Dra. Viviana Riquelme S y col.

Revista Chilena de Radiologa. Vol. 18 N 1, ao 2012; 24-29.

Imaging studies in early diagnosis of childhood leukemia

Drs. Viviana Riquelme S (1), Cristin Garca B (2).
1. Physician, School of Medicine Graduate, Pontificia Universidad Catlica, Santiago, Chile.
2. Departments of Radiology and Pediatrics. School of Medicine, Pontificia Universidad Catlica, Santiago, Chile.

Imaging studies in early diagnosis of childhood leukemia

Abstract: Leukemia is the most commonly encountered cancer in children under the age of 15 and accounts
for approximately 35-40% of all cancers at that age. Acute lymphoblastic leukemia (ALL) is the most common type of leukemia affecting young children between the ages of 2 and 5 years; it accounts for around
80 % of all childhood leukemia cases. Initial clinical and laboratory findings may be non-specific. Imaging
studies in patients with bone pain and extramedullary involvement may provide the clinician with valuable
supplementary information when the first symptoms result from tissue infiltration and haematological series
show a discrete and asymptomatic involvement. The purpose of this work is to review the initial radiological
manifestations of leukemia in children. Given the systemic nature of this disease, the goal is to identify the
key elements found in the study of the different affected organs, in order to facilitate an early diagnosis
of this condition. Late-stage alterations or treatment complications, such as osteonecrosis, infections by
opportunistic pathogens, graft-versus-host disease, etc. where magnetic resonance imaging (MRI) and
computed tomography (CT) play a fundamental role will not be reviewed.
Keywords: Child, Imaging, Leukemia, Pediatrics.
Resumen: La leucemia es el cncer ms frecuente en nios menores de 15 aos y corresponde aproximadamente al 35-40% de todos los cnceres a esa edad. Se presenta con mayor frecuencia entre los 2
y 5 aos de edad y la forma ms frecuente es la leucemia linfoblstica aguda, que corresponde al 80%
de los casos. Las manifestaciones clnicas y de laboratorio pueden ser inicialmente inespecficas. El
estudio imagenolgico en pacientes con dolor seo y compromiso extramedular, puede entregar valiosa
informacin complementaria al clnico cuando los primeros sntomas derivan de la infiltracin de los tejidos y el compromiso de las series hematolgicas es discreto y asintomtico. El propsito de este trabajo
es revisar las manifestaciones radiolgicas iniciales de la leucemia en el nio. Considerando que es una
enfermedad sistmica, el objetivo es identificar los elementos claves en el estudio de los distintos rganos
comprometidos, que permitan al radilogo sospechar el diagnstico en la etapa precoz de la enfermedad.
No se revisarn las alteraciones de la fase tarda o de complicaciones del tratamiento, como osteonecrosis, infecciones por grmenes oportunistas, enfermedad de injerto vs. husped, etc., donde la resonancia
magntica (RM) y la tomografa computada (TC) juegan un rol fundamental.
Palabras clave: Imgenes, Nio, Leucemia, Pediatra.
Riquelme V y cols. Estudios de imgenes en el diagnstico precoz de leucemia en pediatra. Rev Chil Radiol 2012;
18(1): 24-29.
Corresponding. Dr. Cristin Garca B. / cgarcia@med.puc.cl
Manuscript received November 24th, 2011; accepted for publication March 19th, 2012.

Introduction
The expected incidence of cancer in children
under 15 years is 110-150/1.000.000 children a year,
being slightly more common in men(1). Leukemia is the
most commonly encountered cancer and accounts for
around 35-40% of all cancers at that age (1).
U.S. statistics establish an incidence rate of one
case of leukemia every 7,000 children per year(2).
In Chile, the preliminary report of the National Registry of Childhood Cancer Population (RENCI) revealed
in 2007 an incidence of leukemias of 42.7/1.000.000(1).
24

Since the beginning of the Program Cancer in

the Child in 1988, an average of 100-110 new cases
of lymphoblastic leukemia and 30 cases of myeloid
leukemia per year have been reported in the public
health sector(1).
The signs and symptoms that suggest leukemia are
varied and recommendations for diagnostic suspicion
are clearly detailed in the Clinical Guide: Leukemia in
Children Under 15 years, Chilean Ministry of Health (1).
In general, diagnosis should be suspected in any
child with anemia not associated with bleeding, fever

Revista Chilena de Radiologa. Vol. 18 N 1, ao 2012; 24-29.

associated or not with pallor, visceromegaly and CBC

with anemia and/ or neutropenia (sometimes leukocytosis), bone pain not associated with trauma, with
CBC with cytopenia.
Leukemia should be included in the differential
diagnosis in the presence of combination of the following signs and symptoms: Fever of unknown origin;
bone pain not associated with trauma; spontaneous
bruising or associated with minor trauma; nasal or
gingival bleeding; recurrent infections; lymphadenopathy (persisting for more than 4 weeks; lymph nodes
larger than 3 cm; generalized palpable lymph nodes),
and splenomegaly(1-4).
There are genetic as well as environmental factors associated with its pathogenesis. Clearly, there
is an increased risk associated with genopathies
such as Klinefelter syndrome and Down syndrome,
the latter posing a relative risk 15 times higher than
that faced by the general population (2.3). Exposure to chemicals, such as benzene, pesticides and
ionizing radiation are modifiable factors involved in
its etiology(2).
Acute lymphoblastic leukemia (ALL) is defined
by the presence of more than 20% lymphoblasts in
bone marrow (2,3) and represents the most common
type of leukemia in childhood, accounting for 80%
of cases (3,4) It predominates in men and occurs most
often between the ages of 2 and 5 years (3.4).
Acute myeloid leukemia (AML) represents 17% of
leukemias (2). Its occurrence is similar in both sexes
with no predominance for any given age range (4).
Initial clinical manifestations are usually nonspecific
and the most common clinical presentation includes:
pallor, fatigue, bleedings, fever and recurrent infections
as a result of an existing spinal cord dysfunction(2,4). The
CBC may reveal anemia, thrombocytopenia and / or
neutropenia with normal, decreased or increased WBC
count(3,4). In 95% of cases, ALL manifests itself with
some cytopenia in the CBC, whilst anemia is present in
99% of cases. The WBC is normal in 50% of children(3),
being anemia the alarm symptom in these cases.
In AML, 44% of patients present with anemia at
diagnosis, while 69% has neutropenia and 25% exhibits
leukocytosis with CBC count over 100.000/microliter(3);
complications such as cerebral, lung and liver infarction
as a result of leukocytosis may be present(1,3).
Although definitive diagnosis is achieved by studying
the bone marrow, the imaging study, mainly in patients
with bone pain and extramedullary involvement, may
provide the clinician with valuable complementary information when the first symptoms derive from tissue
infiltration and involvement of haematological series
appears discrete and asymptomatic.
The chance of cure depends on the type of leukemia, the presence of associated adverse factors
and the response to treatment, being about 73% for
lymphoblastic leukemia and 50% for myeloid leukemia(1).

IMGENES PEDITRICAS

The purpose of this paper is to review the initial

radiological manifestations of leukemia in children.
Whereas it is a systemic disease, the goal is to identify
the key elements in the study of the various organs
involved, thus allowing the radiologist to suspect
diagnosis in the early stages of the disease.
Late-stage alterations or treatment complications,
such as osteonecrosis, infections by opportunistic
pathogens, graft-vs host disease, etc., where magnetic
resonance imaging (MRI) and computed tomography
(CT) play a fundamental role will not be reviewed.
Leukemia. Bone and extramedullary manifestations
Due to extramedullary tissue infiltration, visceromegaly (hepatomegaly, splenomegaly, nephromegaly,
enlargement of the pancreas), polyadenopathies,
central nervous, renal and testicular system involvement may be observed (1,3,4), the latter being the least
common pathology. Its frequency varies depending
on the type of leukemia.
Imaging findings on those most frequently affected
organs, will be reviewed.
Liver, spleen, kidneys
An estimated 60-70% of patients with ALL present
with hepatosplenomegaly(3), while AML occurs in no
more than half of the cases (5). It is often a finding on
physical examination and rarely causes functional
impairment(1). Bilateral nephromegaly is also a common finding, though less frequent.
Ultrasonography (US) studies allow depiction of
increased size of these organs, which may be associated with decreased liver and splenic parenchymal
echogenicity and increased echogenicity of the renal
parenchyma, conditions that can be reversed with
treatment (6.7) (Figure 1). Along with nephromegaly,
CT scans reveal multiple low- attenuation areas in the
renal parenchyma, usually presenting bilaterally(7,8)
(Figure 2).

Figure 1. Six-month infant with ALL. Abdominal ultrasound

revealed bilateral nephromegaly. On a sagittal section of the
right flank, enlarged kidney on that side (sagittal diameter of
9.0 cm) and slightly increased echogenicity are observed.

25

Dra. Viviana Riquelme S y col.

2a

2b

Figure 2. Four-year-old boy with ALL. Abdominal CT

scan shows in axial (a) and coronal reconstruction (b),
enlargement of both kidneys, with multiple areas of low
attenuation in the parenchyma (arrows). The child also
had hepatosplenomegaly.

Lymphadenopathies
The involvement of cervical, axillary and/or
inguinal nodes occurs in up to 50% of patients
with ALL and in 25% of patients with AML (3,5) .
Ultrasound is useful in the study of lymph nodes,
since along with confirming their presence it allows
their appropiate characterization (9,10).
Generally, adenopathies associated with hepatosplenomegaly (9), are painless, fast growing,
local or generalized (10). Lymph nodes hard in consistency, with anteroposterior diameter greater than
1.0 cm in cervical and axillary nodes and greater
than 1.5 cm in the inguinal region are considered
as suspicious (9).
The normal oval nodal morphology may be
preserved or may exhibit a more rounded shape;
they are commonly grouped in bunches (9). Lymph
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Revista Chilena de Radiologa. Vol. 18 N 1, ao 2012; 24-29.

nodes are usually hypoechoic and nodal hilum

may be absent or eccentrically placed due to tumor
invasion (10,11). On color Doppler studies it usually
shows hilar vascular flow within it. Though none
of the aforementioned signs is pathognomonic of
leukemia, their presence in the appropriate clinical
context increases the index of suspicion (11).
Bone involvement
Bone pain is the most commonly encountered
symptom secondary to proliferation of neoplastic
cells in the bone marrow (7,12,13).
An estimated 30% of patients with ALL present
with bone pain (4) and sometimes this may be the only
alarm symptom in the presence of a CBC without
leukocytosis, which may occur in 1% of cases (3). It
may affect any part of the skeleton, being the pelvis,
vertebrae and long bones of lower extremities the
most commonly affected sites (3).
Clinically, pain is usually insidious in onset, constant, not related to physical activity and exacerbated
at night, progressive in intensity and refractory to the
use of analgesia. It may be accompanied by claudication and rarely presents initially with pathological
bone fractures (4,13).
Though unusual, it may occur as migratory oligoarthralgies of large joints, asymmetrically distributed,
with or without arthritis. Similarity with diseases such
as juvenile idiopathic arthritis may cause a delay in
diagnosis of leukemia (13).
Despite the wide variety of imaging methods
currently available, simple radiography remains the
initial method of choice for evaluation of bone pain (14).
An estimated 50-70% of patients with leukemia reveal evident bone changes on radiographic studies
at diagnosis (15,16).
These alterations encompass:
1. Radiolucent, fine, transverse metaphyseal
bands. They represent the most common
finding suggestive of preschool children
leukemia. In patients under 2 years of age,
their specificity decreases, and may be
found in other chronic diseases that also
alter osteogenesis (6,12,15).They are usually
located in the proximal and radio distal
humerus, and distal femur (7,14), the latter
being the most frequent site (7,13) (Figures
3 and 4).
2. Local or diffuse osteopenia, that may present with back pain or lumbar pain due to
vertebral crushing (6,7,15) (Figure 5).
3. Focal or generalized osteolysis of long and
flat bones (skull, pelvis, ribs and shouldergirdle)(14). It may have a moth-eaten bone
appearence or bone rarefaction, caused
by the presence of small lytic areas with

IMGENES PEDITRICAS

Revista Chilena de Radiologa. Vol. 18 N 1, ao 2012; 24-29.

ill-defined margins (17).

4. Periosteal and subperiosteal reaction, corresponding to areas of thickening of the
periosteum due to new bone formation (6,7,15)
(Figure 6).
5. Osteosclerosis, a late and infrequent manifestation (6).
6. Soft tissue swelling, juxta-articular osteoporosis and joint effusion (15).
Metaphyseal bands and osteolytic lesions
may be observed in up to 70% of cases, whereas
osteopenia is seen in up to 25% of patients and
fractures in only 10% of children (16).

Figure 5. Twelve-year-old child with bone involvement in

leukemia. Lateral radiograph of the thoracic spine depicts
diffuse osteopenia and depression of all visible thoracic
vertebrae (D4-D10).

6a

6b

Figure 3. Five-year-old boy with bone involvement in

leukemia. Anteroposterior radiograph of left ankle shows
well-defined radiolucent bands in the metaphyseal region
of the distal tibia and fibula (arrows).
Figure 6. Bone involvement in leukemia in a of 8-yearold child. (a) Anteroposterior radiograph of right knee (a)
reveals metaphyseal radiolucent bands in the femur and
tibia (arrows). (b) Anteroposterior radiograph of right ankle
showing osteolytic area in the lateral border of the distal
tibial metaphysis and periosteal reaction of distal shaft in
its medial border (arrows).

Figure 4. Bone involvement in leukemia. Anteroposterior

radiograph of both knees revealing diffuse osteopenia and
metaphyseal radiolucent bands relatively poorly defined in
both femurs and tibias (arrows).

Mediastinum
Mediastinal involvement typically occurs in ALL(1).
An estimated 15% of these patients present with
lymphoma-like clinical features, of which 61% exhibit
mediastinal lymph nodes(18,19). Clinical presentation may
vary; it may present with cough, stridor, orthopnea,
dyspnea, superior vena cava syndrome or respiratory
distress syndrome (1,3,4).
Radiologically, it corresponds to an anterior
mediastinal mass, detectable on plain RX views and
confirmed by computed tomography (CT) scans
(Figure 7). The differential diagnosis mainly includes
lymphoma.
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Revista Chilena de Radiologa. Vol. 18 N 1, ao 2012; 24-29.

Dra. Viviana Riquelme S y col.

7a

7b

7c

7d

Figure 7. A 13-year-old girl with ALL presenting with

mediastinal mass and stridor. Chest CT scan shows a
large anterior mediastinal mass, displacing the vascular
structures and reveals (a) compression and displacement
of the trachea (arrow), (b) marked narrowing of the left
main bronchus (arrow), (c) pericardial effusion (arrow). In
a 3D reconstruction of the airway (d) compression of the
left main bronchus is clearly seen (arrow).

Mammary region
Breast involvement in leukemia is manifested as a
lump or breast mass, most often unilateral, which may
be present at disease onset or during their evolution.
On physical examination, they often appear as welldefined, fast-growing, and sometimes painful tumors
(20). On US studies they appear as hypoechoic nodules of well- or ill-defined margins, usually unique (18,19).
They are rarely found as multiple bilateral lesions.
Additionally, diffuse edema of surrounding tissue and
axillary lymph nodes may be observed (20.21).
Testicles
Infiltration of the testes mainly occurs in patients
under 20 years of age (21). Leukemia rarely affects this
organ primarily; rather, it is often a site of recurrence.
The clinical picture is that of a testicular tumor
causing pain, heaviness and/or increased scrotal
volume that may be unilateral or bilateral (22,23).
On ultrasonographic studies, an increase in testicular size determined by focal (with multiple nodules)
or diffuse involvement, with increased or decreased
echogenicity may be observed, being diffuse involvement more frequently encountered (23,24) (Figure
8). In some cases of ALL, there is also infiltration of
the epididymis. On color Doppler study an increased
blood flow is observed (24).
Conclusions

28

Symptoms and signs that suggest an acute leukemia in

children are varied and initial manifestations are often
nonspecific.
The imaging study can provide the clinician with valuable
information, when first symptoms result from tissue infiltra-

tion and involvement of haematological series is discrete

and asymptomatic.
For this reason, the radiologist should be aware of initial
radiological manifestations of the disease in children,
especially extramedullary involvement, in order to suspect
the diagnosis of leukemia in its early stage.
In particular, the radiologist should considered leukemia
in the differential diagnosis of bone pain, visceromegaly
and anterior mediastinal masses in children.

Figure 8. A 9-year-old boy. Treated ALL in remission.

Testicular volume increased due to testicular relapse. Scrotal
transverse color Doppler US image showing an enlarged left
testicle, with an area of lower signal intensity and increased
vascular flow in the testicular anterior half (arrows).

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