A primary malignant ependymoma of the abdominal cavity: a case report and review of the literature


Mogler, C.; Kohlhof, P.; Penzel, R.; Grenacher, L.; Haag, G.M.; Schirmacher, P.; Mueller, W.

Virchows Archiv 454(4): 475-478

2009


Ependymomas generally arise in the central nervous system (CNS). Rare primary extraneural ependymomas have been observed. Here, we describe the first case of an overt malignant primary extraneural ependymoma in a young female patient. Careful reevaluation together with extensive review of the literature and comparison of related cases established the diagnosis after treatment failure and tumor progression. The tumor was large and firm with some small cysts and showed pseudorosettes with strong glial fibrillary acidic protein (GFAP) expression. In conclusion, primary extraneural ependymomas have to be included into the differential diagnosis of abdominal tumors with pseudorosette-formation, even in unusual sites, and GFAP-immunohistochemistry (IHC) supports the diagnosis.

Virchows
Arch
(2009)
454:475-478
DOI
10.1007/s00428-009-0744-8
CASE
REPORT
A
primary
malignant
ependymoma
of
the
abdominal
cavity:
a
case
report
and
review
of
the
literature
Carolin
Mogler
Patricia
Kohlhof
Roland
Penzel
Lars
Grenacher
Georg
M.
Haag
Peter
Schirmacher
Wolf
Mueller
Received:
19
December
2008
/Revised:
29
January
2009
/Accepted:
8
February
2009
/Published
online:
24
February
2009
C
Springer-Verlag
2009
Abstract
Ependymomas
generally
arise
in
the
central
nervous
system
(CNS).
Rare
primary
extraneural
ependy-
momas
have
been
observed. Here,
we
describe
the
first
case
of
an
overt
malignant
primary
extraneural
ependymoma
in
a
young
female
patient.
Careful
reevaluation
together
with
extensive
review
of
the
literature
and
comparison
of
related
cases
established
the
diagnosis
after
treatment
failure
and
tumor
progression.
The
tumor
was
large
and
firm
with
some
small
cysts
and
showed
pseudorosettes
with
strong
glial
fibrillary
acidic
protein
(GFAP)
expression.
In
con-
clusion,
primary
extraneural
ependymomas
have
to
be
included
into
the
differential
diagnosis
of
abdominal
tumors
with
pseudorosette-formation,
even
in
unusual
sites,
and
GFAP-immunohistochemistry
(IHC)
supports
the
diagnosis.
C.
Mogler
R.
Penzel
P.
Schirmacher
Department
of
General
Pathology,
University
Hospital,
Heidelberg,
Germany
P.
Kohlhof
W.
Mueller
Department
of
Neuropathology,
University
Hospital,
Heidelberg,
Germany
L.
Grenacher
Department
of
Radiology,
University
Hospital,
Heidelberg,
Germany
G.
M.
Haag
Department
of
Clinical
Oncology,
National
Center
for
Tumor
Disease,
University
Hospital,
Heidelberg,
Germany
C.
Mogler
(M)
IPH
Heidelberg,
INF
220/21,
69120
Heidelberg,
Germany
e-mail:
Keywords
Ependymoma
GFAP
EMA
Introduction
Ependymomas
generally
arise
in
the
central
nervous
system,
though
primary
extraneural
ependymomas
have
been
observed.
To
date,
only
three
intraabdominal
cases
have
been
reported.
Clinical
history
We
present
a
27-year-old
female
patient
with
a
four
year
history
of
a
primary
extraneural
anaplastic
ependymoma
(WHO
III)
arising
in
the
abdominal
cavity.
Tumor
therapy
included
several
extensive
tumor-debulking
operations,
a
high-dose
imatinib
chemotherapy
(400
and
800
mg
daily),
and
an
ependymoma-targeted
combined
carboplatin/
etoposide
chemotherapy
which
resulted
in
stabilization
of
the
disease.
One
month
after
completion
of
the
chemother-
apy
and
4
years
after
the
initial
tumor
diagnosis,
disease
progressed
again.
Tumor
debulking
resulted
in
an
im-
proved
quality
of
life
with
reduced
need
of
pain
medica-
tion.
Of
note,
the
ependymoma-targeted
therapy
was
delayed
for
6
months
by
misdiagnosing
the
tumor
as
a
gastrointestinal
autonomic
nerve
tumor
(GANT).
An
i.v.-
contrast-enhanced
portal-venous
phase
of
a
standard
abdominal
CT
was
performed
in
the
course
of
re-
evaluation
using
a
MD-CT
Philips
Brilliance
(64-row).
The
tumor
was
mostly
hypodense
and
showed
an
inhomo-
geneous
contrast
enhancement.
Tumor
growth
extended
around
the
liver
with
evidence
of
tumor
infiltration
into
the
caudate
lobe
and
stenosis
of
the
hepatic
veins
near
the
inferior
caval
vein.
4
Y1
Springer
476
Virchows
Arch
(2009)
454:475-478
Materials
and
methods
Automated
IHC
was
performed
on
a
Benchmark
XT
by
Ventana,
Strasbourg,
France
for
c-kit
(CD117;
pH
6,
1:50),
Ki-67
(MIB1;
pH
6,
1:200),
GFAP
(pH
6,
1:25)
and
epithelial
membrane
antigen
(EMA;
pH
6,
1:100)
according
to
standard
protocols.
Results
We
present
the
tumor
specimen,
which
was
obtained
during
the
first
debulking
operation
and
which
was
reviewed
6
months
after
surgery
following
the
failure
of
GANT-
targeted
imatinib
chemotherapy.
The
specimen
measured
13
x
12
x
7
cm
in
size
and
was
macroscopically
well-
delineated
from
surrounding
peritoneum.
The
surface
was
brownish
to
yellowish
in
appearance
and
featured
both
dense
and
knotty
parts
with
some
small
cysts
(Fig.
la,
b).
Microscopically,
the
tumor
featured
a
high
cellularity.
Nuclear
morphology
was
mostly
monomorphic
and
char-
acterized
by
round
to
oval
nuclei
with
"salt
and
pepper"
speckling
of
the
chromatin.
Intratumoral
areas
of
more
extensive
fibrillarity
were
present.
Key
histological
features
of
ependymoma
were
identified,
consisting
of
perivascular
pseudorosettes
(Fig.
1c)
with
perivascular
anuclear
zones
of
dense
fibrillary
processes.
True
ependymal
rosettes
were
not
identified,
but
focally
tumor-derived
tubules,
which
can
be
seen
in
ependymomas
were
present
(Fig.
1d).
Nuclear
atypia
was
moderate
in
some
parts
of
the
tumor,
but
mitotic
activity
was
high
(>25
mitoses/ten
high-power
fields;
Fig.
1
e).
Foci
of
geographic
and
palisading
necroses
were
present
(Fig.
lf).
In
contrast
to
the
macroscopic
impression
of
tumor
delineation
from
surrounding
tissues,
widespread
tumor
invasion
into
the
adjacent
peritoneum
was
seen
microscopically.
IHC
showed
a
homogenous
strong
posi-
tive
reaction
for
GFAP
(Fig.
1
g,
h)
which
was
more
pronounced
in
the
perivascular
pseudorosettes.
Consistent
with
the
diagnosis
of
an
ependymoma,
the
staining
pattern
for
EMA
was
dot-like
in
some
and
cytoplasmatic
in
other
tumor
areas
(Fig.
1i,
j).
The
proliferation
index
clearly
exceeded
4%,
and
the
mitotic
activity
was
brisk
with
up
to
25
mitotic
figures/ten
high-power
fields.
Nuclear
atypia
and
palisading
necroses
together
with
the
brisk
mitotic
activity
were
considered
as
features
of
malignancy
and
the
tumor
was
classified
as
an
anaplastic
ependymoma
WHO
grade
III.
Of
note,
focal
c-kit
expression
was
reported
in
the
tumor
tissue
misleading
to
the
initial
diagnosis
of
a
GANT.
We
repeated
c-kit
IHC
on
all
surgical
specimens
of
the
patient
and
compared
the
results
to
three
anaplastic
ependymomas
with
typical
histology.
We
found
c-kit
expression
in
comparable
frequencies
and
locations
in
both
the
patient's
tumor
specimens
and
the
three
anaplastic
ependymomas
confined
to
single
hematopoetic
cells
within
the
tumor
stroma
(data
not
shown).
The
tumor
specimen
removed
4
years
later
upon
tumor
progression
largely
shared
morphology
and
immunohistochemical
behavior
with
the
primary
tumor.
Discussion
Ependymomas
usually
develop
in
the
brain
or
spinal
cord
possibly
by
neoplastic
transformation
of
ependymal
cells
of
the
ventricular
wall
or
the
spinal
canal.
Extraneural
metastases
have
been
well
described
in
the
literature.
They
may
appear
sporadically
at
many
sites
in
the
body
[1,
2]
including
the
abdominal
cavity
[2].
Primary
extraneural
ependymomas
are
very
rare,
and
to
date,
only
isolated
cases
have
been
documented
[3,
4].
Primary
extraneural
ependy-
momas
may
originate
from
remnant
embryonic
neuro-
ectodermal
cells
due
to
incomplete
regression
[5].
Accordingly,
most
extraneural
ependymomas
were
found
in
or
near
structures
of
the
neural
axis,
i.e.,
mediastinal,
coccygeal
locations
or
in
the
filum
terminale,
where
ependymal
rests
can
be
found
after
birth
[5].
Other
discussed
mechanisms
include
upfront
unidirectional
ter-
atomas
[6],
remnants
of
neural
tissue
following
the
involution
of
the
other
two
germ-layer
components
of
a
teratoma
[6]
or
the
incomplete
closure
of
the
neural
arch
[7],
which,
similar
to
the
findings
in
the
ovary,
would
allow
for
the
development
of
a
neometaplasia
of
heterotopic
Muellerian
duct-derived
tissue
[8]
or
a
heterotopic
mono-
dermal
tumor
[9]
outside
the
central
nervous
system.
The
latter
may
explain
why
extraneural
ependymomas
are
common
in
the
ovary
[10].
In
the
abdominal
cavity,
however,
only
three
cases
of
primary
extraneural
ependy-
momas
have
been
reported,
to
date
[11-13].
Even
though
the
number
of
reported
cases
is
very
low,
they
seem
to
have
features
in
common
with
the
presented
case,
both
morpho-
logically
and
clinically.
All
patients
were
female.
Age
ranged
from
27
to
41
years.
The
initial
finding
usually
was
a
big
solitary
tumor
mass
exceeding
10
cm
in
diameter
causing
unspecific
abdominal
complaints.
Macroscopically,
these
tumors
tended
to
be
firm
and
solid
with
small
intratumoral
cysts.
Diagnostic
difficulties
were
encountered
in
two
cases
[11]
including
the
current
case.
In
both,
the
diagnosis
ependymoma
was
established
only
after
recur-
rence
and
therapeutic
failure.
Histomorphology
of
the
case
presented
here
was
dominated
by
a
"glial"
picture.
Tumor
cell
morphology
and
nuclear
chromatin
speckling
were
suggestive
of
an
ependymoma
respecting
the
fact
that
extraneural
ependymomas
can
demonstrate
a
wider
archi-
tectural
variability
compared
to
ependymomas
of
the
CNS
[14].
Perivascular
pseudorosettes
were
reported
in
all
published
cases,
whereas
true
ependymal
rosettes
were
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477
Fig.
1
Macroscopic,
micro-
scopic
and
immunohistochemi-
cal
findings.
a—b
Macroscopy:
firm
and
solid
tumor
mass
(a)
with
heterogeneous
cutting
sur-
face
(b).
c—f
Histology
with
c
pseudorosettes
(HE;
x100),
d
intra-tumoral
tubules
(HE,
x100),
e
brisk
mitotic
activity
(HE,
x100),
and
f
necrosis.
g—j
Immunohistochemistry,
g,
h
strong
GFAP-expression
in
tumor
cells
highlighting
pseu-
dorosettes
(x200),
i
ependymoma-typical
dot-like
EMA-expression
in
some
(x400)
and
(j)
cytoplasmatic
EMA
expression
in
other
tumor
areas
(x200)
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478
Virchows
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454:475-478
mentioned
only
in
one
report
[11].
Strong
positive
reaction
for
GFAP,
highlighting
the
pseudorosettes
as
in
our
case,
is
a
feature
common
to
all
ependymomas
including
the
intraabdominal
variants.
However,
it
needs
to
be
considered
that
ovarian
carcinomas
can
also
show
a
remarkable
GFAP
expression
which
might
lead
to
diagnostic
predicament
especially
including
tumors
in
the
lower
abdomen
[14].
Here,
tumor
location
especially
in
relation
to
the
ovary,
the
identification
of
perivascular
pseudorosettes
and
additional
immunohistochemical
investigations
may
help
to
clarify
the
diagnostic
dilemma
[14].
The
majority
of
the
tumor
mass
of
the
presented
case
was
found
in
the
abdominal
cavity,
and
only
marginal
pelvic
tumor
extension
was
evident.
Debulk-
ing
operations
did
not
necessitate
ovariectomy
indicating
tumor-free
ovaries
and
leading
us
to
the
assumption
of
a
primary
extraneural
ependymoma
arising
from
the
abdom-
inal
peritoneum.
The
EMA
staining-pattern
with
infra-
cytoplasmic
in
some
and
dot-like
in
other
tumor
parts
was
typical
of
ependymomas
[15].
Extensive
imaging
inves-
tigations
aimed
at
excluding
the
possibility
of
an
extra-
neural
metastasis
of
a
primary
cerebral
ependymoma.
No
further
lesions
were
found,
neither
intracerebral
nor
extra-
neural
throughout
a
period
of
4
years
demonstrating
the
intraabdominal
origin
of
the
ependymoma.
Clinically,
the
three
documented
primary
extraneural
ependymomas
of
the
abdominal
cavity
were
benign
tumors.
Complete
surgical
tumor
resection
with
or
without
adjuvant
ependymoma-targeted
chemotherapy
resulted
in
long-term
recurrence-free
intervals.
However,
recurrences
as
late
as
13
years
after
primary
surgery
did
occur
[11],
and
as
the
presented
case
illustrates,
malignant
transformation
seems
possible.
In
conclusion,
this
is
the
first
report
demonstrating
a
primary
extraneural
anaplastic
ependymoma
(WHO
grade
III)
arising
from
the
peritoneum
in
the
abdominal
cavity.
Conflict
of
interest
statement
We
declare
that
we
have
no
conflict
of
interest.
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M,
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