Eur J Nucl Med Mol Imaging (2010) 37:319–329
DOI 10.1007/s00259-009-1276-9
ORIGINAL ARTICLE
Role of PET/CT in malignant pediatric lymphoma
Raef Riad & Walid Omar & Magdy Kotb & Magdy Hafez &
Iman Sidhom & Manal Zamzam & Iman Zaky &
Hussein Abdel-Dayem
Received: 10 July 2009 / Accepted: 24 August 2009 / Published online: 15 September 2009
# Springer-Verlag 2009
Abstract
Introduction Malignant pediatric lymphoma accounts for
10–15% of all pediatric cancers, (representing 2–3% of all
malignancies), with a peak incidence between 5–9 years.
Chemotherapy is usually the first and most common mode
of treatment. The choice of treatment and prediction of
prognosis depend on the histological type of tumor, initial
staging, evaluating treatment response, and detection of
early recurrence. Conventional imaging modalities have
many limitations. PET/CT is more accurate, however so far
the literature lacks the results of a large group of patients.
Aim of study To report the role of PET/CT in the above-
mentioned objectives at the newly established Children’s
Cancer Hospital in Cairo, Egypt, which is one of the busiest
dedicated pediatric oncology centers of such purposes in
the world. All findings were proven by histopathology,
clinically, and by clinical follow-up.
Supported by grants from The Children’s Cancer Hospital Foundation
and the Cancer Institute Friends Association.
R. Riad : W. Omar
Department of Nuclear Medicine, Children’s Cancer Hospital
(CCH), Cairo University,
Cairo, Egypt
I. Sidhom : M. Zamzam
Department of Pediatric Oncology, Children’s Cancer Hospital
(CCH), Cairo University,
Cairo, Egypt
I. Zaky
Department of Radio-diagnosis, Children’s Cancer Hospital
(CCH), Cairo University,
Cairo, Egypt
M. Kotb
Department of Nuclear Medicine, National Cancer Institute,
Cairo, Egypt
Patient population A total of 152 patients (35 girls and 117
boys) with histologically proven malignant lymphoma (117
HD, 35 NHL) were included in this study. They were divided
into four groups. Group I: 41 patients for initial staging. Group
II: 51 patients for evaluating early treatment response after
two to three cycles of chemotherapy. Group III: 42 patients for
evaluating treatment response 4–8 weeks after the end of their
treatment. Group IV: 18 patients evaluated for long-term
follow-up. Results of PET/CT were compared with the other
conventional imaging modalities (CIM).
Results The sensitivity, specificity, accuracy, and positive
and negative predictive values of PET/CT and CIM were as
follows: In Group I: PET/CT modified staging and
treatment in 11 out of 41 cases (26.8%), upstaged 5
(12.2%) patients and down-staged six (14.6%) patients.
Group II: 100%, 97.7%, 98%, 85.7%, 100%, respectively,
for PET/CT and 83%, 66.6%, 68.6%, 25%, 96.7% for CIM
M. Hafez
Department of Nuclear Medicine, Children’s Cancer Hospital
(CCH), Cairo University,
Cairo, Egypt
H. Abdel-Dayem
Department of Radiology, Nuclear Medicine Section,
St. Vincent`s Catholic Medical Centers of New York, New York
Medical College,
Valhalla, NY, USA
H. Abdel-Dayem (*)
Department of Radiology, New York Medical College,
Nuclear Medicine Service,
St. Vincent’s Catholic Medical Centers of New York,
170 West 12th Street, Cr. 327,
New York, NY 10011, USA
e-mail: husseinad@aol.com
320
respectively Group III: At the end of chemotherapy 100%,
90.9%, 92.8%, 75%, 100%, respectively, for PET/CT and
55.5%, 57.5%, 57.1%, 26.3%, 82.6% for CIM, respectively.
Group IV: For long-term follow-up, all the parameters
scored 100% for PET/CT, 100%, 38.4%, 72.2%, 50%,
100% for CIM, respectively.
Conclusion PET/CT in pediatric lymphoma is more accu-
rate than CIM. We recommend that it should be the first
modality for all purposes in initial staging, evaluating
treatment response and follow-up.
Keywords Malignant lymphoma . Pediatric lymphoma .
Initial staging . Evaluating treatment response . Follow-up
malignant lymphoma . F18-FDG PET/CT
Introduction
Malignant lymphoma accounts for 10–15% of pediatric
cancers, (representing 2–3% of all malignancies). Hodgkin’s
disease (HD) represents 40% of lymphomas in children [1, 2].
The Rye pathological classification distinguishes four catego-
ries, among which the nodular sclerosis (in adolescents) and
the mixed cellularity subtypes (in pre-pubertal children) are
the most frequent [3]. Non-Hodgkin’s lymphoma (NHL)
represents 60% of pediatric lymphomas and occurs with a
peak incidence between the ages of 5 and 9 years [4, 5].
Several histological classifications exist for NHL. The
Revised European—American Lymphoma (REAL) classifi-
cation is among the most widely used and focuses on the
distinction between B and T cell neoplasms [6]. The choice of
treatment strategy essentially depends on the initial stage, the
pathological subtype, and the presence of factors indicating a
poor prognosis, such as B symptoms. Therapeutic options
include various combinations of chemotherapy and radiother-
apy for HD and mainly combinations of chemotherapy for
NHL. With good advances in treatment, there is now a
general trend to decrease the aggressiveness of the treatments
in order to limit the long-term side-effects in these patients
with a long life expectancy. Indeed, the overall survival rate is
higher than 90% in HD [7] and above 75% in NHL [8].
Conventional imaging methods such as computed tomogra-
phy (CT), MRI, and ultrasonography (US) are commonly
used in the evaluation of pediatric lymphomas, along with
physical examination and bone marrow biopsy. Physical
examinations are obviously limited by the location of the
disease, but are of primary importance for peripheral lymph
node staging. All imaging techniques have significant
limitations. CT diagnostic criteria are mainly based on size.
As a result, CT neither identifies malignant involvement in
normal-size lymph nodes nor characterizes enlargement due
to other causes. In addition, CT performs rather poorly in
detecting spleen and liver involvement. MRI is the procedure
Eur J Nucl Med Mol Imaging (2010) 37:319–329
of choice in assessing bone marrow and central nervous
system infiltration, but it is not convenient for the routine
imaging of the entire bone marrow. Some of these limitations
are most evident in post-treatment evaluation, in which
anatomical imaging methods are unable to differentiate
residual tumor from fibrosis or to detect early recurrence.
18
F-fluorodeoxyglucose (18F-FDG) is a glucose analogue that
provides unique information about glucose metabolism of
normal and abnormal tissues, in particular in malignant
diseases. Although adult lymphomas have been widely
investigated with 18F-FDG positron emission tomography
(PET), the literature concerning children is limited and the
number of patients studied in reported articles are small
[9–17]. Currently, in adult oncology imaging, there is a
transition phase from stand-alone PET to PET-computed
tomography (CT), with PET-CT most likely becoming the
accepted international standard in pediatric cancer imaging as
well [40].
We conducted this retrospective study at the newly
established Children’s Cancer Hospital in Cairo, Egypt,
one of the busiest centers in the world for evaluating the
performance of 18F-FDG PET/CT in pediatric lympho-
mas for the purpose of initial staging, evaluating
treatment response early after two to three cycles of
chemotherapy, from 3–8 weeks after chemo treatment
and for long-term follow-up. We also aimed to compare
the 18F-FDG PET/CT results with those of conventional
imaging modalities.
Patient population
Between January 2008 and March 2009, 152 patients (35
girls and 117 boys) with histologically proven malignant
lymphomas received PET/CT at the newly established
Children’s Cancer Hospital. A total of 117 had HD and
35 had NHL. Their age ranged from 3 years to 18 years.
The clinical stage of disease was evaluated according to the
Ann Arbor classification for HD [18] and Murphy
classification for NHL [19]. According to the indication
for the PET/CT scan, the population was divided into four
groups:
Group 1: PET/CT was performed at time of diagnosis, as
part of the initial staging. This group included
41 patients, (39 HD, two NHL Burkett’s
lymphoma). The clinical staging was adopted
by the clinicians based on CIM. Six were stage
I, 15 were stage II, 12 were stage III, and eight
patients were stage IV.
Group 2: PET/CT was performed during the treatment to
evaluate early response to therapy after two to
three courses of chemotherapy. PET/CT was
Eur J Nucl Med Mol Imaging (2010) 37:319–329
performed 12–14 days after the end of two to
three courses of chemotherapy just before the
due date of the coming course. Fifty-one
patients were in this group (45 HD, 6 NHL).
Five patients were stage I, 20 were stage II, 18
were stage III and eight were stage IV.
Group 3: PET/CT was performed 4–8 weeks (mean
5.7 weeks) after completion of treatment to
evaluate the disease status. Forty-two patients
are included in this group (29 HD, 13 NHL).
Three out of the 42 patients were stage I, eight
were stage II, 21 were stage III, and ten were
stage IV.
Group 4: PET/CT was performed 3–12 months (mean
6.8 months) during follow-up of patients in
complete clinical remission. The indication for
the PET/CT studies were either systematic
surveillance or assessment of residual masses
detected on other imaging modalities. A total of
18 patients were included in this group (six HD,
12 NHL).
PET imaging
A total of 196 studies were performed on a dedicated PET/
CT scanner (40-slice Siemens true-point). Patients fasted
for at least 4–6 h prior to examination. Blood glucose levels
were lower than 120 mg/dl. Patient’s weight ranged from
9.5–79 kg with a mean of 35.8 kg. Acquisitions were
started 45–60 min after intravenous injection of 3.7 MBq/
kg 18F-FDG. Whole-body scans were acquired in over-
lapped bed positions usually from mid thigh to base of skull
with the arms extended above the head, with 3-min
acquisition for each bed position. All patients except six
were imaged without sedation. Images were processed
using iterative reconstruction. Attenuation correction was
applied using CT data according to the manufacturer’s
recommended protocol. Semi-quantitative estimation of
tumor glucose metabolism by means of SUV (standardized
uptake value) was done for all cases.
CT acquisition
CT was performed either as low-dose CT for attenuation
correction and anatomical localization or high-dose CT for
diagnostic purposes based on the CT adjusted mA. Oral
contrast was given in 48 studies while IV contrast was
given in 106 studies according to requirements of each case
and the recommendation of the referring physician.
An initial scout view was obtained with 35 mAs and
120 kVp, followed by spiral CT at 0.8 s per rotation with
50 mAs (quality reference), 120 kVp, section thickness of
5 mm, and a 4.25-mm interval in low-dose CT.
321
Diagnostic quality CT was obtained with 170 mAs and
120 kVp.
The radiation exposure dose from low-dose CT was in
average 3.37 mGy while that for diagnostic CT was
11.48 mGy.
Interpretation
PET/CT studies were read by two nuclear medicine
consultants independently while CIM were reviewed by
consultant radiologist.
Data analysis
PET/CT results were compared with the findings of the
physical examination, CT, MRI, US, and bone marrow biopsy
when available. The accuracy of each test was determined
based on either pathological correlation (13 patients) or
clinical follow-up (139 patients).
An IBM compatible PC was used to store and analyze the
data and to produce graphic presentation of important results.
Results
Group 1: Initial staging (41 patients)
PET/CT and conventional imaging methods were concor-
dant in 30 (73.2%) and discordant in remaining 11 patients
(26.8) (Table 1). PET/CT upstaged five patients out of the
11 discordant cases and down-staged six patients. Two
patients were upstaged from stage I to stage II (confirmed by
pathological examination): one patient from stage II to stage
III, one patient from stage II to stage IV, in whom CT
showed a suspicious parenchymal lesion in the right lung
while PET/CT confirmed focal intensely active right pulmo-
nary nodal lesion with maximum SUV 4.2. Follow-up CT
confirmed metastatic lymphomatous lesion in the right lung.
Another patient was upstaged from stage III to stage IV. In
this patient, PET/CT was the only modality to show bone
lesions with maximum SUV ranging from 3.8 to 5.1 and
mean SUV 4.2 (Fig. 1). In the six patients down staged by
PET/CT, one patient from stage II to stage I, three patients
from III to II and two patients from stage IV to stage II
(Table 1). PET/CT thus modified the staging and treatment
options in 11 out of 41 cases (26.8%), upstaging five
(12.2%) patients and down-staging six (14.6%) patients.
Group 2: Early response to therapy (51 patients)
PET/CT and CIM were concordantly negative in 29 (56.8 %)
patients out of the 51 of this group and concordantly positive
in five (Fig. 2). Discordant was in 17/51 cases (33.3%). PET/
322 Eur J Nucl Med Mol Imaging (2010) 37:319–329

Table 1 Results of CIM and PET/CT in the 11 discordant cases of the first group for initial staging

CIM PET/CT Result

1 Rt. Cervical nodes
2 Lt. cervical Lymph node
3 Lt. cervical and mediastinal nodes
4 Mediastinal LN, abnormal suspicious
parenchymatous Rt. lung lesion
5 Cervical, supra-clavicular, mediastinal
LN & splenic hilar LN
6 Rt. cervical & Rt. para-tracheal
7 Cervical, mediastinal, abdominal and pelvic
LN,s
8 Cervical, mediastinal, para-aortic nodes
9 Cervical, common iliac, inguinal nodes
10 Bilateral cervical, hepatic & splenic
focal lesions
11 Supra-& infra diaphragmatic lesions &
hepatic focal lesion
Bilateral cervical, bilateral axillary, mediastinal
active LNs
Bilateral cervical, axillary, sub-carinal active
LN.
Lt. cervical, mediastinal as well as
gasro-splenic and para-aortic nodes
Mediastinal lymph nodes with definite
Rt. pulmonary lymphomtous lesion
Cervical , supra-clavicular, mediastinal
LNs, splenic hilar LNs & multiple active
bone lesions.
Rt. cervical only
Pelvic LN only
Cervical and mediastinal
Common iliac, inguinal nodes
Multiple active splenic focal lesions
only
Infra-diaphragmatic nodes
Upstaging from stage I to II
Upstaging from stage I to II
Upstaging from stage II to III
Upstaging from stage II to IV
Upstaging from stage III to IV
Down staging from stage II to I
Down staging from stage III to stage II
Down staging from stage III to stage II
Down staging from stage III to stage II
Down staging from IV to II
Down staging from IV to II

CT was true-negative in 15 patients out of the 17 discordant
findings, which were false-positive in CT. These 15 patients
were kept under follow-up for 13 months and proved to be
on total remission by all means including follow-up PET/CT.
PET/CT was true-positive in one study out of the 17
discordant cases. It showed active uptake over the left
inguinal lymph node with maximum SUV 2.94. This node
was not reported in the conventional CT due to small size
and open biopsy showed lymphomatous infiltration of this
excised node (Fig. 3).
PET/CT was false-positive in one study of a 5-year-old girl
with HD (mixed cellularity) stage II B. She was evaluated
after three cycles of induction chemotherapy. CT showed near
total resolution of the previously demonstrated cervical and
mediastinal nodes while PET/CT showed intense FDG uptake
in the bowel wall associated with wall thickening max SUV
4:9 and resolution of the supra-diaphragmatic nodes. Open
biopsy showed inflammation of the bowel wall with no
evidence of lymphomatous infiltration (Fig. 4).
In this group, after two to three courses of chemotherapy,
the sensitivity, specificity, accuracy, and positive and
negative predictive values of PET/CT were 100%, 97.7%,
98%, 85.7%, 100%, respectively, as compared to 83%,
66.6%, 68.6%, 25%, 96.7% for CIM (Table 2).
Group 3: Evaluation of treatment response 3–8 weeks
after end of therapy (42 cases)
In 17 patients (40.4%), PET/CT were concordantly true-
negative compared to CIM (Fig. 5), and concordantly true-
positive in five (11.9%) patients. One study was false-positive
in both PET/CT and CIM. This study was for a patient with
HD that showed solitary jugular lymph node involvement in
both with maximum SUV 4.23. The patient didn’t receive any
treatment. Six months later, PET/CT showed complete
resolution of this lesion.
On the other hand, PET/CT was discordant with CIM in
19/42 (45.2%) patients. Thirteen of these 19 patients PET/
CT were negative while conventional CT showed residual
masses. All were kept under follow-up for 10 months and
proved to be in complete remission clinically and by
follow-up PET/CT. In four studies, there was complete
resolution of the previously detected lesions on the
conventional CT while the PET/CT showed residual active
uptake at some of the initial sites of involvement and a
newly developed bone lesion in one; maximum SUVs
ranged from 1.94 to 7.4. These patients, based on clinical
assessment, received second-line chemotherapy. Follow-up
PET/CT after end of treatment showed complete resolution
of the previously reported active lesions. In two of the 19
discordant studies, PET/CT showed false-positive uptake.
In one patient, there was active uptake in the large bowel;
SUV 3.8 with no detectable lesions in the conventional CT
or sonogram. Pathological examination of the surgically
excised bowel lesion showed inflammation with no evidence
of malignancy (Fig. 6a, b). In the other patient, there was
low-grade uptake over small inguinal node that was less than
1 cm in the CT and was considered negative by CT criteria.
Follow-up PET/CT after 6 months of follow-up with no
treatment showed disappearance of this inguinal node.
Eur J Nucl Med Mol Imaging (2010) 37:319–329 323

Fig. 1 a, b Baseline PET/CT

showed right iliac and right
proximal femoral lesions (a) as
well as vertebral bony lesion
(b, arrows)

In this group, the sensitivity, specificity, accuracy, and
positive and negative predictive values of PET/CT were
100%, 90.9%, 92.8%, 75%, 100%, respectively, as com-
pared to 55.5%, 57.5%, 57.1%, 26.3%, and 82.6% for CIM
(Table 2).
Group 4: Follow-up (18 patients)
Concordance between PET/CT and CIM was found in 13/18
patients (72.2%). Eight were true-negative and five were
true-positive in both PET/CT and CIM. Discordance was in

Fig. 2 Results of PET/CT and

CIM in early evaluation of
chemotherapy response
324
Fig. 3 PET/CT showed meta-
bolically active disease in Lt.
inguinal lymph node with SUV
2.94
5/18 cases (27.7%) in which PET/CT was true negative and
confirmed by another follow-up study after 6 months.
PET/CT showed 100% sensitivity, specificity, accuracy,
and positive and negative predictive values while the CIM
showed 100% sensitivity, 38.4% specificity, 72.2% accuracy,
50% PPV, 100% NPV (Table 2).
Discussion
18
F-FDG PET/CT is now considered the most accurate
imaging modality in the management of adult lympho-
mas. Its value has been well documented for initial
staging, at mid chemotherapy, after the end of therapy,
and for assessing tumor recurrence in the follow-up [15,
17, 20–23]. However, few data are available in the
literature about pediatric lymphoma [9–13]. Although
one may expect similar 18F-FDG uptake whether the
patient is a child or an adult, the situation is different as
we are dealing with different populations. The patholog-
ical subgroups are different in children and adults; for
example, the nodular sclerosis and mixed cellularity
subtypes are the most frequent forms of HD in children
[1]. NHLs in children also differ from NHLs in adults. In
children, they present with high-grade malignancy, fre-
Eur J Nucl Med Mol Imaging (2010) 37:319–329
quent extra-nodal sites, and early non-contiguous spread,
particularly to the bone marrow and the central nervous
system. They are mainly a proliferation of immature
lymphoid cells [4]. Regarding treatment, in the past there
was great concern about long-term side-effects related to
cumulative effects of high-dose chemotherapy and asym-
metrical volumes of irradiation [1, 4]. Therapeutic
improvements thus entailed reduction of doses and of
fields of irradiation, fractionation of the doses, and use of
newer chemotherapeutic agents. All of these resulted in
diminishing therapy-related morbidity and late effects.
Improving the patient’s quality of life still remains a big
challenge in pediatric oncology. Surveillance of minimal
residual disease is thus of primary importance in following
those patients cured with less aggressive treatments.
Clinical follow-up is very crucial and has to be supported
by other imaging modalities when needed. The choice
between these has to be in consideration of saving patients
from unnecessary radiation and be as cost-effective as
possible.
Initial staging
Accurate initial staging is of primary importance, especially
in children, as over-treatment increases the risk of long-
Eur J Nucl Med Mol Imaging (2010) 37:319–329 325

Fig. 4 PET/CT showed intense

tracer uptake in the wall of the
descending colon with
suggested wall thickening in the
CT images. Biopsy showed
inflammatory cells

term side-effects, and advanced stages require an aggressive
therapeutic regimen. PET has been reported to affect the
initial staging and treatment planning of up to more than
20% of cases [15, 16, 20, 24–27]. Wiehrauch et al. 2002
showed that PET upstaged four out of 22 patients with HD
[28]. Many studies proved that PET is superior to
conventional imaging modalities in the initial staging of
lymphoma [29–32]. Montravers et al. 2002 reviewed 27
PET studies including 15 studies using a coincidence
system in 27 children [13]. They found very encouraging

Table 2 Sensitivity, specificity,

accuracy, PPV, NPV of PET/CT Early evaluation (Group 2) Late evaluation (Group 3) Recurrence (Group 4)
and CIM of various groups in
the study PET/CT (%) CIM (%) PET/CT (%) CIM (%) PET/CT (%) CIM (%)

Sensitivity 100 83 100 55.5 100 100

Specificity 97.7 66.6 90.9 57.5 100 38.4
Accuracy 98 68.6 92.8 57.1 100 72.2
PPV 85.7 25 75 26.3 100 50
NPV 100 96.7 100 82.6 100 100
326
Fig. 5 Results of PET/CT and
CIM after end of chemotherapy
results in terms of both diagnostic performance and clinical
impact. The population included both HD and NHL, and
the indications for the study were variable. PET changed
the stage of the disease in four out of seven cases, and
affected the choice of treatment in one out of seven.
Depas et al. 2004 indicated that 18F-FDG PET is an
appropriate method for evaluating children with lympho-
mas, but they also showed that its performance and impact
may differ according to the clinical situation [27]. PET
modified both the stage and the treatment approach in
10.5% of the patients. Hermann et al. 2005 carried their
work on 25 patients with pediatric lymphoma for initial
staging comparing FDG PET with conventional CT. They
concluded that the staging of childhood lymphoma using
FDG PET shows differences compared to CT resulting in a
different staging in six of 25 patients [39].
In our study, PET/CT modified the staging and treatment
planning in 11 out of 41 cases (26.8%), upstaging five
(12.2%) patients and down staging (14.6%) patients.
Evaluating response to therapy
Morphologic image abnormality is not a reliable indicator
of active disease. Residual abnormalities occur in 30–60%
after therapy and are usually considered persistent lym-
phoma, as CT scan cannot differentiate between benign
and malignant disease. Only 10–20% of these residual
masses seen at completion of therapy are positive for
lymphoma on biopsy and 18% of these will eventually
relapse. Additionally, distinct subgroups of non-Hodgkin’s
lymphoma respond differently to various therapeutic
approaches [33, 34].
PET has an important role in evaluating the response to
chemotherapy. It is usually performed after completion of
therapy. Earlier assessment is becoming popular as a
routine part of management in patients with HD and
histologically aggressive NHL. Changes in FDG uptake
can occur soon after initiation of chemotherapy and precede
changes in tumor volume seen on morphological imaging
modalities. Few authors correlated between early evaluation
of chemotherapy (after 2–3 weeks) with long-term progno-
sis and survival. Timing in evaluating the response to
therapy is debatable. Kostakoglu et al. 2002 showed that
progression-free survival is better correlated with PET after
Eur J Nucl Med Mol Imaging (2010) 37:319–329
the first cycle of chemotherapy [35]. On the other hand,
Friedberg et al. 2003 showed that PET after 3 cycles of
chemotherapy has higher predictive value for disease
recurrence than PET scanning after completion of therapy
[36]. MacManus et al. 2007 has assessed the value of FDG
early response assessment with PET in aggressive NHL
(predominantly diffuse large B cell lymphoma) and HD.
They concluded that PET imaging after two to three cycles
of chemotherapy is far superior to CT scan in predicting
free survival and is reliable as assessment of response at
end of therapy [37]. In 2007, Strobel et al. compared the
impact of PET/CT during and after chemotherapy in 40
patients with HD and 30 patients with NHL. PET/CT
performed after two to four cycles of chemotherapy in 31/
40 (82%) with HD demonstrated complete remission,
which did not change at the end of therapy by PET/CT
findings. The remaining nine patients with HD (18%) had
partial remission in PET/CT. For NHL 22/30 (73%) patients
had complete remission in PET/CT, which was unchanged
in repeated studies at the end of treatment. In the remaining
eight patients with NHL, PET/CT during treatment revealed
partial remission in seven patients and stable remission in
one patient. None of the complete responders progressed
until the end of therapy. They concluded that end treatment
PET/CT is unnecessary if PET/CT study after two or three
cycles of chemotherapy shows complete remission and the
clinical course is uncomplicated [38].
Depas et al. 2005 [27] reported specificity of conven-
tional imaging methods to be 56% as compared to 94%
specificity for PET in evaluating treatment response.
Patients (15/16) with negative PET scan at the end of
treatment remained in remission, compared to 9/16 patients
for conventional imaging methods. They stated in their
study that here was no standardization regarding the timing
of the PET evaluations during treatment. It is not known
whether studying patients after two to three cycles of
chemotherapy will yield results similar to those obtained
when performing PET at end of therapy.
Similarly, the present study showed that the specificity
of PET/CT was 97.7% as compared to 66.6% of conven-
tional radiological methods in early evaluation of treatment
response. The same results were found in assessment of
response at the end of chemotherapy treatment. The
specificity of PET/CT was 90.9% compared to 57.5% for
Eur J Nucl Med Mol Imaging (2010) 37:319–329 327

Fig. 6 a PET/CT showed in-

tense tracer uptake in the lower
abdomen 3 weeks after
completion of chemotherapy. b
Pathological examination
showing suppurative
inflammation with no malignant
cells
328
conventional radiological measures. Although the follow-
up period for the discordant cases that were negative in
PET/CT (13 months for group II and 10 months for group
IV) is relatively short to judge that PET/CT is right. After
coupling PET/CT results with clinical evaluation and
follow-up laboratory essay and follow-up CT, we come to
great certainty that PET/CT was right at this stage.
Long-term follow-up
Furthermore, in children, the issue of follow-up became one
of particular importance. Although the overall recurrence
rate is fairly low, particularly in HD, the general trend to
reduce the aggressiveness of the therapeutic regimen may
lead to an increase in the number of relapses. The
availability of efficient salvage treatments may further
justify systematic follow-up of those patients who are at
risk of relapse, using an accurate technique. Depas et al.
2005 indicated the ability of PET to detect recurrence after
treatment. Fifty-six out of 59 PET studies were negative in
the systematic long-term follow-up compared with 39/59
for conventional methods evaluations. PET was false-
positive in 3/59 PET studies. False-positive results were
due to muscle uptake, asymmetrical thymus, and atrial
myocardial uptake. They reported high specificity of 95%
for PET versus 66% for conventional methods in detection
of recurrence during long-term follow-up [27].
The results of the current study are comparable to these
results as it showed 100% specificity for PET/CT in
detection of recurrence versus 38.4% for conventional CT.
Conclusion
The current study showed the importance of 18F-FDG PET/
CT as a useful method in the management of pediatric
lymphomas. It showed great value in initial staging of
lymphomas. PET/CT had significant implications in terms of
early assessment of treatment response. PET/CT appears to
be highly specific and allows for accurate characterization of
residual masses, which are not uncommon in pediatric
patients.
References
1. Oberlin O. Hodgkin’s disease. In: Voûte PA, Kalifa C, Barrett A,
editors. Cancer in children. Clinical management. 4th ed. New
York: Oxford University; 1998. p. 137–53.
2. Lanzkowski P. Hodgkin’s disease. In: Lanzkowski P, editor.
Manual of pediatric hematology and oncology. 3rd ed. San Diego:
Academic; 1999. p. 413–43.
3. Lukes R, Butler J, Hicks E. Natural history of Hodgkin’s disease
as related to its pathological picture. Cancer. 1966;19:317–44.
Eur J Nucl Med Mol Imaging (2010) 37:319–329
4. Büyükpamukçu M. Non-Hodgkin’s lymphomas. In: Voûte PA,
Kalifa C, Barrett A, editors. Cancer in children. Clinical
management. 4th ed. New York: Oxford University; 1998. p.
119–36.
5. Lanzkowski P. Non-Hodgkin’s lymphoma. In: Lanzkowski P,
editor. Manual of pediatric hematology and oncology. 3rd ed. San
Diego: Academic; 1999. p. 445–69.
6. Harris NL, Haffe ES, Stein H, et al. A revised European—
American classification of lymphoid neoplasms: a proposal from
the International Lymphoma Study Group. Blood. 1994;84
(5):1361–92.
7. Thomson AB, Wallace WHB. Treatment of paediatric Hodgkin’s
disease: a balance of risks. Eur J Cancer. 2002;38:468–77.
8. Pinkerton CR. Review: the continuing challenge of treatment for
non-Hodgkin’s lymphoma in children. Br J Haematol.
1999;107:220–34.
9. Jadvar H, Connolly LP, Shulkin BL, Treves ST, Fischman AJ.
Positron-emission tomography in pediatrics. In: Freeman LM,
editor. Nuclear medicine annual 2000. Philadelphia: Lippincott
Williams & Wilkins; 2000. p. 53–83.
10. O’Hara S, Donnelly LF, Coleman RE. Pediatric body applications
of FDG-PET. Am J Radiol. 1999;172:1019–24.
11. Thomas B, Manalili E, Leonidas JC, Karayalcin G, Lipton J. 18F
FDG imaging of lymphoma in children using a hybrid PET
system: comparison with 67 Ga [abstract]. J Nucl Med. 2000;41
(Suppl):96P.
12. Moody R, Shulkin B, Yanik G, Hutchinson R, Castle V. PET FDG
imaging in pediatric lymphomas [abstract]. J Nucl Med. 2002;42
(Suppl):39P.
13. Montravers F, McNamara D, Landman-Parket J, et al. 18F-FDG in
childhood lymphoma: clinical utility and impact on management.
Eur J Nucl Med Mol Imaging. 2002;29:1155–65.
14. Zinzani PL, Magagnoli M, Chierichetti F, et al. Role of
positron emission tomography in the management of lympho-
ma patient. Ann Oncol 1999;10:1181–4.38 European Journal of
Nuclear Medicine and Molecular Imaging Vol. 32, No. 1,
January 2005
15. Jerusalem G, Warland V, Najjar F, et al. Whole-body 18FDG-PET
for the evaluation of patients with Hodgkin’s disease and non-
Hodgkin’s lymphoma. Nucl Med Commun. 1999;20:13–20.
16. Kostakoglu L, Goldsmith SJ. Fluorine-18 fluorodeoxyglucose
positron emission tomography in the staging and follow-up of
lymphoma: is it time to shift gears? Eur J Nucl Med.
2000;27:1564–78.
17. Hudson MM, Krasin MJ, Kaste SC. PET imaging in pediatric
Hodgkin’s lymphoma. Pediatr Radiol. 2004;34(3):190–8.
18. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M.
Report of the committee on Hodgkin’s disease staging classification.
Cancer Res. 1971;31:1860–1.
19. Murphy SB. Current concepts in cancer: childhood non-Hodgkin’s
lymphoma. N Engl J Med. 1978;299:1446.
20. Kostakoglu L, Leonard JP, Kuji I, Coleman M, Vallabhajosula S,
Goldsmith SJ. Comparison of fluorine-18 fluorodeoxyglucose
positron emission tomography and gallium-67 scintigraphy in
evaluation of lymphoma. Cancer. 2002;94:879–88.
21. Guay C, Lépine M, Verreault J, Bénard F. Prognostic value of
PET using 18F-FDG in Hodgkin’s disease for posttreatment
evaluation. J Nucl Med. 2003;44:1225–31.
22. Jerusalem G, Beguin Y, Fassotte MF, et al. Whole-body positron
emission tomography using 18-F fluorodeoxyglucose for post-
treatment evaluation in Hodgkin’s disease and non-Hodgkin’s
lymphoma has higher diagnostic and prognostic value than
clinical computed tomography scan imaging. Blood.
1999;94:429–33.
23. Jerusalem G, Beguin Y, Fassotte MF, et al. Early detection of
relapse by whole-body positron-emission tomography in the
Eur J Nucl Med Mol Imaging (2010) 37:319–329
follow-up of patients with Hodgkin’s disease. Ann Oncol.
2003;14:123–30.
24. Moog F, Bangerter M, Diederichs CG, et al. Lymphoma: role of
whole-body 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET in
nodal staging. Radiology. 1997;203:795–800.
25. Moog F, Bangerter M, Diederichs CG, et al. Extranodal malignant
lymphoma detection with FDG PET versus CT. Radiology.
1998;206:475–81.
26. Bangerter M, Moog F, Buchmann I, et al. Whole-body 2-[18F]-
fluoro-2-deoxy-D-glucose positron emission tomography (FDG-
PET) for accurate staging of Hodgkin’s disease. Ann Oncol.
1998;9:1117–22.
27. Depas G, De Barsy C, Jerusalem G, et al. 18F-FDG PET in
children with lymphomas. European Journal of Nuclear Medicine
and Molecular Imaging Vol. 32, No. 1, January 2005.
28. Weihrauch MR, Re D, Bischoff S, et al. Whole body positron
emission tomography using 18F-flurodeoxyglucose for initial staging
of patients with Hodgkin’s disease. Ann Hematol. 2002;81:20–5.
29. Hueltenschmidt B, Sautter-Bihl ML, Lang O, et al. Whole body
positron emission tomography in the treatment of Hodgkin
disease. Cancer. 2001;91:302–10.
30. Buchmann I, Reinhardt M, Elsner K, et al. 2-(fluorine-18) fluro-2-
deoxy-D-glucose positron emission tomography in the detection
and staging of malignant lymphoma. A bicenter trial. Cancer.
2001;91:889–99.
31. Naumann R, Beuthien-Baumann B, Reiss A, et al. Substantial
impact of FDG PET imaging on the therapy decision in patients
with early stage Hodgkin’s lymphoma. Br J Cancer. 2004;90:620–5.
329
32. Rigacci L, Vitolo U, Nassi L, et al. On behalf of Intergruppo
Italiano Linformi. Positron emission tomography in staging of
patients with Hodgkin’s lymphoma. A prospective multi-centric
study by the Intergruppo Italiano Linformi. Ann Hematol.
2007;86:896–903.
33. Burton C, Ell P, Linch D. The role of PET imaging in lymphoma.
Br J Haematol. 2004;126:772–84.
34. Zinzani PL. Lymphoma: diagnosis, staging, natural history,
treatment strategies. Semin Oncol. 2005;32:S4–10.
35. Kostakoglu L, Coleman M, Leonard JP, et al. PET predicts
prognosis after 1 cycle of chemotherapy in aggressive lymphoma
and Hodgkin’s disease. J Nucl Med. 2002;43:1018–27.
36. Friedberg JW, Chengzi V. PET scan in staging of Lymphoma:
current status. Oncologist. 2003;8:438–47.
37. MacManus MP, Seymour JF, Hicks RJ. Overview of early
response assessment in lymphoma with FDG -PET. Cancer
Imaging. 2007;7:10–8.
38. Strobel K, Schaefer NG, Renner C. Cost effective therapy
remission assessment in lymphoma patients using 2-(Fluorine-
18) fluro-2-deoxy-D-glucose positron emission tomography/com-
puted tomography: is an end treatment exam necessary in all
patients? Ann Oncol. 2007;18:658–64.
39. Hermann S, Wormanns D, Pixberg M, Hunold A, Heindel W,
Jürgens H, et al. Staging in childhood lymphoma: differences
between FDG-PET and CT. Nuklearmediziner. 2005;44(1):1–7.
40. Stauss J, Franzius C, Pfluger T, Juergens KU, Biassoni L, Begent J, et
al. Guidelines for 18F-FDG PET and PET-CT imaging in paediatric
oncology. Eur J Nucl Med Mol Imaging. 2008;35:1581–8.