Large paraganglioma of the abdominal cavity: a case report and review of the literature


Kunitz, A.; Pahl, S.; Podrabsky, P.; Wardelmann, E.; Sturm, I.

Onkologie 33(7): 377-380

2010


Paragangliomas are rare tumors that derive from cells of the autonomic nervous system. They are usually located in the neck, i.e. arising from the glomus caroticum or glomus jugulare, but may also be located in the mediastinum and abdominal cavity arising from other ganglia. Paraganglioma located in the adrenal gland are called pheochromocytoma. We report a case of an oligosymptomatic 50-year-old man presenting with a large intraabdominal tumor mass measuring 24 x 22 x 12 cm. Core needle biopsy revealed a tumor of mesenchymal origin with no clear-line differentiation, so the highly vascularized tumor was resected after embolization of the tumor vessels. Histology revealed epithelioid cells with expression of CD68 and CD10 but no expression of Pan-CK, CD30, or CD45. Ki67 staining was 20%. Lymphangiosis and angioinvasion were demonstrated. Differential diagnosis included histiocytic sarcoma and c-kit-negative gastrointestinal stromal tumor; the final diagnosis was paraganglioma. The 6-month follow-up showed no evidence of recurrence. Paraganglioma is a rare disease and should be considered in the differential diagnosis of abdominal masses. To our knowledge, this report is of the largest paraganglioma that has been described in the literature so far. Nomenclature, pathogenesis, and treatment options are discussed.

Case
Report
Kasuistik
ONKOLOGIE
Onkologie
2010;33:377-380
Published
online:
June
22,
2010
DOI:
10.1159/000315749
Large
Paraganglioma
of
the
Abdominal
Cavity:
A
Case
Report
and
Review
of
the
Literature
Annegret
Kunitza
Stefan
Pahl
b
Petr
Podrabskyc
Eva
Wardelmann
d
Isrid
Sturm'
a
Department
of
Hematology
and
Oncology,
b
Department
of
Pathology,
c
Department
of
Radiology,
Charite
Campus
Virchow
Klinik,
Universit8tsmedizin
Berlin,
d
Department
of
Pathology,
Universitatsklinikum
Bonn,
Germany
Key
Words
Paraganglioma:
differential
diagnosis,
treatment
Summary
Background:
Paragangliomas
are
rare
tumors
that
derive
from
cells
of
the
autonomic
nervous
system.
They
are
usually
located
in
the
neck,
i.e.
arising
from
the
glomus
caroticum
or
glomus
jugulare,
but
may
also
be
located
in
the
mediastinum
and
abdominal
cavity
arising
from
other
ganglia.
Paraganglioma
located
in
the
adrenal
gland
are
called
pheochromocytoma.
Case
Report:
We
report
a
case
of
an
oligosymptomatic
50-year-old
man
presenting
with
a
large
intraabdominal
tumor
mass
measuring
24
x
22
x
12
cm.
Core
needle
biopsy
revealed
a
tumor
of
mesenchymal
origin
with
no
clear-line
differ-
entiation,
so
the
highly
vascularized
tumor
was
resected
after
embolization
of
the
tumor
vessels.
Histology
re-
vealed
epithelioid
cells
with
expression
of
CD68
and
CD10
but
no
expression
of
Pan-CK,
CD30,
or
CD45.
Ki67
staining
was
20%.
Lymphangiosis
and
angioinvasion
were
demonstrated.
Differential
diagnosis
included
his-
tiocytic
sarcoma
and
c-kit-negative
gastrointestinal
stro-
mal
tumor;
the
final
diagnosis
was
paraganglioma.
The
6-month
follow-up
showed
no
evidence
of
recurrence.
Conclusions:
Paraganglioma
is
a
rare
disease
and
should
be
considered
in
the
differential
diagnosis
of
abdominal
masses.
To
our
knowledge,
this
report
is
of
the
largest
paraganglioma
that
has
been
described
in
the
literature
so
far.
Nomenclature,
pathogenesis,
and
treatment
op-
tions
are
discussed.
Paragangliom:
Differentialdiagnose,
Behandlung
Zusammenfassu%
Hintergrund:
Paragangliome
sind
seltene
Tumoren,
die
von
Zellen
des
autonomen
Nervensystems
abstammen.
Am
haufigsten
treten
Paragangliome
im
Bereich
des
Halses
auf
(ausgehend
vom
Glomus
caroticum
oder
Glo-
mus
jugulare),
sie
k6nnen
aber
auch
im
Mediastinum
und
im
Abdomen
aus
anderen
Ganglien
entstehen.
Para-
gangliome,
die
in
der
Nebenniere
lokalisiert
sind,
wer-
den
als
Phaochromozytome
bezeichnet.
Fallbericht:
Wir
berichten
von
einem
oligosymptomatischen
50-jahrigen
Mann,
der
sich
mit
einem
riesigen
intraabdominellen
Tumor
(24
x
22
x
12
cm)
prasentierte.
Die
Stanzbiopsie
ergab
eine
mesenchymale
Neoplasie,
eine
weitere
Ein-
grenzung
war
nicht
moglich.
Die
stark
vaskularisierte
La-
sion
wurde
nach
Embolisation
von
tumorversorgenden
Gefallen
ohne
Komplikationen
reseziert.
Histologisch
sah
man
epitheloide
Zellen,
positiv
fur
CD68,
CD10
und
ohne
Expression
von
Pan-CK,
CD30
oder
CD45.
Der
Ki67-
Index
lag
bei
20%.
Es
wurde
eine
Ham-
und
Lymph-
angioinvasion
nachgewiesen.
Differentialdiagnostisch
wurden
ein
histiozytares
Sarkom
und
ein
KIT-Rezeptor-
negativer
gastrointestinaler
Stromatumor
in
Erwagung
gezogen,
die
entgultige
Diagnose
ergab
ein
Paragan-
gliom.
Nach
6
Monaten
besteht
weiterhin
eine
komplette
Remission.
Schlussfolgerungen:
Paragangliome
sind
selten
und
sollten
in
die
Differentialdiagnose
von
abdo-
minellen
Tumormassen
mit
einbezogen
werden.
Nach
unserer
Recherche
ist
dieser
Fall
das
groBte
bisher
publi-
zierte
Paragangliom.
Wir
diskutieren
Nomenklatur,
Pa-
thogenese
und
Therapieoptionen
dieser
seltenen
Entitat.
KARGE
R
Fax
+49
761
4
52
07
14
Information@Karger.de
www.karger.com
C
2010
S.
Karger
GmbH,
Freiburg
Accessible
online
at:
www.karger.com/onk
PD
Dr.
Isrid
Sturm
Charite
Campus
Virchow
Klinikum
Innere
Medizin
m.S.
Hamatologie
und
internistische
Onkologie
Augustenburger
Platz
1,13353
Berlin,
Germany
Tel.
+49
30
450
553-607,
Fax
-914
isrid.sturm@charite.de
Paragangliomas
(synonyms:
chemodectoma,
aortic-body
tumor,
carotid-body
tumor,
glomus
jugulare
tumor)
derive
from
autonomic
nervous
cells
with
an
estimated
incidence
of
1:30,000
[1],
some
cases
are
familiar
forms
[2],
but
80%
of
cases
occur
sporadically
[3].
Overall,
69%
occur
in
the
head
and
neck
[4],
but
the
organ
of
Zuckerkandl
and
other
sites
of
the
paraganglion
system
[5]
have
been
reported
as
sites
of
ori-
gin
as
well.
Abdominal
paragangliomas
often
originate
from
the
organ
of
Zuckerkandl
with
the
highest
incidence
near
the
inferior
mesenteric
artery
[6],
but
may
also
be
located
at
the
aortorenal
ganglion
and
the
bladder
wall.
10-40%
of
the
tumors
are
malignant
[2]
with
occurrence
of
metastatic
lesions
or
local
relapse.
Pheochromocytoma
is
a
sympathetic
para-
ganglioma
developing
in
the
adrenal
medulla.
Only
2%
of
parasympathetic
paragangliomas
produce
catecholamines
[7]
with
the
typical
clinical
symptoms
(flushing,
hypertension,
headache,
palpitations,
weight
loss).
The
precursor
cells
are
chromaffin
(pheochromocytoma)
or
non-chromaffin
cells
de-
rived
from
the
neural
crest.
They
might
be
located
anywhere
in
the
paraaortic
and
paravertebral
sympathetic
plexus.
While
pheochromocytomas
derive
from
chromaffin
cells
of
the
adrenal
medulla
and
produce
predominantly
epinephrine,
paragangliomas
secrete
norepinephrine.
In
the
past
years,
a
number
of
genes
have
been
identified
in
tumor
development
in
familial
forms,
for
example
3
germline
mutations
in
succi-
nate
dehydrogenase
subunits
(SDH)
were
found
in
30%
of
head
and
neck
paraganglioma
[8].
Mutations
of
subunit
gene
SDHB
increase
the
risk
of
malignant
transformation
of
tumors
[9].
Case
Report
We
describe
the
case
of
an
unusually
large
abdominal
paraganglioma
that
based
on
size
and
core
biopsy
was
suspected
to
be
a
sarcoma.
The
patient
presented
in
our
clinic
with
a
medical
history
of
weight
loss,
fatigue,
and
swelling
of
the
abdominal
wall.
The
symptoms
first
occurred
6
months
before
the
first
appointment
in
the
oncology
department.
The
patient
de-
nied
symptoms
of
diarrhea,
nausea/vomiting,
flushing,
and
palpitations.
In
the
physical
examination
(height
1.73
m,
body
weight
75
kg,
blood
pressure
148/85
mmHg,
heart
rate
115/min),
a
large
lesion
in
the
lower
right
abdomen
spanning
to
the
left
abdominal
area
was
palpable
with
no
clear
separation
to
the
liver
and
spleen.
The
patient
also
showed
signs
of
tumor
cachexia
and
reported
to
be
suffering
from
fatigue.
Further
exami-
nation
revealed
no
noticeable
relevant
problems.
Laboratory
studies
were
well
within
the
normal
range,
except
for
a
slight
elevation
of
lactate
dehydrogenase
(LDH)
with
383
U/1
(normal
<
248
U/1).
Computed
tomography
(CT)
scan
revealed
a
24
x
22
x
12
cm
huge,
singular
lesion
spanning
from
the
epigastrium
to
the
pelvis
with
displacement
of
the
bowel,
and
hypodense
and
hyperdense
areas,
reflecting
a
highly
vascular-
ized
solid
mass
with
large-bore
vessels
(fig.
1
A,
B).
The
abdominal
aorta
was
compressed
by
the
tumor,
the
lower
blood
vessels
in
the
pelvis
showed
no
pathological
findings.
Differential
diagnosis
included
sarcoma,
lymphoma,
and
germ
cell
tumor,
so
a
CT-guided
percutanous
core
needle
biopsy
of
the
lesion
was
performed.
Histology
revealed
a
neoplasm
that
4#2
fi,
Fig.
1.
A,
B
CT
scan
of
the
abdominal
cavity
with
intravenous
contrast
showing
the
large,
well
vascularized
tumor
mass
(marked
with
*)
with
displacement
of
stomach
and
bowel,
leading
to
cachexia
(A,
coronar;
B,
transversal).
C,
D
Angiography
of
the
abdominal
vessels
and
tumor
supply
from
the
right
inferior
epigastric
and
internal
iliac
artery
(C,
early
arterial
phase;
D,
late
arterial
phase).
E,
F
Histology
of
the
resection
specimen:
H&E
x
40
(E),
H&E
x
100
(F).
could
not
be
classified
with
certainty.
Lymphoma
or
germ
cell
tumor
were
excluded,
and
a
mesenchymal
origin
was
suggested.
A
preoperative
angiography
(fig.
1
C,
D)
revealed
a
multiarterial
blood
supply.
The
main
blood
supplying
arteries
coming
from
the
right
superior
gluteal
artery,
right
obturator
artery,
right
internal
iliac
artery,
and
inferior
epigastric
artery
were
embolized
in
preparation
of
the
operation.
RO
resection,
lymphonodectomy,
and
adhesiolysis
were
performed.
The
postoperative
convalescence
was
without
complications,
and
the
patient
was
discharged
on
day
15
past
resection.
In
the
follow-up
6
months
later,
the
patient
was
well
and had
gained
weight,
and
the
CT
scan
confirmed
no
evidence
of
disease.
Histology
Macroscopic
exploration
showed
a
245
x
220
x
95
mm
encapsulated
tumor
with
a
grey-brown
cut
surface
and
flesh-colored
areas.
Microscopi-
cally,
the
tumor
exhibited
large
tumor
cells
with
homogenous
eosinophilic
cytoplasm,
eccentric
large
nuclei
and
granular
chromatin,
and
a
promi-
nent
nucleolus
(fig.
1
E,
F).
The
first
immunohistochemical
analysis
revealed
positive
expression
of
CD68
and
CD10,
and
weak
expression
of
CD11c,
but
no
expression
of
Pan-CK,
CD30,
lysozyme,
and
CD45.
Furthermore,
lymphangioinvasion
and
angioinvasion
of
tumor
cells
was
detected.
Histological
differential
diagnosis
included
a
c-kit-negative
378
Onkologie
2010;33:377-380
Kunitz/Pahl/Podrabsky/VVardelmann/Sturm
gastrointestinal
stromal
tumor
(GIST),
but
platelet-derived
growth
factor
(PDGF)
receptor
alpha
staining
showed
only
weak
cytoplasmic
positivity
of
the
tumor
cells.
Histiocytic
sarcoma
was
taken
into
consideration
(mainly
due
to
CD68
expression).
Ki67
showed
nuclear
staining
in
20%
of
the
tumor
cells.
In
the
search
for
a
definitive
histological
diagnosis,
immunohistochemical
staining
was
extended,
and
a
second
Department
of
Pathology
was
consulted
where
additional
immunostaining
was
per-
formed:
some
tumor
cells
exhibited
positive
staining
for
vimentin,
CD10
and
S100
but
no
staining
of
desmin
and
bc12.
The
histiozytic
markers
CD23,
CD68
(repeated),
and
CD35
were
negative
as
well
as
melan
A,
CD45,
and
HMB45.
Ten
to
20%
of
tumor
cells
stained
positive
for
neu-
roendocrine
markers
such
as
chromogranine
A,
NSE
(30%
of
cells),
and
synaptophysin.
Surrounding
spindled
cells
exhibited
strong
expression
of
PGP9.5
and
were
interpreted
as
sustentacular
cells.
From
these
results,
the
tumor
was
classified
as
paraganglioma
with
malignant
potential.
Usually,
as
tumors
with
semimalignant
behavior,
paraganglioma
show
no
metastatic
disease,
but
a
lymph-
and
angioinvasion
of
tumor
cells
may
indicate
a
higher
risk
of
developing
distant
metastases.
However,
only
the
occurrence
of
metastases
is
a
clear
validation
for
malignant
potential
of
these
tumors.
Discussion
A
50-year-old
patient
with
multiple
medical
symptoms
pre-
sented
with
weight
loss
caused
by
a
huge
intraabdominal
tumor
displacing
the
abdominal
organs.
The
very
few
clinical
symptoms
compared
to
the
large
tumor
size
suggested
a
long
evolution
of
the
disease
with
the
tumor
slowly
growing
over
a
long
period
of
time.
The
initial
differential
diagnosis
in-
cluded
lymphoma,
germ
cell
tumor,
GIST,
and
non-GIST
soft
tissue
sarcoma.
These
tumors
are
known
to
generate
large
tumor
masses
[10]
with
few
medical
symptoms
and
similar
CT
findings
[11].
The
final
histological
diagnosis
of
paraganglioma
was
not
taken
into
consideration
initially
be-
cause
this
is
a
very
rare
diagnosis
and
these
tumors
tend
to
not
develop
tumor
masses
exceeding
10
cm
in
diameter
[6].
Paragangliomas
occur
in
the
head
and
neck
[12]
deriving
from
the
carotid
body
or
other
parasympathetic
or
sympa-
thetic
ganglia.
Further
tumor
locations
are
described
in
the
mediastinum
originating
from
the
aortic
glomus
and
in
the
abdominal
wall
deriving
from
the
retroperitoneal
autonomic
nervous
cells
in
the
organ
of
Zuckerkandl
located
at
the
infe-
rior
mesenteric
artery
[13],
and
tumors
may
also
be
located
at
the
aortorenal
ganglion
and
the
bladder
wall.
They
are
often
diagnosed
in
the
third
to
fifth
decade.
The
tumor
presentation
varies
due
to
mass
effect,
incidental
discovery,
and
excess
catecholamine
production
[4].
Interestingly,
only
10%
of
paragangliomas
originate
from
parasympathetic
ganglia
and
only
2%
of
these
tumors
exhibit
increased
levels
of
catecholamine
production
with
corresponding
clinical
symptoms
[7]
such
as
headache
(26%
of
patients),
palpita-
tions
(21%
of
patients),
sweating
(25%
of
patients),
and
episodic
hypertension
(64%
of
patients)
[4,
14].
Patients
with
those
clinical
symptoms
should
be
screened
for
urine
metanephrines
in
a
24
h-urine
collection
which
features
high
sensitivity
(87-90%)
and
specificity
(99%
and
greater)
[15,
16].
Further
radiologic
diagnostics
include
whole-body
CT
scan
with
98%
sensitivity
[17]
and
magnetic
resonance
imag-
ing
(MRI)
with
95%
sensitivity
[18].
A
metaiodobenzylgua-
nidine
(MIBG)
scan
and
positron
emission
tomography
(PET)
especially
as
68-gallium
somatostatin
receptor
PET-
CT
may
be
useful
diagnostic
tools
but
quite
often
produce
false-positive
or
false-negative
results
[4]
and
are
hence
not
the
first
choice
in
the
diagnostic
workup
for
suspected
paraganglioma.
The
main
cornerstone
in
the
treatment
of
paraganglioma
is
complete
surgery
[19].
Because
of
the
usually
small
tumor
size
17.1
cm
3
in
head
and
neck
tumors
and
94.1
cm
3
for
other
locations
[4]
the
operation
is
manageable.
Some
cases
of
large
tumor
masses
initially
assumed
to
be
GISTs
intraoperatively
presented
as
paraganglioma
with
severe
intraoperative
complexity
[6].
Reviewing
the
literature,
the
presented
case
with
a
tumor
volume
of
3,950
cm
3
is
the
largest
paraganglioma
ever
described
to
our
knowledge.
If
curative
surgery
is
not
possible
or
metastatic
disease
is
proven,
radionuclide
treatment
and/or
palliative
chemo-
therapy
are
treatment
options.
Radiopharmaceuticals
such
as
131/_m/BG
[20],
somatostatin
analogues
such
as
111
In-
pentetreotide/
111
In-DOTA-octreotide
[21]
or
90
Y-DOTA-
lanreotide
[22]
are
useful
substances.
Concerning
palliative
chemotherapy,
only
few
reports
are
available.
CVD
(cyclo-
phosphamide,
vincristine,
dacarbazine)
was
reported
as
a
successful
scheme
with
reduction
of
tumor
symptoms
in
50%
of
cases
but
with
short
remission
duration
[23].
Other
treat-
ment
regimes
included
cisplatin
and
VP16
[24]
or
lomustine
and
5-fluorouracil
[25].
New
drugs
such
as
imatinib
mesylate
and
mTOR
inhibitors
seem
to
have
no
significant
tumor
ef-
ficacy
[25].
In
our
patient,
no
metastatic
lesions
or
residual
tumor
were
found
postoperatively
so
no
adjuvant
therapy
was
performed.
Concerning
the
lymphangiosis
and
angioin-
vasion,
we
recommended
a
careful
long-term
follow-up.
Concerning
genetic
familiar
predisposition,
family
history
was
positive
for
intraabdominal
tumors
in
2
cases
(females).
Further
details
are
not
known
or
accessible,
nevertheless,
nothing
hinted
toward
the
diagnosis
of
a
familial
syndrome
that
predisposes
to
developing
catecholamine-secreting
tu-
mors
(e.g.
multiple
endocrine
neoplasia
(MEN2),
neuro-
fibromatosis
type
1
(NF-1),
von
Hippel-Lindau
syndrome
(VHL)).
The
patient
is
childless,
therefore
genomic
muta-
tional
analysis
of
the
succinate
dehydrogenase
(SDH)
com-
plex
has
not
been
performed.
In
about
30%
of
cases
with
head
and
neck
paraganglioma,
a
germline
mutation
of
SDH
subunits
can
be
detected.
In
a
registry
that
included
63
pa-
tients
with
identified
mutations,
SDHD
mutations
were
the
most
common,
occurring
in
71%
of
cases.
SDHB
and
C
mutations
accounted
for
21
and
8%
of
cases,
respectively
[26].
It
is
currently
under
investigation
whether
the
type
of
mutation
is
also
predictive
for
malignant
behavior
of
the
paraganglioma
(preliminary
data
suggest
SDHB
mutations
are
associated
with
malignancy).
Nevertheless,
genetic
trans-
Gigantic
Paraganglioma
Onkologie
2010;33:377-380
379
mission
is
usually
through
the
father,
and
genetic
disease
is
6
times
more
likely
in
paraganglioma
of
the
glomus
caroti-
cum
compared
to
other
locations
[27].
ing
for
metanephrines
should
be
performed.
Complete
surgi-
cal
resection
is
the
treatment
of
choice.
Conflict
of
Interest
Paraganglioma
is
a
rare
disease
and
should
be
considered
in
There
is
no
conflict
of
interests
for
any
of
the
authors.
the
differential
diagnosis
of
abdominal
masses,
and
screen-
References
1
Baysal
BE:
Hereditary
paraganglioma
targets
di-
verse
paraganglia.
J
Med
Genet
2002;39:617-622.
111
'2
Grufferman
S,
Gillman
MW,
Pasternak
LR,
Peterson
CL,
Young
WG
Jr:
Familial
carotid
body
tumors:
case
report
and
epidemiologic
review.
Cancer
1980;46:2116-2122.
II'
3
Petropoulos
AE,
Luetje
CM,
Camarata
PJ,
et
al.:
Genetic
analysis
in
the
diagnosis
of
familial
para-
gangliomas.
Laryngoscope
2000;110:1225-1229.
110
'4
Erickson
D,
Kudva
YC,
Ebersold
MJ,
et
al.:
Benign
paragangliomas:
clinical
presentation
and
treatment
outcomes
in
236
patients.
J
Clin
Endo-
crinol
Metab
2001;86:5210-5216.
II'
5
Martin
TP:
What
we
call
them:
the
nomenclature
of
head
and
neck
paragangliomas.
Clin
Otolaryn-
gol
2006;31:185-186.
6
Lowenthal
MS,
Sadow
PM,
Raut
C,
Metzler
EC:
Intraoperative
diagnosis
of
a
functional
paragang-
lioma
presenting
as
a
gastrointestinal
stromal
cell
tumor
(GIST).
J
Clin
Anesth
2009;21:57-60.
7
Farr
HW:
Carotid
body
tumors.
A
thirty
year
ex-
perience
at
Memorial
Hospital.
Am
J
Surg
1967;
114:614-619.
8
Astuti
D,
Latif
F,
Dallol
A,
et
al.:
Gene
mutations
in
the
succinate
dehydrogenase
subunit
SDHB
cause
susceptibility
to
familial
pheochromocytoma
and
to
familial
paraganglioma.
Am
J
Hum
Genet
2001;69:49-54.
PI'
9
Fuentes
C,
Menendez
E,
Pineda
J,
et
al.:
The
malignant
potential
of
a
succinate
dehydrogenase
subunit
B
germline
mutation.
J
Endocrinol
Invest
2006;29:350-352.
P
1
'10
Basterretxea
BL,
Arevalo
LS,
Zapata
ME,
et
al.:
(Gastrointestinal
stromal
tumors
presenting
as
pelvic
masses).
Gastroenterol
Hepatol
2006;29:
447-450.
X11
Hayes
WS,
Davidson
AJ,
Grimley
PM,
Hartman
DS:
Extraadrenal
retroperitoneal
paraganglioma:
clinical,
pathologic,
and
CT
findings.
MR
Am
J
Roentgenol
1990;155:1247-1250.
X12
Somasundar
P,
Krouse
R,
Hostetter
R,
Vaughan
R,
Covey
T:
Paragangliomas
-
a
decade
of
clinical
experience.
J
Surg
Oncol
2000;74:286-290.
0
'13
Saurborn
DP,
Kruskal
JB,
Stillman
1E,
Parangi
S:
Best
cases
from
the
AFIP:
paraganglioma
of
the
organs
of
Zuckerkandl.
Radiographics
2003;23:
1279-1286.
0
'14
Plouin
PF,
Gimenez-Roqueplo
AP:
Pheochromo-
cytomas
and
secreting
paragangliomas.
Orphanet
J
Rare
Dis
2006;1:49.
X15
Kudva
YC,
Sawka
AM,
Young
WF
Jr:
Clinical
review
164:
the
laboratory
diagnosis
of
adrenal
pheochromocytoma:
the
Mayo
Clinic
experience.
J
Clin
Endocrinol
Metab
2003;88:4533-4539.
X16
Sawka
AM,
Jaeschke
R,
Singh
RJ,
Young
WF
Jr:
A
comparison
of
biochemical
tests
for
pheochro-
mocytoma:
measurement
of
fractionated
plasma
metanephrines
compared
with
the
combination
of
24-hour
urinary
metanephrines
and
catecho-
lamines.
J
Clin
Endocrinol
Metab
2003;88:553-558.
111
'
17
Manger
WM,
Eisenhofer
G:
Pheochromocytoma:
diagnosis
and
management
update.
Curr
Hyper-
tens
Rep
2004;6:477-484.
0
'18
Francis
IR,
Korobkin
M:
Pheochromocytoma.
Radiol
Clin
North
Am
1996;34:1101-1112.
11
'19
Lee
JA,
Duh
QY:
Sporadic
paraganglioma.
World
J
Surg
2008;32:683-687.
X20
Mukherjee
JJ,
Kaltsas
GA,
Islam
N,
et
al.:
Treatment
of
metastatic
carcinoid
tumors,
phaeo-
chromocytoma,
paraganglioma
and
medullary
carcinoma
of
the
thyroid
with
(131)I-meta-iodo-
benzylguanidine
((131)I-m1BG).
Clin
Endocrinol
(Oxf)
2001;55:47-60.
III'
21
Shapiro
B,
Gross
MD,
Shulkin
B:
Radioisotope
di-
agnosis
and
therapy
of
malignant
pheochromocy-
toma.
Trends
Endocrinol
Metab
2001;12:469-475.
0
'22
Kaltsas
GA,
Papadogias
D,
Makras
P,
Grossman
AB:
Treatment
of
advanced
neuroendocrine
tu-
mors
with
radiolabelled
somatostatin
analogues.
Endocr
Relat
Cancer
2005;12:683-699.
0
'23
Averbuch
SD,
Steakley
CS,
Young
RC,
et
al.:
Malignant
pheochromocytoma:
effective
treatment
with
a
combination
of
cyclophosphamide,
vincris-
tine,
and
dacarbazine.
Ann
Intern
Med
1988;109:
267-273.
X24
Schlumberger
M,
Gicquel
C,
Lumbroso
J,
et
al.:
Malignant
pheochromocytoma:
clinical,
biological,
histologic
and
therapeutic
data
in
a
series
of
20
pa-
tients
with
distant
metastases.
J
Endocrinol
Invest
1992;15:631-642.
X25
Chrisoulidou
A,
Kaltsas
G,
Ilias
I,
Grossman
AB:
The
diagnosis
and
management
of
malignant
phaeochromocytoma
and
paraganglioma.
Endocr
Relat
Cancer
2007;14:569-585.
26
Boedeker
CC,
Neumann
HP,
Maier
W,
et
al.:
Malignant
head
and
neck
paragangliomas
in
SDHB
mutation
carriers.
Otolaryngol
Head
Neck
Surg
2007;137:126-129.
27
Drovdlic
CM,
Myers
EN,
Peters
JA,
et
al.:
Propor-
tion
of
heritable
paraganglioma
cases
and
associ-
ated
clinical
characteristics.
Laryngoscope
2001;
111:1822-1827.
380
Onkologie
2010;33:377-380
Kunitz/Pahl/Podrabsky/VVardelmann/Sturm