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939
Pancreatic Angiographic J. Gerlock, Halter,2
Amil
Susan
Some
50
Somatostatinoma: Features
years
ago,
the
immunocytochemistry,
dromes
have
endocrine
endocrine
been
mone
and
identified
with
the
produce
pancreatic secretory associated
cells
are
(VIP) and endocrine
precursor
uptake
and the
neural
in
the
crest
pancreas (islet cell body (paraganglioma). (Wermer
syndrome
serotonin, [3].
reported
these
neuroectodermal called
tumors
be multihormonal always related hormones [3]. angiographic
secretory
The
although
islets
are
endocrine
features
of
carand synprob-
in ac-
as nesimay
are almost
of only one of the histologic, clinical, and are
discussed.
and had thyroid
not
lessen,
even
from
1 to
5
months but
Oral
pertensive
therapy
November
1979
0361 -803X/79/1335-0939
$00.00
She
after
of
was
a year
dose
Her
flushing
This
was
in the
last
1 50
mg/dl);
total
LDH,
sporadic
multivitamins,
obesity, No
109/L) cell
antihy-
therapy
mg/dl;
cholesterol
blood
exami-
pressure
a white
count,
mg/dl;
(normal
amylase,
21
normal;
cell
differential.
4,770,000/mm3
(4.77
mIU/ml;
0 mIU/ml);
was
blood
a normal
SGOT,
90-21
1 47 mg/dl;
was
the clinical
high with
=
0.2
mlU/mI
the
hypotension.
demonstrated
blood
and
antihypertensive
orthostatic
x
few
and at
medwere
The
bilirubin,
240
was
spells
=
012/L); hemoglobin, 9.7 g/dI; platelets, 308,000/mm3 109/L); packed-cell volume, 33.8%; iron 10 mg/dI (normal U/mI;
com-
of thyroid
oral contraceptives and thyroid and iron deficiency anemia therapy,
red
medication
daily
she
a history
She
(16.3
30%;
had
months.
tests
16,300/mm3
therapy, when
medication. having
sulfate
Laboratory
sulfate she
thyroid
began
started.
severe
Vanderbilt deficiency
before
Since
her
frequent
to iron
(308
1
x
50-
SGPT,
glucose,
and stools,
1 219
guaiac-
positive. On
upper
gastric
folds
gastrointestinal in the
series,
fundus
of the
she
was
stomach.
found
folds corresponded varices. Abdominal
selective
angiography
mass
celiac with
and
splenic
neovascularization
and
the tail of the pancreas ing.
The
vein.
No
tumor
invaded
liver
metastases
Because
of
urine
samples
acid,
and
every
24
the
© American
splenic were
patient’s
for
were
hilum
TN 37232.
Roentgen
Ray Society
obstructed
Address
on
of
flushing
were
1 7-hydrocorticosteroid
Nashville,
and
reprint
requests
stain
shuntthe splenic several
vanillylmandelic
normal. and
large further
angiography.
episodes,
cathecolamine, and
tumor
was no arteriovenous
history done
for
a hypervascular
dense
demonstrated
for metanephrine,
5-HIAA hr
the
have
to gastric varices aortography and
showed
persistent
(fig. 1 ). There
to
At endoscopy
evaluation, the large gastric without associated esophageal
Received December 4, 1978; accepted after revision June 18, 1979. 1 Department of Radiology and Radiological Sciences, Vanderbilt University Hospital, Department of Pathology, Vanderbilt University Hospital, Nashville, TN 37232.
133:939-943,
her
more
2
AJR
stopped
admission.
ferrous
ferrous
6 months
fatigue.
though
before
were
started
mental
to discontinue blood pressure
discovered.
spells,
supplementary
2 g.
became
referred
to oral
illness
given
was instructed ication. High
of
in the pan-
tumors
symptoms
a somatostatinoma
increased
x
arising
known
pancreatic
the clinical
with the hypersecretion In our case report, the
did
was
of flushing
responsive
Her and
was
Hematocrit
nonhormonally also
plaints
count
APUD
cell
poorly
lethargy
documented.
have also
tumors
specially
The
she
woman,
evaluation
On admission, other than moderate nation was essentially unremarkable.
carci-
(oat
hormone
cells,
[2-4].
pancreas
[3-6].
These
lung
active
before,
beginning,
function
defect in the development pancreatic tumors producing
hormonally
APUDomas
of the
dioblastomas
which
(medullary
and antidiuretic
The
been
amine
cells,
adenoma or carcinoma), The endocrine neoplasia and Sipple syndrome) are
to a basic Endocrine
to notice
diarrhea
(pheochromocy-
thyroid
was
of hypothyroidism
of the
white for
diarrhea.
hor-
human
prime
medulla
which
chronic
discontinued
[2].
(carcinoid),
tract
ably in part related the APUD system.
tive
hormones
(adenoma),
gastrointestinal
whose
and began
D cells,
secrete
Hospital
four
with an unknown pancreatic cell intestinal poly-
(APUD) and
adrenal
cinoma), carotid
gland
A cells,
which
a 35-year-old
A. ,
anemia,
of
], the which
[1
yet confirmed. cells are part
of polypeptide
present
are
least
insulin;
and D1 cells, of endocrine of vasoactive
decarboxylation
pituitary
creas,
syn-
a specific
into
secrete
PP cells,
toma), noma),
MSH,
at of
divided
gastrin is not pancreatic
are derived from is the production
ACTH,
and
Report
L.
types
classification
which
somatostatin;
peptide These
dromes
Case
University
clinical
many
Langerhans,
Lausanne
polypeptide (HPP); product. The type with the production
are
the
production
B cells,
glucagon;
which
of
the
new
pancreatic
secrete
and
From
islets
tumors
syndrome.
to
endocrine
cells
the
clinical
According
hormones
discovered.
in
pancreatic
and ‘ ‘ nonfunctioning” of radioimmunoanalysis
aid
new
been
cells
have
Clinical,
Jr. , Carlos A. Muhletaler,1 and Victor Goncharenko1
were divided into insulin-producing varieties. Since then, with the and
Histologic,
Urine
collection
1 7-ketosteroid
to C. A. Muhletaler.
were
in
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940
CASE
Fig. 1 -Selective of segmental splenic
Fig.
citrate
2.-A, x29,400).
splenic arteries
Light microscopy
arteriograms. (arrows).
of islet
A, Early
B, Late phase.
cell
tumor.
phase.
Dense
Islands
Hypervascular
tumor
and
REPORTS
mass
AJR:133,
of neovascularity
in tail
of pancreas
and
invading
hilum
November
of spleen.
1979
Encasement
stain.
cords
of tumor
cells
(H and
E x225)
B, Type
D granules
in tumor
cells
(uranyl
acetate,
lead
AJR:133,
also
November
=
within
(normal
normal
50-1
polypeptide invading
tomy,
direct
evidence
the
tibody The
(fig.
cells
containing
tensive
was
workup. blood
differential. still
2A).
et al. [7].
had
Her
fasting
flushing
hypertensive
workup,
data
levels
and
diarrhea.
showed
demonstrated
three
preted
as metastasis
(fig.
normal
and
splenecwas
of the
(fig.
2B),
after
de-
with
the an-
cells. surgery
for
a hematocrit (1 8 x
with
returned
and
a normal
to normal. part
arteries. lesions
a hyper-
of 44%
1 09/L)
Aortography, renal
islet
as
antisomatostatin
of tumor
had
no
of the
staining
using
hypervascular
pan-
There
Celiac in the
She of
her
angiogliver
Somatostatin
[9].
Ex-
of the
microscopy
showed
glucose
raphy
seen.
D granules [8]
pg/mI
examination
Electron
of 1 8,000/mm3
spells
was
5 months
Laboratory count
tail
941
REPORTS
intestinal
demonstrated.
in the
vein
staining
readmitted
cell
not
Immunoperoxidase
intense
1 53.2
pancreatectomy
method
focal
patient
was
Microscopic
cells
antibody-enzyme
was
of vasoactive
tumor
splenic
at surgery.
islet
produced
white
the
gastrin
levels
a large At distal
into
by Deconinck
unlabeled
for
blood
Achlorhydria
spleen.
extension
revealed
The
showed
demonstrated
scribed
Radioassay
normal.
of metastasis
tumor cells
limits.
laparotomy
creas
CASE
55 pg/mI).
were
ploratory
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1979
inter-
requires
the
chemistry. presence hormone
producing
in the oncology
Somatostatinomas are endocrine pancreatic tumors composed of islet D cells. The D cells are now known to produce peptide(s) identical with or very similar to the hypothalamic growth hormone-release inhibiting hormone, somatostatin
type
and
[3].
tumor
It does
immunocyto-
only
not
indicates of the
indicate
cell
which
(x255) of the the somatostatinoma
of cuboidal
hematoxylinin our case
and columnar
the electron microscope, the secretory within the islet cells of this tumor were the morphology in A, B, D, PP,
and and
size of the secretory D1 cells according
classification of endocrine cells [1 ]. Table the islet cell types and the size of the secretory they contain for each type of tumor in which these have
been
statinoma contain
fine
identified
in our secretory
D
by electron
case was granules
structure
of
tumor and
They
granules
and
tumors associated Verner-Morrison
The
Ganda et al. [1 2], the was also examined by
revealed
were were
many
quite not
granules
dissimilar
identical
similar
to either to those
to the size and morphology it does not give any information these
cells
produce.
TABLE
been identified.
hepatic arteriogram 5 months after pancreatectomy hypervascular metastatic lesions (arrows).
pancreatic
They
polypeptide
of
(PP
(B cells), cells),
granules
islet
cell
type
of the secretory about which kinds
To determine
are insulin
cell
or the reported
this
that the islet cells be assayed for their hormonal At present, four hormonal products of the islet Three
to
the A or
of islet
with either the Zollinger-Ellison syndromes. The somatostatinoma
Larsson et al. [1 3] was also composed indistinguishable from those of D cell granules. Although electron microscopy identified the
of hormones
somato-
by
cells
by
according granules,
1 shows granules granules
found by electron microscopy to comparing in size and morpholreported
the
microscopy
cell granules.
B cell
microscopy.
granto Lau-
of D cell granules.
somatostatinoma
electron
3.-Selective splenectomy.
cells
granules then com-
sanne’s
In the
Fig.
type
type.
ogy with those
and
the
peptide
is composed of, nor does it indicate syndrome will be produced by the
it to be composed
pared with ules found
followed
other
arranged in an acinar pattern (fig. 2A). Since this examination only revealed the lesion to be an endocrine pancreatic tumor, electron microscopy was used to determine its islet
Discussion
been
of several
microscopy
pancreatic
[3]. Light microscopy stained sections from
showed
release
microscopy
light
of islet cell the tumor which type of clinical tumor eosin
the
of electron
of an endocrine
clinic.
has
use
inhibits
insulin and glucagon, and may play a in the pancreatic islets [3, 1 0, 1 1 ]. To the other types of islet cell tumors
Histologically,
Using located
3). She
also
hormones, including local regulatory role differentiate it from
glucagon
and
requires
products. cells have
(A cells),
somatostatin
(D
1 : Islet Cell Tumors Type
Insulinomas Gastrinomas Ellison
Islet cell
of Tumor
B (Zollingersyndrome)
uliramorphology
Type
.
. .
(Granule
250 .
.
Size)
± 59 nm
. . .
Predominate
.
Peptide
. . clinical
Hormone
Insulin
Hypoglycemia
Gastrin
Intractable
and
Laboratory
ulcers,
.
Findings
abdominal
pain,
diarrhea Verner-Morrison (vipoma) Glucagonomas
tumor .
.
.
D1 ?
1 35
± 28
A
200
± 1 24
nm nm
Vasoactive peptide Glucagon
intestinal
poly-
Watery diarrhea, hypokalemia, lorhydria Necrolytic migratory tumors:
achery-
thema, diabetes, stomatitis, loss, venous thrombosis Somatostatinoma
D
220
± 48
nm
Somatostatin
Diabetes,
steatorrhea,
achlorhydria
weight
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942
CASE
AJR:133,
REPORTS
November
1979
cells). The remaining types of cells are anticipated to produce as yet unidentified peptide hormones. This explains the question mark in table I next to the D1 cells found in the Verner-Morrison tumor. The secretory product of the D1 cell is not yet defined [3]. The pancreatic polypeptide hormone from the PP cells was omitted from table I because its physiologic significance is still unestablished [14]. In our case, as well as in the other two previously reported somatostatinomas, the hormone somatostatin was identified by immunocytochemical means in the 0 cells of the tumor. On the basis of the electron microscopy identification of the D cell secretory granules and the immunocytochemical localization of somatostatin in these granules, it seems reasonable to classify the tumor in our case as a somatostati-
All islet cell tumors listed in table 1 were seen as hypervascular masses on angiography [4, 15-21]. Insulinomas have ranged in size from 4 to 1 1 cm, and their angiographic
noma.
that
Somatostatinomas
are so rare that there is no distinct clinical presentation. The three lesions occurred in women of ages 36, 46, and 55 years. In the two previously reported cases, the chief complaints of one were excessive urination and thirst accompanied by weight loss [1 2]. Her blood glucose levels were elevated. A pancreatic mass was visualized during a cholecystectomy, and biopsy at that time was consistent with an islet cell carcinoma. Follow-up angiography 7 years later revealed a vascular mass in the head of the pancreas that, after surgical exploration and pathologic examination, was found to be a somatostatinoma. There was no visible metastasis and she was still asymptomatic
20 months
after
surgery.
The
seen with the chief complaints nontoxic goiter [1 3]. This was complaints
headaches, hydroxyindole were
normal.
chlorhydria,
of diarrhea
and
patient
was
initially
later
by complaints
steatorrhea,
and
her condition
a diabetic
a tumor metastasis
deteriorated
glucose
and
nous
samples
glucagon levels. None our patient. The selective splenic in our patient (fig. previously reported
showed
of these
samples
were
they
had
angiography
[1 2].
We
containing
neovascularity,
and no arteriovenous splenic vein occlusion ing
through
the
coronary
a persistent
dense
tumor
vein
into
the
portal
vein.
when
which
in this
lesion
similar
and
not
tumors
were
3-4
cm.
Naylor
for
[1 8, 1 9]. VIP arteriovenous
in the
other
islet
cell
of hypervascular
have seen
of
by the fact
why
descriptions
to those
presence
detected
explain
carcinomas
also
The
be explained
first
may
angiographic
thank
Linda
been
reported
in insulinomas
and
[21 , 22].
assistance
in
preparation
of
this
1.
Solcia E, Polak JM, Pearse AGE, Forssman WG, Larsson LI, Sundler F, Lechago J, Grimelius L, Fujita T, Creutzfeldt W, Gepts W, Falkmer 5, Lefrank F, Heitz P, Bordi C, Hage E, Buchan AMJ, Bloom SA, Grossman MI: Lausanne 1 977 classification of gastroenteropancreatic (GEP) endocrine cells, in Gut Hormones, edited by Bloom SR. Edinburgh, Churchill-
2.
Pearse
Livingstone,
1978,
pp
thology.
Patho!
3.
Larsson
LI: Endocrine
4,
416, 1978 Huguet JF, Clement
Annu
Larsson
tho! AnatJ SO,
Hum
Jean
P, Clerissi J Radio!
types
LI,
9:401
Pathol
J, Burelle E!ectro!
-
H: Les Med
Nuc!
Deconinck
0,
JF, Stadil
abnormalities
Virchows
asso-
Arch
F, Hakanson
[Pa-
Potvliege
Anat]
PA,
pancreatic
islet
A, Svensson
J: Antro-pyloric
nesidioblastosis
Arch [Pathol
JF,
human
Sundler
F, HoIst
pancreatic
Virchows
cell
tumors.
9, 1977
Ljungberg with
of islet
pancreatic
: 209-21
376
Rehfeld
islets.
tumors.
pancreas.
distinct
endocrine
associated
the
JP,
in pa-
1978
with
Larsson
and its implications 1974
pancreatic
du
LI: Two
ciated 6.
9 : 27-42,
endocrines
59:249-260, 5,
10-18
AGE: The APUD concept
tumeurs
proliferation
360 : 305-31
4, 1973
Gepts
cells.
gastrinoma
and W:
The
ultrastructure
Diabetologia
7
of of
: 266-282,
1971 8.
Al-
Sternberger
LA:
Prentice-Hall, 9,
Polak
JM,
Growth and 10.
1
lmmunocytochemistry.
1 974, Pearse
hormone
pancreatic
Alberti
Iversen
stain,
shunting. The venous phase showed with numerous collateral veins drain-
large
of insulinomas and arteriove-
REFERENCES
in
though they are not shown, selective superior mesenteric and celiac angiograms were described as showing a vascular mass in the pancreaticoduodenal arcade. The somatostatinoma in our patient was also seen angiographically as a hypervascular mass of 7.5 x 7.0 x 5.5 cm (fig. 1),
are
[1 8-20]. may
of insuliand their
manuscript.
7.
one
arteries;
ACKNOWLEDGMENT
arteriogram of the somatostatinoma 1 ) is the first in the literature. Of the two cases,
are
is seen
seen
tumors
vasodilator,
Two
These
and
obtained
been
glucagon-secreting
Path-
insulin
has
tumors
shunting
tolerance.
decreased
these
tumors.
of the pancreatic tumor showed it to be Although the clinical presentations of these patients are dissimilar, all three patients were found to have abnormal glucose-tolerance curves. In one case, steatorrhea and achlorhydria were present [1 2, 1 3]. Our patient and one of the two previously reported [1 3] had flushings and diarrhea. In the other two reported cases the blood
feeding
are similar to those have been 5-10 cm,
in these
is a potent
ologic examination a somatostatinoma.
peripheral
shunting
neovascularity
of
she died.
tortuous
angiographic appearances differ from those and gastrinomas only in that neovascularity
localized to the head of was found. Postoperarapidly
enlarged,
angiographic characteristics nomas [16-18]. VlPomas
of abdominal pains and a followed 4 years later by
1 0 years
include:
early, fine reticular network of normal appearing arteries; a dense, well defined capillary stain persisting up to 20 sec; and no vascular shunting, encased vessels, or neovasculature [1 5, 1 8]. Gastrinomas have been 2.5-1 0 cm, and their
tachycardia, and possibly flushing. Urinary 5acetic acid and vanillylmandelic acid values Abnormal laboratory tests confirmed hypo-
During cholecystectomy, the pancreas with liver tively,
other
characteristics
KGMM,
pp AGE,
Grimelius
release-inhibiting D cell.
Lancet
Christensen
J, Lundbeak
Englewood
Cliffs, N.J.,
Bloom
Arimura
129-171
1
NJ,
K, Hansen
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KS, Orskov
SE,
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H: Inhibition of insulin secretion by somatostatin. Lancet 2 : 1 299-1 301 , 1973 1 . Koerker DJ, Ruch W, Chideckel E, Palmer J, Goodner CJ, Ensinck J, Gale CC: Somatostatin: hypothalamic inhibitor of the endocrine pancreas. Science 1 84 : 482-484, 1974
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1 2.
November
Ganda
OP,
YC,
Ebeid
CASE
1979
Weir AM,
GC,
Soeldner
Gabbay
somatostatin-containing
EnglJMed
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tumor
mansson
HoIst
1 4.
TM,
Chance
edited pp 1 5.
NY,
Chick
WL,
Patel
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endocrine
1 7.
‘: a
N
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Lundqvist JF,
G,
Hirsch
Schwartz and
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TW:
Inge-
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Rehfeld
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KUhI SL,
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of
5:
1977
JJ,
S, Jensen
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Reichlin
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tions.
JS,
KH,
943
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Thomas
TJ,
AD,
Levitan
A: Unusual
in ZE syndrome. Aotterdam
characteristics
H,
Ann
Casarella
of the
WDHA
clinical
and
Intern
Med
WJ:
Aadiologic
syndrome.
71:
AJR
1976
ML,
Lamb
GHA,
Barraclough
MA:
Angiographic
dem-
onstration of a pancreatic ‘ ‘vipoma’ ‘ in the WDHA syndrome. AJR 127:1037-1039, 1976 20. Shenoy 55: VIPoma of body of pancreas with hepatic metastases. Semin Roentgenol 1 3 : 301 -302, 1978 21 . McGavran MH, Unger RH, Recant L, Polk HC, Kilo C, Levin ME: A glucagon secreting alpha cell carcinoma of the pancreas. NEnglJMed 274:1408-1413, 1966 22. Ingemansson 5, Lunderqvist A, HoIst J: Selective catheterization
of the
secreting 556,
1976
pancreatic
vein
carcinoma
of the
for
radioimmunoassay
pancreas.
Radiology
in glucagon1 1 9 : 555-
939
Pancreatic Angiographic J. Gerlock, Halter,2
Amil
Susan
Some
50
Somatostatinoma: Features
years
ago,
the
immunocytochemistry,
dromes
have
endocrine
endocrine
been
mone
and
identified
with
the
produce
pancreatic secretory associated
cells
are
(VIP) and endocrine
precursor
uptake
and the
neural
in
the
crest
pancreas (islet cell body (paraganglioma). (Wermer
syndrome
serotonin, [3].
reported
these
neuroectodermal called
tumors
be multihormonal always related hormones [3]. angiographic
secretory
The
although
islets
are
endocrine
features
of
carand synprob-
in ac-
as nesimay
are almost
of only one of the histologic, clinical, and are
discussed.
and had thyroid
not
lessen,
even
from
1 to
5
months but
Oral
pertensive
therapy
November
1979
0361 -803X/79/1335-0939
$00.00
She
after
of
was
a year
dose
Her
flushing
This
was
in the
last
1 50
mg/dl);
total
LDH,
sporadic
multivitamins,
obesity, No
109/L) cell
antihy-
therapy
mg/dl;
cholesterol
blood
exami-
pressure
a white
count,
mg/dl;
(normal
amylase,
21
normal;
cell
differential.
4,770,000/mm3
(4.77
mIU/ml;
0 mIU/ml);
was
blood
a normal
SGOT,
90-21
1 47 mg/dl;
was
the clinical
high with
=
0.2
mlU/mI
the
hypotension.
demonstrated
blood
and
antihypertensive
orthostatic
x
few
and at
medwere
The
bilirubin,
240
was
spells
=
012/L); hemoglobin, 9.7 g/dI; platelets, 308,000/mm3 109/L); packed-cell volume, 33.8%; iron 10 mg/dI (normal U/mI;
com-
of thyroid
oral contraceptives and thyroid and iron deficiency anemia therapy,
red
medication
daily
she
a history
She
(16.3
30%;
had
months.
tests
16,300/mm3
therapy, when
medication. having
sulfate
Laboratory
sulfate she
thyroid
began
started.
severe
Vanderbilt deficiency
before
Since
her
frequent
to iron
(308
1
x
50-
SGPT,
glucose,
and stools,
1 219
guaiac-
positive. On
upper
gastric
folds
gastrointestinal in the
series,
fundus
of the
she
was
stomach.
found
folds corresponded varices. Abdominal
selective
angiography
mass
celiac with
and
splenic
neovascularization
and
the tail of the pancreas ing.
The
vein.
No
tumor
invaded
liver
metastases
Because
of
urine
samples
acid,
and
every
24
the
© American
splenic were
patient’s
for
were
hilum
TN 37232.
Roentgen
Ray Society
obstructed
Address
on
of
flushing
were
1 7-hydrocorticosteroid
Nashville,
and
reprint
requests
stain
shuntthe splenic several
vanillylmandelic
normal. and
large further
angiography.
episodes,
cathecolamine, and
tumor
was no arteriovenous
history done
for
a hypervascular
dense
demonstrated
for metanephrine,
5-HIAA hr
the
have
to gastric varices aortography and
showed
persistent
(fig. 1 ). There
to
At endoscopy
evaluation, the large gastric without associated esophageal
Received December 4, 1978; accepted after revision June 18, 1979. 1 Department of Radiology and Radiological Sciences, Vanderbilt University Hospital, Department of Pathology, Vanderbilt University Hospital, Nashville, TN 37232.
133:939-943,
her
more
2
AJR
stopped
admission.
ferrous
ferrous
6 months
fatigue.
though
before
were
started
mental
to discontinue blood pressure
discovered.
spells,
supplementary
2 g.
became
referred
to oral
illness
given
was instructed ication. High
of
in the pan-
tumors
symptoms
a somatostatinoma
increased
x
arising
known
pancreatic
the clinical
with the hypersecretion In our case report, the
did
was
of flushing
responsive
Her and
was
Hematocrit
nonhormonally also
plaints
count
APUD
cell
poorly
lethargy
documented.
have also
tumors
specially
The
she
woman,
evaluation
On admission, other than moderate nation was essentially unremarkable.
carci-
(oat
hormone
cells,
[2-4].
pancreas
[3-6].
These
lung
active
before,
beginning,
function
defect in the development pancreatic tumors producing
hormonally
APUDomas
of the
dioblastomas
which
(medullary
and antidiuretic
The
been
amine
cells,
adenoma or carcinoma), The endocrine neoplasia and Sipple syndrome) are
to a basic Endocrine
to notice
diarrhea
(pheochromocy-
thyroid
was
of hypothyroidism
of the
white for
diarrhea.
hor-
human
prime
medulla
which
chronic
discontinued
[2].
(carcinoid),
tract
ably in part related the APUD system.
tive
hormones
(adenoma),
gastrointestinal
whose
and began
D cells,
secrete
Hospital
four
with an unknown pancreatic cell intestinal poly-
(APUD) and
adrenal
cinoma), carotid
gland
A cells,
which
a 35-year-old
A. ,
anemia,
of
], the which
[1
yet confirmed. cells are part
of polypeptide
present
are
least
insulin;
and D1 cells, of endocrine of vasoactive
decarboxylation
pituitary
creas,
syn-
a specific
into
secrete
PP cells,
toma), noma),
MSH,
at of
divided
gastrin is not pancreatic
are derived from is the production
ACTH,
and
Report
L.
types
classification
which
somatostatin;
peptide These
dromes
Case
University
clinical
many
Langerhans,
Lausanne
polypeptide (HPP); product. The type with the production
are
the
production
B cells,
glucagon;
which
of
the
new
pancreatic
secrete
and
From
islets
tumors
syndrome.
to
endocrine
cells
the
clinical
According
hormones
discovered.
in
pancreatic
and ‘ ‘ nonfunctioning” of radioimmunoanalysis
aid
new
been
cells
have
Clinical,
Jr. , Carlos A. Muhletaler,1 and Victor Goncharenko1
were divided into insulin-producing varieties. Since then, with the and
Histologic,
Urine
collection
1 7-ketosteroid
to C. A. Muhletaler.
were
in
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940
CASE
Fig. 1 -Selective of segmental splenic
Fig.
citrate
2.-A, x29,400).
splenic arteries
Light microscopy
arteriograms. (arrows).
of islet
A, Early
B, Late phase.
cell
tumor.
phase.
Dense
Islands
Hypervascular
tumor
and
REPORTS
mass
AJR:133,
of neovascularity
in tail
of pancreas
and
invading
hilum
November
of spleen.
1979
Encasement
stain.
cords
of tumor
cells
(H and
E x225)
B, Type
D granules
in tumor
cells
(uranyl
acetate,
lead
AJR:133,
also
November
=
within
(normal
normal
50-1
polypeptide invading
tomy,
direct
evidence
the
tibody The
(fig.
cells
containing
tensive
was
workup. blood
differential. still
2A).
et al. [7].
had
Her
fasting
flushing
hypertensive
workup,
data
levels
and
diarrhea.
showed
demonstrated
three
preted
as metastasis
(fig.
normal
and
splenecwas
of the
(fig.
2B),
after
de-
with
the an-
cells. surgery
for
a hematocrit (1 8 x
with
returned
and
a normal
to normal. part
arteries. lesions
a hyper-
of 44%
1 09/L)
Aortography, renal
islet
as
antisomatostatin
of tumor
had
no
of the
staining
using
hypervascular
pan-
There
Celiac in the
She of
her
angiogliver
Somatostatin
[9].
Ex-
of the
microscopy
showed
glucose
raphy
seen.
D granules [8]
pg/mI
examination
Electron
of 1 8,000/mm3
spells
was
5 months
Laboratory count
tail
941
REPORTS
intestinal
demonstrated.
in the
vein
staining
readmitted
cell
not
Immunoperoxidase
intense
1 53.2
pancreatectomy
method
focal
patient
was
Microscopic
cells
antibody-enzyme
was
of vasoactive
tumor
splenic
at surgery.
islet
produced
white
the
gastrin
levels
a large At distal
into
by Deconinck
unlabeled
for
blood
Achlorhydria
spleen.
extension
revealed
The
showed
demonstrated
scribed
Radioassay
normal.
of metastasis
tumor cells
limits.
laparotomy
creas
CASE
55 pg/mI).
were
ploratory
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1979
inter-
requires
the
chemistry. presence hormone
producing
in the oncology
Somatostatinomas are endocrine pancreatic tumors composed of islet D cells. The D cells are now known to produce peptide(s) identical with or very similar to the hypothalamic growth hormone-release inhibiting hormone, somatostatin
type
and
[3].
tumor
It does
immunocyto-
only
not
indicates of the
indicate
cell
which
(x255) of the the somatostatinoma
of cuboidal
hematoxylinin our case
and columnar
the electron microscope, the secretory within the islet cells of this tumor were the morphology in A, B, D, PP,
and and
size of the secretory D1 cells according
classification of endocrine cells [1 ]. Table the islet cell types and the size of the secretory they contain for each type of tumor in which these have
been
statinoma contain
fine
identified
in our secretory
D
by electron
case was granules
structure
of
tumor and
They
granules
and
tumors associated Verner-Morrison
The
Ganda et al. [1 2], the was also examined by
revealed
were were
many
quite not
granules
dissimilar
identical
similar
to either to those
to the size and morphology it does not give any information these
cells
produce.
TABLE
been identified.
hepatic arteriogram 5 months after pancreatectomy hypervascular metastatic lesions (arrows).
pancreatic
They
polypeptide
of
(PP
(B cells), cells),
granules
islet
cell
type
of the secretory about which kinds
To determine
are insulin
cell
or the reported
this
that the islet cells be assayed for their hormonal At present, four hormonal products of the islet Three
to
the A or
of islet
with either the Zollinger-Ellison syndromes. The somatostatinoma
Larsson et al. [1 3] was also composed indistinguishable from those of D cell granules. Although electron microscopy identified the
of hormones
somato-
by
cells
by
according granules,
1 shows granules granules
found by electron microscopy to comparing in size and morpholreported
the
microscopy
cell granules.
B cell
microscopy.
granto Lau-
of D cell granules.
somatostatinoma
electron
3.-Selective splenectomy.
cells
granules then com-
sanne’s
In the
Fig.
type
type.
ogy with those
and
the
peptide
is composed of, nor does it indicate syndrome will be produced by the
it to be composed
pared with ules found
followed
other
arranged in an acinar pattern (fig. 2A). Since this examination only revealed the lesion to be an endocrine pancreatic tumor, electron microscopy was used to determine its islet
Discussion
been
of several
microscopy
pancreatic
[3]. Light microscopy stained sections from
showed
release
microscopy
light
of islet cell the tumor which type of clinical tumor eosin
the
of electron
of an endocrine
clinic.
has
use
inhibits
insulin and glucagon, and may play a in the pancreatic islets [3, 1 0, 1 1 ]. To the other types of islet cell tumors
Histologically,
Using located
3). She
also
hormones, including local regulatory role differentiate it from
glucagon
and
requires
products. cells have
(A cells),
somatostatin
(D
1 : Islet Cell Tumors Type
Insulinomas Gastrinomas Ellison
Islet cell
of Tumor
B (Zollingersyndrome)
uliramorphology
Type
.
. .
(Granule
250 .
.
Size)
± 59 nm
. . .
Predominate
.
Peptide
. . clinical
Hormone
Insulin
Hypoglycemia
Gastrin
Intractable
and
Laboratory
ulcers,
.
Findings
abdominal
pain,
diarrhea Verner-Morrison (vipoma) Glucagonomas
tumor .
.
.
D1 ?
1 35
± 28
A
200
± 1 24
nm nm
Vasoactive peptide Glucagon
intestinal
poly-
Watery diarrhea, hypokalemia, lorhydria Necrolytic migratory tumors:
achery-
thema, diabetes, stomatitis, loss, venous thrombosis Somatostatinoma
D
220
± 48
nm
Somatostatin
Diabetes,
steatorrhea,
achlorhydria
weight
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942
CASE
AJR:133,
REPORTS
November
1979
cells). The remaining types of cells are anticipated to produce as yet unidentified peptide hormones. This explains the question mark in table I next to the D1 cells found in the Verner-Morrison tumor. The secretory product of the D1 cell is not yet defined [3]. The pancreatic polypeptide hormone from the PP cells was omitted from table I because its physiologic significance is still unestablished [14]. In our case, as well as in the other two previously reported somatostatinomas, the hormone somatostatin was identified by immunocytochemical means in the 0 cells of the tumor. On the basis of the electron microscopy identification of the D cell secretory granules and the immunocytochemical localization of somatostatin in these granules, it seems reasonable to classify the tumor in our case as a somatostati-
All islet cell tumors listed in table 1 were seen as hypervascular masses on angiography [4, 15-21]. Insulinomas have ranged in size from 4 to 1 1 cm, and their angiographic
noma.
that
Somatostatinomas
are so rare that there is no distinct clinical presentation. The three lesions occurred in women of ages 36, 46, and 55 years. In the two previously reported cases, the chief complaints of one were excessive urination and thirst accompanied by weight loss [1 2]. Her blood glucose levels were elevated. A pancreatic mass was visualized during a cholecystectomy, and biopsy at that time was consistent with an islet cell carcinoma. Follow-up angiography 7 years later revealed a vascular mass in the head of the pancreas that, after surgical exploration and pathologic examination, was found to be a somatostatinoma. There was no visible metastasis and she was still asymptomatic
20 months
after
surgery.
The
seen with the chief complaints nontoxic goiter [1 3]. This was complaints
headaches, hydroxyindole were
normal.
chlorhydria,
of diarrhea
and
patient
was
initially
later
by complaints
steatorrhea,
and
her condition
a diabetic
a tumor metastasis
deteriorated
glucose
and
nous
samples
glucagon levels. None our patient. The selective splenic in our patient (fig. previously reported
showed
of these
samples
were
they
had
angiography
[1 2].
We
containing
neovascularity,
and no arteriovenous splenic vein occlusion ing
through
the
coronary
a persistent
dense
tumor
vein
into
the
portal
vein.
when
which
in this
lesion
similar
and
not
tumors
were
3-4
cm.
Naylor
for
[1 8, 1 9]. VIP arteriovenous
in the
other
islet
cell
of hypervascular
have seen
of
by the fact
why
descriptions
to those
presence
detected
explain
carcinomas
also
The
be explained
first
may
angiographic
thank
Linda
been
reported
in insulinomas
and
[21 , 22].
assistance
in
preparation
of
this
1.
Solcia E, Polak JM, Pearse AGE, Forssman WG, Larsson LI, Sundler F, Lechago J, Grimelius L, Fujita T, Creutzfeldt W, Gepts W, Falkmer 5, Lefrank F, Heitz P, Bordi C, Hage E, Buchan AMJ, Bloom SA, Grossman MI: Lausanne 1 977 classification of gastroenteropancreatic (GEP) endocrine cells, in Gut Hormones, edited by Bloom SR. Edinburgh, Churchill-
2.
Pearse
Livingstone,
1978,
pp
thology.
Patho!
3.
Larsson
LI: Endocrine
4,
416, 1978 Huguet JF, Clement
Annu
Larsson
tho! AnatJ SO,
Hum
Jean
P, Clerissi J Radio!
types
LI,
9:401
Pathol
J, Burelle E!ectro!
-
H: Les Med
Nuc!
Deconinck
0,
JF, Stadil
abnormalities
Virchows
asso-
Arch
F, Hakanson
[Pa-
Potvliege
Anat]
PA,
pancreatic
islet
A, Svensson
J: Antro-pyloric
nesidioblastosis
Arch [Pathol
JF,
human
Sundler
F, HoIst
pancreatic
Virchows
cell
tumors.
9, 1977
Ljungberg with
of islet
pancreatic
: 209-21
376
Rehfeld
islets.
tumors.
pancreas.
distinct
endocrine
associated
the
JP,
in pa-
1978
with
Larsson
and its implications 1974
pancreatic
du
LI: Two
ciated 6.
9 : 27-42,
endocrines
59:249-260, 5,
10-18
AGE: The APUD concept
tumeurs
proliferation
360 : 305-31
4, 1973
Gepts
cells.
gastrinoma
and W:
The
ultrastructure
Diabetologia
7
of of
: 266-282,
1971 8.
Al-
Sternberger
LA:
Prentice-Hall, 9,
Polak
JM,
Growth and 10.
1
lmmunocytochemistry.
1 974, Pearse
hormone
pancreatic
Alberti
Iversen
stain,
shunting. The venous phase showed with numerous collateral veins drain-
large
of insulinomas and arteriove-
REFERENCES
in
though they are not shown, selective superior mesenteric and celiac angiograms were described as showing a vascular mass in the pancreaticoduodenal arcade. The somatostatinoma in our patient was also seen angiographically as a hypervascular mass of 7.5 x 7.0 x 5.5 cm (fig. 1),
are
[1 8-20]. may
of insuliand their
manuscript.
7.
one
arteries;
ACKNOWLEDGMENT
arteriogram of the somatostatinoma 1 ) is the first in the literature. Of the two cases,
are
is seen
seen
tumors
vasodilator,
Two
These
and
obtained
been
glucagon-secreting
Path-
insulin
has
tumors
shunting
tolerance.
decreased
these
tumors.
of the pancreatic tumor showed it to be Although the clinical presentations of these patients are dissimilar, all three patients were found to have abnormal glucose-tolerance curves. In one case, steatorrhea and achlorhydria were present [1 2, 1 3]. Our patient and one of the two previously reported [1 3] had flushings and diarrhea. In the other two reported cases the blood
feeding
are similar to those have been 5-10 cm,
in these
is a potent
ologic examination a somatostatinoma.
peripheral
shunting
neovascularity
of
she died.
tortuous
angiographic appearances differ from those and gastrinomas only in that neovascularity
localized to the head of was found. Postoperarapidly
enlarged,
angiographic characteristics nomas [16-18]. VlPomas
of abdominal pains and a followed 4 years later by
1 0 years
include:
early, fine reticular network of normal appearing arteries; a dense, well defined capillary stain persisting up to 20 sec; and no vascular shunting, encased vessels, or neovasculature [1 5, 1 8]. Gastrinomas have been 2.5-1 0 cm, and their
tachycardia, and possibly flushing. Urinary 5acetic acid and vanillylmandelic acid values Abnormal laboratory tests confirmed hypo-
During cholecystectomy, the pancreas with liver tively,
other
characteristics
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pp AGE,
Grimelius
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Christensen
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Cliffs, N.J.,
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OP,
YC,
Ebeid
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1979
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GC,
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Chance
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TJ,
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H,
Ann
Casarella
of the
WDHA
clinical
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Aadiologic
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1976
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GHA,
Barraclough
MA:
Angiographic
dem-
onstration of a pancreatic ‘ ‘vipoma’ ‘ in the WDHA syndrome. AJR 127:1037-1039, 1976 20. Shenoy 55: VIPoma of body of pancreas with hepatic metastases. Semin Roentgenol 1 3 : 301 -302, 1978 21 . McGavran MH, Unger RH, Recant L, Polk HC, Kilo C, Levin ME: A glucagon secreting alpha cell carcinoma of the pancreas. NEnglJMed 274:1408-1413, 1966 22. Ingemansson 5, Lunderqvist A, HoIst J: Selective catheterization
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vein
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of the
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pancreas.
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