BONE TUMOURS Day : Tuesday Date : 11-12-2007 Time : 1.00-2.00

Bone Tumours Understand the clinical algorithm WHAT SHOULD YOU KNOW Understand the clinical algorithm Correlate clinical presentation with radiological features Understand the classification and types of bone tumours Comprehend the management of bone tumours Understand the necessity for a team-approach Correlate Pathological findings with clinical presentation (Clinico-pathological correlation)

BONE TUMOURS may result in amputation rare but may result in amputation disfigurement and great physical challenge

Classification of bone tumours Simple classification A i. Primary ii Secondary- more common B i. Benign - oma ii. Malignant - sarcoma

Primary Bone tumors are classified according to the cell of origin

Histologic Type Benign Malignant Hematopoietic (40%)   Myeloma Malignant lymphoma Chondrogenic (22%) Osteochondroma Chondrosarcoma Chondroma Dedifferentiated chondrosarcoma Chondroblastoma Mesenchymal chondrosarcoma Chondromyxoid fibroma Osteogenic (19%) Osteoid osteoma Osteosarcoma Osteoblastoma Unknown origin (10%) Giant cell tumor Ewing tumor Adamantinoma Histiocytic origin Fibrous histiocytoma Malignant fibrous histiocytoma Fibrogenic Metaphyseal fibrous defect (fibroma) Desmoplastic fibroma Fibrosarcoma Notochordal Chordoma Vascular Hemangioma Hemangioendothelioma Hemangiopericytoma Lipogenic Lipoma Liposarcoma Neurogenic Neurilemmoma

Diagnosis of Bone Tumours 1. Age of patient 2. Location of tumour 3. Radiological appearance 4. Histological features

AGE(probably the most important clinical clue). Age group Most common benign lesions Most common malignant tumors 0-20 non-ossifying fibroma fibrous dysplasia simple bone cyst aneurysmal bone cyst osteochondroma (exostosis) osteoid osteoma osteoblastoma chondroblastoma chondromyxoid fibroma eosinophilic granuloma Ewing's sarcoma leukemic involvement metastatic neuroblastoma osteosarcoma, Ewing's sarcoma, 21 - 40 enchondroma giant cell tumor chondrosarcoma 40 & above osteoma metastatic tumors myeloma leukemic involvement chondrosarcoma osteosarcoma (Paget's associated) MFH chordoma

SITE OF LONG BONE INVOLVEMENT (most primary bone tumors have favored sites within long bones; this may provide a clue to diagnosis). Diaphyseal lesions centered in the cortex: Osteoid osteoma Diaphyseal intramedullary lesions: Ewing's sarcoma, lymphoma, myeloma. Common for fibrous dysplasia and enchondroma Metaphyseal intramedullary lesions: Osteosarcoma is usually centered in the metaphysis. Chondrosarcoma and fibrosarcoma often present as metaphyseal lesions. Osteoblastoma, enchondroma, fibrous dysplasia, simple bone cyst, and aneurysmal bone cyst are common in this location. Metaphyseal lesions centered in the cortex: Classic location for a non-ossifying fibroma (NOF). Also, a common site for osteoid osteoma. Epiphyseal lesions: Chondroblastoma (Ch) and Giant Cell Tumor (GCT) are almost invariably centered in the epiphysis. Chondroblastoma is a rare tumor seen in children and adolescents with open growth plates. GCT is the most common tumor of epiphyses in skeletally mature individuals with closed growth plates. GCT often shows metaphyseal extension. Metaphyseal exostosis: Osteochondroma

Radiological Features

Benign Tumours Osteochondroma Also known as an exostosis, is a cartilage –capped out growth. Men are affected three times more often than women Develop in bones of endochondral origin and arise from the metaphysis near the growth plate of long bones especially about the knee

Development over time of an osteochondroma beginning with an outgrowth from the epiphyseal cartilage

Osteochondroma Clinically present as slow growing masses Can be painful if they impinge on a nerve or if stalk is fractured. In many cases, they are detected as an incidental finding. Rarely they give rise to chondrosarcoma

Osteochondroma of femur The white arrows point to a mushroom-shaped, peduculated bony excresence arising from the anteromedial aspect of the distal femoral metaphysis, attached to the parent bone and pointing away from the metaphyisis Osteochondroma of femur

Osteochondroma

Chondroma Benign tumours of hyaline cartilage May arise within the medullary cavity-enchondroma May arise on the surface of bone – subperiosteal chondroma Enchondromas are the most common Located in the metaphyseal region of tubular bones Most enchondromas are asymptomatic and detected as incidental finding

Enchondroma of the phalanx with a pathological fracture

Enchondroma with a nodule of hyaline cartilage encased by a thin layer of reactive bone.

Osteoid osteoma and Osteoblastoma Have identical histology Osteoblastoma larger than osteoid osteoma

Osteoid osteoma < 2 cm in greatest dimension Affects teenagers and adolescents 75 % of patients < 25 years Affects cortex of femur or tibia Painful lesion Relieved by salicylate

Osteoid osteoma of Femoral neck

Osteoid osteoma

1. Compare and contrast : with respect to: Chondrosarcoma Osteosarcoma Chondrosarcoma Giant cell tumor Ewing's tumor with respect to: Histogenesis age of group affected location in the skeleton histologic hallmarks clinical behaviour prognosis

Osteosarcoma (OS) Most common primary malignant tumor of the bone Mesenchymal tumor Cancerous cells produce bone matrix 75 % occur in patients younger than 20 years of age

Osteosarcoma (OS) Primary osteosarcoma arise in the metaphysis of long bones of the extremities Secondary osteosarcomas occur in older patients with Paget’s disease More common in men than women Common sites are distal end of femur or proximal tibia

Osteosarcoma (OS) Patients with Mutation of Rb gene are predisposed to osteosarcoma Concurrent trauma to bones and joints In the elderly OS often arises from pre existing bone diseases eg: Paget’s disease of bone

Osteosarcoma (OS) Clinical Presentation Painful and progressively enlarging masses Spread through blood stream The tumour breaks through the cortex and lifts the periosteum Often metastasizes to the lungs

Osteosarcoma on distal end of femur Cortex is destroyed

Neoplastic osteoblasts forming osteoid

Chondrosarcoma Frequency is about half of osteosarcoma Second most common malignant matrix producing tumor Mean age for chondrosarcoma is 43 years Men are affected more than women

Chondrosarcomas Commonly arise in the central portions of the skeleton including Pelvis, proximal femur, ribs, sternum and shoulder girdle

Chondrosarcoma Present as painful progressively enlarging masses Prognosis depends on size of tumor Spreads to lungs and skeleton

Chondrosarcoma

Chondrosarcoma Tumor has developed in the proximal femur Not destroyed the cortex Has a bluish, glassy appearance , reminiscent of cartilage

Malignant neoplastic cells produce a chondroid matrix

The aggressiveness of chondrosarcomas can be predicted by their histologic grade. Grading system is based on three parameters: cellularity, degree of nuclear atypia and mitotic activity. Grade 1 (low-grade) Very similar to enchondroma. However, the cellularity is higher, and there is mild cellular pleomorphism. The nuclei are small but often show open chromatin pattern and small nucleoli. Binucleated cells are frequent. Mitoses are very rare. Grade 1 chondrosarcomas are locally aggressive and prone to recurrences, but usually do not metastasize. Grade 2 (low-grade) The cellularity is higher than in Grade 1 tumors. Characteristic findings are moderate cellular pleomorphism, plump nuclei, frequent bi-nucleated cells, and occasional bizarre cells. Mitoses are rare. Foci of myxoid change may be seen. Unlike Grade 1 tumors, about 10% to 15% of Grade 2 chondrosarcomas produce metastases. Grade 3 (high-grade) Characteristic findings are high cellularity, marked cellular pleomorphism, high N/C ratio, many bizarre cells and frequent mitoses (more than 1 per hpf). These are high grade tumors with significant metastatic potential.

Giant cell tumour of bone (GCT) Contains a profusion of multinucleated osteoclast type giant cells Relatively uncommon benign But locally aggressive Usually arises during 5th decade Slight female predominance

Involve both epiphysis and metaphysis Giant cell tumour of bone (GCT) Involve both epiphysis and metaphysis In adolescents limited to metaphysis Common sites are distal femur and proximal tibia

Ewing sarcoma(ES) Primary malignant small round cell tumour Ewing sarcoma has the youngest average age at presentations (10-15 years) Boys slightly more often affected than girls

Ewing sarcoma(ES) Pelvis is the most common site usually arises in the diaphysis of long bones especially femur followed by tibia and humerus

Ewing sarcoma of tibia from a child

The following studies are required to support the diagnosis of ES and PNET: Demonstration of t(11;22) or EWS-FLI-1 fusion transcript (present in both ES and PNET) Immunostains(both ES and PNET are positive for CD99/O13. In addition, PNET shows positive staining with neural markers) EM (ES cells are undifferentiated and show prominent glycogen deposits; PNET shows neural differentiation)

The pathways of spread include Ewing sarcoma(ES) The pathways of spread include Direct extension Lymphatic or vascular dissemination Intraspinal seeding

Secondary tumours of bone Metastatic cancer to bone is more common than primary cancer of bone

75% of bone metastasis originate from Cancers of prostate breast kidney lung thyroid Metastatic lesions are multifocal Produce a lytic and or blastic reaction

Bone metastasis

Bone metastasis

Prostatic carcinoma metastatic to bone