Angiography
of Multiple
Asynchronously The
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MURALI
SUNDARAM,’
SOMNUK
APUD
SRIVISAL,2
Manifest Concept
DAPHNE
The APUD (amine precursor uptake and decarboxylation) concept [1] is a currently favored explanation for multiple primary pheochromocytoma. We discuss the relevance of this concept and report the angiographic demonstration of at least a dozen discrete tumors in a girl who was first seen with an extraadrenal pheochromocytoma. Two of the metastases showed angiographic appearances indistinguishable from the primary tumors.
Pheochromocytomas:
DE MELLO,3
histologically
AND
consistent
RICHARD
with
K. DANIS4
pheochromocytoma.
Lymph
nodes showed no tumor. The patient was discharged 1 week after surgery only to be readmitted 9 months later (2 years after initial
Total
presentation).
creased
(over 3,000
catecholamines
.g/24
were
greatly
in-
hr) and VMA was correspondingly
elevated. Chest radiograph revealed no abnormalities. Midstream aortography showed persistence of tumors in the thorax (fig. 3A) and additional tumors adjacent to the left
external abdominal,
iliac artery
and aortic
and
tumors
pelvic
bifurcation were
(fig. 3B). Thoracic,
surgically
removed
and
13
specimens Case A 12-year-old
Caucasian
submitted for histology. Seven primary pheochromocytomas and three nodal metastasis were identified (fig. 4). One metastasis was at the aortic bifurcation: the other two were
Report
girl
had a 1 year
history
of exces-
in the left iliac
sive sweating, flushing, and frontal headaches. She was of average height and weight and of normal intelligence. Physical examination revealed a blood pressure of 140/110 mm/Hg and evidence of papilbedema on the right side. A chest radiograph and intravenous urogram showed no abnormality. The major biochemical abnormality was elevated total catecholamines on two consecutive occasions: 3,000 and 2,630 tg/24 hr (normal, less than 230). On a repeat test, total catecholamines consisted of
32%
noradrenaline
and
68%
adrenaline.
with
invasion
Her blood pressure total catecholamines Chest radiographs
before
and
after
surgery
of the renal
was
The
only
radiographic
abnormality
blood
pressure
before
mm/Hg.
followed 2’/2 years since readmitted for medical
initial
presen-
investigation.
remains at approximately 130/70 mm/Hg, are 681 g/24 hr and VMA is 4.6 mg/24 hr. remain clear. Angiography has not been
vein.
Discussion
Apart from being the greatest number of pheochromocytomas angiographically demonstrated, this case illustrates the relevance of the APUD concept. The second aortogram (fig. 1) 1 year after removal of the primary tumor suggested recurrence at the site of the initial tumor, although no other tumors were seen. No tumor tissue was detected in the material surgically removed at that time. The subsequent angiogram a few months later showed multiple tumors (fig. 2) in the thorax and abdomen. It seems likely that several of these tumors were present and functioning at the time of the
The
110/60
mm/Hg.
earlier
was
several
areas
accepted after revision February St. Louis University Hospital,
The
of
17, 1978. 1325 South
angiogram
but
were
too
small
to be detected.
Of the 13 specimens available for histology, three were lymph nodes containing tumor. Angiographically, at least two of these were identical to the other tumors (fig. 3B). The remainder were consistent with primary pheochromocytoma. Considering that the first tumor discovered 2 years previously had invaded the renal vein without evidence of peripheral spread, it is unlikely that hematogenous metastatic disease could have selectively confined its passage to the sympathetic chain and pelvis. Therefore, the tumors within lymph nodes were presumably the result of local extension of disease, and the nonnodal tumors were probably primary pheochromo-
tumor blush on aortography (fig. 2). No tumors were seen in the pelvis or adjacent to the distal aorta. Three tumor masses were excised from the right paravertebral area from about Dl 1 to Li. Several lymph nodes were removed from the level of the diaphragm to the right kidney. The retroperitoneal masses were
Received August 30, 1977; I Department of Radiology,
130/90
repeated.
patient was discharged shortly after surgery. Three months later, the patient was readmitted when total catecholamines rose, fluctuating between 700 and 2,900 zg/24 hr.
The patient’s
Vanilbylmandelic
patient was discharged 1 week after surgery. After remaining well for 12 months, she was admitted for reinvestigation when total catecholamines were found to be elevated. The only symptoms were night sweats; chest radiographs and intravenous urogram were normal. Midstream aortography suggested possible recurrence of the tumor at the original site. No other tumors were seen in the abdomen and pelvis (fig. 1). At surgery the left adrenal gland and some mesenteric and paraaortic lymph nodes were removed. Histologically, neither a primary pheochromocytoma nor metastasis was identified. The patient’s total catecholamine level did decrease, however, from 870 .tg to 400 g. Blood pressure
nodes.
was about
The patient has been tation and was recently
acid (VMA) was 112 mg/24 hr. Aortography demonstrated a left extraad renal pheoch romocytoma just below and medial to the left renal hilus. At surgery a 6 x 10 cm tumor was found invading the renal vein, necessitating removal of the left kidney. Histology confirmed the tumor to be a pheochromocytoma
lymph
and after surgery
Grand
Boulevard,
St.
Louis,
Missouri
63104.
Address
reprint
requests
to M.
Sundaram.
2 Department of 3
Department
Radiology, of Radiology,
4
Department
of Surgery,
Am J Roentgenol
i30:ii68-lilO,
© 1978 American
Roentgen
St. Mary’s Hospital, St. Louis, Missouri 63117. Cardinal Glennon Memorial Hospital for Children, St. Louis, Missouri 63104. Glennon Memorial Hospital for Children, St. Louis, Missouri 63104.
Cardinal
June i978
Ray Society
1168
0361-803X/78/0600-1
168 $02.00
Downloaded from www.ajronline.org by 41.161.66.14 on 11/05/15 from IP address 41.161.66.14. Copyright ARRS. For personal use only; all rights reserved
CASE
1169
REPORTS
..,:‘,.I
!#;,&. (‘.
.
I_
f
-.,
.i
Fig. of
1 -Midstream
aortogram
12 months
after
removal
first pheochromocytoma.
recurrence
cytomas
No tumors to right of aorta; on left (arrowhead).
suspected
consistent
with
the
APUD
concept
[1].
The
Fig. 2.-Subtraction gram 16 months after
aortodensely staining discrete tumor masses (arrowheads). Three tumors above level of hepatic artery were removed and histologically found to be consistent with pheochromocytoma.
acronym APUD refers to cells of neuroectodermal origin that display amine precursor uptake and decarboxylation characteristics. omas. A recent ectopic APUD
Tumors of the publication
hormones cells are
occasionally why APUDomas
hormonally (of which
the
clinical
has
behaving
believe
wider
as recognition
a
A further unanticipated may be an
extension
has
practical
of
the
of the
on
a
concept, more
to
this In
for
4].
there
have
We espe-
ectopically
children, tumors
potential
be
a case
group. a review
of
multiple occurred
100
cases
for
of
tumors were sequentially
and sequentially
centricity
all
to
tumors
seen
angiography
clinical
appearing
tumors
more
often
judiciously
employed
is that
an
were
metastatic
or
tween
primary
would
suggest
prior belong
pheochromocytoma
present in 32%. as in our case
in children
pheochromocytoma
the
pressor
appropriate
during angiography of the APUD series
concept
of
elaborate
biochemical tests to be undertaken of any unknown tumor that might
a phenomenon Clearly
Since
the
may
evaluation and to angiography
growing
[3,
maldevelopment.
erable value in the follow-up and management patients. The fact that two of the tumors graphically on either side of the left external
APUD
hypertensive crisis indication of a tumor
amines,
and could
has described an abnormal pressor
APUD reveal
crest series
interest
pheochromocytoma
cially by angiographers, would located functioning tumors.
neural APUD
tumors
which
some
and explain are but
locations concept
of such
concept,
One of us (M. Sundaram) paranganglioma containing
amines
APUDand
tumors. migratory,
found in ectopic hormones. This
This
also
are called APUDomas
active. These features pheochromocytomas
multiplicity
basis.
bearing,
radiologists. intravagal
be
occasional
nonmetastatic
type lists
produced by these said to be totipotential,
one tumor type) may produce inappropriate explain
cell [2]
film of thoracoabdominal first surgery. Note multiple
that
the and
in In 5% the [5]. Multi-
seem
to be
than
adults.
is of
consid-
of these seen angioiliac artery
distinction local
metastases
be-
CASE
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1170
Fig.
3.-Midstream
aortograms
REPORTS
20
months after initial surgery.A, Tumors (arrowheads) in thorax and abdomen and two discrete tumors at 17. B, Two additional tumors adjacent to left cxternab iliac artery. Histologically these represent metastatic pheochromocytoma. Tumor mass to left of aorta at its bifurcation be primary tasis.
was shown tumor and
at surgery to nodal metas-
#{149}c,;, , ,. ,.. , ‘
‘
C;
f
‘
.
,i’...”.’
.
!
“s’3
,
‘..:
‘
.‘
“
1.
if,
:...
of Multiple
Asynchronously The
Downloaded from www.ajronline.org by 41.161.66.14 on 11/05/15 from IP address 41.161.66.14. Copyright ARRS. For personal use only; all rights reserved
MURALI
SUNDARAM,’
SOMNUK
APUD
SRIVISAL,2
Manifest Concept
DAPHNE
The APUD (amine precursor uptake and decarboxylation) concept [1] is a currently favored explanation for multiple primary pheochromocytoma. We discuss the relevance of this concept and report the angiographic demonstration of at least a dozen discrete tumors in a girl who was first seen with an extraadrenal pheochromocytoma. Two of the metastases showed angiographic appearances indistinguishable from the primary tumors.
Pheochromocytomas:
DE MELLO,3
histologically
AND
consistent
RICHARD
with
K. DANIS4
pheochromocytoma.
Lymph
nodes showed no tumor. The patient was discharged 1 week after surgery only to be readmitted 9 months later (2 years after initial
Total
presentation).
creased
(over 3,000
catecholamines
.g/24
were
greatly
in-
hr) and VMA was correspondingly
elevated. Chest radiograph revealed no abnormalities. Midstream aortography showed persistence of tumors in the thorax (fig. 3A) and additional tumors adjacent to the left
external abdominal,
iliac artery
and aortic
and
tumors
pelvic
bifurcation were
(fig. 3B). Thoracic,
surgically
removed
and
13
specimens Case A 12-year-old
Caucasian
submitted for histology. Seven primary pheochromocytomas and three nodal metastasis were identified (fig. 4). One metastasis was at the aortic bifurcation: the other two were
Report
girl
had a 1 year
history
of exces-
in the left iliac
sive sweating, flushing, and frontal headaches. She was of average height and weight and of normal intelligence. Physical examination revealed a blood pressure of 140/110 mm/Hg and evidence of papilbedema on the right side. A chest radiograph and intravenous urogram showed no abnormality. The major biochemical abnormality was elevated total catecholamines on two consecutive occasions: 3,000 and 2,630 tg/24 hr (normal, less than 230). On a repeat test, total catecholamines consisted of
32%
noradrenaline
and
68%
adrenaline.
with
invasion
Her blood pressure total catecholamines Chest radiographs
before
and
after
surgery
of the renal
was
The
only
radiographic
abnormality
blood
pressure
before
mm/Hg.
followed 2’/2 years since readmitted for medical
initial
presen-
investigation.
remains at approximately 130/70 mm/Hg, are 681 g/24 hr and VMA is 4.6 mg/24 hr. remain clear. Angiography has not been
vein.
Discussion
Apart from being the greatest number of pheochromocytomas angiographically demonstrated, this case illustrates the relevance of the APUD concept. The second aortogram (fig. 1) 1 year after removal of the primary tumor suggested recurrence at the site of the initial tumor, although no other tumors were seen. No tumor tissue was detected in the material surgically removed at that time. The subsequent angiogram a few months later showed multiple tumors (fig. 2) in the thorax and abdomen. It seems likely that several of these tumors were present and functioning at the time of the
The
110/60
mm/Hg.
earlier
was
several
areas
accepted after revision February St. Louis University Hospital,
The
of
17, 1978. 1325 South
angiogram
but
were
too
small
to be detected.
Of the 13 specimens available for histology, three were lymph nodes containing tumor. Angiographically, at least two of these were identical to the other tumors (fig. 3B). The remainder were consistent with primary pheochromocytoma. Considering that the first tumor discovered 2 years previously had invaded the renal vein without evidence of peripheral spread, it is unlikely that hematogenous metastatic disease could have selectively confined its passage to the sympathetic chain and pelvis. Therefore, the tumors within lymph nodes were presumably the result of local extension of disease, and the nonnodal tumors were probably primary pheochromo-
tumor blush on aortography (fig. 2). No tumors were seen in the pelvis or adjacent to the distal aorta. Three tumor masses were excised from the right paravertebral area from about Dl 1 to Li. Several lymph nodes were removed from the level of the diaphragm to the right kidney. The retroperitoneal masses were
Received August 30, 1977; I Department of Radiology,
130/90
repeated.
patient was discharged shortly after surgery. Three months later, the patient was readmitted when total catecholamines rose, fluctuating between 700 and 2,900 zg/24 hr.
The patient’s
Vanilbylmandelic
patient was discharged 1 week after surgery. After remaining well for 12 months, she was admitted for reinvestigation when total catecholamines were found to be elevated. The only symptoms were night sweats; chest radiographs and intravenous urogram were normal. Midstream aortography suggested possible recurrence of the tumor at the original site. No other tumors were seen in the abdomen and pelvis (fig. 1). At surgery the left adrenal gland and some mesenteric and paraaortic lymph nodes were removed. Histologically, neither a primary pheochromocytoma nor metastasis was identified. The patient’s total catecholamine level did decrease, however, from 870 .tg to 400 g. Blood pressure
nodes.
was about
The patient has been tation and was recently
acid (VMA) was 112 mg/24 hr. Aortography demonstrated a left extraad renal pheoch romocytoma just below and medial to the left renal hilus. At surgery a 6 x 10 cm tumor was found invading the renal vein, necessitating removal of the left kidney. Histology confirmed the tumor to be a pheochromocytoma
lymph
and after surgery
Grand
Boulevard,
St.
Louis,
Missouri
63104.
Address
reprint
requests
to M.
Sundaram.
2 Department of 3
Department
Radiology, of Radiology,
4
Department
of Surgery,
Am J Roentgenol
i30:ii68-lilO,
© 1978 American
Roentgen
St. Mary’s Hospital, St. Louis, Missouri 63117. Cardinal Glennon Memorial Hospital for Children, St. Louis, Missouri 63104. Glennon Memorial Hospital for Children, St. Louis, Missouri 63104.
Cardinal
June i978
Ray Society
1168
0361-803X/78/0600-1
168 $02.00
Downloaded from www.ajronline.org by 41.161.66.14 on 11/05/15 from IP address 41.161.66.14. Copyright ARRS. For personal use only; all rights reserved
CASE
1169
REPORTS
..,:‘,.I
!#;,&. (‘.
.
I_
f
-.,
.i
Fig. of
1 -Midstream
aortogram
12 months
after
removal
first pheochromocytoma.
recurrence
cytomas
No tumors to right of aorta; on left (arrowhead).
suspected
consistent
with
the
APUD
concept
[1].
The
Fig. 2.-Subtraction gram 16 months after
aortodensely staining discrete tumor masses (arrowheads). Three tumors above level of hepatic artery were removed and histologically found to be consistent with pheochromocytoma.
acronym APUD refers to cells of neuroectodermal origin that display amine precursor uptake and decarboxylation characteristics. omas. A recent ectopic APUD
Tumors of the publication
hormones cells are
occasionally why APUDomas
hormonally (of which
the
clinical
has
behaving
believe
wider
as recognition
a
A further unanticipated may be an
extension
has
practical
of
the
of the
on
a
concept, more
to
this In
for
4].
there
have
We espe-
ectopically
children, tumors
potential
be
a case
group. a review
of
multiple occurred
100
cases
for
of
tumors were sequentially
and sequentially
centricity
all
to
tumors
seen
angiography
clinical
appearing
tumors
more
often
judiciously
employed
is that
an
were
metastatic
or
tween
primary
would
suggest
prior belong
pheochromocytoma
present in 32%. as in our case
in children
pheochromocytoma
the
pressor
appropriate
during angiography of the APUD series
concept
of
elaborate
biochemical tests to be undertaken of any unknown tumor that might
a phenomenon Clearly
Since
the
may
evaluation and to angiography
growing
[3,
maldevelopment.
erable value in the follow-up and management patients. The fact that two of the tumors graphically on either side of the left external
APUD
hypertensive crisis indication of a tumor
amines,
and could
has described an abnormal pressor
APUD reveal
crest series
interest
pheochromocytoma
cially by angiographers, would located functioning tumors.
neural APUD
tumors
which
some
and explain are but
locations concept
of such
concept,
One of us (M. Sundaram) paranganglioma containing
amines
APUDand
tumors. migratory,
found in ectopic hormones. This
This
also
are called APUDomas
active. These features pheochromocytomas
multiplicity
basis.
bearing,
radiologists. intravagal
be
occasional
nonmetastatic
type lists
produced by these said to be totipotential,
one tumor type) may produce inappropriate explain
cell [2]
film of thoracoabdominal first surgery. Note multiple
that
the and
in In 5% the [5]. Multi-
seem
to be
than
adults.
is of
consid-
of these seen angioiliac artery
distinction local
metastases
be-
CASE
Downloaded from www.ajronline.org by 41.161.66.14 on 11/05/15 from IP address 41.161.66.14. Copyright ARRS. For personal use only; all rights reserved
1170
Fig.
3.-Midstream
aortograms
REPORTS
20
months after initial surgery.A, Tumors (arrowheads) in thorax and abdomen and two discrete tumors at 17. B, Two additional tumors adjacent to left cxternab iliac artery. Histologically these represent metastatic pheochromocytoma. Tumor mass to left of aorta at its bifurcation be primary tasis.
was shown tumor and
at surgery to nodal metas-
#{149}c,;, , ,. ,.. , ‘
‘
C;
f
‘
.
,i’...”.’
.
!
“s’3
,
‘..:
‘
.‘
“
1.
if,
:...
