Infection Mimicking Malignancy: Two Cases to Learn From

Abstract

A suspected malignancy should be confirmed in a timely manner so appropriate therapy is initiated. Although pediatric cancers present with typical features, non-malignant conditions with atypical presentations must also be considered. Here we present two pediatric cases referred with presumptive malignant diagnoses. Extensive work up revealed Mycobacterium tuberculosis and Epstein-Barr virus infection as the cause of their presentations.

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Infection Mimicking Malignancy: Two Cases to Learn From
Hatel R. Moonat 1,*, Ossama M. Maher 1,3, Jorge G. Silva 1, Alaa A. Almohammedsalim 2, Soumen Khatua 1,
Wafik Zaky 1
1. Department of Pediatrics Patient Care; 2. Department of Pathology, The University of Texas MD Anderson Cancer Center | Houston, Texas, USA.
3. National Cancer Institute, Department of pediatrics, Cairo University. Egypt
INTRODUCTION
Pediatric cancers can present with typical clinical, laboratory, and radiographic findings. It is imperative, however, that non-neoplastic
conditions be considered in the differential as they can mimic cancers in their clinical and radiographic presentations. The initial
recognition of such cases is essential as it may allow for the avoidance of surgical intervention and unnecessary treatment. We report
here two cases referred to our institution with presumptive diagnoses of cancer. After extensive evaluations, both were found to have
infectious etiologies.
CASE PRESENTATION
Case 1
A 15 year old, previously healthy female presented with 2 weeks of abdominal pain, distention, and night sweats. She also reported
an unintentional 10-pound weight loss over several months. She denied any sick contacts or recent travel. Initial laboratory studies
were pertinent for anemia, a mildly abnormal coagulation profile, and elevated lactate dehydrogenase (LDH) (1001 IU/L). Computed
tomography (CT) of the abdomen/pelvis showed significant omental thickening, multiple intraperitoneal nodules, pleural plaques in
the lower chest, enlarged mesenteric lymph nodes, and suspicious adnexal masses concerning for peritoneal carcinomatosis/
sarcomatosis (Figure 1). Beta-human chorionic gonadotropin and alpha fetal protein were done as tumor markers for germ cell tumors
and were within normal limits. A moderate left pleural effusion was noted on chest CT imaging. Exploratory laparoscopy and omental
biopsy showed diffuse non-caseating granulomatous disease. Pathology specimens confirmed no malignancy, but a few acid fast bacilli
were identified (Figure 2), later identified as Mycobacterium tuberculosis complex, confirming peritoneal tuberculosis. The patient
commenced to a four drug anti-tuberculosis regimen.
C
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tat
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on: Moon
at
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R,
M
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r OM, S
il
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a
JG, A
lm
oh
amme
ds
alim
AA, Kh
at
u
a
S,
et
al
. (2014) Prog S
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1(5)
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07 | do
i:
10.14721
/
ps
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.2014.
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07
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d: 10
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07
/
2014 |
P
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li
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e
d: 10
/
08
/
2014
Copy
ri
ght:
©
2014 Moon
at and Maher
et
al
. Pub
li
sh
e
d by
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F
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Comp
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* A
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E-ma
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: hr
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rson.org,
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Case 2
A six year old male was transferred to the Intensive Care Unit with respiratory distress after a newly diagnosed nasopharyngeal mass.
He had a three day history of fevers, bilateral cervical swelling, and a positive rapid strep test. His laboratory data showed elevated
liver enzymes and a markedly elevated LDH (1745 IU/L). Magnetic resonance imaging of the face and neck showed a large, bulky
nasopharyngeal mass measuring approximately 4.6 cm x 2.4 cm x 1.8 cm and associated extensive bilateral cervical lymphadenopathy
(Figure 3). Imaging evaluations including a CT chest/abdomen/pelvis scan revealed generalized lymphadenopathy and
hepatosplenomegaly, highly suspicious of neoplastic disease. Differential diagnosis included Burkitt’s lymphoma, nasopharyngeal
carcinoma or an infectious etiology. The mass and bone marrow biopsies were performed and steroids were initiated. Two days later,
his Epstein-Barr virus (EBV) serology panel and pathology were consistent with acute EBV infection (Figure 4). The patient clinically
improved after steroid initiation and was able to be discharged home a few days later.
Fi
gu
re
1 | C
T
s
c
an of abdom
e
n and p
el
v
i
s. (A) 2.3
cm
x 1.9
cm
, h
ete
rog
e
n
e
ous
l
y
e
nh
a
n
ci
ng
nodu
le/ma
ss
i
n r
e
g
i
on of
t
h
e
le
f
t
a
dn
e
x
a
,
c
on
ce
rn
i
ng for
i
nvo
l
v
eme
n
t
of
le
f
t
ov
a
ry (
a
rrow). Nodu
la
r
it
y
no
te
d
al
ong p
el
v
ic
p
e
r
it
on
e
u
m
. (B) S
i
gn
i
f
ica
n
t
nodu
la
r
it
y
a
nd
t
h
ic
k
e
n
i
ng
i
nvo
l
v
i
ng
t
h
e
o
me
n
t
u
m
.
Mu
lti
p
le
,
i
nnu
me
r
a
b
le
p
e
r
it
on
eal
nodu
le
s
i
n
cl
ud
i
ng
m
u
lti
p
le
me
s
e
n
te
r
ic
nod
e
s
mea
sur
i
ng up
t
o 1.8
cm
(
a
rrow).
Fi
gu
re
2 |
O
m
e
nta
l
b
i
opsy. (A) Mu
lti
nodu
la
r gr
a
nu
l
o
mat
ous
i
nf
lammati
on (H
&E
, 20x). (B)
Non-
ca
s
eati
ng gr
a
nu
l
o
ma
c
o
m
pr
i
s
e
d of p
ali
s
a
d
i
ng h
i
s
ti
o
c
y
te
s
a
nd
m
u
lti
nu
cleate
d g
ia
n
t
cell
s, h
i
gh pow
e
r
(H
&E
, 200x). (C) R
a
r
e
aci
d f
a
s
t
b
acilli
w
it
h
i
n
a
m
u
lti
nu
cleate
d g
ia
n
t
cell
(
a
rrow, 400x).

M
oon
at et a
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Br
i
ef Re
po
rt
|
In
fect
ion
M
i
m
i
ck
ing
Ma
lign
a
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P
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|
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.
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3
O
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V
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|
I
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DISCUSSION
Confirmation of a suspected malignant process should be done in a timely manner so that appropriate therapy is initiated without
delay. Some presentations of certain non-neoplastic conditions like infections and autoimmune disease can be diagnostically challenging
and can present clinically and radiographically as a neoplasm [1-7]. However, even in patients who undergo surgery, the appropriate
preparation of the specimen is of crucial importance for the correct pathological diagnosis, since tumors and non-neoplastic lesions
share some common histopathological features.
Extrapulmonary tuberculosis (ETB) comprises 18.7% of all tuberculosis cases in the United States. Peritoneal tuberculosis is an
uncommon form of ETB and is seen only in 4.7% of all ETB cases, and is usually a result of either hematogenous spread from a
pulmonary focus, direct spread from adjacent organs, or oral ingestion of infectious material. The disease is usually subacute with
Fi
gu
re
3 |
M
agn
e
t
ic
re
sonan
ce
i
mag
i
ng of fa
ce
and n
ec
k. (A)
T
1 w
ei
gh
te
d
ima
g
e
s (pos
t
c
on
t
r
a
s
t
)
s
a
g
ittal
v
ie
w show
i
ng
a
la
rg
e
bu
l
ky
a
v
i
d
c
on
t
r
a
s
t
e
nh
a
n
ci
ng n
a
soph
a
ryng
eal
ma
ss
mea
sur
i
ng 4.6
cm
x
2.4
cm
x 1.8
cm
(
a
rrowh
ea
d). No
e
v
i
d
e
n
ce
of
i
n
t
r
ac
r
a
n
ial
e
x
te
ns
i
on. (B)
T
2 w
ei
gh
te
d
ima
g
e
s,
a
x
ial
v
ie
w
show
i
ng hyp
e
r
i
n
te
ns
it
y of
t
h
e
ma
ss w
it
h
c
on
t
r
a
s
t
e
nh
a
n
ceme
n
t
(
a
rrowh
ea
d).
Fi
gu
re
4 | Lymph nod
e
and bon
e
ma
rr
ow b
i
ops
ie
s. (A) H
&E
shows nu
me
rous
imm
unob
la
s
t
s, p
la
s
ma
cell
s, s
mall
l
y
m
pho
c
y
te
s. I
mm
unoh
i
s
t
o
c
h
emi
s
t
ry s
tai
ns
c
h
a
r
acte
r
i
s
tic
of
imm
unob
la
s
t
s
i
n
cl
ud
i
ng (B)
CD3, (C) CD20,
a
nd (D) CD30. (E)
T
h
e
r
e
i
s
i
n
c
r
ea
s
e
d pro
li
f
e
r
ati
on
a
s d
em
ons
t
r
ate
d by K
i
-67
a
nd (
F
)
EBER i
n s
it
u hybr
i
d
izati
on h
i
gh
li
gh
t
s nu
me
rous pos
iti
v
e
EB cell
s. M
a
gn
i
f
icati
on
:
(A) 1000X. (B-
F
)
400X.

M
oon
at et a
l.
Br
i
ef Re
po
rt
|
In
fect
ion
M
i
m
i
ck
ing
Ma
lign
a
n
cy
P
r
og
ress
i
ve Sc
i
e
n
ce
|
www.p
s
.
tra
n
sc
i
e
n
ce
.o
r
g
4
O
ct
ob
er 2014
|
V
olu
me 1
|
I
ss
u
e 5
|
e07
!
!
abdominal pain, ascites, and fever being the most common clinical findings that can mimic malignant tumors such as peritoneal
carcinomatosis, ovarian germ cell tumor, lymphomas and soft tissue sarcoma. Only 15–20% of cases have concomitant pulmonary
involvement on chest radiographs. The gold standard for diagnosis of peritoneal tuberculosis is growth of mycobacterium tuberculosis
from ascitic fluid or peritoneal biopsy specimen. The recommended treatment for peritoneal tuberculosis is conventional anti-
tuberculosis therapy for 6 months.
The literature also reports cases of infectious mononucleosis (IM) mimicking lymphoma [4, 6]. IM typically presents as
tonsillitis/pharyngitis with cervical lymphadenopathy and fever. Atypical presentations with a fulminant course and generalized
lymphadenopathy and hepatosplenomegaly are challenging to physicians and often difficult to distinguish from a rapidly growing
tumor such as Burkitt’s lymphoma. Unfortunately, these biopsies can lead to a misdiagnosis of lymphoma, as involvement of lymphoid
tissue by an acute EBV infection can morphologically resemble both Hodgkin lymphoma (atypical Reed-Sternberg-like cells) and
non-Hodgkin lymphoma (immunoblasts with marked cytological atypia). IM should be considered in any immunoblastic proliferation
occurring in cervical lymph nodes and Waldeyer’s ring tissue. The distinction between IM and lymphoma is challenging but
immunophenotypic profile and molecular testing can differentiate both cases.
Our cases highlight the difficult task facing clinicians in terms of making a correct distinction between infection and malignancy. In
addition to the correct treatment being implemented, the clinician’s awareness of these atypical presentations of non-neoplastic
conditions will further reduce unnecessary hospital referrals, extensive work-up, and prolonged hospitalizations. Most importantly, it
will avoid distress to the child and his/her family.
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