Kitakanto Med J

2004 ; 54 : 147-151

147

Giant Cell-Rich Osteosarcoma Simulating

Giant Cell Tumor of Bone

Tetsuya Shinozaki,1 Toshio Fukuda,2 Hideomi Watanabe,1

and Kenji Takagishi1

A seventeen-year-old boy was referred to our hospital, complaining of continuous pain of his left wrist

joint. Plain roentgenogram showed an osteolytic lesion at the distal end of the radius. An operation

in which the tumor was curetted was performed suspecting giant cell tumor. Pathological diagnosis was

of a giant cell tumor. One month after the operation, radiological findings showed local recurrence with

an expanded lysis. Wide resection of this tumor followed by a vascularized fibular graft was performed.

Six months after the second operation, soft part swelling suggesting local recurrence was again prominent.

Upper arm amputation was performed because of the bad local condition. The pathological diagnosis

of these operative specimens was of giant cell tumor similar to that of the initial specimen. Multiple

metastases appeared eight months after the third operation. In spite of intensive treatment, the patient

died of respiratory failure. Autopsy revealed that pathological features from metastatic specimens were

similar to those of osteosarcoma, not giant cell tumor. When we encounter patients presenting with a

giant cell tumor, especially when they are younger than the age at which such lesions usually occur, we

should bear in mind the possibility of an osteosarcoma and perform intensive chemotherapy and surgery.

(Kitakanto Med J 2004 ; 54 : 147•`151)

Key words : giant cell tumor, osteosarcoma, autopsy, clinical diagnosis, surgical treatment

Introduction

Giant cell tumor of bone comprises a characteristic

mixture of varying numbers of multinucleated giant

cells dispersed in mononuclear stromal cells.L2 Its

pathological features are utilized to assess clinical

behavior.' However, the prognostic significance of

histological grading remains controversial.4•`6 More-

over, local aggressiveness on clinical or radiological

grounds cannot be correlated with any specific find-

ings.4,6 Metastases are rare events : pulmonary metas-

tases have been reported in less than 5 % of patients

with conventional giant cell tumor of bone.5•`8 It is

sometimes stressful for clinicians to decide how to treat

giant cell tumor of bone.

Giant cell-rich osteosarcoma is a rare tumor

subtype accounting for only 1 - 2 % of all osteosar-

comas.9,10 Incorrect histological diagnosis as a giant

cell tumor may be made because of similarities between

these tumors. Clinical information including the

prognosis and optical treatment is limited.10 This report describes a case of rare giant cell-rich osteosar-coma with an aggressive clinical course and rapidly

fatal outcome.

Case Report

A seventeen-year-old boy was referred to our hospi-tal on August 1991 complaining of continuous pain of his left wrist joint. He had initially noted the pain in

May 1991 while playing volleyball. On physical

examination, his wrist joint showed severe swelling with local heat and tenderness ; the range of motion of

his left wrist joint was slightly limited. Laboratory data showed only a slightly elevated serum alkaline

phosphatase activity. Plain roentgenogram showed an osteolytic lesion at the distal end of the radius (Fig. 1). Arteriography demonstrated hypervascularity at

that area. An operation by which the tumor was

1 Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine 2 Department of Laboratory Sciences

& Pathology, Gunma University School of Health Sciences

Received : December 12, 2003

Address : TETSUYA SHINOZAKI Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22

Showa Maebashi, Gunma, 371-8511 JAPAN

148 Giant Cell-Rich Osteosarcomas

curetted was performed in August 1991. Investiga-

tions of other lesions, such as bone or extraskeletal metastases, were not performed at that time because

giant cell tumor was suspected because of clinical and radiological findings. Pathological diagnosis was

indeed of a giant cell tumor with spindle-shaped or ovoid-shaped stromal cells, a few mitotic figures and

osteoclastic type giant cells (Fig. 2). In September 1991, radiological findings of his left wrist joint showed local recurrence with an expanded lysis and

loss of the sclerotic margin (Fig. 3). Wide resection of

this tumor followed by a vascularized fibular graft with fusion of the left wrist joint was performed in

October 1991. Pathological findings were similar to those at the time of the initial operation. However, in April 1992, soft part swelling suggesting local recur-rence was again prominent (Fig. 4). We consulted

pathologists to confirm that pathological findings were truly compatible with those of giant cell tumor because

this local recurrence was unexpectedly early. They unanimously replied that thesefindings were compat-

ible with those of giant cell tumor, not those of osteosarcoma. Because of deterioration in the clinical

findings, we started chemotherapy using pirarubicin, ifosfamide and carboplatin ; despite that treatment, local swelling worsened with severe pain. Upper arm

amputation was performed in September 1992 because of the bad local condition. Pathological findings

were similar to those of the previous two operations. In December 1992, the patient complained of low back

pain. Plain roentgenography showed a compression fracture of the third lumbar vertebral body. Chest

roentgenography also showed pulmonary metastasis at that time. In June 1993, the patient became unable to walk because of spinal cord palsy below the level of

Fig. 1 Plain roentgenogram of the left distal radius at the time

of presentation in August 1991. The arrow indicates the

osteolytic lesion.

Fig. 2 Operative specimen, taken in August 1991, showing

spindle-shaped or ovoid-shaped stromal cells with a few

mitotic figures and osteoclastic type giant cells (HE, •~

50).

Fig. 3 Plain roentgenogram showing local recurrence with

expanded lytic lesion and loss of the sclerotic margin

(arrow) in September 1991.

149

the tenth thoracic spine. Radiation therapy, total 50

Gy, was administered to the lumbar spine in June 1993.

In October 1993, 99mTc-DMSA scintigraphy" showed

increased uptake at skull, sternum, cervical spine, thor-

acic spine, lumbar spine, and pelvis. Chemotherapy

using high-dose methotrexate, cisplatin and ifosfamide

was continued ; little effect was obtained. The

patient died in January 1995 of respiratory failure. At autopsy, metastases were found in the bilateral upper

pulmonary lobes and posterior thoracic walls, thoracic and lumbar spines, sacral bone, lumbar spinal cord,

and skull. Metastases of the lung and posterior pul-

monary walls included hemorrhagic foci and ossifica-

tions. The metastases comprised multinucleated giant

cells interspersed with spindle-shaped stromal cells

showing a compact or striform pattern with a few

mitoses. Little atypism of the stromal cells differed

from that of the operative specimens. However,

tumorous osteoid formation was prominent compared

with that of the operative specimens, especially in

pulmonary and thoracic wall metastases (Fig. 5). They also showed a telangiectatic and hemangio-

pericytoma-like pattern. Considering these findings from the autopsy specimens, the final pathological diagnosis was giant cell-rich osteosarcoma.

Discussion

Osteosarcomas are composed of heterogeneous cell

populations including giant cells.12 Whereas reports

of giant cell-rich types are fewa) because of histological

similarity, it is often difficult to differentiate from

benign or malignant GCT.9 Radiological findings

including tumor location and histological characteris-

tics such as anaplasia of stromal cells and osteoid

formation can assist in making a definite diagnosis.9

However, clinical features are important to make the

correct diagnosis.

In our case, the radiological finding presenting an

osteolytic lesion that was typical of a giant cell tumor.

As we mentioned above, recurrence was noted only a

couple of months after initial surgical treatment

because curettage was performed alone.1,2 Expecting

local control, we tried wide resection with reconstruc-

tion of the wrist using a vascularized fibular autograft.

However, several months after the second surgery,

roentgenography showed soft part swelling suggesting

local recurrence again. Locally aggressive disease and

multiple recurrences appear to be risk factors for

pulmonary metastases in benign giant cell tumor of bone.7 Further, local recurrence and the primary

lesion at the distal radius seem to be associated with an

increased risk of lung metastases.13 Patients of a giant

cell tumor with lung metastases had favorable progno-

sis independent on the type of treatment used7,8,13

because spontaneous regression was reported.8,13,14

However, we initiated chemotherapy using pirarubicin,

ifosfamide, and carboplatin because we suspected that

this aggressive radiological finding might show a

Fig. 4 Plain roentgenogram showing prominent soft part swell-

ing (arrow) in July 1992.

Fig. 5 Autopsy specimen, taken from the right thorax in Janu-

ary 1995, showing spindle-shaped stromal cells with a few

mitotic figures and osteoclastic type giant cells. Tumor-

ous osteoid formation was prominent (HE, •~ 75).

150 Giant Cell-Rich Osteosarcomas

malignant bone tumor such as osteosarcoma. How-

ever, when we consulted pathologists about pathologi-

cal features of operation specimens, they replied consis-

tently that the features were characteristic of a conven-

tional giant cell tumor, not osteosarcoma or malignant

giant cell tumor. In spite of the intensive chemother-apy and radiation therapy, the patient died of progres-

sive metastases. Autopsy revealed that pathological

features from the metastatic lesions showing tumorous

osteoid formation were similar to those of osteosar-

coma, not giant cell tumor. Malignant transforma-

tion of giant cell tumor is less likely because the

malignant transformation of the formerly conventional

lesion should take many years without prior history

such as local irradiation. It is rare to find patients

younger than age 20 with malignant transformation.5 Differential diagnosis between giant cell-rich osteosar-

coma and benign and malignant giant cell tumor is

controversial even though histological findings such as

tumor osteoid formation and anaplasia of the

osteoclast-like giant cells were reported to be impor-

tant for the diagnosis of osteosarcoma.5,9 Malignant

giant cell tumor never produces tumor osteoid, bone,

or cartilage in the manner that an osteosarcoma does.

Bizarre giant cell forms are found with osteosarcoma,

but the anaplastic nuclei are usually multilobulated,

unlike the multinucleated osteoclast-like giant cells

that characterize malignant giant cell tumors.5 Clini-

cal features of the tumor location such as metaphyseal

or diaphyseal centering and the existence of radiogra-

phic Codman's triangle, intralesional fluffs, cortical ballooning, and faint onion-skin-like periosteal reac-

tion also aid osteosarcoma diagnosis.5,9,10 Malignant

giant cell tumor usually occurs in patients of advanced age, i.e., over 60 years, whereas most conventional

giant cell tumors occur in patients of 20-50 years old.5 This case reports a seventeen-year-old patient. The

tumor located in the epimetaphysis to epiphysis.

Cortical ballooning was seen radiographically,

although small Codman's triangle and intralesional

fluffs were apparent. Tumor osseous tissue produc-

tion could be seen in metastatic lesions. Radiation-

induced sarcomatous change can be excluded because

of the short duration after radiation therapy15 and

occurrence out of the irradiated areas. Based on these

findings, the final diagnosis was a giant-cell-rich

osteosarcoma.

Clinical features of the case provide clues to differ-

entiating giant cell-rich osteosarcoma from the giant

cell tumor of bone, a relatively common neoplasm

occurring in the epiphyseal regions of patients of 20-40

years.2,16 When we meet patients presenting with

giant cell tumor in terms of radiological and his-

tological findings, especially when they are younger

than the age at which giant cell tumor usually occurs,

we should bear in mind giant cell-rich osteosarcoma

and perform intensive chemotherapy and surgery.

Acknowledgments

We are grateful to Drs. Yokoo Hideaki, First

Department of Pathology, Gunma University Faculty

of Medicine, and Rikuo Machinami, Department of

Pathology, Kawakita General Hospital for their valu-

able discussions regarding pathological diagnosis.

We thank Professor Kenneth P.H. Pritzker, Depart-

ment of Pathology and Laboratory Medicine, Univer-

sity of Toronto, for his valuable suggestions. We also

thank Mr. Kiichi Osawa for his technical assistance in

making the figures.

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