A thirty-six-year-old man came to us with a two-month history
of pain and swelling in the right knee. The patient had been taking
ibuprofen to relieve the pain, which initially had been a mild, constant
ache involving both the knee and the distal part of the anterior
aspect of the thigh. The pain was exacerbated by activity. The patient
also noticed mild swelling in the anterior aspect of the thigh.
The pain worsened acutely two weeks prior to presentation, when
the patient landed on the right leg while playing basketball. Since
that time, the pain had begun to awaken him at night and had not
been relieved by over-the-counter medications.
During the same two-month period, the patient had a firm, painless
lump in the left axillary region; the lump had increased slightly
in size. He also reported that swelling had been present in the
popliteal region of the contralateral knee for approximately two
years. He reported no fevers, chills, or night sweats and had noted
no decrease in energy level or appetite.
Upon referral to his local orthopaedic surgeon, the patient was
evaluated with radiographs of the right knee, a magnetic resonance
imaging study of the right knee, and a total-body bone scan. The
left axillary mass was evaluated with an incisional biopsy in the
office.
The medical history was unremarkable. A review of the family
history revealed that the patient's brother had undergone excision
of three benign cysts from the axillary region, leading the patient to
believe that his own axillary lesion was also a benign cyst.
On physical examination, the distal part of the right thigh was
slightly swollen and warm but was nonerythematous and minimally
tender. The circumference of the right thigh was approximately one
centimeter larger than that of the left thigh in the immediate suprapatellar
region but tapered back to normal at a point approximately ten centimeters
proximal to the superior pole of the patella. The swelling of the
distal part of the right thigh was most noticeable anteriorly and
laterally and appeared to be associated with a mass in the femoral
metaphysis. The active range of motion of the right knee was from
full extension to 140 degrees of flexion. No instability or effusion
in the knee was found. The left knee was normal except for a posteromedial
cystic swelling, two centimeters in diameter, that was consistent
with a Baker cyst. Just distal to the left axilla, in line with
the anterior axillary fold, a fresh transverse three-centimeter scar
was seen directly over a subcutaneous soft-tissue mass. The mass
was firm and slightly warm, and it measured three centimeters in
diameter. Examination of the skin and the lymph nodes did not reveal
any caf笡u-lait spots or adenopathy. Neurovascular examination
of both the upper and the lower extremities revealed no abnormalities.
Radiographs showed a sclerotic lesion in the right distal femoral
metaphysis (Fig. 1-A and Fig. 1-B). Magnetic resonance images showed
that the lesion extended to the soft tissues anteriorly and laterally
and into the epiphysis distally (Fig. 2). A technetium-99m bone scan showed
increased uptake in the right distal femoral metaphysis as well
as in the soft tissue of the left lateral part of the chest wall,
just distal to the axilla (Fig. 3). Magnetic resonance images of
the chest wall, made after the biopsy, showed a heterogeneous mass
(Fig. 4-A and Fig. 4-B). Subsequent
radiographs and computerized tomographic scans of the chest revealed
normal findings except for the subcutaneous mass in the left part
of the chest wall. There was no evidence of mineralization of the
mass in the chest wall on any study. A magnetic resonance image
of the left knee showed only a small Baker cyst.
A core-needle biopsy of the mass in the distal part of the right
femur was performed. Both the soft-tissue lesion of the left part
of the chest wall, which had previously undergone a biopsy, and
the le-sion in the distal part of the right femur showed the typical
histological features of high-grade (grade III of IV) osteosarcoma
(Fig. 5-A and Fig. 5-B). The neoplastic
cells were osteoblast-like, spindle-shaped, or highly pleomorphic.
The osteoblast-like cells exhibited an increased nuclear-to-cytoplasmic
ratio as well as eccentric and hyperchromatic nuclei with prominent
nucleoli. Mitotic figures with atypical forms were seen frequently.
Lace-like osteoid associated with malignant cells was present, representing
tumoral matrix pro-duction. Small scattered foci of chondroid differentiation
(composed of atypical chondrocytes with chondroid matrix) and fibroblastic differentiation
(composed of highly atypical spindle cells) were also identified
in both specimens. No associated lymphoid tissue that would otherwise
suggest lymph-node involvement was evident in the soft-tissue lesion
of the chest wall.
The patient received neoadjuvant multiagent chemotherapy, including
two cycles of ifosfamide (3.5 grams per square meter of skin for
five days), mesna, and etoposide (100 milligrams per square meter
of skin for five days), followed by one cycle of high-dose methotrexate
for two consecutive weeks and then by cisplatin and Adriamycin (doxorubicin)
on an outpatient basis. Following the first cycle of chemotherapy, Staphylococcus
aureus cellulitis developed around the incision in the
left part of the chest wall and around the Infuse-a-port (Horizon
Medical Products, Manchester, Georgia) (an indwelling venous catheter
with a subcutaneous access port). Following a ten-day course of
intravenous administration of vancomycin, the soft-tissue mass in
the chest wall, which had become more swollen with the associated
infection, decreased to a size of three by two centimeters. The mass
continued to shrink for the remainder of this course of chemotherapy
(Fig. 6-A and Fig. 6-B).
Fourteen weeks after the diagnosis was made, the patient underwent
a wide intra-articular resection of the mass in the distal part
of the right femur and a wide resection of the mass in the chest
wall, both of which resulted in negative margins. The distal part
of the femur was reconstructed with a prosthesis. The chest-wall
wound was closed primarily. Histological examination of the two
specimens showed 99 percent necrosis of the tumor at both sites.
The patient completed chemotherapy according to the Pediatric
Oncology Group protocol (number 9450). He remained disease-free
until twenty-four months after the resection (twenty-eight months after
the diagnosis), at which time he was found to have metastatic pulmonary
disease. Four months later, he was alive with disease and was receiving salvage
chemotherapy.
The case of our patient, who had metastasis of osteosarcoma to
soft tissue at the time of the initial diagnosis of the primary
lesion, appears to be unique in the literature. While it has been
estimated that as many as 80 percent of patients with osteosarcoma
have circulating micrometastases at the time of presentation, only
20 percent have demonstrable metastases at the time of diagnosis
(no numbers reported)10. The most
frequent sites of clinically or radiographically identified metastasis
of osteosarcoma are the lungs and bones, in diminishing order of frequency10. Metastasis of osteosarcoma to other
sites rarely is seen in the absence of disseminated disease. However,
autopsy studies have revealed cases of metastasis to the regional
lymph nodes, kidney, liver, brain, skin, and heart10.
We are aware of two other reports in which a positive radionuclide
scan was used to diagnose soft-tissue metastasis in a patient with
osteosarcoma1,4. In 1974, Flowers
reported the case of a patient in whom a primary osteosarcoma metastasized
to the soft tissue of the proximal part of the left thigh in the
presence of pulmonary metastases4.
The soft-tissue metastasis was heavily mineralized, and a technetium-99m
bone scan showed moderate uptake. In 1990, Arrington et al. reported a
case in which metastases to the lungs, brain, and two soft-tissue
sites (the proximal part of the right arm and the left calf) were
diagnosed with use of a technetium-99m bone scan one year after
the patient had been managed with amputation and chemotherapy for
the treatment of osteosarcoma1.
The soft-tissue metastases were clinically unsuspected. Magnetic
resonance imaging of the calf confirmed the presence of an intramuscular
mass1. Tissue was not obtained
for confirmation in either report1,4.
The value of nuclear scintigraphy to localize soft-tissue metastases
of osteosarcoma was previously documented in a rat model11.
Soft-tissue osteosarcoma occurs much more often as a primary
lesion than as a metastatic lesion3.
Given the simultaneous presentation of the two lesions in our patient
and the equal duration of symptoms at each site, we considered the
possibility that the patient had a primary soft-tissue osteosarcoma
with bone metastasis to the distal part of the femur. However, we
considered the distal femoral bone lesion to be the primary site
because of its more typical location and its much larger size. The
soft-tissue nodule, which we believed to be a metastatic deposit,
was atypical of a primary soft-tissue osteosarcoma because of its
subcutaneous location and lack of characteristic peripheral mineralization3.
Other sarcomas that have been reported to metastasize to soft
tissue include chondrosarcoma, synovial sarcoma, and angiosarcoma2,5-7. The occurrence of soft-tissue
metastasis from any musculoskeletal sarcoma therefore appears to
be extremely rare. However, given the demonstrated plausibility
of its occurrence, metastasis should be considered during the evaluation
of any soft-tissue mass in a patient with primary sarcomatous disease.
Any such soft-tissue mass in a patient with known or suspected osteosarcoma
should be approached as potentially resectable disease.
The case of our patient is unique in that a solitary soft-tissue
metastasis was present at the time of diagnosis of the primary osteosarcoma,
there were no other sites of metastatic disease, and the soft-tissue
metastasis was confirmed on both magnetic resonance imaging and
histological studies. Very little in the way of treatment recommendations
can be drawn from this single case. However, the current case is
instructive in that the response to chemotherapy was similar at
both the metastatic soft-tissue site and the primary site. Although
our patient had metastatic disease at the two-year follow-up examination,
we favor standard neoadjuvant multiagent chemotherapy and wide surgical
resection of both the primary and the metastatic lesion when this
situation is encountered.
Note: The authors thank Brett Greenky, M.D., and Shehandrah Haghir,
M.D., for their contributions during the preparation of this manuscript.