MSK Tumours Osteosarcoma Introduction and Epidemiology A malignant mesenchymal tumor in which the cancerous cells produce bone matrix. Most common primary malignant tumor of bone approximately 20% of primary bone cancers. Bimodal age distribution: 75% occur in persons younger than 20 years of age, the rest in patients above 60 (assc with Pagets dz, bony infarcts, radiation). May affect any bone but most commonly involves the long-bone metaphyses, especially around the knee. Pathogenesis Approximately 70% of osteosarcomas have acquired genetic abnormalities such as ploidy changes and chromosomal aberrations, none of which are specific. Examples of abnormalities: a) RB gene mutation b) p53 gene mutation c) Abnormalities in INK4a gene )Strong association with sites of active bone growth. Morphology and Description Site of origin (intramedullary, intracortical, or surface). Degree of differentiation Multicentricity (synchronous, metachronous) Primary (underlying bone is unremarkable) or secondary to preexisting disorders such as benign tumors, Paget disease, bone infarcts, previous irradiation. Histologic features (osteoblastic, chondroblastic, fibroblastic, telangiectatic, small cell, and giant cell). Most common subtype
Arises in the metaphysis of
long bones and is primary, solitary, intramedullary and poorly differentiated. Gross Features Big bulky tumors that are gritty, gray-white, and often contain areas of hemorrhage and cystic degeneration. Frequently destroy the surrounding cortices and produce soft-tissue masses. They spread extensively in the medullary canal, infiltrating and replacing the marrow surrounding the preexisting bone trabeculae. Infrequently, they penetrate the epiphyseal plate or enter the joint. When joint invasion occurs, the tumor grows into it along tendoligamentous structures or through the attachment site of the joint capsule. Histological Features The formation of bone by the tumor cells is characteristic. The tumor cells vary in size and shape and frequently have large hyperchromatic nuclei. Bizarre tumor giant cells are common, as are mitoses. The neoplastic bone usually has a coarse, lace-like architecture but also may be deposited in broad sheets or as primitive trabeculae. Other matrices, including cartilage or fibrous tissue, may be present in varying amounts. Variants of OsteoSa 1. Parosteal Sa .This is a low-grade sarcoma situated on the surface of one of the tubular bones, usually at the distal femoral or proximal tibial metaphysis. 2. Periosteal Sa .True osteosarcoma, but characteristically the sections show a prominent cartilaginous element. 3. Pagets Sa .High grade tumour with f eatures of Pagets disease, but with areas of bone destruction and soft-tissue invasion Clinical Features Painful, progressively enlarging masses. Pain is usually worse at night. Sometimes a sudden fracture of the bone is the first symptom. Features of metastases to the lungs, brain and other bones. Radiological Features Hazy osteolytic areas may alternate with unusually dense osteoblastic areas. The endosteal margin is poorly defined. Often the cortex is breached and the tumour extends into the adjacent tissues. When this happens, streaks of new bone appear, radiating outwards from the cortex (sunburst effect). Where the tumour emerges from the cortex, reactive new bone forms at the angles of periosteal elevation (Codmans triangle). Ewings Sarcoma Introduction and Epidemiology Ewing sarcoma family of tumors encompasses Ewing sarcoma and primitive neuroectodermal tumor (PNET), which are primary malignant small round-cell tumors of bone and soft tissue. Believed to arise from endothelial cells in the bone marrow. Occurs most commonly between the ages of 10 and 20 years, usually in a tubular bone and especially in the tibia, fibula or clavicle. Boys are affected slightly more frequently than girls, whites are affected more than blacks. Pathogenesis Most Ewing sarcoma/PNET have a translocation involving the EWS gene on chromosome 22 and a gene encoding an ETS family transcription factor. The most commonly involved ETS gene is FLI1, as part of a (11;22) (q24;q12) translocation. Morphology and Description The tumor is soft, tan-white, and frequently contains areas of hemorrhage and necrosis. It is composed of sheets of uniform small, round cells that are slightly larger than lymphocytes. They have scant cytoplasm, which may appear clear because it is rich in glycogen. The presence of Homer-Wright rosettes is indicative of neural differentiation. Relatively few mitotic figures in relation to the dense cellularity of the tumor. Clinical Features Similar to osteoSa. With systemic manifestations such as intermittentfevers,anemia,leukocytosis, increasedESR. Radiological Features An area of bone destruction that is predominantly in the mid-diaphysis. New bone formation may extend along the shaft and sometimes it appears as fusiform layers of bone around the lesion onion peel effect. Sunburst appearance and Codmans triangle. Secondary Metastatic Disease Origins Adults: a) Male: Prostate b) Female: Breast c) Others: RCC, thyroid ca, lung ca, liver ca. )Children: )Neuroblastoma, Wilms tumor, OsteoSa, Ewing Sa, rhabdomyoSa Staging of MSK Tumours Enneking System Grade G0 - Benign lesion G1 - Low-grade malignant lesion G2 - High-grade malignant lesion Site T0 - A benign tumor that is confined within a true capsule and the lesion's anatomic compartment of origin (ie, a benign intracapsular, intracompartmental lesion) T1- An aggressive benign or malignant tumor that is still confined within its anatomic compartment (ie, an intracompartmental lesion) T2 - A lesion that has spread beyond its anatomic compartment of origin (ie, an extracompartmental lesion) Metastasis M0 - No regional or distant metastasis M1 - Regional or distant metastasis Staging of Malignant Tumors