Bone Tumors PDF

Bone Tumors http://www.radiologyassistant.nl/ Dr. H. Kemal Türköz Classification Bone-Forming Tumors Cartilage-Forming Tumors Fibrous / Fibroosseous Tumors Miscellaneous Bone Tumors Bone-Forming Tumors Osteoma benign most frequent: head and neck middle age histologic examination recapitulate cortica...

Bone Tumors http://www.radiologyassistant.nl/ Dr. H. Kemal Türköz Classification Bone-Forming Tumors Cartilage-Forming Tumors Fibrous / Fibroosseous Tumors Miscellaneous Bone Tumors Bone-Forming Tumors Osteoma benign most frequent: head and neck middle age histologic examination recapitulate cortical-type bone They are not locally aggressive Multiple lesions=> Gardner syndrome Pathout server Osteoid Osteoma and Osteoblastoma Benign same histologic features, different size and clinical features 2-3rd decades, male predilection. Osteoid osteomas- proximal femur and tibia or posterior spinal elements and are by definition less than 2 cm in diameter. - Localized pain, severe at night, aspirin => osteoid osteoma. Osteoblastomas- larger. - Most often in the vertebral column; pain is not localized, not responsive to aspirin Local excision is the treatment of choice. interlacing trabeculae of woven bone surrounded by osteoblasts. The intervening stroma is loose, vascular connective tissue. Rim of sclerotic noneoplastic bone Osteosarcoma. Bone-producing malignant mesenchymal tumor. 3rd most frequent malignant bone tumor (After myeloma and lymphoma). 75% of patients are younger than 20 years of age, with a second peak occurring in elderly persons.. most tumors arise in the metaphyseal region of the long bones of the extremities, with almost 60% occurring about the knee Sites of greatest bone growth (rapidly dividing cells provide a fertile soil for mutations). Several subtypes: - site of involvement (medullary / cortical), - degree of differentiation. The most common type of osteosarcoma is primary, solitary, intramedullary, and high grade, producing a predominantly bony matrix Painful enlarging masses Radiographic imaging => large, destructive mass The tumor frequently breaks through the cortex and lifts the periosteum => reactive periosteal bone formation. A triangular shadow on the x-ray film between the cortex and raised periosteum (Codman triangle) is characteristic of osteosarcomas. Osteosarcomas typically spread hematogenously; at the time of diagnosis, approximately 10% to 20% of patients have demonstrable pulmonary metastases Pleomorphism, hyperchromasia, nucleomegaly, bizarre tumor giant cells, common mitotic figures. The production of mineralized or unmineralized bone (osteoid) by malignant cells is essential for diagnosis Cartilage and fibroblastic differentiation can also be present (osteoblastic, chondroblastic , fibroblastic) Therapy Neoadjuvant Chemotherapy + limb salvage therapy Despite aggressive behavior, standard treatment with chemotherapy and limb salvage therapy currently yields long-term survivals of 60% to 70%. Secondary osteosarcomas occur in older adults most commonly in the setting of Paget disease or previous radiation exposure. They do not respond well to therapy and are usually fatal. Cartilage-Forming Tumors Osteochondroma Chondroma Chondrosarcoma Osteochondroma Benign, cartilage-capped tumors with a bony stalk Solitary osteochondromas: Late adolescence and early adulthood (male-to-female ratio of 3 : 1) Multiple osteochondromas=> childhood (multiple hereditary osteochondromas, an autosomal dominant disorder) Bones of endochondral origin arising at the metaphysis near the growth plate of long tubular bones Tend to stop growing once the normal growth of the skeleton is completed 1 to 20 cm in size Cartilaginous cap that is usually less than 2 cm in thickness. (Thicker cap => Malignancy?) Solitary osteochondromas rarely progress to chondrosarcoma or other sarcomas, multiple hereditary osteochondromas => more frequent malignant transformation Chondroma benign neoplasms of hyaline cartilage 20 - 50 years of age. Solitary type: metaphyseal region of tubular bones (short tubular bones of the hands and feet) Ollier disease: multiple chondromas. one side of the body Maffucci syndrome: multiple chondromas + soft tissue spindle cell hemangiomas. Pathogenesis: Syndromic types=>point mutations in either isocitrate dehydrogenase I (IDH1) or IDH2. l l l l l Gray-blue, translucent nodules usually smaller than 5 cm Well circumscribed and composed of hyaline cartilage containing cytologically benign chondrocytes. Malignant transformation: Solitary / Enchondromatoses Maffucci syndrome is associated with an increased risk for development of other types of malignancies. Chondrosarcoma Malignant connective tissue tumor (sarcoma) Cells produce and secrete cartilage matrix Classification: - Location: intramedullary / juxtacortical - Histologic variants: Classic, Myxoid, Clear cell, mesenchymal, dedifferentiated Frequent localizations: Axial skeleton + pelvis and shoulder (in contrast with enchondromas, chondrosarcomas rarely involve the distal extremities) Most patients are at 5th decade or older. Most conventional chondrosarcomas are indolent and low-grade. 5-year survival rate 80% to 90% (versus 43% for grade 3 tumors) Grade 1 => rarely metastasize, Grade 3 => %70 dissemination (hematogenous) Conventional chondrosarcomas are treated with wide surgical excision; chemotherapy is added for the mesenchymal and dedifferentiated variants. Effectiveness??? Fibrous / Fibroosseous Tumors Fibrous Cortical Defect and Nonossifying Fibroma Fibrous Dysplasia Fibrous Cortical Defect / Nonossifying Fibroma Fibrous cortical defects Probably developmental abnormalities The vast majority are smaller than 0.5 cm Eccentrically in the metaphysis of the distal femur or proximal tibia Nonossifying fibromas Larger (5-6 cm) Sharply demarcated, zone of sclerosis. Activating mutations in RAS-MAPK pathway Microscopy: Fibroblasts and activated macrophages, including multinucleate forms Hemorrhage and hemosiderin Fibrous cortical defects are asymptomatic spontaneous differentiation into normal cortical bone No Biopsy Indication The few that enlarge into nonossifying fibromas => Pathologic fracture Biopsy is necessary Fibrous Dysplasia Benign All components of normal bone, but failure to differentiate into mature structures Mutations of the GNAS gene=>constitutively active G protein Clinical Patterns: (1) Monostotic involvement of a single bone %70. 2-3. decade. Ribs, femur, tibia, jawbones (2) Polyostotic involvement of multiple bones. Majority of the rest. Slightly younger. Femur, skull, tibia, humerus. (3) Polyostotic disease, café au lait skin pigmentations and endocrine abnormalities (McCune- Albright syn) Morphologic features: Well-circumscribed, intramedullary lesions. Curved trabeculae of woven bone (Chinese characters). No osteoblastic rimming around bone trabeculae.. A moderately cellular fibroblastic proliferation monostotic disease - minimal symptoms. Polyostotic - progressive disease and more severe skeletal complications (e.g., fractures, long bone deformities, craniofacial distortion). Rarely, polyostotic disease can transform into osteosarcoma. Miscellaneous Bone Tumors Ewing Sarcoma (Primitive Neuroectodermal Tumor) Primary malignant small round cell tumors of bone and soft tissue After osteosarcoma, it is the second most common pediatric bone sarcoma 10 to 15 years of age, and 80% are younger than 20 years t(11;22)(q24;q12) fusion transcript by RT-PCR of FLI1-EWS genes t(21;22)(q12q12) of ERG-EWS genes t(7;22)(p22;q12) of ETV1-EWS genes t(17;22)(q12;q12) of E1AF-EWS genes t(2;22)(q33;q12) of FEV-EWS genes Product of translocation is chimeric protein => transcription factor Ewing Diaphyses of long tubular bones (especially the femur) and the pelvic flat bones. Imaging => destructive lytic tumor Periosteal reaction with deposition of bone in an onion-skin pattern. Treatment includes chemotherapy and surgical excision with or without irradiation. The 5-year survival rate: 75% Sheets of uniform small, round cells The presence of Homer-Wright rosettes (tumor cells circled about a central fibrillary space) Giant Cell Tumor of Bone Multinucleate osteoclast-type giant cells (osteoclastoma) Benign but locally aggressive Age: 20s to 40s Neoplastic component is the mononuclear cells, no the giant cells These cells may be related to osteoblast precursor cells, as they express RANK ligand, which may stimulate the development of surrounding non-neoplastic osteoclastlike cells. Uniform oval mononuclear cells and scattered osteoclast-type giant cells containing upto around 100 nuclei Majority arise in the epiphysis in the long bones around the knee Pain and fractures. Most are solitary tumors. Radiographically, GCTs are large, purely lytic, and eccentric; the overlying cortex frequently is destroyed Although GCTs are considered benign, roughly half recur after simple curettage, and as many as 2% spread to the lungs as localized lesions that are cured by local excision. Metastatic Disease Metastatic tumors are the most common malignant tumors involving bone. Certain tumors exhibit a distinct skeletal predilection. Adults more than 75% of skeletal metastases=> prostate, breast, kidney, and lung. Children=> neuroblastoma, Wilms tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma