hepatoma associated with anabolic steroid therapy - AJR

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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.

I I.

of

1973,

I.

2.

3.

J. E., and

12.

G. S. Diagnosis of hepatoma using multiple radionuclide approach. Radiology, 1972, 102, 387-389. BERNSTEIN, M. S., HUNTER, R. L., and YACHNIN, S. Hepatoma and peliosis hepatis developing in patient with Fanconi’s anemia. New England 7. Med., 1971, 281, ‘35-’ 136. BIELER, E. U., MEYER, B. J., and JANSEN, C. R. Liver scanning as method for detecting primary liver cancer. AM. J. ROENTGENOL., RAD. THERAPY & NUCLEAR MED., 1972, 115, 709ANDERSON,

5.

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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8.

M. and

J. T., RICHMOND, J., and SUMERD. Androgenic-anabolic steroid therhepatocellular carcinoma. Lancet,

and VALDES with andro7. Pediat.,

SCHULTZ, F. R., P. B. T. Hepatic adenoma in Fanconi anemia treated with oxymethalone. To be published. MUROFF, L. R., and JOHNSON, P. M. Use of multiple radionuclide imaging to differentiate focal intrahepatic lesion. AM. J. ROENTGENOL., RAD. THERAPY & NUCLEAR MED., 1974, 121,

R. L.,

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