Tumors of bone Tumors of bone - Cause usually unknown (Primary, idiopathic) - Genetic factors may play a role (p53 and RB mutations) - Bone infarcts, trauma, osteomyelitis, Pagets disease, radiation and metal prosthesis predispose to tumors Tumors of bone - Clinical presentation - Incidentally detected - Swelling and pain - Pathological fracture Interpret bone tumors with full knowledge of - Clinical picture - Radiology and imaging - Pathological findings Tumors of bone - Diverse in their gross and morphologic features, and clinical behavior. - Benign tumors outnumber malignancies and are commoner in young - Classification is done on the basis of tissue of origin Bone tumors Histologic type Benign Hematopoietic (40%) Malignant Myeloma, lymphoma Chondrogenic (22%) Osteochondroma, chondroma, chondroblastoma, chondromyxoid fibroma Chondroscarcoma, dedifferentiated and mesenchymal chondrosarcoma Osteogenic (19%) Osteoid osteoma, osteoblastoma Osteosarcoma Unknown (10%) Giant cell tumor Ewing sarcoma, giant cell tumor, adamantinoma Histiocytic Fibrous histiocytoma Malignant fibrous histiocytoma Fibrogenic Fibroma Desomplastic fibroma, fibrosarcoma Notochordal Chordoma Vascular Hemangioma Hemangioendothelioma, hemangiopericytoma, angiosarcoma Lipogenic Lipoma Liposarcoma Neurogenic Neurilemmoma (schwannoma) Tumors and tumor-like conditions of bone - Diverse in their gross and morphologic features, and clinical behavior. - Benign tumors outnumber malignancies and are commoner in young - Specific tumor types have preferential age and sex distribution - Specific tumor types preferentially involve specific bones and specific regions within a bone Metaphysis Osteogenic Sarcoma 10 20 30 40 50 60 70 yrs Chondrosarcoma 10 20 30 40 50 60 70 yrs Bone tumors All bone tumors should be studied along with x rays - Osteochondroma is the commonest benign tumor - Osteosarcoma is the commonest non-hematopoietic malignancy - Specific tumors target specific bones and sites and age groups - Osteosarcomas are more common in adolescence and arise from metaphysis around the knee. - Chondrosarcomas and giant cell tumors arise in epiphysis - Ewings sarcoma arises in diaphysis Histologic grade is the most important prognostic factor of a bone sarcoma Bone tumors Histologic type Benign Hematopoietic (40%) Malignant Myeloma, lymphoma Chondrogenic (22%) Osteochondroma, chondroma, chondroblastoma, chondromyxoid fibroma Chondroscarcoma, dedifferentiated and mesenchymal chondrosarcoma Osteogenic (19%) Osteoid osteoma, osteoblastoma Osteosarcoma Unknown (10%) Giant cell tumor Ewing sarcoma, giant cell tumor, adamantinoma Histiocytic Fibrous histiocytoma Malignant fibrous histiocytoma Fibrogenic Fibroma Desomplastic fibroma, fibrosarcoma Notochordal Chordoma Vascular Hemangioma Hemangioendothelioma, hemangiopericytoma, angiosarcoma Lipogenic Lipoma Liposarcoma Neurogenic Neurilemmoma (schwannoma) Osteoid osteoma - Benign bone tumor seen often in teens and young adults - < 2 cm diameter and have predilection for cortex of long bones - Painful lesions and can mimic osteomyelitis (PGE2) - Well circumscribed mass of woven bone rimmed by osteoblasts - This is called the nidus and is surrounded by reactive bone Osteosarcoma - Malignant mesenchymal tumor in which cancerous cells produce bone matrix - Most common non-hematopoietic bone tumor - 75% occur before the age of 20 years. Second peak in elderly - Commoner in males (1.6:1) - Arises from metaphysis of long bones. 60% arise around the knee - Patients with hereditary retinoblastomas have a 1000 fold risk - Metastasizes through hematogenous route (90% to lungs) - Advances in treatment (chemotherapy and limb salvage therapy) has improved long term survival to 60-70% Osteogenic Sarcoma 10 20 30 40 50 60 70 yrs Osteosarcoma - subcategorization Based on Subtypes Location Intramedullary / intracortical / periosteal etc Differentiation Well / poorly Histology Osteoblastic / chondroblastic / fibroblastic, telangiectatic / giant cell / small cell Others Solitary / multicentric Primary / secondary Osteosarcoma Gross: Bulky, gritty, hemorrhage and necrosis,bone destructive and spreading in different directions Microscopy: - Bizarre tumors cells with pleomorphic nuclei - Multinucleated giant cells - Formation of “lacy osteoid” - Formation of other types of matrix - Conspicuous vascular invasion - metastasize to lungs, brain X-ray: - Large destructive lytic and osteoblastic mass with infiltrating margins - Lifts periosteum (Codman triangle) and produces reactive periosteal bone formation Tumor grading - Low grade - High grade - Cell pleomorphism - Tumor differentiation - Necrosis - Mitotic activity Hematogenous spread is very common and 10-20% have pulmonary metastases at the time of diagnosis Bone tumors Histologic type Benign Hematopoietic (40%) Malignant Myeloma, lymphoma Chondrogenic (22%) Osteochondroma, chondroma, chondroblastoma, chondromyxoid fibroma Chondroscarcoma, dedifferentiated and mesenchymal chondrosarcoma Osteogenic (19%) Osteoid osteoma, osteoblastoma Osteosarcoma Unknown (10%) Giant cell tumor Ewing sarcoma, giant cell tumor, adamantinoma Histiocytic Fibrous histiocytoma Malignant fibrous histiocytoma Fibrogenic Fibroma Desomplastic fibroma, fibrosarcoma Notochordal Chordoma Vascular Hemangioma Hemangioendothelioma, hemangiopericytoma, angiosarcoma Lipogenic Lipoma Liposarcoma Neurogenic Neurilemmoma (schwannoma) Benign cartilage tumors: Osteochondroma: Bony spur / exostosis. Mushroom shaped bone projection covered by cartilage cap Chondroma: - Enchondroma ( intramedullary) or juxtacortical - Usually solitary and metaphyseal in short tubular bones and < 3 cms dia - Multiple tumors form part of Olliers disease (enchondromatosis) - Develop from rests of growth plate cartilage - Contain well circumscribed nodules of cartilage and cytologically benign chondrocytes - Endochondral ossification is seen at periphery - X-ray shows typical “O ring” sign - Malignant transformation more common in Ollier disease Chondrosarcoma - Malignant tumors that form neoplastic cartilage - Subtypes: a) Intramedullary and juxtacortical b) Conventional (hyaline / myxoid), clear cell, dedifferentiated, mesenchymal c) Low grade to high grade - Usually seen in patients above 40, more in men (2:1) - More often in central parts of skeleton - Large bulky tumors with glistening cut surface with central necrosis - Tumor spreads by pushing margins - Low grade tumors almost similar to enchondromas - High grade show marked pleomorphism and bizarre morphology Bone tumors Histologic type Benign Hematopoietic (40%) Malignant Myeloma, lymphoma Chondrogenic (22%) Osteochondroma, chondroma, chondroblastoma, chondromyxoid fibroma Chondroscarcoma, dedifferentiated and mesenchymal chondrosarcoma Osteogenic (19%) Osteoid osteoma, osteoblastoma Osteosarcoma Unknown (10%) Giant cell tumor Ewing sarcoma, giant cell tumor, adamantinoma Histiocytic Fibrous histiocytoma Malignant fibrous histiocytoma Fibrogenic Fibroma Desomplastic fibroma, fibrosarcoma Notochordal Chordoma Vascular Hemangioma Hemangioendothelioma, hemangiopericytoma, angiosarcoma Lipogenic Lipoma Liposarcoma Neurogenic Neurilemmoma (schwannoma) Ewing Sarcoma and PNET (primitive neuro-ectodermal tumor) - Primary malignant small round cell tumors of bone and soft tissue - Share similar neural phenotype and chromosomal translocation - Second commonest malignant non-hematopoietic bone tumor in children - Children 10-15 years old, boys more affected. Diaphysis of long bones - 85% show t(11;22) - Tumors arise from medullary cavity, invade cortex, spread to soft tissue - Comprised of small round cells slightly larger than lymphocytes - Cells are rich in glycogen. - May show Homer-Wright rosettes. Necrosis is seen - Xray shows typical layers of reactive bone (“Onion-skin” pattern Gross: - Arise in medullary cavity (diaphysis) - Invade cortex and periosteum - Tan white colour with hemorrhage and necrosis Microscopy: - Sheets of uniform small cells - Rosettes (Homer-Wright) - Few mitotic figures Giant Cell Tumor: (Osteoclastoma) - Contains numerous osteoclast type of giant cells (monocyte macrophage) - Benign but locally aggressive - Patients between 20 to 40 years - Involve both epiphysis and metaphysis and are common in long bones - Xray shows typical soap bubble appearance and thin reactive shell - Tumor comprised of oval mononuclear cells growing in sheets mixed with osteoclast type of giant cells with more than 100 nuclei - Necrosis and hemorrhage common - Biologically unpredictable tumors Involve both epiphysis and metaphysis Large purely lytic - “Soap bubble” tumors Gross: - Large, red-brown - Hemorrhage and cystic degeneration - Uniform mononuclear cells in sheets with increased mitoses - Numerous osteoclast type of giant cells with > 100 nuclei