Joon Hyuk Choi, M.D.

Department of Pathology

College of Medicine, Yeungnam University

Grading of Bone Tumors

Introduction to grading system of bone

tumor used at Mayo Clinic

Bone-forming tumorsBenign

OsteomaOsteoid osteoma and osteoblastoma

IntermediateAggressive (malignant) osteoblastoma

MalignantConventinal central osteosarcomaTelangiectatic osteosarcomaIntraosseous well differentiated (low grade) osteosarcomaRound-cell osteosarcomaParosteal (juxtacortical) osteosarcomaPeriosteal osteosarcomaHigh grade surface osteosarcoma

Cartilage-forming tumorsBenign

EnchondromaPeriosteal (juxtacortical) chondromaSolitary osteochondromaMultiple hereditary osteochondromasChondroblastoma (epiphyseal chondroblastoma)Chondromyxoid fibroma

MalignantChondrosarcomaJuxtacortical (periosteal) chondrosarcomaMesenchymal chondrosarcomaDedifferentiated chondrosarcomaClear cell chondrosarcomaMalignant chondroblastoma

Giant cell tumor (osteoclastoma)Marrow tumors (round cell tumors)

Ewing sarcomaPrimitive neuroectodermal tumor of bone (PNET)Malignant lymphoma of boneMyeloma

Vascular tumorsBenign

HemangiomaLymphangiomaGlomus tumor (glomangioma)

Intermediate or indeterminateHemangioendotheliomaHemangiopericytoma

MalignantAngiosarcomaMalignant hemangiopericytoma

Other connective tissue tumorsBenign

Benign fibrous histiocytomaLipoma

IntermediateDesmoplastic fibroma

MalignantFibrosarcomaMalignant firbrous histiocytomaLiposarcomaMalignant mesenchymomaLeiomyosarcomaUndifferentiated sarcoma

Other tumorsChordomaAdamantinoma of long bonesNeurilemomaNeurofibroma

Unclassified tumorsTumor-like lesions

Solitary bone cyst (simple or unicameral bone cyst)Aneurysmal bone cystJuxta-articular bone cyst (intraosseous ganglion)Metaphyseal fibrous defect (nonossifying fibroma)Eosinophilic granuloma (histiocytosis X, Langerhans cell granulomatosis)Fibrous dysplasiaOsteofibrous dysplasiaMyositis ossificans (heterotopic ossification)Brown tumor of hyperparathyroidismIntraosseous epidermoid cystGiant cell (reparative) granuloma

WHO Histologic Classification of Bone Tumors (1993)

OsteochondromaChondromaChondroblastomaChondromyxoid fibromaOsteoid osteomaOsteoblastomaGiant cell tumor

Fibrous histiocytomaHamartoma

Hemangioma

LipomaNeurilemoma

Tumor No.of CasesBenign

872335119

45331

87568

91

108

714

2,496

3,749694775120120

341,649

69512

35348312

255356

8013

1

8,591

MyelomaLymphomaChondrosarcomaSecondary chondrosarcomaDedifferentiated chondrosarcomaMesenchymal chondrosarcomaOsteosarcomaParosteal osteosarcomaEwing’s sarcomaMalignancy in giant cell tumorAdamantinomaMalignant fibrous histiocytomaDesmoplastic fibromaFibrosarcomaChordomaHemangioendotheliomaHemangiopericytomaLiposarcoma

40.07

21.83

19.27

10.36

0.832.42

3.211.81

0.070.13

100.00

4,443

2,420

2,136

1,149

92268

356201

814

11,087

Hematopoietic

Chondrogenic

Osteogenic

Unknown

HistiocyticFibrogenic

NotochordalVascular

LipogenicNeurogenicTotal

Tumor No.of Cases%No.MalignantTotal cases

Classification of tumors of bone in Mayo Clinic patients

( Unni KK: Dahlin’s Bone tumor, 5th ed., 1996)

Grading of squamous cell carcinoma of lip (Broders, 1920)

Grade 1 : <25% undifferentiated cells

Grade 2 : 25 - 50%

Grade 3 : 50 - 75%

Grade 4 : >75%

(JAMA 74:656-64,1920)

Osteosarcoma : G1∼4

Chondrosarcoma : G 1∼3

Fibrosarcoma : G1∼4

Angiosarcoma : G1∼3

Graded bone tumors

Benign tumors

Ewing's sarcoma

Mesenchymal chondrosarcoma

Chordoma

Adamantinoma

Giant cell tumor

Not graded bone tumors

Cellularity (+)

Cytologic atypia (+)

Mitosis (-)

Necrosis (-)

Histological parameters

Conventional osteosarcoma : G 3, 4OsteoblasticChondroblasticFibroblasticOther

Giant cell richEpithelioid

Small cell : G 4Telangiectatic : G 4

Classification of osteosarcoma

(Hematol Oncol Clin North Am 9:545-69,1995)

Low-grade central : G 1Parosteal : G 1, 2Periosteal : G 2, 3High-grade surface : G 3, 4Secondary : G 4

Paget's sarcomaPostirradiationOther

Grade No. of cases 5 y. SR(%)

1 2

2 63 27.0

3 218 19.7

4 128 17.2

Total 411

Survival according to Grade in osteosarcoma

(J Bone Joint Surg 49A:101-10,1967)

Grade No. of cases Death during first 3 yr(%)

1 11 0.0

2 49 10.2

3 132 28.0

4 207 30.4

Total 399

Survival according to Grade in osteosarcoma

(J Natl Cancer Inst 81:21-30, 1989)

Grade Histologic features

1 Relatively hypercellular compared with enchondroma

moderate cytologic atypia

2 More cellular than Grade 1

cytologic atypia is more pronounced

3 Extreme cellularity

marked cytologic atypia

Grading of chondrosarcoma

Dahlin Evans Gitelis

Cellularity + + +

Cytologic atypia + + +

Mitosis - + +

Necrosis - + +

Growth pattern - - +

Histologic parameters used in different grading system of chondrosarcoma

No. of cases %

No mitosis 311 92.0

1∼3/tumor 20 5.9

1/1 HPF 7 2.1

Total 338 100.0

Mitosis in chondrosarcoma

(Cancer 83:2105-19,1998)

Grade No. of cases %

1 207 61.2

2 120 35.5

3 11 3.3

Total 338 100.0

Grades of chondrosarcoma

(Cancer 83:2105-19,1998)

Grade Recurrence rate(%) Metastatic rate(%)

1 15.2 4.6

2, 3 36.2 29.3

Recurrence and metastatic rate according to Grade

in chondrosarcoma

(Cancer 83:2105-19,1998)

Grade 5 y. SR(%)

1 88.5

2, 3 57.1

Survival according to Grade in chondrosarcoma

(Cancer 83:2105-19,1998)

Grade Histologic features

1 Marked collagen production, elongated nuclei with

tapered ends, mitotic figures are uncommon

2 Greater cellularity than do Grade 1 tumor, nuclei are

somewhat more atypical appearing, mitotic figures

3 Darkly stained spindle cells in a herringbone pattern with

little collagen production, mitotic figures are abundant, necrosis

4 The cells are closely packed together,

prominent mitotic figures, necrosis

Grading of fibrosarcoma

Grade No. of cases %

1 1 0.9

2 35 30.7

3 48 42.1

4 30 26.3

Total 114 100.0

Grades of fibrosarcoma

(Cancer 23:35-41,1969)

Grade No. of cases 5 yr SR(%) 10 yr SR(%)

1 1

2 35 40.0 25.0

3 48 30.8 27.3

4 30 13.6 10.0

Total 114 28.7 21.6

Survival according to Grade in fibrosarcoma

(Cancer 23:35-41,1969)

Grade Histologic features

1 Well formed vascular spaces lined by tumor cells

slight cytologic atypia

2 Vasoformative features are less readily identified

cytologic atypia is more pronounced

3 Little to no recognizable vasoformation

marked cytologic atypia

Grading of angiosarcoma

Grade No. of case %

1 33 29

2 51 46

3 28 25

Total 112 100

Grades of angiosarcoma

(Am J Surg Pathol 6:59-70,1982)

Grade No. of cases Disease free survival(%)

1 22 95

2 45 62

3 25 20

Survival according to Grade in angiosarcoma

(Am J Surg Pathol 6:59-70,1982)

• The grade of bone tumors depends on the cellularity and cytologic

atypia.

• Grading is simple, fairly reproducible and useful.

• Grading is important for many of the primary sarcomas of bone,

especially osteosarcoma, fibrosarcoma, chondrosarcoma, andangiosarcoma

Summary