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Review article

GIANT-CELL TUMOUR OF BONE


M. Szendri
From Semmelweis University, Budapest, Hungary

Giant cell tumour (GCT) is still one of the most obscure and
intensively examined tumours of bone. Its histogenesis is
uncertain. The histology does not predict the clinical outcome; and there are still many unanswered questions with
regard to both its treatment and prognosis.
The World Health Organisation has classified GCT as
an aggressive, potentially malignant lesion,1 which means
that its evolution based on its histological features is unpredictable. Statistically, 80% of GCTs have a benign course,
with a local rate of recurrence of 20% to 50%. About 10%
undergo malignant transformation at recurrence and 1% to
4% give pulmonary metastases even in cases of benign histology.

Pathogenesis
GCT is a true neoplastic process originating from the undifferentiated mesenchymal cells of the bone marrow. Multinucleated giant cells and mononuclear stromal cells can be
distinguished by light microscopy. These giant cells are
derived from stromal cells, either by the fusion of mononuclear cells or, less probably, by amitotic division or
nuclear segmentation of the stromal cells without the corresponding cytoplasmic division.2 These multinucleated giant
cells resemble osteoclasts in their phenotype and function:
their size is approximately 60 m; their numerous nucleoli
are centrally located in the cytoplasm. They stain positive
for tartrate-resistant acid phosphatase and naphthyl alpha
esterase enzymes,3 and possess receptor sites for calcitonin,
a phenotypic marker for osteoclasts.
Further histochemical, immunohistochemical, cytogenetic, and molecular-genetic studies in cell cultures
derived from GCTs have confirmed that there are two differ-

ent cell lines within the mononuclear stromal cells. One


population consists of mononuclear round cells, which are
non-neoplastic and express monocyte-macrophage markers
(tartrate-sensitive acid phosphatase, naphthyl alpha esterase) and react with monoclonal antibodies to CD 13 and
CD 68 which suggests that these cells have a monocyticmacrophage origin.4-6
The second cell line which appears as mononuclear spindle-shaped (fibro-osteoblast-like) stromal cells is considered
to be responsible for the neoplastic character of the GCT. It
produces type-I and type-II collagens and alkaline phosphatase, has receptor sites for parathormone and proliferates
extensively. This cell line is genetically unstable, as has
been found in recent molecular genetic studies. It shows
chromosomal abnormalities, a higher incidence of expression of p53 protein and alterations in different oncogenes
(C-myc, C-fos, N-myc) which are also found in frankly
malignant osteosarcomas.7,8 These spindle-shaped stromal
cells secrete a variety of cytokines and differentiation factors (macrophage colony stimulating factor (M-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor alpha
(TNF-alpha)), which have chemotactic, differentiationinducing and activating effects on monocytes-macrophages
and are essential for the differentiation of osteoclasts.
These features support the hypothesis that the genetically
unstable spindle-shaped neoplastic mononuclear stromal
cells stimulate the immigration of blood monocytes into the
tumour tissue and promote the formation of the osteoclastlike giant cells. The characteristic cell types, the monocytes
and osteoclast-like giant cells, are therefore simply reactive
components of the GCT, while the spindle-shaped stromal
cells represent the neoplastic component of the tumour.4,9-11

Clinical appearance

M. Szendri, MD, Professor


Department of Orthopaedics, Semmelweis University, Budapest, Hungary.
Correspondence should be sent to Professor M. Szendri at H-1113 Budapest, Karolina t, Hungary.
2004 British Editorial Society of Bone and Joint Surgery
doi:10.1302/0301-620X.86B1.14053 $2.00
J Bone Joint Surg [Br] 2004;86-B:5-12.
VOL. 86-B, No. 1, JANUARY 2004

The typical clinical and pathological appearance of GCT


has been discussed in detail in various articles12-18 and
monographs.2,19-21 It represents 15% of benign and 3% to
8% of all bone tumours and is more common in China and
India where it constitutes approximately 20% of all bone
tumours.22 Nearly 50% of cases occur in the region of the
knee, but other frequent sites are the distal part of the radius,
the proximal humerus and fibula, and the pelvic bones. It is
usually situated in the epiphysis, grows eccentrically, and
5

M. SZENDRI

Table I. The rate of recurrence after different intralesional treatments of


primary GCT of bone (minimum follow-up 2 years)
Number
of patients Adjuvant treatment

Rate of local
recurrence
(%)

Goldenberg et al17
(multicentre)
Campanacci et al12
Capanna et al52
(multicentre)
Lausten et al85
Richardson and
Dickinson62
Blackley et al51
McDonald et al35
Capanna et al52
(multicentre)
Szendri29
Komiya and Inoue63
Gitelis et al46

120

None

43

128
490

None
None

30
45

None/radiotherapy
(Burr) none

56
0
12
34
17

ODonell et al49
Bini et al57
Malawar and Dunham59
Labs et al48

60
38
102
15

Burr, none
Burr, phenol, alcohol
PMMA,* phenol,
liquid nitrogen
Phenol, PMMA
Burr, PMMA
Burr, phenol, alcohol,
PMMA
PMMA/burr phenol
PMMA
(Burr)+liquid nitrogen
PMMA

Author/s

18
16
59
85
187
11
11
16

9
0
0
25
8
7.9
12

* polymethylmethacrylate
Fig. 1
Photograph showing the gross pathology of a GCT. The defect in the proximal tibia is filled by extensive soft fleshy tissue and the cortex is destroyed
(surface of transsected specimen).

may later also affect the metaphysis. A GCT starting from


the metaphysis has been described in skeletally immature
patients at an open growth plate.23 It appears most often in
the second to fourth decades of life (60% to 75% of all
cases) and the male:female ratio is 1:1.5.
The main clinical symptoms are non-specific, local
swelling, warmth, and pain radiating independently of
weight-bearing. Pathological fracture is the first sign in
approximately 15% of cases.24 The duration of symptoms
varies between two to six months and by then, in one-third
of cases, the size of the tumour exceeds 50% of the diameter
of the affected bone, it has destroyed the cortical bone and
reached the subchondral region.
GCT appears as a pure lytic cystic lesion, growing often
but not exclusively eccentrically in the epimetaphyseal
region of the bone. The affected part of the bone may be
expanded and the cortical bone thinned. In an advanced
stage, the GCT breaks through the cortex (Fig. 1), and there
is a lack of periosteal reaction with formation of spicules
around the tumour. According to the radiological classification of Lodwick, Wilson and Farrel,25 GCT belongs,
depending on its stage, to group IA to IB or IC. GCT is
commonly hypervascularised. With modern MRI, the need
for angiography has been reduced.
CT is useful in the evaluation of the cortical bone. The
density of GCT tissue as measured by CT is between 20 and
70 Housefield units. Below these values a cyst is more likely

those of an aneurysmal bone cyst as has been demonstrated


both by CT and MRI. The MR signs of GCT are a highsignal intensity in T2-weighted images, high contrast media
enhancement and signs referring to tissue haemorrhages.26
Dynamic contrast-enhanced MRI shows a characteristic
perfusion pattern with a steep slope and maximum intensity
value followed by an early and rapid washout phase.27
Tumours and tumour-like lesions containing giant cells
with a similar radiographic appearance such as juvenile solitary or aneurysmal bone cysts, chondroblastoma, chondromyxoid fibroma, giant-cell reparative granuloma, nonossifying fibroma, eosinophylic granuloma, high-grade central osteosarcoma should be considered in the differential
diagnosis.
There is a high rate of recurrence, especially after intralesional curettage (Table I), in most cases within the first 12
to 36 months,28,29 and rarely after five to six years. The first
symptoms of recurrence are pain and enhanced isotope
uptake by bone scanning.

Grading and staging systems for GCT


Based on the degree of histological appearance of the stromal cells and the number of giant cells and mitoses, Jaffe et
al,18 classified GCT as benign, aggressive and malignant.
Dahlin19 distinguished only benign and malignant forms of
GCT. The grade-3 malignant GCTs should be treated as
high-grade bone sarcomas otherwise the practical value of
grading is limited. The prediction of the clinical behaviour
of GCT based on its histological features is impossible.2,30
Enneking20 and Campanacci et al12 developed a similar
classification for GCT based on their clinical, radiographic
and histological features. Ennekings surgical stages 1, 2
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GIANT-CELL TUMOUR OF BONE

Fig. 2a

Fig. 2b

Radiographs showing a) a grade-2 active GCT of the tibia and b) within one year progression of the tumour from the
tibia to the head of the fibula.

and 3 represent the clinically latent, active and aggressive


forms of GCT. The radiographic grade-1 of Campanacci et
al12 represents a quiescent form, in which the cortical
involvement is minimal, if at all. Only 10% to 15% of GCTs
belong to this rare stage which can even be asymptomatic.
The most common active grade-2 lesions show extensive
cortical thinning and bulging. The aggressive grade-3
lesions break through the cortical bone and have a softtissue component covered by a pseudocapsule and periosteum. On rare occasions, the tumour extends its barrier, the
articular cartilage, and enters the joint.
Although Campanacci nominates this latter group of
GCT as malignant, the term aggressive is more justified
because in most cases this tumour has a benign histology
and can be cured by conservative surgery, namely curettage.
This final stage has, however, a greater risk of local recurrence.

Special forms of GCT


GCT is typically a monostotic process, but multicentric
(polyostotic) forms have been described occasionally.31,32
This rare condition can appear simultaneously or
metachronal33 with an interval of more than ten years. A
direct, continuous extension of GCT from one bone to the
next (Fig. 2), which occurs mostly in the short bones of the
hand and feet,34 should be excluded.
A rare form is the malignant GCT, which can be divided
into primary and secondary groups. The primary form (1%
to 3% of all GCTs)16,35 is malignant from the onset.
VOL. 86-B, No. 1, JANUARY 2004

Frankly sarcomatous stroma is juxtaposed to areas of typical GCT.15 Secondary malignant GCT (5% to 10% of all
GCTs)36 may develop during recurrence of a benign GCT,
or undergo a malignant transformation after radiotherapy.
On very rare occasions, the development of a bone sarcoma
has been seen after a very long period (18 to 25 years) after
the treatment of a primary GCT.37
Benign metastasing GCTs have been described in 1% to
3% of all and 6% of the recurrent GCTs.38-40 In these cases
the histology of the nodules found in the lung is identical to
that of the benign tumour of the primary site. Some authors
explain this as secondary to the tumour emboli often seen in
the peripheral vessels of GCTs and regard the nodules found
in the lung as implants and not as true metastases.41,42
Others30,43 have not found any correlation between the frequency of finding tumour emboli in vessels and that of pulmonary involvement. Recent basic studies have shown
enhanced matrix metalloproteinases, expression of p53 protein and overexpression of the C-myc oncogene in metastasising GCTs.7,44 Lung metastases usually appear two to
three years after the treatment of the primary tumour.38,45
They have also been occasionally observed at the first presentation of a benign GCT. A chest radiograph is therefore
justified both at the first presentation and in the course of the
follow-up.

Treatment
In most benign aggressive bone tumours control can be
achieved by wide surgical excision. Following en-bloc

M. SZENDRI

Fig. 3a

Fig. 3b

GCT in the distal part of the radius. Figure 3a Radiograph showing the lytic lesion with an ill-defined border to normal bone. Figure 3b MRI showing a high
signal on the T2-weighted image, representing
necrotic areas in the tumour tissue. Figure 3c Radiograph showing en-bloc resection of the tumour and
transposition of the fibular autograft. There have been
no symptoms for four years.

Fig. 3c

resection, the rate of the recurrence is between 0% and 5%


in primary lesions.46-50 Because it is found in the epiphysis,
the GCT often invades the subchondral bone. En-bloc resection usually requires sacrifice of the articular surface and a
complex reconstruction procedure, which can lead to complications, revision operations, and decreased quality of life
in the long term.

Resection is usually performed in GCTs found in the


proximal fibula, radius, distal ulna or in the wing of the
ilium in which a reconstruction is not necessary, or in malignant types of GCTs. Stage-3 GCTs, which have already
destroyed the cortex tend to recur more often and when the
defect is large and the joint surface destroyed, resection is
indicated. We try to preserve the joint even in a stage-3
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GIANT-CELL TUMOUR OF BONE

lesion, taking into account the higher probability of recurrence. It is also important to know whether it is the first,
second or third recurrence. Although repeated recurrences
have little influence on the final outcome in most cases and
can be treated by curettage as for the primary lesion, it is
customary to deal more radically35 with recurrences.
The treatment of choice in most GCTs is curettage and
bone grafting. Historically,12,17 however, curettage has been
associated with a high rate of recurrence (30% to 50%,
Table I) and therefore different adjuvants have been introduced. These presumably remove the tumour cells which
remain after curettage because of their thermal (liquid nitrogen, methylmethacrylate) or chemical (phenol, hydrogenperoxide, alcohol) effects.29,49,51-56
The use of cement has advantages in that it is cheap, and
immediate weight-bearing is allowed. Furthermore, a local
recurrence is easily recognised around the cement both by
radiographic and MR investigations.28,49,57 Extended curettage and application of bone cement are therefore the most
accepted methods in the treatment of GCT.
Rinsing the curetted defect with liquid nitrogen seems to
be the most effective treatment for local control of the
tumour. Malawer et al58 observed a rate of recurrence of
only 7.9% after cryosurgery in 102 patients with GCT.
However, because the depth of the necrotic margin is difficult to control, there is a high risk of bone and skin necrosis
and fracture.59-61
Good results have been published recently of the use of
high-pressure pulsatile lavage and a high-speed dental burr,
which allows the surgeon to remove the contaminated
margin up to normal bone.16,51,62
The data summarised in Table I suggest that the use of
adjuvants combined with careful curettage may decrease the
rates of local recurrence, which were reported in the historical series of Goldenberg et al17 and Campanacci et al12 as
being from 30% to 43% and 8% to 17%. Some authors
found no recurrence either with63 or without46,62 the use of
additional adjuvants, but the number of the patients reported
was small. It is of interest that Blackley et al51 using a highspeed burr at the time of curettage and bone grafting
achieved a very acceptable rate of recurrence with 12% in
59 patients.
Complete removal of the tumour tissue is more difficult
when the tumour is in the distal part of the radius or in the
metacarpal bones. There are reports that GCT in the radius
is more aggressive and metastasises more often to the
lung.38-40,51,64-66 En-bloc resection is strongly recommended especially in grade-3 tumours. When the distal part
of the radius is removed, an ulnocarpal arthrodesis can be
performed,67 or the defect can be replaced by either nonvascularised (Fig. 3) or vascularised autologous fibula.47,61
Treatment is especially difficult when the GCT has
affected the vertebral column,68 the sacrum or the periacetabular region of the pelvis. Marcove et al69 successfully
performed an incomplete curettage of the sacrum with cryosurgery in a patient with GCT. Complications, such as extenVOL. 86-B, No. 1, JANUARY 2004

sive intra-operative bleeding, can be avoided by embolisation


of the supplying arteries in huge GCTs of the innominate
bone (Fig. 4). Kattapuram et al70 recommended combined
surgery and radiotherapy for GCT located in the pelvis.
Radiotherapy. Three to four decades ago, radiation of
aggressive GCT with appendicular, pelvic, sacral and spinal
lesions was commonly undertaken. Orthovoltage equipment
was used but the bone and tumour dosimetry was poor,
since doses below 35 Gy were given. The results were disappointing. The rate of local recurrence was between 50%
and 70%. Malignant transformation14,17,36 occurred in 7%
to 25% of the irradiated GCT.
According to some reports,71-73 the use of modern equipment (supervoltage therapy,60Co or linear accelerator), and
doses of 40 to 60 Gy (1,8 - 2,0 Gy/fraction, 3 to 5 times/
week) can result in local oncological control of 85% to
90%. The risk of secondary radiation-induced malignant
tumour is very small (0% to 8%).71,74,75
In selected cases, therefore, if curettage is only incomplete (pelvis, vertebra, etc) resection will result in significant neurological or functional morbidity (sacral lesions).
Radiation is an effective alternative.
Prognosis and final outcome. The evaluation of prognostic
factors is difficult for various reasons. GCT is relatively
rare,2 and there are only a few multicentre studies which
have described a large number of cases, the indications,
treatment philosophy and statistical methods used vary and,
there is a lack of prospective, randomised studies. A number
of publications deal, however, with potential prognostic factors which may influence or predict the recurrence and
malignant transformation of GCT.
The histological grading has little prognostic
value.14,17,30,42 The benign or malignant nature of the
tumour can be determined. Benign histology does not necessarily relate to the clinical behaviour of the tumour.
Immunohistological and cytogenetic examinations give
additional information which may be useful. There is a relationship, for example, between the increasing rate of proliferation and the probability of recurrence.30,76,77 The value
of flow cytometry is disputed.78,79 Our results with smear
cytometry which allows separate examination of the stromal
cell population showed a significant difference in the ploidity of non-recurring and recurring GCTs during follow-up
studies. Two-thirds of non-recurring GCTs were characterised by euploidity and most of the recurrence GCTs by aneuploidity.76,80
Bridge et al81,82 found that all but one of their recurrent
GCTs had some type of chromosomal abnormality, which
could also be detected in highly malignant osteosarcomas.
Schoedel et al44 demonstrated an excessive metalloproteinase expression in recurrent or metastasising GCTs, which is
also found in the degradation of extracellular matrix and in
tissue invasion. An overexpression of c-myc oncogen32 and
p539 was found in GCTs metastasising to the lung.
The clinicoradiological staging systems of Enneking20
and Campanacci et al12 and their prognostic significance

10

M. SZENDRI

Fig. 4a

Fig. 4b

Radiographs showing a) an expansively growing GCT of the innominate bone, and b) after embolisation and curettage of the tumour
followed by reconstruction with PMMA cement and screws. There have been no symptoms for six years.

are also disputed. Rock83 and Wuismann et al84 observed a


sequential increase in local rates of recurrence from stage
1 through to stage 3. However, many authors, including
ourselves, do not regard these staging systems as predictive of the prognosis.13,38,76,85,86 Most GCTs show a tendency to progress and without treatment they reach stage 3
sooner or later, as we have seen in many cases of retrospective analysis of radiographs of untreated patients
(Fig. 2). In Rocks series,83 however, the 16 patients with
metastases had an equal distribution between stages 2
and 3.
McDonald et al35 analysing the data of 221 patients with
GCT did not find any correlation between the rate of recurrence and the size, localisation, the surgical stage of the
tumour and involvement of the subchondral bone. Pathological fracture in itself does not significantly increase the
risk of recurrence.24,83 The most significant factor is the
surgical procedure employed for removal of the tumour i.e.,
curettage with adjuvant therapy (34% recurrence) versus
resection (7% recurrence). This observation has been confirmed by many others authors.46-48,85
When evaluating the results of the very different surgical
methods, there is a lack of prospective randomised studies
comparing the effects of the adjuvants with the results of
curettage using a high-speed burr and bone grafting alone.
In addition, resection and curettage have been performed in

different percentages of the material, which may have significantly influenced the rate of recurrence. Gitelis et al46
performed en-bloc resection in 50% of their patients and
curettage with adjuvants in the other 50% without observing
any recurrence. In the series of McDonald et al35 curettage
was performed in 80% and the rate of recurrence increased
to 34%.
The management of local recurrence of GCT varies.
Some authors,12,16,85 recommend wide excision for any
recurrent lesion, whereas others24,60 believe that repeated
intralesional surgery with adjuvants for the second or third
recurrence is justified.
Malignant transformation or pulmonary metastases of
benign GCT have been observed after radiotherapy and
after multiple recurrences of a locally aggressive GCT,
especially when the tumour has affected the radius and the
small tubular bones of the hand or feet.38-42,64 Cheng and
Johnston38 collected about 50 published cases of metastasising GCT from the literature with an overall survival rate
of 80% to 85%. Sporadically, spontaneous regression of the
nodules in the lung has been reported,39,45 but the mortality
is about 15% to 20%.39,40 The treatment of choice is the
surgical excision of the nodules.38,41 When this is technically impossible, whole-lung radiotherapy is recommended.87 The effects of chemotherapy are not convincing.
The prognosis of malignant GCT is poor with a five-year
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GIANT-CELL TUMOUR OF BONE

survival of 50%,88 despite the combination of surgery and


chemotherapy.
Malignant transformation occurs, however, only in 5% to
10%, with pulmonary metastases in another 2% to 6%.
According to the results of larger series, most authors report
a disease-free survival of 96% to 100% as the final outcome
of the treatment.15,46,49,51,83
Recurrence of GCT is not fatal in most cases, but can
lead to disability and to a poor quality of life as a result of
repeated and radical operations, loss of bone stock, and secondary arthritis of the joints. Optimal treatment should
include: 1) careful curettage and the use of adjuvants to
decrease the rate of recurrence; 2) joint-sparing surgery at
revision operations and in stage-3 tumours whenever it is
possible; 3) in cases of proven malignancy: resection
according to oncological criteria; and 4) comparative histological and molecular biological evaluation of the primary
and recurrent tumours. In the future, histochemistry, DNA
cytometry, examination of the expression of certain oncogens, proteins, cytokines and the quantitative-qualitative
measurement of molecular genetic instability of the tumour
will have a greater influence on the surgical planning.
Because of the relative rarity of the tumour and the special operative techniques involved, it is recommended that
GCT be treated in tumour clinics. Inadequate primary intervention by a non-specialist can lead to major technical challenges at an advanced stage of the tumour.
This paper is based on an Instructional Course Lecture. European Instructional Course Lectures, Vol. 6, 2003, 89-98.

References
1. Schajowicz F. Histological typing of bone tumours. Berlin: SpringerVerlag, 1993:20-2.
2. Schajowicz F. Tumors and tumorlike lesions of bone and joints. New
York: Springer-Verlag, 1981:220-8.
3. Clohisy DR, Vorlicky L, Oegema TR Jr, Snover D, Thompson RC.
Histochemical and immunohistochemical characterization of cells constituting the giant cell tumor of bone. Clin Orthop 1993;287:259-65.
4. Kito M, Moriya H, Mikata A, et al. Establishment of a cell line from
a human giant cell tumor of bone. Clin Orthop 1993;294:353-60.
5. Komiya S, Sasaguri Y, Inoue A, et al. Characterization of cells cultured
from human giant-cell tumors of bone: phenotypic relationship to the
monocyte-macrophage and osteoclast. Clin Orthop 1990;258:304-9.
6. Roessner A, Vassallo J, Vollmer E, et al. Biological characterization of
human bone tumors: X the proliferation behaviour of macrophages as
compared to fibroblastic cells in malignant fibrous histiocytoma and
giant cell tumor of bone. J Cancer Res Clin Oncol 1987;113:559-62.
7. Gamberi G, Benassi MS, Bohling T, et al. Prognostic relevance of Cmyc gene expression in giant-cell tumor of bone. J Orthop Res
1998;16:1-7.
8. Radig K, Schmider-Stock R, Mittler U, Neumann HW, Roessner A.
Genetic instability in osteoblastic tumors of the skeletal system. Pathol
Res Pract 1998;194:669-77.
9. Masui F, Ushigome S, Fujii K. Giant cell tumor of bone: an immunohistochemical comparative study. Pathol Int 1998;48:355-61.
10. Miyamoto N, Higuchi Y, Tajima M, et al. Spindle-shaped cells derived
from giant-cell tumor of bone support differentiation of blood monocytes to osteoclast-like cells. J Orthop Res 2000;18:647-54.
11. Wulling M, Engels C, Jesse N, et al. The nature of giant cell tumor of
bone. J Cancer Res Clin Oncol 2001;127:467-74.
12. Campanacci M, Giunti A, Olmi R. Giant-cell tumours of bone: a study
of 209 cases with long term follow up in 130. Ital J Orthop Traumatol
1975;1:249-77.
VOL. 86-B, No. 1, JANUARY 2004

11

13. Campanacci M, Baldini N, Bariani S, Sudanese A. Giant-cell tumor


of bone. J Bone Joint Surg [Am] 1987;59-A:106-14.
14. Dahlin DC, Cupps RE, Johnson RE Jr. Giant-cell tumor: a study of
195 cases. Cancer 1970;25:1061-70.
15. Dahlin DC. Giant-cell tumor of bone: highlights of 407 cases. AJR Am
J Roentgenol 1985;144:955-62.
16. Eckhardt JJ, Grogan ThJ. Giant cell tumor of bone. Clin Orthop
1986;204:45-58.
17. Goldengerg RK, Campbell CJ, Bonfiglio M. Giant cell tumor of bone:
an analysis of two hundred and eighteen cases. J Bone Joint Surg [Am]
1970;52-A:619-64.
18. Jaffe HL, Lichtenstein L, Portis RB. Giant cell tumor of bone: its
pathologic appearance, grading, supposed variants and treatment.
Archives of Pathology 1940;30:993-1031.
19. Dahlin DC. Bone tumours. Third ed. Springfield, Illinois: Charles C
Thomas, 1978:99-115.
20. Enneking WF. Musculoskeletal tumor surgery. Vol. 1, New York:
Churchill Livingstone, 1983:1436-76.
21. Ewing J. A review and classification of bone sarcomas. Archives of surgery 1922;4:485-533.
22. Sung HW, Kuo DP, Ihu WP, et al. Giant-cell tumor of bone: analysis
of two hundred and eight cases in Chinese patients. J Bone Joint Surg
[Am] 1982;64-A:755-61.
23. Kransdorf MJ, Sweet DE, Buetow P, Giudici MA, Moser RP Jr.
Giant cell tumor in skeletally immature patients. Radiol 1992:233-7.
24. Dreinfhfer KE, Rydholm A, Bauer HCF, Kreicbergs A. Giant-cell
tumours with fracture at diagnosis. J Bone Joint Surg [Br] 1995; 77-B:
189-93.
25. Lodwick GS, Wilson AJ, Farrel C. Determining growth rates of focal
lesions of bone from radiographs: estimating rate of growth in bone
lesions: observer performance and error. Radiology 1980;134:577-83.
26. Breitenseher M, Dominkus M, Schritzer M, et al. Diagnostic imaging
of giant cell tumours. Radiologe 2001;41:568-76.
27. Liebicher M, Bernd L, Schenk JP, et al. Characteristic perfusion
pattern of osseo giant cell tumor in dynamic contrast-enhanced MRI.
Radiologe 2001;41:577-82.
28. Remedios D, Saiffudin A, Pringle J. Radiological and clinical recurrence of giant-cell tumor of bone after the use of cement. J Bone Joint
Surg [Br] 1997;79-B:26-30.
29. Szendri M. Adjuvant therapy (phenol, bone cement) in giant cell
tumour. Z Orthop 1992;130:95-9.
30. Sanerkin NG. Malignancy, aggressiveness, and recurrence in giant cell
tumor of bone. Cancer 1980;46:1641-9.
31. Cummings CA, Scarborough MRT, Enneking WF. Multicentric giant
cell tumor of bone. Clin Orthop 1996;322:245-52.
32. Peimer CA, Schiller AL, Mankin HJ, Smith RJ. Multicentric giantcell tumor of bone. J Bone Joint Surg [Am] 1980;62-A:652-6.
33. Sadat-Ali M. Metachronous multicentric giant-cell tumor: a case
report. Indian Journal of Cancer 1997;34:169-76.
34. Szendri M, Antal I, Perlaky G. Mid-foot reconstruction following
involvement of five bones by giant cell tumour. Skeletal Radiol
2000;29:664-7.
35. McDonald DJ, Sim FH, McLeod RA, Dahlin DC. Giant cell tumor of
bone. J Bone Joint Surg [Am] 1986;68-A:235-42.
36. McGrath. Giant cell tumor of bone: analysis of fifty-two cases. J Bone
Joint Surg [Br] 1972;54-B:216-29.
37. Mori Y, Tsuchiya H, Karita M, et al. Malignant transformation of a
GCT 25 years after initial treatment. Clin Orthop 2000;381:185-91.
38. Cheng JC, Johnston JO. Giant-cell tumor of bone: prognosis and treatment of pulmonary metastases. Clin Orthop 1997;338:205-14.
39. Siebenrock KA, Unni KK, Rock MG. Giant cell tumor of bone metastasising to the lungs: a long-term follow-up. J Bone Joint Surg [Br]
1998;80-B:43-7.
40. Tubbs WS, Brown LR, Beabout JW, Rock MG, Unni KK. Benign
giant-cell tumor of bone with pulmonary metastases: clinical findings
and radiological appearance of metastases of 13 cases. AJR Am J
Roentgenol 1992;158:331-4.
41. Bertoni F, Present D, Enneking WF. Giant-cell tumour of bone with
pulmonary metastases. J Bone Joint Surg [Am] 1985;67-A:890-900.
42. Rock MG, Pritchard DJ, Unni KK. Metastases from histologically
benign giant-cell tumor of bone. J Bone Joint Surg [Am] 1984; 66-A:
269-73.

12

M. SZENDRI

43. Maloney WF, Vangham LM, Jones HH, Ross J, Nagel DA. Benign
metastasizing giant-cell tumor of bone: report of three cases and review
of the literature. Clin Orthop 1989;243:208-15.
44. Schoedel KE, Greco MA, Stetler-Stevenson WG, et al. Expression of
metalloproteinases and tissue inhibitors of metalloproteinases in giant
cell tumor of bone: an immunohistochemical study with clinical correlation. Hum Pathol 1996;27:1144-8.
45. Kay RM, Eckhardt JJ, Seeger LL, Mirra JM, Hok DJ. Pulmonary
metastasis of benign giant cell tumor of bone: six histologically confirmed cases, including one of spontaneous regression. Clin Orthop
1994;302:219-30.
46. Gitelis S, Mallin AB, Piasecki P, Turner F. Intralesional excision compared with en bloc resection for giant-cell tumors of bone. J Bone Joint
Surg [Am] 1993;75-A:1648-55.
47. Kumita SM, Leong PC, Yip K, et al. Vascularized bone grafts in the
treatment of juxta-articular giant-cell tumors of the bone. J Reconst
Microsurg 1998;14:185-90.
48. Labs K, Perka C, Schmidt GR. Treatment of stages 2 and 3 giant-cell
tumor. Arch Orthop Traum Surg 2001;121:83-6.
49. ODonell RKJ, Springfield DS, Motwani HK, et al. Recurrence of
giant-cell tumors of long bones after curettage and packing with cement.
J Bone Joint Surg [Am] 1994;76-A:1827-33.
50. Yip KM, Leung PC, Kumita SM. Giant cell tumor of bone. Clin
Orthop 1996;323:60-4.
51. Blackley HR, Wunder JS, Davis AM, et al. Treatment of giant-cell
tumors of long bones with curettage and bone-grafting. J Bone Joint
Surg [Am] 1999;81-A:811-20.
52. Capanna R, Fabbri N, Bettelli G. Curettage of giant cell tumor of
bone: the effect of surgical technique and adjuvants on local recurrence
rate. Chir Organi Mov 1990;(Suppl):206-8.
53. Frassica FJ, Sim FH, Pritchard DJ, Chao YE. Subchondral replacement: a comparative analysis of reconstruction with methyl-methacrylate or autogenous bone graft. Chir Org Mov (Suppl) 1990;75:
189-90.
54. Leeson MC, Lippitt SB. Thermal aspects of the use of polymethylmethacrylate in large methaphyseal defects in bone. Clin Orthop
1993;295:239-45.
55. Quint U, Mller RT, Mller G. Characteristics of phenol. Arch Orthop
Trauma Surg 1998;117:43-6.
56. Vidal J, Mimran R, Allieu Y, Goalard JM. Plastie de comblement par
mecacrylate de mthyle traitement de certaines tumeurs osseuses
bnignes. Montepellier Chir 1969;15:389-97.
57. Bini SA, Gill K, Johnston JO. Giant cell tumor of bone: curettage and
cement reconstruction. Clin Orthop 1995;321:245-50.
58. Malawer MM, Bickels J, Meller J, et al. Cryosurgery in the treatment
of giant cell tumor: a long-term follow-up study. Clin Orthop
1999;359:176-88.
59. Malawer MM, Dunham W. Cryosurgery and acrylic cementation as
surgical adjuncts in the treatment of aggressive (benign) bone tumors:
analysis of 25 patients below the age of 21. Clin Orthop 1991;262:
42-57.
60. Marcove RC. A 17-year review of cryosurgery in the treatment of bone
tumors. Clin Orthop 1982;163:231-4.
61. Sheth DS, Healey JH, Sobel M, Lane JM, Marcove RC. Giant cell
tumor of the distal radius. J Hand Surg Am 1995;20:432-40.
62. Richardson MJ, Dickinson K. Giant cell tumor of bone. Bull Hosp Jt
Dis 1998;57:6-10.
63. Komiya S, Inoue A. Cementation in the treatment of giant cell tumor.
Arch Orthop Trauma Surg 1993;112:51-5.
64. Athanasian EA, Wold LE, Amadio PC. Giant-cell tumors of the bones
of the hand. J Hand Surg Am 1997;22:91-8.
65. Cheng CY, Shih H-N, Hsu KY, Hsu RWW. Treatment of giant cell
tumour of the distal radius. Clin Orthop 2001;383:221-8.

66. Szendri M. Giant-cell tumor in the radius: aggressiveness and soft-tissue recurrence. Chir Organi Mov 1990;75:241-3.
67. Ben N, Amor H, Zouari M, Karray S, et al. Giant cell tumors of the
distal end of the radius treated by resection-arthrodesis. Acta Orthop
Belg 1998;64:41-6.
68. Ozaki T, Lijenqvist U, Halm H, et al. Giant cell tumor of the spine.
Clin Orthop 2002;401:194-201.
69. Marcove RC, Sheth DS, Brient EW, Huvos AG, Healey JH. Conservative surgery for giant cell tumors of the sacrum: the role of cryosurgery
as a supplement to curettage and partial excision. Cancer 1994;74:
1253-60.
70. Kattapuram AS, ODonnell RJ, Huszar M, et al. Surgical management of innominate giant cell tumor. Clin Orthop 1996;329:281-7.
71. Malone S, OSullivan B, Catton C, et al. Long-term follow-up of efficacy and safety of megavoltage radiotherapy in high-risk giant cell
tumors of bone. Int J Radiat Oncol Biol Phys 1995;33:689-94
72. Schwartz LH, Okunieff PG, Rosenberg A, Suit HD. Radiation therapy in the treatment of difficult giant cell tumours. Int J Radiat Oncol
Biol Phys 1989;17:1085-8.
73. Suit H, Spiro I. Radiation treatment of benign mesenchymal disease.
Semin Radiat Oncol 1999;9:171-8.
74. Bell RS, Harwood AR, Goodman SB, Fornasier VL. Supervoltage
radiotherapy in the treatment of difficult giant-cell tumors of bone. Clin
Orthop 1983;174:208-16.
75. Bennett CJ, Marcus RB, Million RR, Enneking WF. Radiation therapy for giant cell tumor of bone. Int J Radiat Oncol Biol Phys
1993;26:229-304.
76. Antal I, Spi Z, Szendri M. The prognostic significance of DNA cytophotometry and proliferation index (Ki-67) in giant cell tumors of bone.
Orthop 1999;23:315-9.
77. Fornasier VL, Protzner K, Zhang I, Mason L. The prognostic significance of histomorphometry and immunohistochemistry in giant cell
tumours of bone. Hum Pathol 1996;27:754-60.
78. Fukunaga M, Nikaido T, Shimoda T, Ushigome S, Nakamori. A flow
cytometric DNA analysis of giant cell tumors of bone including two
cases with malignant transformation. Cancer 1992;70:1886-94.
79. Krober SM, Greschniok A, Bohm P, Kaiserling E. Giant cell tumor
of bone: morphological, immunohistochemical, morphometric and
DNA flow-cytometric findings. Verh Dtsch Ges Pathol 1998;82:279-83.
80. Antal I, Spi Z, Szendri M. Malignant transformation of giant-cell
tumour in the distal radius: value of the DNA cytophotometry. Ortopde
2000;29:677-83.
81. Bridge JA, Mouron BJ, Neff JR, Bhatia PS. Significance of chromosomal abnormalities in a malignant giant cell tumor of bone. Cancer
Genet Cytogenet 1991;57:87-92.
82. Bridge JA, Neff JR, Bhatia PS, Sanger WG, Murphey MD. Cytogenetic findings and biologic behaviour of giant cell tumors of bone. Cancer 1990;65:2697-703.
83. Rock M. Curettage of giant cell tumor of bone: factors influencing local
recurrences and metastasis. Chir Organi Mov 1990;75(Suppl.1):204-5.
84. Wuismann P, Hrle A, Nommensen B. et al. Giant-cell tumour of
bone: an analysis of 69 cases. Z Orthop 1989;127:392-5.
85. Lausten GS, Jensen PK, Schiodt T, Lund B. Local recurrences in
giant cell tumour of bone: long-term follow up of 31 cases. Int Orthop
1996;20:172-6.
86. Masui F, Ushigome S, Fujii K. Giant cell tumor of bone: a clinicopathologic study of prognostic factors. Pathol Int 1998;48:723-9.
87. Feigenberg SJ, Marcus RB, Zlotecki RA, Scarborough MT, Enneking WF. Whole-lung radiotherapy for giant cell tumors of bone with pulmonary metastases. Clin Orthop 2002;401:202-8.
88. Anract P, De-Piueus G, Cottias P, et al. Malignant giant-cell tumor of
bone: clinical-pathological types and prognosis: a review of 29 cases. Int
Orthop 1998;22:19-26.

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