Osteosarcoma

•Giant cell

•Epithelioid

Telangiectatic Well differentiated

•The most common bone tumor in children and adolescents, representing approximately 35% of primary sarcomas of bone

•Rare in the first decade of life (less than 5%)

•Approximately 60% of patients are between 10 and 20 years old

•Occurs most frequently during the adolescent growth spurt

•Bimodal age distribution: the first peak during second decade of life, and a small peak (controversial) in patients older than 50 years

•Male to female ratio is 1.3–1.6:1

•Peak incidence in second decade of life is somewhat higher in white males than in males of other races

13.3Location

•Skeletal regions affected by greatest growth rate, that is, distal femoral and proximal tibial metaphyses

•Approximately 50% of osteosarcoma in knee region

•Humerus is third most frequently involved bone, usually proximal humeral metaphysis and diaphysis

•Pelvis, that is, ilium, occurs in approximately 10% of cases

13.4Etiology and Tumor Genetics

•Etiology is unknown

•Relation between rapid bone growth as in adolescence and development of osteosarcoma

•Ionizing radiation

•No evidence for a viral etiology

•Alkylating agents and anthracyclines may be involved in secondary osteosarcoma.

•Association with Paget disease

•Familial osteosarcoma has been reported

•Osteosarcoma following hereditary retinoblastoma or associated with mutations in the retinoblastoma (RB) gene without manifestation of a retinoblastoma are

well described. However, normal RB alleles are found in most investigated osteosarcomas

•Further evidence of genetic background of osteosarcoma is reflected by frequently observed mutations in the TP53 suppressor gene

•Li-Fraumeni syndrome, a familial cancer syndrome associated with a germline TP53 mutation is strongly associated with osteosarcoma

13.5Pathology

•Morphological classification (e.g., osteoblastic, chondroblastic, fibroblastic)

•Classification according to growth pattern, e.g., intramedullary osteosarcoma (origin and growth primarily within bone tissue) and surface osteosarcoma (growth at surface of bone with periosteal or parosteal tissue)

•There are various classification systems without standardization

•Classification is mainly descriptive; there is often a variability of several tissue types, that is, production of osteoid, anaplastic stroma cells, different amount of bone tissue, small and large round cells, giant cells, normal osteoclasts. There is no clear phenotypic association with the morphological subtypes

•Approximately 50% of bone tumors are malignant

•Telangiectatic osteosarcoma is a rare type osteosarcoma that appears to be a separate entity, although similar to conventional osteosarcoma in clinical aspects

•The previously reported poor prognosis of this subtype, being much worse than conventional osteosarcoma, has improved and now is not different from conventional.

–Management as conventional osteosarcoma

•Small-cell osteosarcoma may be confused with Ewing sarcoma, but distinguishable by osteoid production

–Biopsy: adequate tumor sample is required for diagnosis

–Management as for conventional osteosarcoma

13.6Clinical Manifestations

•The most frequent symptom is pain originating from the involved region, often for weeks or even months

•Sometimes swelling with local signs of inflammation

•Loss of function

•Weight loss is unusual an points to metastatic disease if present

13.7Metastasis

•At time of diagnosis, macrometastases are present in approximately 15–20% of patients present, but micrometastases (mainly lungs) much more frequently present

•Lung is the most frequent site of metastasis

•Rarely, skeletal metastases with or without simultaneous lung metastases can occur

•Multiple bone metastases may also reflect multifocal osteosarcoma with a poor prognosis

13.8Evaluation

•Clinical work-up: history, physical examination (pain, location, swelling, signs of inflammation, function)

•Radiology: plain radiographs in two planes, magnetic resonance imaging (MRI) of primary site, at least complete involved bone plus adjacent joints (tumor extent in bone and soft tissues); MRI is more appropriate than computed tomography (CT) scan

•Metastases: chest X-ray, CT scan of thorax, skeletal radionuclide scan with MRI or CT of presumed sites of involvement

•Open biopsy of tumor (before chemotherapy)

•Biopsy preferably performed by the same orthopedic team involved in future surgery of the patient

•Close collaboration: pediatric oncology, orthopedics, pathology, radiology (interdisciplinary tumor board)

13.9Radiology

•High variability

•Radiological classification of lytic and sclerotic tumors; both components are often present

•Tumor matrix may be mineralized, resulting in variable dense opacities of different sizes and shapes

•Tumor margins may be poorly defined. Destructive growth pattern with lytic and sclerotic areas and normal bone tissue are commonly observed

•Cortex exhibits frequently destructive growth; the tumor is rarely limited to medullary space

•Extension into soft tissue common

•Periosteal reaction often present, with various features, occasionally as radiating striations called “sunburst signs,” or as open triangles overlying the diaphyseal side of the lesion, (Codman’s triangle) or in the form of multiple layers (“onion skin”)

13.10 Differential Diagnosis

•May be confused with benign and malignant bone lesions

•Callus formation following fracture

•Osteogenesis imperfecta (type I)

•Acute and chronic osteomyelitis

•Osteoblastoma