Grading of Bone Tumors Joon Hyuk Choi, M.D. Department of Pathology College of Medicine, Yeungnam University
Introduction to grading system of bone tumor used at Mayo Clinic
WHO Histologic Classification of Bone Tumors (1993) Bone-forming tumors Benign Osteoma Osteoid osteoma and osteoblastoma Intermediate Aggressive (malignant) osteoblastoma Malignant Conventinal central osteosarcoma Telangiectatic osteosarcoma Intraosseous well differentiated (low grade) osteosarcoma Round-cell osteosarcoma Parosteal (juxtacortical) osteosarcoma Periosteal osteosarcoma High grade surface osteosarcoma Cartilage-forming tumors Benign Enchondroma Periosteal (juxtacortical) chondroma Solitary osteochondroma Multiple hereditary osteochondromas Chondroblastoma (epiphyseal chondroblastoma) Chondromyxoid fibroma Malignant Chondrosarcoma Juxtacortical (periosteal) chondrosarcoma Mesenchymal chondrosarcoma Dedifferentiated chondrosarcoma Clear cell chondrosarcoma Malignant chondroblastoma Giant cell tumor (osteoclastoma) Marrow tumors (round cell tumors) Ewing sarcoma Primitive neuroectodermal tumor of bone (PNET) Malignant lymphoma of bone Myeloma Vascular tumors Benign Hemangioma Lymphangioma Glomus tumor (glomangioma) Intermediate or indeterminate Hemangioendothelioma Hemangiopericytoma Malignant Angiosarcoma Malignant hemangiopericytoma Other connective tissue tumors Benign Benign fibrous histiocytoma Lipoma Intermediate Desmoplastic fibroma Malignant Fibrosarcoma Malignant firbrous histiocytoma Liposarcoma Malignant mesenchymoma Leiomyosarcoma Undifferentiated sarcoma Other tumors Chordoma Adamantinoma of long bones Neurilemoma Neurofibroma Unclassified tumors Tumor-like lesions Solitary bone cyst (simple or unicameral bone cyst) Aneurysmal bone cyst Juxta-articular bone cyst (intraosseous ganglion) Metaphyseal fibrous defect (nonossifying fibroma) Eosinophilic granuloma (histiocytosis X, Langerhans cell granulomatosis) Fibrous dysplasia Osteofibrous dysplasia Myositis ossificans (heterotopic ossification) Brown tumor of hyperparathyroidism Intraosseous epidermoid cyst Giant cell (reparative) granuloma
( Unni KK: Dahlin s Bone tumor, 5 th ed., 1996) Classification of tumors of bone in Mayo Clinic patients Total cases Benign Malignant No. % Tumor No.of Cases Tumor No.of Cases Hematopoietic Chondrogenic Osteogenic Unknown Histiocytic Fibrogenic Notochordal Vascular Lipogenic Neurogenic Total 4,443 2,420 2,136 1,149 92 268 356 201 8 14 11,087 40.07 21.83 19.27 10.36 0.83 2.42 3.21 1.81 0.07 0.13 100.00 Osteochondroma Chondroma Chondroblastoma Chondromyxoid fibroma Osteoid osteoma Osteoblastoma Giant cell tumor Fibrous histiocytoma Hamartoma Hemangioma Lipoma Neurilemoma 872 335 119 45 331 87 568 9 1 108 7 14 2,496 Myeloma Lymphoma Chondrosarcoma Secondary chondrosarcoma Dedifferentiated chondrosarcoma Mesenchymal chondrosarcoma Osteosarcoma Parosteal osteosarcoma Ewing s sarcoma Malignancy in giant cell tumor Adamantinoma Malignant fibrous histiocytoma Desmoplastic fibroma Fibrosarcoma Chordoma Hemangioendothelioma Hemangiopericytoma Liposarcoma 3,749 694 775 120 120 34 1,649 69 512 35 34 83 12 255 356 80 13 1 8,591
(JAMA 74:656-64,1920) 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%
Graded bone tumors Osteosarcoma : G1 4 Chondrosarcoma : G 1 3 Fibrosarcoma : G1 4 Angiosarcoma : G1 3
Not graded bone tumors Benign tumors Ewing's sarcoma Mesenchymal chondrosarcoma Chordoma Adamantinoma Giant cell tumor
Histological parameters Cellularity (+) Cytologic atypia (+) Mitosis (-) Necrosis (-)
Classification of osteosarcoma Conventional osteosarcoma : G 3, 4 Osteoblastic Chondroblastic Fibroblastic Other Giant cell rich Epithelioid Small cell : G 4 Telangiectatic : G 4 Low-grade central : G 1 Parosteal : G 1, 2 Periosteal : G 2, 3 High-grade surface : G 3, 4 Secondary : G 4 Paget's sarcoma Postirradiation Other (Hematol Oncol Clin North Am 9:545-69,1995)
Survival according to Grade in osteosarcoma Grade No. of cases 5 y. SR(%) 1 2 2 63 27.0 3 218 19.7 4 128 17.2 Total 411 (J Bone Joint Surg 49A:101-10,1967)
Survival according to Grade in osteosarcoma 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 (J Natl Cancer Inst 81:21-30, 1989)
Grading of chondrosarcoma 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
Histologic parameters used in different grading system of chondrosarcoma Dahlin Evans Gitelis Cellularity + + + Cytologic atypia + + + Mitosis - + + Necrosis - + + Growth pattern - - +
Mitosis in 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 (Cancer 83:2105-19,1998)
Grades of chondrosarcoma Grade No. of cases % 1 207 61.2 2 120 35.5 3 11 3.3 Total 338 100.0 (Cancer 83:2105-19,1998)
Recurrence and metastatic rate according to Grade in chondrosarcoma Grade Recurrence rate(%) Metastatic rate(%) 1 15.2 4.6 2, 3 36.2 29.3 (Cancer 83:2105-19,1998)
Survival according to Grade in chondrosarcoma Grade 5 y. SR(%) 1 88.5 2, 3 57.1 (Cancer 83:2105-19,1998)
Grading of fibrosarcoma 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
Grades 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 (Cancer 23:35-41,1969)
Survival according to Grade in fibrosarcoma 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 (Cancer 23:35-41,1969)
Grading of angiosarcoma 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
Grades of angiosarcoma Grade No. of case % 1 33 29 2 51 46 3 28 25 Total 112 100 (Am J Surg Pathol 6:59-70,1982)
Survival according to Grade in angiosarcoma Grade No. of cases Disease free survival(%) 1 22 95 2 45 62 3 25 20 (Am J Surg Pathol 6:59-70,1982)
Summary 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, and angiosarcoma