Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis

Giant cell tumour of bone (GCTB) is a rare and intriguing primary bone neoplasm. Worrisome clinical features are its local destructive behaviour, its high tendency to recur after surgical therapy and its ability to create so-called benign lung metastases (lung ‘plugs’). GCTB displays a complex and difficult-to-understand cell biological behaviour because of its heterogenous morphology. Recently, a driver mutation in histone H3.3 was found. This mutation is highly conserved in GCTB but can also be detected in glioblastoma. Denosumab was recently introduced as an extra option of medical treatment next to traditional surgical and in rare cases, radiotherapy. Despite these new insights, many ‘old’ questions about the key features of GCTB remain unanswered, such as the presence of telomeric associations (TAs), the reactivation of hTERT, and its slight genomic instability. This review summarises the recent relevant literature of histone H3.3 in relation to the GCTB-specific G34W mutation and pays specific attention to the G34W mutation in relation to the development of TAs, genomic instability, and the characteristic morphology of GCTB. As pieces of an etiogenetic puzzle, this review tries fitting all these molecular features and the unique H3.3 G34W mutation together in GCTB.

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ANALYSIS OF GIANT CELL TUMOUR OF BONES: ITS PATTERN, VARIOUS TREATMENT MODALITIES AND THEIR RESULTS

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v2i5.35 ◽

2018 ◽

Author(s):

Anil Pandey ◽

Pratyush Goyal ◽

Deepak S , Maravi ◽

S Uikey

Keyword(s):

Knee Joint ◽

Giant Cell ◽

Giant Cell Tumour ◽

Lung Metastases ◽

Histopathological Examination ◽

Cell Tumour ◽

Treatment Modalities ◽

Tumour Mass ◽

Intralesional Curettage ◽

Extended Curettage

Background: Giant cell tumour is a benign aggressive tumour of bone accounting for 5% of all primary bone tumours with feature of local recurrence, potential for metastasis and malignant transformation and usually seen at the end of long bones after skeletal maturity. The incidence of lung metastases from a histologically-proven GCT ranges from 1% to 9%. The recurrence rate after intralesional curettage without adjuvant therapy is reported to be up to 50%. Extended curettage with use of adjuvents is the treatment of choice for treating the most GCT of bones. Material and method: 25 patients presented with GCTBs included.In all patients standard plain anteroposterior and lateral radiographs of the involved extremity were done.MRI of involved extremity was done in 19 cases. Diagnosis confirmed by biopsy and histopathological examination. The treatment of GCT is directed towards local control without scarifying joint function. This has been traditionally achieved by intralesional curettage with autograft reconstruction by packing the cavity of excised tumour with iliac cortico-cancellous bone. Results: We have treated 25 patients of GCTBs. Females (15) were more commonly affected than male (10). Most common site for GCT was around the knee joint mostly in proximal tibia (6 out of 25). Average range of motion of knee joint was 60 to 112 degree and in wrist joint it was 0 to 45 degree of palmar flexion and 0 to 30 degree of dorsi flexion. Conclusion: We believe that removal of most of tumour mass by extended curettage is very essential step in preventing recurrence and achieving good functional outcome in future. Key words: giant cell tumour of bones, autograft, extended curettage

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Lung metastases of diffuse giant cell tumour of the fibular tendon sheath at the ankle: A case report

Orthopaedics & Traumatology Surgery & Research ◽

10.1016/j.otsr.2016.10.018 ◽

2017 ◽

Vol 103 (3) ◽

pp. 399-402 ◽

Cited By ~ 1

Author(s):

P.-S. Marcheix ◽

T. Roger ◽

J.-M. Coindre ◽

I. Pommepuy ◽

J.-L. Charissoux ◽

...

Keyword(s):

Case Report ◽

Giant Cell ◽

Giant Cell Tumour ◽

Lung Metastases ◽

Tendon Sheath ◽

Cell Tumour

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H3F3A mutation in giant cell tumour of the bone is detected by immunohistochemistry using a monoclonal antibody against the G34W mutated site of the histone H3.3 variant

Histopathology ◽

10.1111/his.13190 ◽

2017 ◽

Vol 71 (1) ◽

pp. 125-133 ◽

Cited By ~ 22

Author(s):

Julian Lüke ◽

Alexandra von Baer ◽

Jordan Schreiber ◽

Christoph Lübbehüsen ◽

Thomas Breining ◽

...

Keyword(s):

Monoclonal Antibody ◽

Giant Cell ◽

Giant Cell Tumour ◽

Cell Tumour ◽

Histone H3.3 ◽

H3f3a Mutation

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Correction to: Denosumab does not decrease the risk of lung metastases from bone giant cell tumour

International Orthopaedics ◽

10.1007/s00264-018-4166-6 ◽

2018 ◽

Vol 43 (2) ◽

pp. 491-491

Author(s):

Shinji Tsukamoto ◽

Andreas F. Mavrogenis ◽

Giulio Leone ◽

Alberto Righi ◽

Manabu Akahane ◽

...

Keyword(s):

Giant Cell ◽

Giant Cell Tumour ◽

Lung Metastases ◽

Cell Tumour

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A rare case of giant cell tumour (GCT) of bone with lung metastases

BMJ Case Reports ◽

10.1136/bcr-2017-221667 ◽

2018 ◽

pp. bcr-2017-221667

Author(s):

Dheerendra Kumar Sachan ◽

Nupur Bansal ◽

Surabhi Gupta ◽

Sanjeev Kumar

Keyword(s):

Giant Cell ◽

Rare Case ◽

Giant Cell Tumour ◽

Lung Metastases ◽

Cell Tumour

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The role of Denosumab in joint preservation for patients with giant cell tumour of bone

The Bone & Joint Journal ◽

10.1302/0301-620x.103b1.bjj-2020-0274.r1 ◽

2021 ◽

Vol 103-B (1) ◽

pp. 184-191

Author(s):

David Louis Perrin ◽

Julia D. Visgauss ◽

David A. Wilson ◽

Anthony M. Griffin ◽

Albiruni R. Abdul Razak ◽

...

Keyword(s):

High Risk ◽

Local Recurrence ◽

Giant Cell ◽

Giant Cell Tumour ◽

Lung Metastases ◽

Cell Tumour ◽

Joint Surface ◽

Intralesional Curettage ◽

Tissue Mass

Aims Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Methods Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma. Results A total of 25 patients with a mean age of 33.8 years (18 to 67) with high-risk GCTB received median six cycles of Denosumab before surgery. Tumours occurred most commonly around the knee (17/25, 68%). The median follow-up was 57 months (interquartile range (IQR) 13 to 88). The joint was salvaged in 23 patients (92%). Two required knee arthroplasty due to intra-articular fracture and arthritis. Local recurrence developed in 11 patients (44%) at a mean of 32.5 months (3 to 75) following surgery, of whom four underwent repeat curettage and joint salvage. One patient developed secondary osteosarcoma and another benign GCT lung metastases. Conclusion The use of Denosumab for joint salvage was associated with a higher than expected rate of local recurrence at 44%. Neoadjuvant Denosumab for joint-sparing procedures should be considered with caution in light of these results. Cite this article: Bone Joint J 2021;103-B(1):184–191.

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