The disease progresses rapidly
to severe hemorrhage, liver failure,
renal failure, and shock. Laboratory
investigation often reveals a metabolic acidosis, severe thrombocytopenia, and markedly prolonged INR
and PTT.
Most infants who have fulminant

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index of suspicion

hepatitis die within a few days of presentation, despite intensive supportive therapy.

Diagnosis
The initial presentation of infants
who have enteroviral infections is indistinguishable from that of infants
who have bacterial, fungal, or herpes
simplex sepsis. Therefore, management in the early stages should include consideration of these infections. A sample of CSF should be
sent for viral culture and PCR analysis. In this case, the WBC count of
15103/mcL (15109/L) was
within the normal range for the
childs age, but culture proved the
presence of infection. It is worth
sending CSF for viral culture or PCR
because during enteroviral season
one of those tests will be positive in
10% to 15% of CSF specimens, even if
the WBC count is not elevated.
PCR has revolutionized the ability to determine the presence of enteroviruses quickly from oropharyngeal secretions, stool, blood, CSF,
and tissues obtained at autopsy. Serologic testing is impractical because
of the existence of many viral subtypes and the delay in obtaining results of testing acute and convalescent specimens for many weeks.

Treatment
Unfortunately, there is no definitive
treatment for enteroviral infections
of the newborn. Supportive care
should be undertaken, including
management of respiratory failure,
coagulopathy, and shock. Intravenous immune globulin never has
been proven to be effective, but has
been thought to be useful in case
reports. Therefore, its administration
should be considered. Pleconaril is
an oral antiviral drug currently undergoing investigation for treatment
of severe enteroviral infections, but it
is available only on compassionate

grounds from the manufacturer.

(Elaine Gilfoyle, MD, Marina Salvadori, MD, Ram Singh, MD, Childrens Hospital of Western Ontario,
London, Ontario, Canada)

Case 2 Discussion
Diagnosis
The association of chronic cough and
absent breath sounds in the presence
of normal percussion suggests the
possibilities of foreign body (FB) aspiration, bronchial compression by
lymph nodes, or congenital lobar
emphysema. A normal chest radiograph increases the likelihood of FB
aspiration. Diagnostic bronchoscopy
was performed, and a plastic pen cap
(1.25 cm long) was removed from
the left main bronchus. The patient
could not recollect any episode consistent with aspiration.

Clinical Picture
If asthma and sinusitis are excluded,
FB aspiration is one of the most common causes of chronic cough in children. Most patients who have aspirated an FB have a history of an
immediate episode of choking, gagging, and paroxysmal coughing,
which may lead to medical consultation. However, if this acute episode
does not occur or is missed, the aspiration may lead to complications
ranging from occasional coughing or
wheezing to recurrent lobar pneumonia, intractable asthma, or even
chronic bronchopulmonary disease.
Rarely, a patient who has aspirated an
FB presents with hemoptysis, sometimes months or years after aspiration.
Physical findings in a patient who
has aspirated an FB vary and are determined by the degree of obstruction produced by the object. An FB
may cause airway obstruction by one
of two mechanisms. The ball-valve
mechanism allows air to pass only

during the inspiratory phase but not

in the expiratory phase, thereby producing obstructive overinflation. In
contrast, a stop-valve mechanism
leads to atelectasis because no air can
pass, and the air in the portion of the
lung distal to the obstruction is absorbed. Physical findings associated
with these types of obstruction include limited chest expansion, decreased vocal fremitus, percussion
notes that are hyperresonant (due to
overinflation) or impaired (due to atelectasis), and diminished breath
sounds distal to the FB.

Laboratory Testing
Chest radiography may reveal signs
of atelectasis or overinflation, depending on the type of obstructive
mechanism. In obstructive atelectasis, the heart and mediastinum are
drawn toward the obstructed side
and remain there during both phases
of respiration. In obstructive overinflation, the obstructed lung remains
expanded during expiration, but the
heart and mediastinum shift to the
opposite side. Fluoroscopy also may
be useful in certain cases. However,
bronchial FB is diagnosed definitively by direct visualization with a
bronchoscope. If results of the history and physical examination are
equivocal, a fiberoptic instrument
can be used. However, flexible bronchoscopy generally is not useful for
removal of an FB because it does not
permit adequate airway control or
instrumentation. If the history, physical findings, and radiograph strongly
suggest bronchial FB, the diagnostic
instrument of choice is a rigid or
open-tube bronchoscope.

Treatment
Endoscopic removal of the FB is the
treatment of choice and should be
performed as soon as possible. Chest
thrusts can be applied to infants and
abdominal thrusts to young children
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index of suspicion

who are choking and aphonic. Chest

physiotherapy and bronchodilators
should not be administered because
of the risk of dislodging the FB,
which may lead to more severe airway
obstruction. Treating complications
such as infections also is important.

Lessons For The Clinician

FB aspiration in children can have
myriad manifestations. This case reminds the clinician that the possibility of an FB must be considered in
children who have acute or chronic
pulmonary symptoms and signs, regardless of the absence of a history of
aspiration.
One interesting aspect of this case
is the physical findings produced by
the FB. Although the breath sounds
were completely absent in the left
hemithorax, there were no signs of
obstructive overinflation or atelectasis (such as tracheal or mediastinal
shift and differences in percussion
note). This situation was due to the
presence of a small hole in the center
of the foreign body (plastic pen cap),
which prevented atelectasis or overinflation but was not big enough to
allow audible air entry. For the same
reason, the chest radiograph did not
reveal any abnormality. Even extensive radiographs may not rule out
completely the presence of an airway
FB. Clinicians must suspect FB aspiration when evaluating children who
have pulmonary symptoms and signs
that do not have a clear cause.
(Ramasubramanian V. Kalpatthi,
MD, Lincoln Medical and Mental
Health Center, Bronx, NY; Joan M.
Mavrinac, MD, MPH, Mercy Hospital, Pittsburgh, PA)

Case 3 Discussion
This clinical presentation was consistent with the diagnosis of congestive
heart failure, and the ECG findings
were consistent with lateral wall

myocardial infarction. Such a presentation is typical of an anomalous origin of the left coronary artery from
the pulmonary artery (ALCAPA). If
the cardiomegaly had not been recognized on the chest radiograph and
electrocardiography not been performed, the patient would have been
diagnosed as having only an RSV
infection.

Cause
The coronary arteries are believed to
originate from primordial buds on
the undivided conotruncus. These
buds eventually fuse with the developing coronary circulation. The
cause of the abnormal origin of the
coronary artery is believed to occur
embryologically in one of two ways.
The first theory states that two primordial buds are present and that
ALCAPA is formed by abnormal aortopulmonary septation of the
conotruncus or abnormal placement
of one of the primordial buds. The
second theory states that there are
numerous primordial buds and that
all but two regress. In this theory, a
misaligned bud persists while the
correct bud regresses. Each theory
results in a coronary bud arising from
the pulmonary artery and fusing with
the developing left main coronary artery to result in ALCAPA.

Pathophysiology
Patients who have ALCAPA usually
present in early infancy at about 2 to
3 months of age. Because the left
coronary artery is connected to the
pulmonary artery, in the newborn
period the myocardium supplied by
the left coronary artery is perfused by
blood that is somewhat hypoxic but
under relatively normal pressure.
Ischemia is transient initially, occurring only with crying or feeding. As
the pulmonary vascular resistance
and pulmonary artery pressure drop,
flow into the left coronary artery

from the pulmonary artery becomes

tenuous and eventually stops; the
pressure in the pulmonary artery is
not sufficient to force blood into the
coronary artery. The body tries to
compensate through collateral vessels that develop from the right coronary artery to the left coronary artery. Because these collaterals have
formed, oxygenated blood may be
supplied to that portion of the myocardium filled by the left coronary
arterys vascular bed. The right coronary artery thus becomes the main
source of oxygenated blood for the
myocardium because it arises from
the aorta.
As the pulmonary artery pressure
decreases further due to reduced pulmonary vascular resistance, flow
through the left coronary artery decreases as well. Because the right coronary artery is supplied by the highpressure aorta and the left and right
coronary circulations are connected
by collateral vessels, blood flows
from the right coronary artery to the
left coronary artery (via collateral vessels) and into the pulmonary circulation rather than into the myocardial
branches of the left coronary artery.
This phenomenon, which has
been described as the pulmonarycoronary steal, usually is not a problem in the fetus or neonate, in whom
the pulmonary artery pressures are
high. However, at 6 to 8 weeks of
age, when the pulmonary artery pressure drops below a critical value and
myocardial requirements for oxygen
have increased, coronary perfusion of
the myocardium becomes insufficient through the steal, and myocardial infarction results. Patients who
do not form collaterals will become
ill much more quickly. Mitral insufficiency from subendocardial ischemia
also can be problematic in patients
who have ALCAPA.

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Differential Diagnosis
Prompt and accurate recognition of
infants who are in congestive heart
failure is important for successful
management. Many types of congenital heart disease in infants can cause
congestive heart failure. These conditions may be divided into groups
by the age of presentation. At birth,
volume overload lesions such as severe tricuspid or pulmonary insufficiency and large systemic arteriovenous fistulas are most common. In
the first week of life, transposition of
the great arteries, patent ductus arteriosus (in small preterm infants), hypoplastic left heart syndrome, total
anomalous pulmonary venous return, and critical aortic stenosis or
pulmonary stenosis can cause congestive heart failure.
At 1 to 4 weeks after birth, coarctation of the aorta with associated
anomalies and all other lesions previously listed may present. At 4 to
6 weeks, some left-to-right shunt lesions such as endocardial cushion defects predominate. Finally, at 6 weeks
to 4 months of age, a large ventricular septal defect, patent ductus arteriosus, and lesions such as ALCAPA
are likely to be the causes of congestive heart failure.
Although the congenital heart
diseases previously mentioned may
present with congestive heart failure,
few present with myocardial infarction in infants. Besides ALCAPA,
other causes of myocardial infarction
in infancy and childhood include
other congenital coronary artery
anomalies, Kawasaki disease, congenital heart disease (pre- and postsurgical), and dilated or hypertrophic
cardiomyopathy.

Clinical Presentation
The initial symptoms of ALCAPA are
caused by transient ischemia and
consist of tachypnea, pallor, poor
feeding, paroxysms of crying, dia-

phoresis, and severe agitation. A further increase in myocardial oxygen

demand from stresses such as a viral
infection may lead to infarction of
the left ventricular free wall. This effect on the myocardium leads to the
development of congestive heart failure. Infants may present with wheezing and be diagnosed mistakenly as
having bronchiolitis.

Laboratory Findings
A chest radiograph usually demonstrates cardiomegaly with evidence of
interstitial pulmonary edema. The
electrocardiogram classically shows
abnormal Q waves in leads I, aVL,
and V4 through V6 as well as ST
segment elevation in leads V4
through V6, consistent with an anterolateral infarct (Figure). The presence of these electrocardiographic
findings in an infant raises the suspicion of anomalous origin of the left
coronary artery from the pulmonary
artery.
Echocardiography
with
Doppler color flow mapping currently is the method of choice to
confirm the abnormal origin of a coronary artery. Doppler color flow documents blood flowing from the coronary artery into the pulmonary
artery. In infarcted ventricles, mitral
insufficiency, decreased cardiac function, and regional left ventricular wall
motion abnormalities can be seen.
Cardiac catheterization, with selective coronary cineangiography to
identify the origin and course of coronary arteries, is necessary only when
diagnosis by echocardiography is not
clear.

Management
The definitive treatment for this
anomaly is surgical. Left coronary artery reimplantation into the aorta is
the preferred approach. Historically,
simple ligation of the anomalous left
coronary artery close to its origin
from the pulmonary artery was per-

formed to prevent steal from the

myocardium to the pulmonary artery.
Prior to surgical repair, supplemental oxygen should be administered to prevent hypoxia. Sedation
and analgesia should be employed to
reduce anginal pain and prevent the
tachycardia that increases myocardial
oxygen demand and decreases oxygen supply. The patient should be
monitored for arrhythmias. Inotropic support, to raise diastolic pressure
and coronary artery perfusion,
should be used cautiously because it
also may increase afterload, myocardial work, and myocardial oxygen
demand.

Prognosis
The prognosis for patients after surgery is fairly good. The heart becomes smaller, the ventricular function improves, and congestive heart
failure resolves. However, the postoperative prognosis depends to a
large extent on the degree and duration of preoperative myocardial insult. Patients diagnosed beyond infancy can sustain permanent myocardial damage, and a heart transplant
may be the only therapeutic option.
(David Epstein, MD, Anjan S. Batra,
MD, Childrens Hospital of Los Angeles,
University of Southern California, Los
Angeles, CA)

Case 4 Discussion
The girls serum beta-human chorionic gonadotropin (HCG) level was
280,000 mIU/mL (280,000 IU/
L). Pelvic ultrasonography showed a
thickened, heterogeneous endometrial lining (swiss cheese appearance) with multiple hypoechoic
spaces typical of molar pregnancy.
The next day the patient underwent
suction evacuation of the endometrial cavity, and histopathologic exPediatrics in Review Vol.23 No.11 November 2002 397

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index of suspicion

Figure. Electrocardiogram showing abnormal Q waves in leads I, aVL, and V4 through V6 as well as ST segment elevation in leads
V4 through V6, consistent with an anterolateral infarct. (This tracing is 50% the standard size in amplitude.)

amination of the specimen confirmed

the diagnosis.

The Disorder
Gestational trophoblastic diseases
(GTDs) represent a spectrum of benign and malignant conditions derived from early embryonic tissues of
conception. GTDs are categorized
into four distinct forms. Hydatidiform mole is defined as products of
conception that lack an intact fetus
and show gross cystlike swellings of
the chorionic villi due to accumulation of fluid. There is disintegration
and loss of blood vessels in the villous
core.
Hydatidiform mole has two principal forms: partial and complete.
Partial moles are characterized by focal hydropic villi with scalloping, focal mild-to-moderate trophoblastic

hyperplasia, and identifiable fetal or

embryonic structures. Chromosome
analysis reveals a polypoid karyotype,
which most frequently is triploid.
Complete moles are characterized by
hydropic swelling of all villi, marked
hyperplasia and anaplasia of the trophoblast, and complete absence of
fetal structures. The karyotype of the
complete mole is 46xx. Chromosomal banding studies show that the
chromosomal material of complete
hydatidiform moles is inherited completely from the paternal contribution and is not chromosome Yrelated.
About 80% of complete hydatidiform moles resolve after evacuation
of the uterus. The remaining patients
develop malignant trophoblastic sequelae (invasive mole or choriocarcinoma), with local uterine invasion

being almost four times as common

as distant spread. In contrast, patients who have a partial molar pregnancy are much less likely to develop
persistent trophoblastic disease, with
a range from 0 to 6.6%.
Invasive hydatidiform mole is a
locally invasive, rarely metastatic lesion characterized microscopically by
trophoblastic invasion of the myometrium and identifiable villous
structures. Microscopically, this lesion is characterized by hyperplasia of
cytotrophoblastic and syncytial elements as well as persistence of villous
structures.
Choriocarcinoma is an uncontrolled growth of the cytotrophoblast and syncytiotrophoblast without the presence of villous structures.
Columns and sheets of trophoblastic
tissue invade normal tissues and

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spread to distant sites, the most common of which are lungs, brain, liver,
pelvis, vagina, spleen, intestines, and
kidney. Most cases of choriocarcinoma appear to follow a recognizable gestation. About 50% of choriocarcinomas are preceded by a
hydatidiform molar pregnancy, 25%
follow a spontaneous abortion,
22.5% follow a normal pregnancy,
and 2.5% follow ectopic pregnancy.
About 1 of every 40 molar gestations
is followed by choriocarcinoma.
Abnormal uterine bleeding is the
most frequent clinical presentation of
choriocarcinoma. Other common
signs include bizarre neurologic
symptoms and asymptomatic lesions
on routine chest radiography. Choriocarcinoma can be divided into
nonmetastatic and metastatic forms,
the latter being subdivided into those
having a good prognosis and those
carrying a poor prognosis. Nonmetastatic choriocarcinoma is diagnosed
when HCG titers are persistently elevated or there is a tissue diagnosis of
uterine choriocarcinoma in the absence of detectable metastatic disease.
Metastatic choriocarcinoma with
a good prognosis is associated with
the last pregnancy having occurred
fewer than 4 months previously, a
low HCG titer (100,000 IU in
a 24-h urine specimen or
40,000 mIU/mL [40,000 IU/L]
in the blood), absence of liver or
brain metastases, and no prior chemotherapy. Metastatic choriocarcinoma with a poor prognosis is characterized by the last pregnancy
having occurred more than 4 months
previously, an elevated HCG titer
(100,000 IU in a 24-h urine
sample or 40,000 mIU/mL
[40,000 IU/L] in the blood), liver
or brain metastases, prior chemotherapy, and occurrence after a term
pregnancy.
Placental-site trophoblastic dis-

ease is an extremely rare tumor arising from the placental implantation

site. It resembles an exaggerated
form of syncytial endometritis.
In addition to its potential for developing malignancy, molar pregnancy is associated with other significant complications, including hemorrhage, infection, and toxemia. Molar
pregnancy rates in population-based
studies range from 0.2 to 1.2 cases
per 1,000 pregnancies. The two clinical risk factors most associated with
molar pregnancy are being at the extremes of the reproductive years and
having a history of prior molar pregnancy. The mechanisms leading to
molar pregnancy are not well known.
A maternal locus responsible for the
familial form of hydatidiform mole
was mapped on chromosome
19q13.313.4. Recent research focusing on the molecular bases of
GTD has uncovered important data
concerning the roles of certain receptors, adhesion molecules, oncoproteins, and mitochondrial factors in
the pathogenesis of this disease.

Diagnostic Factors
Frequent clinical manifestations of a
molar pregnancy are uterine size
larger than dates, hyperemesis,
pregnancy-induced hypertension in
the first or second trimester, vaginal
bleeding or passage of vesicles, abdominal pain, and clinical hyperthyroidism. The differential diagnosis
should include those disorders that
are associated with the presenting
complaint. Currently, because of sophisticated ultrasonographic technology and the practice of obtaining
ultrasonography in the first trimester, a significant proportion of patients who have molar pregnancy are
diagnosed before they develop symptoms.

Management
Once a hydatidiform mole has been
diagnosed, suction evacuation of the
uterus should be performed, followed by curettage of the endometrium. A baseline chest radiograph
should be obtained to rule out metastatic disease. Normally, the serum
beta-HCG level falls toward zero
10 to 12 weeks after evacuation of
molar pregnancy. Declining serum
levels of beta-HCG may be assessed
every 1 to 2 weeks until the level is
negative twice, and then monthly for
1 year. A physical examination, including a pelvic examination, is recommended every 2 weeks until remission, then every 3 months for 1
year. Patients must be advised to use
contraception for 1 year.
Invasive mole, nonmetastatic
choriocarcinoma, and metastatic
good-prognosis
choriocarcinoma
usually are treated with single-agent
chemotherapy, although hysterectomy has been performed on the occasional patient in whom preservation of reproductive function is not
an issue. Single-agent chemotherapy
usually employs methotrexate with
leucovorin unless the patient has abnormal liver function, in which case
actinomycin-D is used.
Poor-prognosis metastatic choriocarcinoma and persistent, relapsing, or resistant disease require
complex regimens of chemotherapy
and surgery. One regimen used in
patients who have high-risk disease is etoposide, methotrexate,
actinomycin-D, cyclophosphamide,
and vincristine/oncovin. Patients
who have relapsing or resistant disease require surgery and cisplatin
together with a combination of etoposide, platinum-etoposide, methotrexate, and actinomycin-D. Hysterectomy is the treatment of choice for
patients who have placental-site trophoblastic disease
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index of suspicion

Lessons For The Clinician

In this case, the patient knew that
she was pregnant based on a positive urinary HCG test. She had no
prenatal care. The diagnosis could
easily have been missed because of
mild symptoms and the patients
obesity. Pregnancy at a young age is
a high risk factor for molar pregnancy, and whenever there is a pre-

senting complaint suggestive of abnormal progression of pregnancy,

the diagnosis of GTD should be entertained. Findings on evaluation, including high levels of beta-HCG
(100,000 mIU/mL [100,000 IU/
L]), raised the suspicion of molar
pregnancy. Ultrasonography that
showed no viable fetus and an endometrial lining with multiple hypo-

echoic spaces further supported the

diagnosis, and the histopathology
confirmed it. The current gold standard for diagnosing molar pregnancy
is confirmation by histopathologic
examination. (Yasser Mansour, MD,
Gheorghe R. Ganea, MD, Albert Einstein College of Medicine, BronxLebanon Hospital Center, Bronx,
NY)

Experienced clinicians and specialists have much to teach us. Although textbooks
and journal articles can be valuable sources of information, the person who deals
regularly with specific clinical situations often can provide important insights
that may be overlooked in general education. We would like to offer readers a
chance to submit questions regarding problems they have encountered in their
clinical practices to experts in the field. Have you noticed a changing clinical
trend in your practice that you cant explain? Did you have a patient just last
week whose presentation caused you to think twice before proceeding with treatment? Have you read of new medications or techniques, but have not had a chance
to apply them to your patients? Whatever your question, please submit it to us, and
we will pass it on to an expert in the field to provide you with the information you
need. Send your questions to:
Robert J. Haggerty, MD
Department of Pediatrics
University of Rochester
School of Medicine and Dentistry
601 Elmwood Avenue, Box 777
Rochester, NY 14642
We will handle your question promptly and publish a reply as quickly as possible.

400 Pediatrics in Review Vol.23 No.11 November 2002

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Index of Suspicion
Pediatrics in Review 2002;23;393
DOI: 10.1542/pir.23-11-393

Updated Information &

Services

including high resolution figures, can be found at:

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Index of Suspicion
Pediatrics in Review 2002;23;393
DOI: 10.1542/pir.23-11-393

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/content/23/11/393

Data Supplement at:

http://pedsinreview.aappublications.org/content/suppl/2002/10/29/23.11.393.DC1.html

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2002 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601.

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