Pediatrics International (2019) 61, 122–139 doi: 10.1111/ped.

13755

Review Article

Pediatric oncologic emergencies: Clinical and imaging review for

pediatricians

Atsuhiko Handa,1,2 Taiki Nozaki,1 Akari Makidono,1,3 Tetsuhiko Okabe,1,4 Yuka Morita,1,5 Kazutoshi Fujita,3,6
Masaki Matsusako, Tatsuo Kono, Yasuyuki Kurihara, Daisuke Hasegawa, Tadashi Kumamoto, Chitose Ogawa,7,8
1 3 1 7 7,8

Yuki Yuza9 and Atsushi Manabe7

Departments of 1Radiology and 7Pediatrics, St Luke’s International Hospital, Departments of 3Diagnostic Radiology and
9
Hematology and Oncology, Tokyo Metropolitan Children’s Medical Center, 8Department of Pediatric Oncology, National
Cancer Center Hospital, Tokyo, 4Department of Radiology, Yokohama City University School of Medicine, 6Department of
Radiology, Kanagawa Children’s Medical Center, Yokohama, 5Department of Radiology, University of the Ryukyus
Hospital, Okinawa, Japan and 2Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA

Abstract Children with cancer are at increased risk of life-threatening emergencies, either from the cancer itself or related to
the cancer treatment. These conditions need to be assessed and treated as early as possible to minimize morbidity
and mortality. Cardiothoracic emergencies encompass a variety of pathologies, including pericardial effusion and
cardiac tamponade, massive hemoptysis, superior vena cava syndrome, pulmonary embolism, and pneumonia.
Abdominal emergencies include bowel obstruction, intussusception, perforation, tumor rupture, intestinal graft-
versus-host disease, acute pancreatitis, neutropenic colitis, and obstructive uropathy. Radiology plays a vital role in
the diagnosis of these emergencies. We here review the clinical features and imaging in pediatric patients with
oncologic emergencies, including a review of recently published studies. Key radiological images are presented to
highlight the radiological approach to diagnosis. Pediatricians, pediatric surgeons, and pediatric radiologists need to
work together to arrive at the correct diagnosis and to ensure prompt and appropriate treatment strategies.

Key words computed tomography, magnetic resonance, pediatric oncologic emergency, radiograph, ultrasound.

Children with cancer are at increased risk of life-threatening
emergencies, either from the cancer itself or related to the
cancer treatment.1 These conditions need to be assessed and
treated as early as possible to minimize morbidity and mortal-
ity. Radiological imaging plays a vital role in the diagnosis.
We here review the clinical features and imaging in pediatric
patients with oncologic emergencies, including a review of
recently published studies.
Cardiothoracic oncologic emergencies
Pericardial effusion and cardiac tamponade
Pericardial effusions are excessive fluid in the pericardial
space.2 They can result in cardiac tamponade if the fluid com-
presses the heart to the extent that venous return and cardiac
output are compromised. Pericardial effusion may be caused
by tumor, opportunistic infection attributable to the patient’s
immunocompromised state, or fibrosis from previous radia-
tion.3 The most common tumors to invade the pericardium are
Correspondence: Taiki Nozaki, MD PhD, Department of Radiol-
ogy, St Luke’s International Hospital, 9-1 Akashi-cho, Chuo-ku,
Tokyo 104-8560, Japan. Email: nojyakki@gmail.com
Received 15 March 2018; revised 10 November 2018; accepted
13 December 2018.
leukemia and lymphoma.3–5 Cardiac hemangioma and pericar-
dial teratoma may cause neonatal pericardial effusion.6 The
classical findings of cardiac tamponade, known as Beck’s
triad, consist of hypotension, increased jugular venous pres-
sure, and muffled heart sounds. Symptoms and signs such as
cough, chest pain, dyspnea, tachycardia, and pulsus paradoxus
may also be present. The rate of accumulation contributes
more significantly to the development of cardiac tamponade
than the ultimate volume or composition of the pericardial
fluid.7
Chest radiograph shows a globular-shaped enlarged cardiome-
diastinal silhouette, classically called a “water bottle” shape
(Fig. 1a).8 Echocardiography shows a sonolucent area between
the heart and pericardium, and may also show thickening of the
pericardium suggestive of pericarditis or pericardial tumor
(Fig. 1b). Computed tomography (CT) demonstrates compres-
sion of the cardiac chambers by effusion and may also show
nodular lesions, thickening of the pericardium, or hemorrhage.
Other CT findings in patients with tamponade include enlarge-
ment of the superior vena cava (SVC) or inferior vena cava
(IVC), periportal edema, reflux of contrast material into the IVC
or azygos vein, and enlargement of hepatic and renal veins.9 CT
is superior to echocardiography in characterizing pericardial effu-
sion and pericardial mass because it provides a larger field of
view and better visualization of anatomical details.10 Magnetic

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a pulmonary aspergillosis12 or diffuse alveolar hemorrhage.13
b
Fig. 1 Cardiac tamponade in a 4-year-old girl with myelodys-
plastic syndrome. (a) Antero-posterior chest radiograph showing a
globular-shaped enlarged cardiac silhouette classically called a
“water bottle” shape. (b) Echocardiography showing a large
sonolucent area (asterisks) between the heart and pericardium that
is compressing the cardiac chambers.
resonance (MR) imaging can further characterize effusions,11 but
it is less often used to diagnose pericardial effusion.
Hemoptysis
Hemoptysis can occur in children with cancer.1 Mild hemopty-
sis is usually attributable to aspiration of epistaxis. Moderate
to severe hemoptysis can occur in patients with invasive
Pediatric oncologic emergencies 123
Invasive pulmonary aspergillosis typically occurs in immuno-
compromised patients, especially those with prolonged
chemotherapy-induced neutropenia. Imaging in patients with
invasive pulmonary aspergillosis will be discussed later in the
Pneumonia section. Diffuse alveolar hemorrhage, a rare but
severe non-infectious complication of hematopoietic cell trans-
plantation (HCT), presents with respiratory failure and hemop-
tysis around the time of white blood cell engraftment,13 and is
associated with a high mortality rate.14 A recent study on
autopsies of children with cancer found a high incidence of
pulmonary hemorrhage (40%), this being the most frequently
missed clinical diagnosis.15 The absence of hemoptysis does
not exclude a diagnosis of diffuse alveolar hemorrhage in
adults;16 this may also be true for children.
Chest radiograph in patients with diffuse alveolar hemor-
rhage may show air space opacification or ground-glass opac-
ity predominantly in the perihilar region (Fig. 2a). Classically,
lesions are bilateral and symmetric, but they can also be
asymmetric or unilateral.11 CT shows patchy or diffuse
ground-glass or air space opacities (Fig. 2b). The differential
diagnosis of these CT findings includes acute respiratory dis-
tress syndrome/acute lung injury (diffuse alveolar damage),
cardiogenic pulmonary edema, and pneumonia. In the acute
phase, diffuse alveolar damage manifests as interlobular septal
thickening and traction bronchiectasis and tends to have a geo-
graphic distribution.17 Cardiogenic pulmonary edema mani-
fests as cardiomegaly, engorged pulmonary vessels,
interlobular septal thickening, and pleural effusion. Neuroblas-
toma may cause congestive heart failure due to cate-
cholamine-induced cardiomyopathy (Fig. 3).18 Pneumonia is
typically a focal process, as detailed in the Pneumonia section.
Follow-up imaging of diffuse alveolar hemorrhage shows reso-
lution of hemorrhage from alveolar spaces and thickening of
interlobular septa, resulting in the classical finding of a
“crazy-paving” pattern.
Mediastinal tumor causing SVC syndrome and airway
narrowing
Superior vena cava syndrome is a constellation of signs and
symptoms caused by venous congestion due to obstruction of
the SVC.19 Given that infants and young children have a soft
and compressible airway, airway narrowing often accompanies
SVC syndrome in this age group (“superior mediastinal syn-
drome”). Older children may have isolated tracheal narrowing
or SVC syndrome. SVC syndrome can be caused by extrinsic
compression or intrinsic obstruction. The most common cause
of SVC syndrome is an anterior mediastinal mass, such as
lymphoma and leukemia (such as precursor T-cell lymphoblas-
tic lymphoma or T-cell acute lymphoblastic leukemia;
ALL).19 Neuroblastoma, germ-cell tumors, and sarcomas are
also common etiologies.19 Prolonged placement of central
venous catheter puts children at risk of acquiring SVC throm-
bosis.20 Classical symptoms of SVC syndrome in adults
include edema and plethora of the face, neck, and arm, as well
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124 A Handa et al.
a
b Steroids or radiation treatment may be beneficial even before
Fig. 2 Diffuse alveolar hemorrhage resulting from hemophago-
cytic lymphohistiocytosis in a 12-year-old boy with myelodysplas-
tic syndrome who had massive hemoptysis. (a) Antero-posterior
chest radiograph showing bilateral patchy ground-glass opacities
that predominate in the perihilar region (arrowheads). (b) Axial
unenhanced computed tomography showing bilateral patchy
ground-glass opacity and consolidation that is most marked cen-
trally.
as venous distention of the cervical and anterior chest wall
veins.20 In pediatrics, patients more commonly present with
cough, dyspnea, orthopnea, and wheeze, which may mimic
upper respiratory tract infection or asthma.19
Chest radiograph may show mediastinal widening20 and
airway compression21 in cases of mediastinal mass (Figs 4–6).
CT with intravenous contrast materials may demonstrate tumor
and its involvement of the surrounding vasculature and airway
(Figs 4–6). CT can also provide tracheal cross-sectional area,
although the correlation of symptoms with imaging degree of
obstruction is poor.21 Care must be taken during CT, since the
© 2018 Japan Pediatric Society
supine position may aggravate respiratory symptoms. CT may
be obtained in the prone position in such cases. MR venogra-
phy can provide evaluation of vascular flow without the use
of contrast material,11 but MR often requires sedation and
may not be optimal in the setting of acute respiratory compro-
mise. CT is still preferred over MR because of its speed and
ability to demonstrate pulmonary pathology.22
Diagnosis of SVC syndrome caused by mediastinal mass
should be made in a step-wise approach starting with the least
invasive and lowest risk technique possible to avoid cardiores-
piratory compromise.21,23 Peripheral blood test, pleural fluid
cytology and analysis, bone marrow aspiration, or open/needle
biopsy of accessible extra-thoracic disease lesions (e.g. lymph
nodes) should be attempted before open biopsy requiring gen-
eral anesthesia. Multiple specialists (anesthesiologists, oncolo-
gists, surgeons, pulmonologists, and radiologists) should be
involved, and the diagnostic as well as the therapeutic plan
should be fully discussed. Benefits and risks for sedation
should be carefully weighed, given that a loss of negative tho-
racic pressure caused by sedation can further narrow a thin-
walled SVC and flexible airway, which can exacerbate pre-
existing symptoms,24 or, in the worst case, may lead to car-
diopulmonary arrest. Cases of peri-anesthetic death are well
known, even in children who did not have airway symptoms.
establishing a diagnosis to prevent airway compromise.
Image-guided needle biopsy of a mediastinal mass or enlarged
lymph node can be performed under local (or general) anes-
thesia by a skilled interventional radiologist.23
Pulmonary embolism
Pediatric patients with cancer are at high risk of pulmonary
thromboembolism (PE).25 The risk of venous thromboem-
bolism, including both deep venous thrombosis and PE, is
four–sevenfold higher in patients with cancer than in those
without cancer.26 Another study found that 25% of children
with venous thromboembolism have an underlying neoplasm
and that cancer is a major cause of mortality in children with
deep venous thrombosis.27 Surprisingly, almost 2% of routine
thoracic CT of pediatric patients with cancer showed evidence
of PE.25 Many factors may contribute to the development of
PE in children with cancer, including the use of a central
venous catheter, disease- or treatment-related (such as
asparaginase) coagulopathy, tumor lysis, parenteral hyperali-
mentation, and platelet microaggregates from transfusions.28
In addition to being at risk of thromboembolism, pediatric
patients with cancer are at risk of tumor thrombus and embo-
lism (Fig. 7).25
Radiographic findings of PE are non-specific. Chest radio-
graph is commonly normal.11 Classical signs of PE such as
oligemia (“Westermark sign”) and peripheral wedge-shaped
infarction (“Hampton hump”) are rarely seen. CT pulmonary
angiography, currently the preferred procedure for detecting
PE, demonstrates emboli as arterial filling defects. The lung
parenchymal finding of wedge-shaped peripheral consolidation
 Pediatric oncologic emergencies 125

a b

Fig. 3 Catecholamine-induced cardiomyopathy associated with neuroblastoma in a 3-year-old boy. (a) Baseline chest radiograph
3 weeks prior to the referral when patient started to have fever. Retrospectively, the patient had abnormal calcification in the paraspinal
regions (arrow). (b) At the time of referral, the patient had persistent fever. Chest radiograph showing engorged pulmonary vessels with
mild cardiomegaly (arrowheads). (c) Axial contrast-enhanced computed tomography showing a large retroperitoneal tumor with punctate
calcifications (arrow).

is significantly associated with PE.29 The utility of MR
angiography has been demonstrated in adults, albeit with cer-
tain limitations.30 There is no clinical evidence for the useful-
ness of MR angiography in detecting PE in children, making
the role of this procedure uncertain. Nuclear ventilation perfu-
sion or conventional pulmonary angiography are seldom used
in children with suspected PE.
Pneumonia/pulmonary infection
Pediatric patients with cancer may be at increased risk of
pneumonia because their underlying malignancies (such as
ALL) and/or chemotherapy may compromise their immune
systems.31 Pneumonia is the commonest location of infection
and is a major cause of mortality. Fever may be the only ini-
tial symptom because of impairment of the inflammatory cell
response.
Imaging plays a major role in several ways. It may help by
distinguishing infection manifesting as an interstitial disease
(often bilateral, symmetric, diffuse ground glass and reticulon-
odular opacities) from a focal air space lesion (often unilat-
eral, asymmetric, patchy air space opacification).31,32 It can
also show complications such as parapneumonic effusion/
empyema or lung abscess and exclude other thoracic causes of
abnormality.33 Because a specific organism can cause a vari-
ety of imaging patterns and there is significant overlap
between imaging findings of pneumonia caused by different
organisms, the causative organism can rarely be determined
on the basis of imaging alone. Sometimes more than one
organism is responsible for infection in immunocompromised
children. Nevertheless, chest radiograph and chest CT play
important roles in the diagnostic workup. Chest CT is often
necessary to evaluate the possibility of a lung infection
because the initial chest radiograph findings in patients with
fungal infection or pneumocystis pneumonia may be very sub-
tle or even non-existent. Indeed, evaluation of the possibility
of lung infection is a common reason for performing chest CT
in such children.

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b c

Fig. 4 Severe superior vena cava (SVC) and airway narrowing caused by an anterior mediastinal mass from T-cell lymphoblastic lym-
phoma in a 14-year-old girl who presented with facial swelling and dyspnea. (a) Frontal chest radiograph showing a massive right-sided
pleural effusion (asterisk). (b,c) Axial contrast-enhanced computed tomography showing an anterior mediastinal tumor compressing the
trachea (arrowheads) and SVC (arrows). Collateral veins including hemiazygos and paravertebral veins have developed due to severe
stenosis of SVC (dotted arrow). A large pleural effusion is again shown.

If chest radiograph shows a pattern of interstitial disease,
viruses (including cytomegalovirus [CMV], Herpes simplex
virus, Varicella zoster virus, Epstein–Barr virus, and respira-
tory syncytial virus), Pneumocystis jiroveci, mycoplasma
(early phase), and Chlamydophila should be considered. CT
may show ground glass opacities in a centrilobular distribu-
tion (sometimes with patchy air space opacity), mosaic perfu-
sion, and/or air trapping. Typical CT findings of CMV
pneumonia are centrilobular or randomly distributed nodules
in addition to patchy or widespread air space consolidation
and ground glass opacities. Of note, in children <2 years of
age, viral pneumonia (such as respiratory syncytial virus, rhi-
novirus, parainfluenza virus, human metapneumovirus, aden-
ovirus, influenza virus) is typically associated with
hyperinflation with prominent bilateral symmetric peri-
bronchial markings and patchy areas of subsegmental atelec-
tasis.34 Viruses that commonly cause mild pneumonia in
healthy children may display greater virulence in children
who have undergone HCT and have impaired cellular immu-
nity. Epstein–Barr virus can cause post-transplantation lym-
phoproliferative disease.31
When chest radiograph shows focal, asymmetrical air
space lesions, bacterial, mycobacterial, and fungal infections
should be considered. Chest radiograph/CT may show (i)
lobar (or segmental, spherical) pneumonia with air bron-
chogram (typically caused by nosocomial bacteria, myco-
plasma (later phase), mycobacteria, and fungi; Fig. 8); or (ii)
bronchopneumonia with patchy nodules of soft-tissue density
in a centrilobular distribution, correlating with endobronchial
spread of organisms (typically caused by Staphylococcus
aureus, Pseudomonas aeruginosa, Escherichia coli, mycobac-
teria, and fungi), often associated with bronchial wall thick-
ening and airway impaction (although when the latter are
isolated findings, viral or atypical organisms are more
likely). Tree-in-bud appearance suggests infection with pyo-
genic bacteria (such as Streptococcus pneumoniae,

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 Pediatric oncologic emergencies 127

b c

Fig. 5 Severe airway narrowing caused by a large pleuropulmonary blastoma in a 2-year-old girl. (a) Frontal chest radiograph showing
complete opacification of the left hemithorax, and tracheal deviation as well as mediastinal shift to the right. (b) Coronal and (c) axial
contrast-enhanced computed tomography showing a large mixed solid and cystic tumor occupying the left hemithorax (arrows) with
mediastinal shift to the right.

Staphylococci) or mycobacteria. Encapsulated bacteria (such
as S. pneumoniae, Haemophilus influenzae) show increased
virulence in children who have undergone HCT and have
impaired humoral immunity.
Relatively large nodules and cavities commonly denote
bacterial lung abscesses, nocardiosis, fungal/mycobacterial
infection, or septic embolism. Multiple, scattered, bilateral
nodular or mass-like consolidation (without bronchial wall
thickening) is the typical manifestation of aspergillosis
(Fig. 9), mucormycosis (Fig. 10), and candida infections, all
of which warrant special attention in neutropenic children. A
halo of ground glass opacity may be seen surrounding nodules
(“halo sign”); in the setting of neutropenia; this may suggest
angioinvasive aspergillosis infection.35 A crescent-shaped area
of radiolucency in a region of nodular opacity (“air-crescent
sign”) may also be seen, but these findings are infrequent in
younger children.36
Random patterns of small nodules may be seen with mil-
iary tuberculosis or miliary fungal infection (including histo-
plasmosis and coccidiomycosis).
Last, immunocompromised children who have undergone
HCT deserve special note because they tend to be affected
sequentially by various conditions during the post-transplant
period.37 During the initial neutropenic phase (2–3 weeks
after transplantation), bacterial pneumonia and fungal infec-
tion may occur. Non-infectious complications include pul-
monary edema, diffuse alveolar hemorrhage, and engraftment
syndrome. Engraftment syndrome is characterized by fever,
rash, pulmonary edema, weight gain, liver and renal dysfunc-
tion, and/or encephalopathy, and occurs approximately
10 days after HCT.38 CT findings are similar to pulmonary
edema but without cardiomegaly.39 During the early phase
(between 2–3 weeks and 100 days), humoral immunity is still
impaired and there is a significant risk of Pneumocystis or
cytomegalovirus pneumonia. Idiopathic pneumonia syndrome
is a common non-infectious complication, which is a clinical
diagnosis made by signs and symptoms of pneumonia (such
as hypoxia) associated with widespread alveolar injury in the
absence of lower respiratory tract infection.40 Chest radio-
graph/CT shows multilobar air space opacification or ground

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b c

Fig. 6 Severe airway narrowing caused by a metastatic mediastinal lymph node due to hepatoblastoma in a 1-year-old-girl who pre-
sented with abdominal distention. (a) Frontal chest radiograph showing near complete opacification of the left hemithorax without marked
mediastinal shift. Tortuous coursing of the nasogastric tube (black arrows) suggest esophageal deviation to the right. (b,c) Axial contrast-
enhanced computed tomography (CT) of the (b) chest shows a metastatic lymph node compressing the left mainstem bronchus (white
arrow), and (c) of the abdomen shows a large heterogeneous tumor replacing the left liver with peritoneal implants over the liver capsule
(arrowheads). There also is associated peritoneal free fluids (asterisk) with increased CT density suggestive of intra-abdominal tumor
rupture.

glass opacities in the bilateral lung with basilar or dorsal pre-
dominance. During the late phase (between 100 days and
1 year), non-infectious complications such as obliterative
bronchiolitis, organizing pneumonia, and pulmonary veno-
occlusive disease may occur. Obliterative bronchiolitis (or
bronchiolitis obliterans) is an inflammatory/fibrosing process
involving the small airways that often results in progressive,
irreversible obstructive pulmonary disease.41 CT shows geo-
graphic areas of hyperlucency and bronchial wall thickening
with mosaic pattern of lung attenuation.42 Organizing pneu-
monia (previously known as bronchiolitis obliterans organiz-
ing pneumonia, BOOP) is an alveolar inflammation that may
occur secondary to HCT.43 CT may show peripheral patchy
air space infiltrates.44 Central ground glass opacification with
surrounding consolidation (atoll or reverse halo sign) may be
seen. Pulmonary veno-occlusive disease is a narrowing or
occlusion of the pulmonary venules or small veins resulting
in pulmonary hypertension.45 Smooth diffuse interlobular sep-
tal thickening in the absence of left-sided heart disease is the
most suggestive sign on CT.46
Abdominal oncologic emergencies
Intestinal obstruction and intussusception
Acute small bowel obstruction can be caused by external or
internal abnormalities.11 Adhesion and stricture are common
causes of obstruction in children who have undergone

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Fig. 7 Tumor thrombus in a 4-year-old boy with rhabdomyosar-
coma. Axial contrast-enhanced computed tomography showing a
tumor thrombus (arrow) severely narrowing the right main
pulmonary artery. Bilateral lung metastases are also evident (as-
terisks). The thrombus resolved after chemotherapy.
Fig. 8 Klebsiella pneumonia in a neutropenic 12-year-old boy
during chemotherapy for Burkitt lymphoma. Axial unenhanced
computed tomography showing a focal peripheral area of air
space opacification (asterisk) with air bronchogram (arrow) and
bronchial wall thickening (arrowhead). Blood cultures grew Kleb-
siella pneumoniae.
abdominal/pelvic surgery. Tumors that may cause bowel
obstruction include sarcoma, abdominal lymphoma, large
renal/adrenal tumor, ovarian and colon tumors, and presacral
teratoma.1 Narcotics and vinca alkaloids can cause non-
obstructive adynamic ileus. Children typically present with
persistent bilious vomiting and abdominal pain.
Abdominal radiograph classically shows multiple dilated
loops of bowel with air–fluid levels on upright or decubitus
images and absence of stool and gas in the bowel distal to the
obstruction (Fig. 11a).11 With adynamic ileus, there is typi-
cally uniform dilatation of the entire small and large bowels.
Although abdominal radiograph may suggest the location of
obstruction, CT with intravenous contrast better demonstrates
Pediatric oncologic emergencies 129
Fig. 9 Invasive aspergillosis in a 2-year-old boy with prolonged
neutropenia during chemotherapy for acute lymphoblastic leuke-
mia. Axial unenhanced computed tomography at the level of the
lung apex showing bilateral ground glass opacity surrounding
nodular lesions (“halo sign” [arrows]). The area of radiolucency
surrounding a region of nodular opacity in the right apex is a
fully developed “air-crescent” (asterisk). Serum antigen testing
was positive for Aspergillus.
Fig. 10 Mucormycosis in a 10-year-old girl with relapsed acute
lymphoblastic leukemia. Axial unenhanced computed tomography
of the chest showing an area of air space opacification in the right
apex with surrounding areas of ground glass opacity (“halo sign”
[arrows]). Polymerase chain reaction was positive for Mucormy-
cetes.
both the location and cause, including tumor (Fig. 11b), and is
the modality of choice.11 CT is especially helpful in patients
with closed-loop obstruction and obstruction related to adhe-
sions, demonstrating dilated bowel loops proximally and col-
lapsed bowel distal to the obstruction.
Intussusception can be caused by benign small bowel
tumors (polyps, especially those associated with Peutz–Jeghers
syndrome, hemangioma/vascular malformations, neurofibroma,
fibroma, leiomyoma, gastrointestinal (GI) stromal tumor
(GIST), lipoma, and lipoblastoma) or malignant tumors (Bur-
kitt lymphoma and carcinoid tumor).11 Intussusception is the
initial presentation in 17–25% patients with abdominal Burkitt
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130 A Handa et al.
a are transient and of no clinical significance.50 Findings that
b
Fig. 11 Small bowel intussusception and obstruction resulting
from diffuse large B-cell lymphoma in a 5-year-old boy. (a)
Upright abdominal radiograph showing multiple dilated loops of
small bowel with air–fluid levels (white arrowheads) suggestive
of small bowel obstruction. (b) Axial contrast-enhanced computed
tomography showing small bowel obstruction caused by intussus-
ception (arrow), with enlarged lymph nodes being a pathological
lead point (black arrowhead).
lymphoma.47,48 Physicians should strongly suspect underlying
pathology when older children (aged >6 years) present with
intussusception.48
Abdominal radiograph may show evidence of obstruction,
as noted in the previous section. Ultrasound (US) and CT
show bowel within bowel (“target/doughnut sign”, “pseudo-
kidney sign” or “concentric ring sign” on US).49 Of note, most
© 2018 Japan Pediatric Society
small bowel intussusceptions found in children on US or CT
suggest transient small bowel intussusception on US include
(i) small size without wall swelling; (ii) short segment; (iii)
preserved wall motion; and (iv) absence of the lead point.51
Findings that suggest pathological intussusception include
intussusception length >3.5 cm, and evidence of bowel
obstruction or an identifiable lead point.51,52 Repeat focused
US can document spontaneous resolution when necessary.
Gastrointestinal perforation, tumor rupture, and
hemorrhage
Gastrointestinal perforation may be caused by persistent
obstruction, gastritis/peptic ulcers, or erosion caused by tumor
infiltration. Because of its tendency to involve the full thick-
ness of the bowel wall and sensitivity to chemotherapy, post-
chemotherapy intestinal rupture can occur in patients with
Burkitt lymphoma.53 Neuroblastoma (especially in neonates),
Wilms tumor, hepatoblastoma, and ovarian tumor may rarely
present with tumor rupture.54–57 Affected children typically
present with severe abdominal pain and evidence of shock
and/or peritonitis. Ovarian tumor can also present with acute
abdomen due to torsion (Fig. 12), which is often associated
with hemorrhagic necrosis in the later phase.58
Abdominal radiograph typically shows free abdominal air
in patients with bowel perforation, and free fluids in those
with intraabdominal hemorrhage or tumor rupture.11 US may
show a large amount of fluid in the peritoneal cavity. CT may
show the responsible tumor, hemoperitoneum (unclotted bleed
usually has attenuation of 20–60 Hounsfield units [HU], and
clotted blood, higher attenuation [60–90 HU]), and the source
of bleeding, especially if intravenous contrast demonstrates
extravasation (Figs 6c,13). Ovarian torsion presents with ovar-
ian enlargement with or without an underlying mass, but it is
non-specific. A twisted pedicle, although not often detected on
imaging, is pathognomonic when seen.58
Intestinal graft-versus-host disease
Graft-versus-host disease (GVHD), a serious complication of
HCT,59 occurs when donor T lymphocytes react with the tis-
sues of the host, such as those in the skin, liver, and GI tract.
For GVHD to develop, (i) the graft must contain immunologi-
cally competent cells; (ii) the recipient must express tissue
antigens that are not present in the transplant donor; and (iii)
the recipient must be incapable of mounting a response cap-
able of destroying the transplanted cells.60 The most important
risk factor for the development of GVHD is human leukocyte
antigen mismatch.61 Acute GVHD is usually diagnosed on a
clinical basis, but it is often difficult to differentiate from
thrombotic microangiopathy or CMV infection clinically. It
occurs in the first 100 days after transplantation. Patients usu-
ally present with a pruritic maculopapular rash, hepatitis (jaun-
dice), and GI abnormalities (crampy abdominal pain, nausea,
vomiting, and profuse diarrhea). Pathologically, acute GVHD
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a b

Fig. 12 Left adnexal torsion in a 14-year-old girl who presented with acute abdomen. (a) Axial unenhanced computed tomography (CT)
of the pelvis showing a large mass with internal septations and increased CT density in the dependent portion (arrowhead) suggestive of
hemorrhagic component. (b) Axial contrast-enhanced CT of the pelvis showing a large tumor without solid enhancing components. The
adnexal mass also appears to lack wall enhancement suggestive of necrosis. (c) Coronal contrast-enhanced CT of the pelvis showing mild
surrounding fat stranding and free fluid in the pelvic floor (asterisk).

is characterized by selective epithelial damage in target
organs.61 In intestinal GVHD, destruction of intestinal crypts,
especially at the base of the crypts (which contain a high pro-
portion of stem cells), results in patchy or diffuse mucosal
ulceration.
Abdominal radiograph shows ileus with separation of bowel
loops, thickening of the bowel wall, and air–fluid levels.62 US
shows bowel wall thickening (>3 mm) and dilated fluid-filled
loops of bowel. CT with intravenous contrast shows striking
mucosal enhancement that correlates histopathologically with
mucosal destruction (Fig. 14).63 The mucosal and serosal sur-
faces avidly enhance, thus appearing hyperattenuating, and cre-
ate a “target” sign with a hypoattenuating middle layer
representing intramural or submucosal bowel wall edema.64
Bowel wall thickening and luminal narrowing may affect any
part of the intestine, but the small intestine is characteristically
most severely affected. Pneumatosis intestinalis can be seen, as
detailed in the next paragraph (Fig. 15).65 Common extra-intest-
inal findings include engorgement of the mesenteric vessels and
ascites. Abnormal enhancement of the gallbladder or bladder
wall may also occur, but these findings are non-specific. The
differential diagnosis includes neutropenic colitis, infectious
enterocolitis including pseudomembranous colitis and viral
infection, and tumor involvement (Fig. 16).64 Neuroblastoma
and ganglioneuroblastoma may also cause refractory diarrhea as
a paraneoplastic syndrome.66 Neutropenic colitis, as detailed in
a following section, most commonly involves the cecum and
occasionally the ileum. Pseudomembranous colitis usually man-
ifests as a pancolitis with marked fold thickening and rarely
involves the small bowel. The distribution of CMV colitis is

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132 A Handa et al.

Fig. 13 Wilms tumor rupture in a 2-year-old girl. (a) Coronal

and (b) axial contrast-enhanced computed tomography showing a
left renal tumor with obscured anterior–inferior margin (arrow)
and massive hemorrhage (asterisks) into the retroperitoneal and
peritoneal spaces. Histopathology showed ruptured Wilms tumor.

similar to that of neutropenic colitis. Although there is some

overlap between GVHD and other conditions, the location and
extent of bowel involvement and presence of associated findings
can help narrow the differential diagnosis. Given that differenti-
ation of intestinal GVHD from infective enteritis is critical to
selecting the appropriate treatment, tissue sampling via biopsy
may be required.
Pneumatosis intestinalis is occasionally associated with
intestinal GVHD. In a recent study, 10.1% of children who
Fig. 14 Intestinal graft-versus-host disease (GVHD) in a 9-year-
old girl with acute lymphoblastic leukemia who developed severe
vomiting 50 days after hematopoietic cell transplantation. (a) Cor-
onal and (b) axial contrast-enhanced computed tomography show-
ing dilated fluid-filled loops of bowel, diffuse bowel wall
thickening (arrowheads) and striking contrast enhancement of the
bowel wall. Upper and lower gastrointestinal endoscopy indicated
mucosal erythema, and biopsy confirmed the diagnosis of intesti-
nal GVHD.

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 Pediatric oncologic emergencies 133

a b

Fig. 15 Extensive pneumatosis associated with intestinal graft-versus-host disease (GVHD) in an 11-year-old girl with malignant lym-
phoma who had undergone hematopoietic cell transplantation. (a) Supine abdominal radiograph showing curvilinear foci of gas outlining
the ascending and transverse colon with dilated bowel suggestive of extensive pneumatosis coli (white arrows). There is no evidence of
intra-abdominal free air. (b) Coronal contrast-enhanced computed tomography (CT) in the lung window showing extensive circumferen-
tial collections of air in the wall of the colon that runs parallel to the ascending and transverse colon (black arrows), indicating a rela-
tively benign form of intestinal GVHD. (c) Axial contrast-enhanced computed tomography again showing pneumatosis without what
would be clinically more worrisome features such as bowel wall thickening, loss of contrast enhancement, or surrounding fat stranding.
There is diffuse mild thickening of the small bowel wall (black arrowheads) attributable to GVHD. The patient recovered without
surgery.

had received allogenic HCT developed pneumatosis intesti-
nalis a median of 94 days after transplant; they were success-
fully managed medically.67 Surprisingly, extensive
pneumatosis indicates a relatively benign form of intestinal
GVHD, whereas bowel wall thickening, free peritoneal fluid,
and peri-intestinal soft-tissue stranding are associated with
more serious clinical manifestations.68
Acute pancreatitis
Acute pancreatitis can be caused by drugs such as asparaginase,
an agent used in the treatment of ALL and lymphoma.69,70
Affected patients present with abdominal pain, nausea, and
vomiting, typically soon after starting asparaginase therapy.
Recent studies have tried to identify genetic risk factors for
asparaginase-related pancreatitis in children with ALL, but the
findings have been inconsistent, and no strong basis has been
established for such genetic risk factors.71,72 Other medication
associated with pancreatitis includes corticosteroids, 6-mercap-
topurine, and trimethoprim–sulfamethoxazole.69
The diagnosis of acute pancreatitis rests on clinical and lab-
oratory findings (an elevation of amylase and lipase), and
imaging can both help confirm the diagnosis and detect com-
plications.69,70 Depending on local practice, imaging may not
necessarily be pursued, but the relatively high incidence of
pseudocysts probably warrants imaging in all cases.70 US can
be normal in mild acute pancreatitis. In moderate–severe
cases, the pancreas is enlarged and hypoechoic (Fig. 17a).11
CT demonstrates focal or diffuse pancreatic enlargement,
mildly decreased enhancement, surrounding fat inflammation,
and often peripancreatic fluid collection (Fig. 17b). Pseudocyst
formation is the commonest complication, occurring in 18–

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134 A Handa et al.

b c

Fig. 16 Langerhans cell histiocytosis in a 7-month-old girl presenting with profuse diarrhea. (a) Coronal and (b) axial contrast-enhanced
computed tomography of the abdomen and pelvis showing diffuse dilatation of the bowels, intraperitoneal free fluids (asterisks), and sple-
nomegaly suggestive of gastrointestinal involvement. (c) Contrast-enhanced fat-saturated axial T1-weighted magnetic resonance imaging
showing an enhancing mass in the hard palate (arrows).

30% of patients.69,70,73 Other complications include necrosis,

abscess, and hemorrhage. Plain film findings are non-specific,
but certain findings are suggestive.11 Reactive ileus of nearby
GI structures (“sentinel loops”), air–fluid levels in stomach
and duodenum, focal dilatation of the duodenal sweep, and
dilatation of the transverse colon ending abruptly at the sple-
nic flexure (“colon cut-off sign”), are rare but classical find-
ings in patients with moderate–severe pancreatitis. Left pleural
effusion may also occur.
Re-treatment with asparaginase after an episode of mild
pancreatitis is associated with a higher risk of recurrent pan-
creatitis. The risk of the second episode of asparaginase-asso-
ciated pancreatitis, however, does not depend on the severity
of the first episode, and the second episode does not have a
greater risk of complications.70 The current consensus on deci-
sions about asparaginase re-exposure appears to be that they
should be based on balancing the importance of asparaginase
in achieving leukemia survival versus the risk of the second
episode of asparaginase-associated pancreatitis.70
Neutropenic colitis
Neutropenic colitis, or typhlitis, is a necrotizing colitis that
usually involves the cecum, ascending colon, appendix, and
terminal ileum, typically in neutropenic children with hemato-
logic malignancies.1,74 Neutropenic colitis can occur else-
where: the transverse, descending colon, or rectum being
involved in 40% of cases.74 Most (but not all) children with
neutropenic colitis present with abdominal pain, fever,
abdominal tenderness, and diarrhea.74 Typically, neutropenic
colitis develops when the absolute neutrophil count declines
sharply to a nadir after chemotherapy for acute leukemia.75
The postulated mechanism is that chemotherapy-related
destruction of the normal mucosal architecture is followed by
bacterial/fungal invasion of the bowel facilitated by decreased
defenses due to neutropenia, leading to neutropenic coli-
tis.76,77
Ultrasound or CT typically show bowel wall thickening
(>3 mm), pneumatosis intestinalis, surrounding soft-tissue

© 2018 Japan Pediatric Society


b chemotherapy for acute lymphoblastic leukemia. Axial contrast-
Fig. 17 Acute pancreatitis caused by asparaginase in a 4-year-
old boy with acute lymphoblastic leukemia. (a) Abdominal ultra-
sound showing an enlarged and hypoechoic pancreas (arrow). (b)
Axial contrast-enhanced computed tomography showing an
enlarged and edematous pancreas (arrow) with a large amount of
ascites (asterisks), consistent with acute pancreatitis.
edema in the affected region, and free fluid (Fig. 18).74,78 US is
as sensitive as CT, avoids radiation exposure, and may provide
a more accurate measurement of bowel wall thickness with its
higher spatial resolution.74,79 Perforation may complicate neu-
tropenic colitis; this is better evaluated on radiograph or CT.
Given that neutropenic colitis can involve the appendix, it
may mimic acute appendicitis.80 The incidence of these two
diseases is similar and they must be differentiated because
most patients with neutropenic colitis recover with medical
treatment alone, whereas acute appendicitis often requires sur-
gery. Distinguishing clinical features in children with neu-
tropenic colitis include the presence of fever and diarrhea. Of
note, appendicitis in children with hematologic malignancies
may present with atypical clinical findings and an absence of
characteristic imaging findings.
Other differential diagnoses, including infectious enterocoli-
tis (such as pseudomembranous colitis and viral infection),
and intestinal GVHD are described in detail in the earlier
section.
Pediatric oncologic emergencies 135
Fig. 18 Neutropenic colitis in a 14-year-old boy receiving
enhanced computed tomography showing diffusely thickened
large bowel wall, most prominent in the cecum and ascending
colon (arrow), and less prominently involving the transverse colon
(arrowheads). There is also diffuse mesenteric edema.
Genitourinary emergencies
Acute genitourinary complications in children with malignan-
cies may be caused by pre-renal causes (septic shock), renal
injury (tumor lysis syndrome, chemotherapeutic agents such as
methotrexate or cisplatin, or anti-vascular endothelial growth
factor therapy), or post-renal obstruction.1,81 Children with
acute urinary complications usually present with reduced or
absent urine output with high serum creatinine concentration.
Post-renal obstruction may be caused by large abdominal or
pelvic masses (such as Wilms tumor, retroperitoneal sarcoma,
lymphoma, germ cell tumor, ovarian tumor, adrenal neuroblas-
toma, and bladder rhabdomyosarcoma) compressing the ureter
or bladder. Blood clots from hemorrhagic cystitis can also
obstruct the urinary outflow from the bladder.81 Cyclophos-
phamide is a cause of hemorrhagic cystitis. Recent data sug-
gest that BK virus is associated with hemorrhagic cystitis in
children undergoing HCT.82 Terminal renal failure is a rare
event: pediatric malignancies account for only 0.9% of
patients on renal replacement therapy, and many of these
patients have been treated for bilateral Wilms tumor.81
Renal and bladder US is the first diagnostic test in patients
with azotemia because it is the least invasive and avoids radia-
tion or use of contrast media. A > 10 mm anteroposterior
diameter of the renal pelvis is associated with obstructive
uropathy (100% sensitivity, 90.3% specificity).83 Contrast-
enhanced CT may be performed provided renal function is
preserved and may show delayed renal parenchymal enhance-
ment (“delayed nephrogram” sign) in patients with obstruc-
tion, as well as demonstrate the tumor itself or hydro-
ureteronephrosis (Fig. 19). MR urography can help further
evaluation of obstructive uropathy.84 In patients with hemor-
rhagic cystitis, US shows either focal or diffuse bladder wall
thickening (>3 mm in a distended bladder), often with echo-
genic debris (Fig. 20).85
© 2018 Japan Pediatric Society
136 A Handa et al.

a b c d

Fig. 19 Obstructive uropathy in a 12-year-old boy caused by desmoid tumor associated with Gardner syndrome. (a) Coronal
contrast-enhanced computed tomography showing horseshoe kidney, right hydroureteronephrosis (arrows), and a large amount of ascites
(asterisks). (b,c) Coronal balanced fast field echo magnetic resonance imaging showing an intrapelvic tumor (long arrow) with
hydroureteronephrosis (short arrows) invading the distal right ureter and sigmoid colon causing a urinoma (star) and proximal obstruction
(arrowhead). (d) Ureterogram showing a large urinoma (star) in the distal ureter and proximal obstruction (arrowhead). The ascites was
likely urinary ascites.

a b

Fig. 20 Hemorrhagic cystitis caused by cyclophosphamide in a 2-year-old girl with germ cell tumor. (a) Ultrasound showing diffuse bladder
wall thickening (arrows) with echogenic debris (asterisk). (b) Axial T2-weighted and (c) contrast-enhanced fat-saturated coronal T1-weighted
magnetic resonance imaging showing a thick-walled, hyperemic bladder (arrows) with minimal perivesical inflammatory changes.

In conclusion, we have discussed the clinical and imag-
ing findings in pediatric patients with oncologic emergen-
cies, including a review of recently published studies. We
have provided key radiological imaging to illustrate radio-
logical approaches to making diagnoses. A multidisciplinary
approach involving specialists such as pediatricians, pediatric
surgeons, pediatric anesthesiologists, pediatric radiation
oncologists, and pediatric radiologists is vital in determining
the correct diagnosis and ensuring prompt and appropriate
treatment strategies.

© 2018 Japan Pediatric Society


Acknowledgments
The authors would like to thank Dr Gen Nishimura for help
with radiological diagnosis.
Disclosure
The authors declare no conflict of interest.
Author contributions
A.H. wrote this review article. T.N. contributed to the concep-
tion and design of this article, verified the scientific content,
and edited the manuscript. A.Mak., T.O., Y.M., K.F., T.Ko.,
M.M., Y.K., D.H., T.Ku., C.O., Y.Y., A.Man. reviewed and
edited the manuscript. All authors read and approved the final
manuscript.
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