Giant Cell Tumor of Bone (1)

Giant Cell Tumor of Bone: 

1 Giant Cell Tumor of Bone Dr. Prabesh K Choudhary 2 nd Year; Dept of Pathology

Overview: 

2 Overview Introduction Epidemiology Location Presentation Radiology Histopathology Differential diagnosis Genetics Histogenesis Treatment Prognosis Summary

Introduction: 

3 Introduction Primary bone neoplasm First described Cooper & Travers 1818 Lebert microscopic description 1845 Its local aggressiveness was described by Nelaton. Its malignant potential by Virchow. Generally benign Potential for : Recurrence Pulmonary metastasis Frank malignancy

Epidemiology: 

4 Epidemiology 4-5%: Primary bone tumors 20%: benign bone tumors F : M: 1.5 : 1 70-80% :20-45 Yrs Rare in skeletally immature individual Epiphyseal

Location: 

5 Location Ends of long bones: distal femur, proximal tibia, distal radius, sacrum & proximal humerus. 5% cases: Flat bones e.g. pelvis <5% of cases: tubular bones of the hands & feet Jaw & spine: (Paget’s disease) Multicentric GCT : rare; small bones of the distal extremities Soft tissue: very rare

Presentation: 

6 Presentation Pain Swelling Limitation of movement Pathologic #: 5-10% Neuro-deficit (spine / sacrum) incidental

Radiology: 

7 Radiology Expansile & eccentric area of lysis Epipysis & adjacent metaphysis Subchondral/joint Soap bubble appearance Reactive bone: seldom

PowerPoint Presentation: 

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Other modalities: 

9 Other modalities CT Cortical thinning MRI Intraosseous spread Soft tissue extension Bone Scan Suspect multicentric loci ie. HAND

Radiological grading (campanacci): 

10 Radiological grading (campanacci) Grade1(Quiescent): well defined margin with surrounding sclerosis; cortex: slightly thinned but not deformed Grade2(Active): well defined margin, lack sclerosis; cortex-thinned and expanded Grade3(Aggressive): ill defined margin, often with cortical destruction and soft tissue extension

PowerPoint Presentation: 

11 Radiological grading does not correspond with the histological grading.

Gross: 

12 Gross Intact specimen mirrors the radiological appearance Eccentric, well defined area of bone destruction Incomplete shell of reactive bone Soft & reddish brown Blood filled cystic spaces the curettage material is soft and dark brown

Histology: 

13 Histology Multinucleated giant cells Mononuclear stromal cell Round / ovoid / spindle Benign fibrous histiocytoma Indistinct cell membrane ABC changes (10%) Mitoses(2-10/10hpf) Bone formation: fracture Intravascular plugs(1/3 rd )

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PowerPoint Presentation: 

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Jaffe’s 3 Histological grades of GCT: 

16 Jaffe’s 3 Histological grades of GCT Grade I tumor; benign, low aggressive behavior: dense layer of huge giant cells with up to 100 or more nuclei, almost covering the tumor tissue proper of mononuclear cells. Grade II tumor; benign highly aggressive behavior: Considerable reduction in the size and number of giant cells, and mononuclear cells may be pleomorphic to some degree. Grade III tumors; malignant : Giant cells are further reduced in number and there is an increase in pleomorphic mononuclear cells.

PowerPoint Presentation: 

17 Histological grades do not correspond with the clinical behavior of the lesion.

Differential diagnosis: 

18 Differential diagnosis Giant cell rich osteosarcoma Aneurysmal bone cyst Malignant fibrous histiocytoma Brown tumor Chondroblastoma Chondromyxoid fibroma

Enneking Staging: 

19 Enneking Staging Stage 1 Stage 2 Stage 3 Pt % 10-15% ~70% 10-15% Symptoms asymptomatic pain pain Radiograph sclerotic rim expanded cortex cortical perforation Histology benign benign benign

Genetics: 

20 Genetics Telomere association (loss of 500bp) Most commonly affected 11p, 13q, 14p, 15p,19q,20q, & 21p GCT with fibrohistiocytic reaction: similar karyotype Some cases:16q22 or 17p13 rearrangements

Telomeric association: 

21 Telomeric association

Histogenesis: 

22 Histogenesis Mononuclear cell: primitive mesenchymal stromal cell ; RANKL expression and produces OPG-L>> formation & maturation of osteoclast from osteoclast precursor Stromal cells: neoplastic component Two mononuclear cell types 1.Round cell: resembling monocytes 2.Spindle cell: fibroblast like stromal cells

Histogenesis: 

23 Histogenesis

Prognostic factor: 

24 Prognostic factor Capable of locally aggressive behavior & occasionally of distant metastasis Following Rx with curettage, supplemented with bone grafting, cementation, cryotherapy or instillation of phenol; local recurrence: 25% Histology does not predict local aggression, recurrence & metastatic potential

Prognostic factor: 

25 Prognostic factor Pulmonary metastasis: 2%; benign pulmonary implants/spontaneous regression/progressive Local recurrence, surgical manipulation & location in distal radius: increased risk of metastasis

Malignancy in GCT: 

26 Malignancy in GCT Primary & secondary Syn: malignant GCT; dedifferentiated GCT Most cases are secondary to radiation Primary malignant GCT: rare Overall malignant risk in GCT: 1% Recurrence of pain & swelling after Rx: Common sites: around knee

Malignancy in GCT: 

27 Malignancy in GCT Histology: high grade spindle cell sarcoma with or without osteoid Vacular invasion, soft tissue extension & high mitotic activity do not establish malignancy No residual giant cell tumor Primary cases: conventional GCT present Prognosis of primary better than secondary ones

Malignancy in GCT: 

28 Malignancy in GCT In the Mayo Clinic files, 31 of the 36 malignant giant cell tumors were judged to have developed after the treatment of a benign giant cell tumor. Twenty-five of these 31 had previously been irradiated. Only five patients were shown to have malignancy in a giant cell tumor at the time of diagnosis.

Treatment Strategies: 

29 Treatment Strategies 1. curettage 2. curettage and cytotoxic agents such as 5%phenol,zinc chloride,70% alcohol, and H 2 O 2. 3. curettage and a physical adjuvant (polymethylmethacrylate, liquid nitrogen and cryosurgery) 4. curettage & bone grafting 5. radical resection 6. radiation therapy 7. amputation 8. embolization: in unresectable tumors.

Summary: 

30 Summary Primary benign bone neoplasm Eccentric epiphyseal osteolytic lesion Stromal cell: neoplastic component Histology does not correspond with the clinical behavior Pulmonary metastasis: 2% Malignant potential: 1% Malignancy in GCT: secondary to radiation.

Thank you !: 

31 Thank you !