Apr 19, 1974 - anabolic steroid. 2612. 13,19. In our patient with. Fanconi's anemia, who was treated with anabolic steroids for. 50 months and had multiple.
HEPATOMA ANABOLIC By LAWRENCE BEATRICE
C.
chromosomal
placed
on
(CH2III04) prematurely
remained
low.
red
cell
morphology
remained
abnormal
blood
macrocytes and blood cell survival
response,
profoundly
and
after
anemic.
In
2
months
blood
cell
cell
count
was
effect
of
bleeding.
only
6 blood
*
From
College
The
Radioisotope
The
Children’s
Laboratory, Medical
Cincinnati Center,
General
more
2
had
trials
the
in to that
first
May,
point
of
the
symptoms 1971, with
he had
received
transfusions.
was
first
Center,
pigmentation,
blood
seen
at Children’s
Cincinnati,
asymmetry and
toes,
no
small
testes. hematocrit count 3,100
cell
phils,
Ohio,
Hos-
in Sep-
per
52
per
cent
The
The
fetal
B12
level was 500 nanograms/ml.
The
Department Department
cent
and
hemoglobin
vitamin
and The
33 6 per
marrow
mild 12
cent
lymphocytes,
bone
was
megaloblastic
of Pediatrics, ofRadiology,
ears, a large
was 6.i and white per cent poly-
per
with
with was
defects,
hemoglobin 17
cellular
Hospital, Ohio
The
cent.
folate
of external radial
neutrophils,
monocytes.
The
Cincinnati,
with
gm. per cent,
ig/Ioo
Hospital
was
again.
1971. Physical examination revealed a boy, at the twenty-fifth percentile for height, normocephalic, normotensive, with mu!tiple bruises, petechiae, and patchy areas of
ml. The plasma erythropoietin was increased approximately 30 times normal. The intravenous pyelogram was normal. The karyotype was normal
Oncology,
oxymetholone
pancytopenic
short
morphonuclear
normal.
blood
ranged
tember,
sucrose lysis, and urine were negative, and urinary were
normal
white
platelets
the
He
Up
The patient pita! Medical
cent, the hemosiderin
i8c level
and
When seen
with
The
thrombocytopenia
gum
and
tryptophane
thiamin, pantothenic
normal
normal,
was
penis,
of
to
bomb.”
fingers
was
vitamin
pyridoxine, niacin,
he became
tinued,
short
iron
a “hematinic
morphology.
6o-Ioo,ooo.
skin
serum
given
returned
red from
again
was
marked poikilocytosis. time was significantly
contained
hemoglobin
August, 2, abor-
was
he
The
riboflavin, vitamin B i 2, acid, folate, ascorbate, vitamin C, and crude liver extract for 2 months, following which the
eva1-
metabolites
1969,
was
which
uated in Columbia, Missouri. He was pancytopenic. The bone marrow was normocellular, with scaht megakaryocytes and the M: E ratio was 3.8:!. The fetal hemoglobin was I I mg. per thrombin, tests
May,
He
bomb”
“vitamin
born in 5, para
within
hemoglobin
shortened.
tions 3 with a birth weight of pounds and 32 ounces. At to 5 years of age, he was anemic and in October, 1968, was diagnosed as having acquired hypoplastic anemia and was given prednisone and methandrostenolone (Dianabol) for 2 months. He experienced a good but transient
a reticulocytosis
his
with Red
CASE
was of a gravida
13
however,
No
T.C.S.
was
months and months;
oxymetholone
developed
discon
1963,
He
for
M.D., M.D.,
OHIO
without
1971, 10 cases of hepatocellular carcinoma have been reported in patients receiving long term androgenic or anabolic steroid 2612 13,19 In our patient with Fanconi’s anemia, who was treated with anabolic steroids for 50 months and had multiple blood transfusions, the possibility of hepatoma was recognized, and both static and dynamic scintigraphy of the liver was carried out. We are reporting this case in order to call attention to this association and to illustrate the sequential scintigraphic appearance of an avascular hepatoma superimposed upon hepatocellular disease.
A
fragmentation.
E. HOLDER, M.D.,t DAVID J. GNARRA, LAMPKIN, M.D., HIROSHI NISHIYAMA, and PATRICK PERKINS, M.D.
S INCE
OF
1975
ASSOCIATED WITH STEROID THERAPY*
CINCINNATI,
REPORT
AUGUST,
eosino-
per cent was 6. gm. 9
slightly
hypo-
changes. picograms/ml.
The The
ImmunoelectroDivision The
University
of Hematologyof Cincinnati,
of Medicine.
This investigation was supported by Training Grant TIGM Tos GM 01247-14 CAO 5196-07 from The National Cancer Institute, Grant RR-0o123 from the GCRC A. Fraser Memorial Grant from The American Cancer Society. t Current address: Union Memorial Hospital, Baltimore, Maryland.
638
from the NIGMS, branch of the NIH
NIH, Training Grant -Toi and Grant CI-8B, an Andrew
VOL.
Anabolic
No.
124,
Steroid
phoresis was normal, and acid hemolysis for paroxysmal nocturnal hemoglobinuria was negative. Chromosomal analysis showed breakage well above normal. Cells cultured from blood with phytohemagglutin had 24 per cent abnorma!
cells,
while
without
cultured
phytohemagglutin
abnormal cells
cells
cells.
showed
genetic
showed
The
majority
a deleted
to represent
a clone
findings
from
marrow per
i
of bone
D chromosome,
of abnormal
are
to
be
cent
marrow believed
cells.
reported
The
cyto-
moeba plasma
histolytica. complement
sociated the
antigen
test
that gram
bleeding
persisted
(Fig.
ryngeal melena,
hematoma, for which
continued
for
sions
every
to
2
transfusions.
In
3 weeks,
retropha-
hematoma, and blood transfu-
and
multiple platelet 1973 he became white blood cell
November,
profoundly neutropenic, with counts below i,ooo. In December,
veloped pain, gram was
cough,
fever,
and hepatomegaly. showed a right jaundiced with
Bacterial sputum
cultures were
I.
Tc’”
and anterior
upper
The middle elevated as
and
de-
quadrant
chest roentgenolobe infiltrate. He liver enzymes.
of blood,
negative,
for cytomegalovirus,
FIG.
right
he
1973,
stool, were
stool
urine
exam
urine,
and
in D.
to
He
study
scintiwas
in causing with methi-
remained
febrile
tender
was added, but the
liver.
and defect
clinically on the
A-D).
The
clindamycin
and
the
normal.
A
trial
each
liver
was
2
he scan
was size
of nandrolone
of o week
and
After
3 months,
3,
was
showed
the colloid Oxymetholone
of its role was treated
(Deca-Durabolin)
muscularly
dedeca-
milligrams
intra-
He conevery 2 to
attempted.
require blood transfusions and had continued elevation of bilirubin and liver enzymes. Repeat scintiscans continued to demonstrate the lesion (Fig. 3, E-H).
tinued 3 weeks
to
In May, progressive result At
cm.
sulfur colloid liver scan on December 39, 1973. (D) views with io cm. marker (io) demonstrate
radioactivity, increased density of splenic uptake, defect in the posterolateral part of the right lobe marked
creased noate
on 2).
but
weeks clindamycin gradually improved,
cultures
for Enta-
area
nega-
scintigram
dynamic
a large,
with
were
liver
(Fig.
gentamicin
serious
including
The cold
histoasand
radioimmunoassay,
colloid
discontinued because hepatic dysfunction.
and
skin test, test, hepatitis
examinations
the discrete was avascular
tachypneic,
esophageal he required
by
tive. A Tc9Sm sulfur obtained (Fig. I).
He was treated with prednisone and the anabolic steroids fluxoxymesterone (Halotestin) or oxymetholone (Adroyd). He continued to have problems
Tuberculin fixation
alpha-fetoprotein
cillin
elsewhere.
639
Therapy
spinal (arrow
1974
loss
he of
developed consciousness
of an intracerebral necropsy
was
found.
Anterior
an enlarged bone marrow in C). Xiphoid
headache
and
and
as a
died
hemorrhage.
a hepatic
It was
(A),
a
tumor
pale,
posterior
measuring
and
(B),
4 X3.5
histologic
right
lateral
sec-
(C),
liver with heterogeneous uptake of uptake of radiocolloid, and a focal (X) and costal margin (CM) are
Holder,
640
Gnarra,
Fic. 2. (A and B) Selected frames of dynamic flow study December shows
absent
slice of liver scintiphoto
vascular
(arrow
perfusion
in B) which
is confirmed
graphically
Lampkin,
(retrieved 2!, of
from
3973,
done
the focal
included (arrow
Nishiyama
magnetic in right
defect
the cold
Perkins
AUGUST,
1975
tape lateral
(arrow area.
and
and displayed digitally) from arterialp hase position with 5 mc of’I’c*m sulfur colloid in A). A count profile (C) was taken through a
The
decrease
in activity
seen visually
on the analog
in C).
tion showed a well differentiated hepatoma, devoid of any hemosiderin as was present in the other portions of the liver. There was no evidence of cirrhosis. DISCUSSION
The original liver and spleen scintigraphy was obtained not only to locate a possible abscess, but also because of the known association between long term anabolic steroid therapy and the development of hepatocellular carcinoma. The fact that our patient was febrile, had acute hepatitis, and may have had subclinical hepatitis previously, complicated our differential diagnosis. It is well known that fibrosis associated with cirrhosis, cysts, neoplasms, and abscesses can all become manifest as a cold area on sulfur colloid scintiphotos.” Recently, a cold intrahepatic focal lesion in acute viral hepatitis has been reported.9 Dynamic hepatic scintigraphy has been advocated to differentiate vascular from avascular processes. Hepatomas have been almost uniformly reported as vascu-
lar.”35”5’8 usually
This not
invaded,
is so because and,
arteries along
are the
with
tumor provide
vessels present in these neoplasms, the basis for the tumor’s visibility during the dynamic vascular study.’5 Dynamic scintigraphy should not be confused with blood pool imaging,’#{176} in which hepatomas often appear similar to normal liver tissue.’4 The initial static scintigram and dynamic study showed hepatocellular disease which was manifested by a diffusely enlarged heterogeneous liver, and by increased spleen and bone marrow uptake. The cold area present was dynamically avascular and
this
suggested
either
an
abscess
or
a
fibrotic pseudotumor (Fig. 2). Hepatoma was thought less likely. A 67 gallium or 75 selenomethionine study was not done. We perform liver scintigraphy with Tc99m sulfur colloid. The time required to obtain 300,000 counts, with the gamma camera positioned anteriorly over the liver to include the right lobe and as much of the left lobe as possible, is noted and used for all other views. We feel that this technique
VOL.
No.
324,
4
Anabolic
Fio. 3. January i8, 1974. Anterior (A), posterior lateral (D) views show decrease in liver and defect is present, but less well defined (arrow April 19, 1974. Anterior (E), right anterior (H) views demonstrate the lesion which has shown) the lesion continued to be avascular.
Steroid
64!
(B), anterior scintiscan with cm. marker (C), and right spleen size, but continued bone marrow activity. The focal in D). oblique (F), right posterior oblique (G), and right lateral become very well defined. On a repeat dynamic study (not
enables us to make a more accurate visual assessment of differences in relative liver and spleen uptakes of radiocolloid. At Children’s Hospital Medical Center, a high resolution collimator is used with the Ohio Nuclear Series 100 Radioisotope Camera. Dynamic scintiphotography is done utilizing the Series 100 camera coupled to an Ohio Nuclear Series I 50 Data System. One second frames are obtained for 6o seconds. Visual impressions are verified with area of interest and count profile determinations
(Fig.
Therapy
2).
Liver scintigrams in the other reported cases of anabolic steroid induced hepatomas included 2 with single filling defects, 2 with multiple defects, and i with a diffuse infiltrative process. Two patients did not have a liver scan done and 3 patients had normal liver scans. None of these patients had a dynamic hepatic study. Five of these 10 patients had Fanconi’s anemia, had idiopathic aplastic anemia and I was under
therapy
for impotence. CONCLUSION
Nuclear
radiologists
should
be
aware
of
the association between anabolic steroid therapy and hepatocellular carcinoma. Liver scintigraphy provides the prime mechanism for discovering focal lesions in patients whose other liver function studies are
often
abnormal
secondary
to
hepatitis,
induced hepatocellular toxicity. As this case illustrates, avascularity on the dynamic study cannot rule out hepatoma from the list of differential diagnostic possibilities. cirrhosis,
or
drug
SUMMARY
A patient with Fanconi’s anemia who developed a hepatoma after 50 months of therapy with anabolic steroids is reported. The lesion presented as a cold focal defect on a TcS9m sulfur colloid scintigram, but was avascular on dynamic scintigraphy. Both the unusual avascularity of the
Holder,
642
hepatoma, steroid
and
its association
therapy
are
E. Holder,
Lawrence
Radioisotope
Gnarra,
with
Lampkin,
Nishiyama velopment
anabolic
cet,
discussed.
9.
M.D.
Laboratory
Cincinnati
General
Cincinnati,
Ohio
10.
Hospital 45267
Cytogenetics
was
done
by
Dr.
S. Soukup.
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FREEMAN,
G. L.,
STADALNIK,
L. M., and MANDELL, C. H. Dynamic vascular scintiphotography of liver. Scm. Nuclear Med., 3972, 2, 133-138. 6. GUY, J. T., and AUSLANDER, M. 0. Androgenic steroids and hepatocellular carcinoma. Lancet, 1973,
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