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GIANT CELL TUMOR OF DISTAL RADIUS

CASE SUMMARY

Mr. J is a 33 years old Malay man, who complained right wrist swelling for 5 months
duration. He had a history injury to his wrist 6 month ago which occurred while he
washing dining plates and he twisted his right wrist. He then had pain of the wrist and
associated with swelling. The pain is worst during night time and partially relieved with
analgesia. He went for traditional massage but the pain and swelling worsened. He had no
fever, numbness or weakness of right upper extremities. He denied any other trauma
incidence before. He had no loss of appetite of weight or loss of weight prior to that. He
also had no family history of similar problem. He went to Malacca general hospital and
was referred here for further management. On clinical examination revealed young
healthy man and vital signs were stable. On the right wrist showed diffuse swelling which
firm to hard in consistency. There were no signs of inflammation but the skin was slightly
warm. There was no sinus discharge and the range of motion of the wrist was limited.
The distal extremities sensation and muscle power was intact. Radial and ulna pulse was
palpable and equal. Plain radiograph of right radius and ulna including the wrist joint
showed diffuse radiolucent lesion at the metaphyseal and epiphyseal region of distal
radius. The cortex is thinning but no signs of calcification. Other part of bone looks
normal. Chest radiograph did not reveal any abnormalities. The provisional diagnosis was
giant cell tumor of distal radius.

Case was discussed with visiting hand surgeon which suggested wide local excision
fusion of wrist joint with vascularized fibula graft. However the consultant in charge had
decided for tricortical iliac bone graft and fusion. He was planned for wide local excision
biopsy and iliac tricortical bone graft reconstruction and radiocarpal joint fusion on 6th
February. The findings intraoperatively were a ballooning tumor at distal left radius
measuring 6 x 4 cm. The cortex thin and area perforated during excision at the dorsal
area. Cartilage at radiocarpal joint not bleached. However the extensor tendon and
abductor pollicis longus and flexor pollicis brevis tendon bound down to the bone with
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the tumor mass. The approach is from volar aspect where dissection directs down to
quadratus muscle which is partially cut and tumor is dissected from the surrounding
tissue.radiocarpal joint opened and distal radioulnar joint incised. Radius bone excised at
7.5cm from the distal end. Tricortical bone was taken from iliac crest and shaped to fit as
distal radius defect. Cartilage of lunate and scapoid excised and bone graft inserted.
Plating incorporating the bone graft and radicarpal joint done.

Postoperatively was uneventful and he was discharged well five days later. He was
reviewed two weeks later which revealed clean surgical wound and no signs of infection.
The histopathology examination of the specimen showed consistent with giant cell tumor.
On latest review of the patient did not show any signs of graft or implant failure.

INTRODUCTION

Giant cell tumor of bone is a benign bone tumor but an aggressive, locally recurrence and
low grade neoplastic lesion with low metastatic potential. It account for almost 18% of all
benign bone tumor and 9% of all primary bone tumor. Giant cell sarcoma of bone refers
to a de novo, malignant giant cell tumor and not to the tumor that arise from the
transformation of benign cell tumor.

CLINICAL FEATURES AND DIAGNOSIS

Most of giant cell tumor occurs after the epiphyseal plate has closed. Therefore it arise
more often in girls who are less than seventeen years old than in boys of same age.
However most of the patients age range from 15 to 40 years old. The most common
location is distal femur followed by the proximal tibia and distal radius.

True malignant of giant cell tumor are rare and most of these are secondary malignancies
arising from a benign giant cell tumor that was irradiated previously or had multiple
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recurrences. Each recurrence increases the risk of malignant transformation. A recurrence

after 5 years is extremely suspicious for a malignancy. Primary malignant of giant cell
tumor generally has a better prognosis than secondary malignant transformation of
typical giant cell tumor especially if it occurs after radiation.

Most of the patients complain of pain around the adjacent affected joint and may be
preceded with a history of trauma. Campanacci et al (1986) reported pain is the majority
presenting symptoms in 293 patients who had giant cell tumor (50%). Presenting pain
maybe insidious as the tumor grows or can be sudden onset due to pathological fracture.
Diffuse slow growing swelling of adjacent joint is another common complain and
clinically it is tender and hard but have no signs of inflammation. Systemic complaints
are unusual but patients with involvement of spine or sacrum may have neurological
signs and symptoms.

Giant cell tumor of bone has characteristic features on plain radiographic. This includes
eccentric radiolucent lesion without matrix production, with a narrow zone of transition.
Most of the location is at the metaphyseal with a juxtaepiphyseal component and most of
the time the cortex appeared involved. The margin is contras from other benign tumor
lesion which is lack of a complete sclerotic rim. If this tumor escapes the boundaries of
the cortex, a soft tissue mass may be present. The lesion also may extend to and involve
within 1 cm of the subchondral bone. Magnetic resonance imaging is the most useful
technique for determining the extent of tumor within the bone or soft tissue mass, the
subchondral penetration, joint involvement and to stage of a local giant cell tumor. The
typical appearance of MRI of giant cell tumor of bone is low to intermediate signal on
T1 weighted images and an intermediate to high heterogeneous signal intensity on
the T2 weighted images. Computered tomography scan is quite helpful in detecting
thinning of the bone and evaluating an associated thin rim of bone surrounding the lesion.
It is not effective in evaluating subchondral cortical penetration or joint involvement.

Grossly the tumor appears brownish-tan to yellow color and may have hemorrhagic spot
with cystic component. Histological it contains predominantly osteoclast like giant cells
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and spindle shaped stromal cells. This giant cell never shows mitotic figures and it is not
possible to predict the biological behavior of a particular tumor on the basis of its
histological appearance.

Campannaci et al (1986) has developed a specific staging system for this tumor that was
base on a combination of clinical, radiographic and pathological findings:
1. Grade 1: a well marinated border of a thin rim of mature bone and the cortex was
intact or slightly deformed. It has latent radiographic findings and has a benign
histological pattern. However it almost always causes symptoms.
2. Grade 2: has a relative well defined margins but no radiopaque rim, the
combined cortex and rim of reactive bone was rather thin and moderately
expanded but still present. It may cause symptoms and has an active radiographic
appearance and still benign histological pattern.
3. Grade 3: a tumor with a well extended borders which suggesting a rapid and
possible permeative growth, these represent aggressive radiographic findings. The
tumor bulged into the soft tissue but the mass did not follow the contour of the
bone and was not limited by an apparent shell of reactive bone.

It exhibits a wide variety of biological activity. Some of this lesion are benign, remain
local and non invasive and do not metastasize while other are extremely destructive
locally or metastasize to the lungs though rare. This lesion usually has benign histological
features similar to its primary lesion and has a favorable prognosis when treated with
pulmonary resection of the nodules. Campanacci et al (1986) reported lung metastases
occur in 1- 2 % of patients reviewed by him. Bertoni et al (1985) reviewed seven cases
of giant cell tumor with proven metastases to lung. He found all seven had a stage 3
aggressive , benign lesion with interruption of the cortex and soft tissue extension. The
main histological features of the primary lesion were identical to those of the pulmonary
lesion. This shows grade 3 diseases are at risk of developing metastases. All patients
received chemotherapy followed with surgical resection of the nodules. However
complete resections of multiple nodules are technically difficult due to anatomical
location especially at the hilar region. The out come was favorable even in patients
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MANAGEMENT

Basically the treatment of giant cell tumor of bone is surgical removal. Traditionally it
was treated with curettage or intraregional resection and with bone grafting but this
resulting a very high rate of local recurrence ranging from 30% to 60%. Campanacci et
al (1987) reported the rate of local recurrence was 27% in the 151 intralesional
procedures, 8% in the 122 marginal excision and none in 58 case who underwent wide or
radical procedures. With this figure some surgeons opted to another alternative of
management which is more extensive involving enbloc resection which mainly removing
the involved joint and followed with reconstruction with either vascularized or no
vascularized bone grafting.

However Blackley et al (1999) has different opinion. He reviewed retrospectively 59

patients with giant cell tumor of long bone from 1986-1996 who were managed with
extensive curettage with a high speed burr and reconstructing the defect with autogenous
bone graft with or without allograft. The results showed only seven (12%) had a local
recurrence within three years after operation. This figure is much lower than as reported
by Campanacci (1986) who noted that thirty eight (29%) of 130 tumors recurred and is
comparable to that observed after use of cement and other adjuvant treatment. Blackely
et al (1999) concluded that the risk of recurrence is not only related to adjuvant treatment
but also how much and the adequacy of the removal of the tumor. He attribute this
relative low rate of recurrence to improvement to the extensive use of a high speed burr
as well as the availability of allograft bone which allows the surgeon to resects involved
bone extensively without concerned for how to fill the defect. He also noted an increase
in number of patients referred to his unit with recurrence of giant cell tumor after use of
cement, with or without chemical adjuvants.

SURGICAL CURETTAGE

Despite the incidence of recurrence an intralesional or curettage is still a method of

choice for removal of most giant cell tumors of the bone. A modification of technique in
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curettage and additional few procedures has been introduced in order to achieve adequate
removal of tumor. Simple curettage usually leaves residual microscopic evidence of
disease. The use of some local modalities (phenol, liquid nitrogen or
polymethylmethacrylate) found help to kill these residual microscopic. Many reported
literatures had advocated techniques of this extensive curettage:
1. Wide decortications or windowing of all bone overlying the area of tumor to
visualized the entire area in need of curettage properly.
2. Gross tumor is removed with large curette and preferable to cover the soft
tissue with sponges to prevent contamination.
3. The bone cavity is thoroughly washed using a power pulse lavage.
4. A high speed burr is then used to remove a layer of cancellous bone and
cortical bone as well.
5. The cavity is lavaged repeatedly after each burring session and the process of
burring and water lavage should be repeated few times till nothing should be
visible except normal cortical and medullary bone.

ADJUVANT THERAPY

After this procedure, the next step can be followed with use of adjuvant agent. However
to some surgeons the roles of these agent in lessening the recurrence rate of giant cell
tumor is not clear. The additional adjuvant treatment of the giant cell tumor of the bone
with liquid nitrogen or phenol has been advocated to reduce the risk of local recurrence
when cement used alone. It extends the margin of a simple curettage or resection
curettage and makes it biologically equivalent to wide resection. Compared with other
techniques, cryosurgery with composite fixation not only preserves joint function but also
decrease the rate of local recurrence. There are five mechanisms involved in the
cytotoxicity produced by liquid nitrogen. These include thermal shock, electrolyte
changes, formation of intracellular ice crystals and membrane disruption, denaturation of
cellular protein and microvascular failure. Liquid nitrogen results in effective
osteonecrosis about 1 to two centimeters. However because the depth of the osteonecrosis
induced by nitrogen is difficult to control, there is a high risk of fracture. The adjacent
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soft tissue and skin may be exposed to liquid nitrogen and cause skin injury with wound
healing problem and temporary neuropraxia. Malawer et al (1999) reviewed 102
patients with giant cell tumor ( including newly diagnosed and local recurrence) who
were treated with thorough curettage of tumor, burr drilling of the tumor and cryotherapy
by direct pour technique using liquid nitrogen and followed with reconstruction either
with bone cement or bone grafting with or without internal fixation. He found local
recurrence among 86 patients
With no prior treatment was only 2.3% (two) and six (37.5%) from 16 patients who
treated for local recurrence. Postoperative fractures occur in six patients (5.9%) who had
no internal fixation. The author therefore recommended the use of internal fixation in all
patients with giant cell tumor who are undergoing cryosurgery. The incidence of skin
necrosis can be reduced with wide exposure and adequate mobilization of skin flaps and
adjacent neurovascular bundle, along with continuous irrigation of tissues with warm.

Phenol was noted to be safer than liquid nitrogen for adjuvant therapy. Its mechanism of
Action includes causes protein coagulation, damages DNA and causes necrosis. The main
Advantage of this solution is that its penetration reduced to one and half millimeters of
bone injury only. This enhance reduce rate of fracture. Its use alone without cement after
removal of giant cell tumors has been less effective than phenol used with cement.

FILLING MATERIAL

Bone graft with autograft or allograft has been the traditional standard for filling the
defect after curettage of benign bone tumor. There has been an evolution of treatment of
giant cell tumor with the use of polymethylmethacrylate (PMMA) as a filling defect.
Though autograft has the biologic advantages of osteoinduction and eventual
incorporation to produce a better long term biologic construct, PMMA has become the
preferred material.

The disadvantage of using bone graft , including the donor site morbidity, the risk of
disease transmission from allograft bone , limited supply of graft to fill the large cavities ,
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delay of return to full function to allow sufficient time for graft incorporation and
difficulty of visualizing recurrence within the bone graft during radiological follow up.
The cavities that have been filled with bone graft often contain both static and
progressive radiolucent areas, due to incomplete packing, inflammatory changes,
resorption of graft or a low grade infection. These changes can be difficult to distinguish
roentenographically from recurrent tumor. The technique of cementation varies from
essentially pouring PMMA in a liquid state into the cavity to packing the cement while it
is doughy. The prophylactic use of internal fixation incorporated in the cement is not
needed in most patients.

The use of PMMA has allowed a much faster return to function especially when used in
large cavities near weightbearing joints. It is readily available, inrelatively inexpensive
easy application. It had been suggested that free radicals and the thermal effect of the
polymerization reaction that cause about two to three mm of necrosis in cancellous
region. The reported advantage of using bone cement includes low cost, ease use, lack of
donor site morbidity, eliminating the risk of transmission of disease with allograft,
immediate structural stability and easier for earlier detection of local recurrence.
However the long term effect related to the use of cement including difficulty associated
with the removal of acrylic material in case of local recurrence or fracture and the risk of
long term of osteoarthritis when cement is placed in near to particular cartilage especially
at subchondral region. However it has been shown, the incidence of degenerative joint
changes is actually related to the proximity of the cavity to the articular cartilage.
Malawer et al (1999) noted when the distance of the tumor from the articular cartilage is
less than 1cm; the incidence of degenerative changes was 2.5 times greater than when the
distance was greater than 1 cm. Though articular degeneration occur in patient managed
with bone grafting but the incidence is relatively low if compared with the use of bone
cement. Campanacci et al (1986) advocated the use of subchondral bone graft which
acts as a thick bony interface between the bone cement and the articular cartilage.
Vander et al (1993) who treat five cases of giant cell tumor of distal radius with
extended curettage and bone cement, found no incidence of premature degenerative
arthritis or any adverse effect of the joint after 9 years of follow up.
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ODonnel et al (1994), found the incidence of recurrence in sixty patients who had had a
giant cell tumor of a long bone after being treated with curettage and packing with
polymethylmethacrylate cement was 16%. However he also noted seven (17%) of forty
one patients who had had treatment with burr or phenol or both had recurrence. There
few factors have been identified that might predispose to recurrence. These include site:
distal radius (50%), proximal tibia (28%), distal femur (13%), fracture: three patients
who had initial pathological fracture, noted to have recurrence, grading: none of grade 1
tumor had recurrence while 23% of grade 2 and 30% of grade 3 tumor had local
recurrence. Highest rate of recurrence was in the patients whom the procedure did not
include use of burr or phenol.

Recurrence of giant cell tumor after curettage and cementing is easier to detect. Therefore
most surgeon do not remove the PMMA and if local recurrence occurred, curettage of
only the area involved is performed without removal of the original cement bolus.
Additional cement is then used to fill the void. Remedies et al (1994) who reviewed 13
postoperative radiology of 11 patients with giant cell tumor using curettage and
polymethylmethacrylate during follow up found the most specific radiological signs were
lysis of 5mm or more at the cement-bone interface. Recurrence must be suspected when
this lucent rim around the cementoma are visualized at any point on either of the two
standard projections. This preceded clinical signs by a mean of four months and
identified at a mean of 3.75 months after operation. Therefore Remedies had advocated
for frequent follow up with plain radiograph for one year after operation irrespective of
clinical signs of recurrence. Whenever the appearance suggests recurrence, Magnetic
Resonance Imaging (MRI) should be performed and followed by image-guided needle
biopsy. MRI also will distinguish recurrent tumor from local osteoporosis resulting from
altered stresses since the latter did not result in signal changes around the cementoma.
Production of sclerotic rim was initially thought as signs of recurrence however it is
probably a normal host response to physical and thermal damage during cementing.
Presence of this is not significant and does not need further radiological review.
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When deciding a treatment protocol for giant cell tumor, surgeon must decide few things
in making decision. This includes whether to perform an intralesion or enbloc resection,
whether to use adjuvant therapy to eradicate residual microscopic disease, and what
material to use to fill the resultant defect in the bone. Gitelis et al (1993) reviewed the
results for forty consecutive patients with giant cell tumor of bone in extremity between
1976 till 1990 who been managed with enbloc resection in twenty and an intralesional
excision of tumor with adjunctive local insertion of methylmethacrylate or phenol in
twenty patients. He found both procedures were an excellent and equal effective. There
was only one recurrence reported with intralesional excision group after three to nine
years. No recurrence reported in enbloc resection group. However there are fewer
complication and better functional outcome after intralesional procedures. A total of 13
complications occurred in enbloc resection group which included articular degeneration
of an osteoarticular graft that necessitated prosthetic arthroplasty, infection and loosening
implant, peroneal and ulnar nerve palsy and limb length discrepancy. All twenty patients
who had intralesional procedure had a functional score of more than 25 points and ten
had perfect scores (30) whereas only four patients who had an enbloc resection had
perfect score. Gitellis et al (1993) concluded that for expandable bone such as fibula and
distal radius are preferably treated with en bloc resection

GIANT CELL TUMOR OF DISTAL RADIUS

Giant cell tumor of the distal radius is particularly aggressive and has a high rate of local
recurrence. As the lesion grows, the dorsal and palmar cortices are expanded and the shell
is permeated by the tumor. Though cortical breakthrough is common, the tumor usually is
contained by the periosteal covering dorsally and pronator quadratus volarly.
Occasionally it breakthrough into radiocarpal and radioulnar joint. The goal of treatment
is to remove the tumor, lessen the chance of recurrence and preserve the function of the
joint.
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In the distal part of the radius, the curettage and bone grafting has been associated with a
high rate of recurrence. The surgical option for this region is mainly depend to few
factors. As based on Campanacci grading system, grade 1 and 2 tumor are amenable for
extended curettage combined with cryosurgery and packing with bone cement or bone
graft. However for grade 3 tumor the choice is still open. Cheng et al (2001) and Vander
et al (1993) found for grade 3 tumor of distal radius, extended curettage and adjuvant
therapy still can be used if:
1. Tumor is intraosseous and with minimal cortical perforation.
2. Does not involve intraarticular joint
3. Single and not multiple defect.
4. Involvement of less than 50% of the circumference of the bone.
5. Absence of extraosseous mass.

Cheng et al (2001) reviewed retrospectively 12 patients with grade 3 giant cell tumor of
distal radius which half of them were treated extended intraregional curettage and
adjuvant therapy another half underwent enbloc resection with reconstruction. He found
no local recurrence of both group during average follow up of 6 years.
If the lesion does not fulfill above criteria, enbloc resection with reconstruction is the
only option. The procedures that have been used for reconstruction include resection
arthroplasty, prosthetic replacement, and arthrodesis with use of massive autogenous graft
from tibia or iliac crest, ulnar translocation, use of non vascularized or vascularized
fibular graft with or without arthrodesis and allograft replacement. Primary arthrodesis
with use of iliac crest or the tibia to bridge the defect to provide a stable wrist. Is
preferred by some surgeons as it avoids complications of residual volar subluxation of the
carpus. Some motion of the wrist might remain after this procedure since the midcarpal
joint is preserve by achieved union between the graft and the proximal carpal row.
However overall this have resulted with very limited motion which may concerned the
patients which majority are young and have previous active normal life. It also associated
with fairly high rates of fracture of the graft and donor site morbidity and delayed union.
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The nonvascularized graft has reported satisfactory result though the average time for
union takes up to 6 months. The revasculaization of this graft is inadequate and may lead
to radiographic changes thight might suggest long term results might unpredictable.
However Vander et al (1993) who reconstruct distal radius after resection of giant cell
tumor with arthrodesis incorporating either a nonvascularized fibular graft or a graft from
distal part of ulna that was fixed with a single plate from carpus to remaining radius,
found the results are successful. He advocated none vascularized is much favor for distal
radius for little reason:
1. vascularized graft is less important in this area due to relative short length of graft
(less than nine centimeters)
2. the ability to cover at least part of the graft with extensor pollicis or extensor carpi
ulnaris muscle
3. use of stable plate fixation that protect the graft while undergoes revascularization

Ihara et al (1999) has reported the use of surgical arthroplasty after enbloc resection
giant cell tumor of distal radius. A proximal vascularized fibula graft with fibula head
as an articular surface has been used in a 35 years old lady who had painful swelling of
right wrist which eventually was diagnosed as giant cell tumor. The result was promising
as the time for union to complete 3 months postoperative and the reconstructed joint was
maintained radiographically and functionally more than 10 years after surgery.
Functionally range of motion was 40 degree supination, 30 degree pronation and 40
degree extension. She able to hold 2kg of weight with the wrist and the grip strength at 20
kg was 65% of that normal side. This procedure though technically demanding but it
achieves a mobile and stable joint and much superior than arthrodesis.

Kocher et al (1998) had advocated the use of an osteoarticular allograft for

reconstruction after resection of distal radius due to giant cell tumor. This especially
when there is extensive local disease, poor residual bone stock and recurrent disease. This
procedure have few theoretical advantages, including preservation of wrist function,
restoration of anatomy, ability to repair due to lot of allograft supply, avoidance donor-
site morbidity that can associated with autogenous bone graft. He reviewed 24 patients
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who had reconstruction of distal radius with use of osteoarticular allograft after excision
of giant cell tumor between 1972 and 1992. He found there was low rate of recurrence
(one patient) but a moderately high rate of revision (18 patients) with majority due to
fracture and volar dislocation. There were good function of hand with common daily
activities though nine reported to have limitation of performing strenuous activities. The
range of motion was moderate.

Pulmonary metastases are one of well known complication of benign giant cell tumor
though rare. This lesion usually has benign histological features similar to its primary
lesion and has a favorable prognosis when treated with pulmonary resection of the
nodules. Bertoni et al (1985) reviewed seven cases of giant cell tumor with proven
metastases to lung. He found all seven had a stage 3 aggressive, benign lesion with
interruption of the cortex and soft tissue extension. The main histological features of the
primary lesion were identical to those of the pulmonary lesion. This shows grade 3
diseases are at risk of developing metastases. All patients received chemotherapy
followed with surgical resection of the nodules. However complete resection of multiple
nodules is technically difficult due to anatomical location especially at the hilar region.
The out come was favorable even in patients

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