Download Osteoblastic Osteogenic Sarcoma in a 35-month

Osteoblastic Osteogenic Sarcoma in a
35-month-old Girl
Report of a Case
G E N E P. S I E G A L , M.D.,
D A V I D C. D A H L I N , M.D.,
FRANKLIN H. SIM,
M.D.
Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Siegal, Gene P., Dahlin, David C., and Sim, Franklin H.: Osteoblastic
osteogenic sarcoma in a 35-month-old girl. Report of a case. Am J Clin
Pathol 63: 886-890, 1975. A girl, aged 2 years, 11 months, who had pain
and swelling of the proximal humerus, was found to have osteoblastic
osteogenic sarcoma of the humerus. Among 937 consecutive patients with
osteogenic sarcoma examined at the Mayo Clinic, she is the youngest child
seen, as well as only the sixth child younger than 6 years of age in this series.
(Key words: Osteosarcoma; Pediatric oncology; Neoplasm of bone; Osteogenic sarcoma; Cancer.)
O S T E O G E N I C SARCOMAS are extremely
rare in infants and children of preschool
age. At the Mayo Clinic from January
1905 through J u n e 1974, a total of 937
cases of osteogenic sarcomas was recorded. This total includes 63 cases with
the primary lesion located in either the
mandible or the maxilla and 34 cases with
the lesion classified as parosteal (juxtacortical) o s t e o s a r c o m a . Previously, the
youngest patient in the entire series was a
girl, aged 3 years, 11 months, with a
sarcoma of the proximal end of the
femur. Only four other cases of osteosarcoma in preschool-age children are to be
found in the records of the Mayo Clinic;
two of the tumors were in girls, aged 4!4
and 5 years, in both of whom the tumor
involved the distal right femur, and two
Received October 29, 1974; accepted for publication November 11, 1974.
Address reprint requests to Dr. Siegal, c/o Section
of Publications, Mayo Clinic, 200 First Street SW,
Rochester, MN 55901.
were in boys, also aged 4V2 and 5 years, in
whom the tumor involved the distal right
femur and the proximal right femur,
respectively.
In a large series reported from another
center, 11 the youngest patient among 552
with osteogenic sarcoma was 4 years old;
the median age of patients in the series
was 26 years. Other reports 15,16,18,20 have
given comparable age statistics.
We now report a case of osteogenic
sarcoma in a girl, aged 2 years, 11
months. She becomes the 937th in the
Mayo Clinic series. When she was first
seen at another hospital, the lesion was
thought to be either an infectious process
or Ewing's sarcoma. Osteogenic sarcoma
was not considered in the differential
diagnosis, ostensibly because of the patient's young age. We report this case to
emphasize that, though extremely rare,
osteogenic sarcoma does occur during the
first 5 years of life.
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June 1975
OSTEOGENIC SARCOMA IN A CHILD
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FIG. 1 (left). Predominantly sclerosing, destructive lesion of proximal end of left humeral diaphysis. Note
irregular destruction of cortex of most of shaft.
FIG. 2 (right). Gross features of partially ossified osteogenic sarcoma of left humerus with
greatest dimensions in proximal portion of humeral shaft.
Report of a Case
A Caucasian girl, aged 2 years, 11
months, was in her usual state of health
until she awoke one night complaining of
pain in the left shoulder and arm. There
was no associated fever or chill. On the
following morning, her father noticed
swelling and induration over the painful
area. Roentgenograms revealed a destructive lesion of the left proximal humeral
metaphysis with sclerosis and periosteal
reaction. She was referred to the Mayo
Clinic 4 days later.
T h e patient, the sixth child of a 37year-old woman, gravida 7, para 7, abortus 0, had been delivered at term as a
normal infant by forceps. She had had no
serious illness. There was no history of
trauma or injury to the left shoulder or
extremity. A review of the family history
revealed that one sister had died as a
premature neonate and that all her other
siblings were living and well. There was a
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SIEGAL, DAHLIN AND SIM
A.J.C.P.—Vol.63
FIG. 3. Microscopic appearance of sarcoma. Alt h o u g h it is p r e d o m i nantly "spindling" in this
area, note chondroid and
osteoid matrix production. Hematoxylin and
eosin. x250.
strong family history of malignancy of
tissues other than bone. There was also a
family history of diabetes mellitus, heart
disease, and mental retardation.
Results of system review were unremarkable. T h e patient's height was 94 cm.
(37 inches), and her weight was 14.25 kg.
(31.5 lb.); both height and weight were in
the 50th percentile for her age. The
temperature was 36.7 C. (98.2 F.), pulse
rate 88 per min., and blood pressure
98/72 mm Hg. T h e left upper arm was
swollen and tender; a large firm mass was
palpated in the proximal humerus. There
was no axillary or cervical adenopathy.
Results of routine blood counts and
urinalysis were within normal limits, as
were the calcium and phosphorus values.
T h e serum alkaline phosphatase concentration, however, was greatly increased, to
2,100 U. per 1. (normal, 87 to 250 U. per
1.). Roentgenograms revealed a malignant
neoplasm of the proximal metaphysis of
the left humerus (Fig. 1). A skeletal
survey yielded no evidence of metastasis.
Stereoscopic anteroposterior and lateral
chest roentgenograms and whole-lung
tomograms appeared normal. Frozen sec-
tions revealed high-grade osteogenic sarcoma, and the patient immediately underwent interscapulothoracic (forequarter) amputation.
Centered in the upper metaphysis of
the humerus was a grade 4 osteoblastic
osteogenic sarcoma, measuring 14 by 5 by
5 cm. It extended into the soft tissues
circumferentially to a maximum distance
of 2 cm. The tumor also extended into
the medullary canal and subperiosteal
areas as far as the distal end of the
humerus. Approximately one-third of the
upper epiphysis was filled with tumor
(Fig. 2). The lymph nodes and major
veins were not affected. Microscopically,
the tumor was an osteoblastic osteogenic
sarcoma (Fig. 3).
Recovery was uneventful. An adjunctive
chemotherapy program was started 3
weeks after operation; this consisted of
administration of vincristine, adriamycin,
and methotrexate (in high doses), with
citrovorum rescue.
Discussion
Bone cancer is a rare form of neoplasia.
T h e age-adjusted death rate for Ameri-
June 1975
OSTEOGENIC SARCOMA IN A CHILD
can white females is 0.7480/100,000
population 1 ; in other words, approximately 800 American females die each
year of bone cancer. 19 Osteogenic sarcomas constitute 20 to 60% of all bone
tumors and, with the possible exception of
myeloma, are the most common primary
malignant neoplasms of bone. They develop most commonly in bone that is growing rapidly (i.e., the metaphyseal region
of the long bones of the extremities). 5,13
This is one explanation of the high
incidence of osteogenic sarcoma in
adolescence—the pubertal growth spurt.
However, increased growth is also evident
in preschool children, and one would
therefore anticipate an even higher incidence in children of preschool age than is
actually reported.
The patient whose case we have described presented initially with the classic
symptoms and signs of osteogenic sarcoma, and the roentgenographic appearance was completely consistent with that
diagnosis. Despite these features, the
diagnosis might have been missed solely
because the patient was only 2 and not 12
years old. We are unable to confirm the
existence of the report of an osteogenic
sarcoma in a child of similar age or in a
younger child but, because many authors
have not specifically stated the ages of
their patients, the true frequency of osteogenic sarcomas in children of preschool age cannot be determined.
One of us (D.C.D.) has seen in consultation the slides of a 2-year-old girl with
sclerosing osteogenic sarcoma of the right
femur. In light of the sclerotic lesion
visualized roentgenographically and of
decreased abduction and external rotation of the right hip, this child was
followed by her home pediatrician for
more than a month because the diagnosis
of osteogenic sarcoma seemed impossible.
We are confident that other young children, similarly affected, do occasionally
present to the clinician. It is obviously
889
imperative that the clinician be alert to the
possibility of osteogenic sarcoma in children of this age group.
Because there are so few cases of
osteogenic sarcoma in children aged 5
years or younger, we have been unable to
gather a large enough series for statistical
analysis of 5-year survival and prognosis.
Overall, though, it appears that 5-year
survival is in the range of 20%2-4-7,8-10'14-21
and that age probably does not influence
prognosis. 9 Age, however, does appear to
affect the onset of pulmonary metastasis 10
in that the younger the patient, the more
rapid the onset of metastasis.
Associated diseases, especially other
malignant neoplasms and diabetes mellitus, have often been reported to occur in
families of patients with osteogenic
sarcoma. 5-6,12,17 Our patient's family included one paternal uncle who had died
from stomach cancer, one half-sister who
had had breast cancer with metastases to
the neck, and the patient's father who had
had skin cancer; additionally, one maternal aunt had died of brain cancer and her
maternal grandmother also had had
breast cancer. All family members died
elsewhere and, therefore, none of the
cancers could be confirmed histologically.
Whether there is some hidden environmental carcinogen or a genetic predisposition is at this point mere speculation.
T h e great importance of a team approach to the diagnosis and treatment of
the pediatric patient with bone disease
merits emphasis. T h e pathologist needs
the assistance of his clinical colleagues as
well as the radiologist in reaching the final
and correct diagnosis.
ADDENDUM
The patient did well for 14 weeks after her
initial amputation. During the fifteenth week,
roentgenograms of the chest showed changes
consistent with bilateral pulmonary metastases.
Exploration of the left chest and of the right
chest two weeks later demonstrated seven isolated lesions, involving all lobes. These lesions
890
SIEGAL, DAHLIN AND SIM
w e r e all successfully excised. T h e p a t i e n t was
c o n s i d e r e d to be free of metastatic disease a n d
was p l a c e d o n a t r a n s f e r factor p r o t o c o l .
T h r e e weeks later, a n t e r i o r a n d p o s t e r i o r chest
wall n o d u l e s , a left p l e u r a l effusion, a n d a
m e d i a s t i n a l mass w e r e f o u n d . T h i s was clinically
c o n s i s t e n t with r e c u r r e n t t u m o r from t h e
p r i m a r y o s t e o g e n i c s a r c o m a . T h e patient's
parents refused any further treatment, a n d the
p a t i e n t d i e d 193 d a y s after h e r initial d i a g n o sis. A u t o p s y was n o t p e r f o r m e d .
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