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 patient’s 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. It’s 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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O’Donnel 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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