Pintor

Chapter 501 – Neoplasms of Bone

Carola A.S. Arndt

501.1 Malignant Tumors of Bone

The annual incidence of malignant bone tumors in the USA is approximately 7 cases per million white children <14 yr of age, with a slightly lower incidence in African-American children. Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, followed by Ewing sarcoma (Table 501-1 ; Fig. 501-1 ). In children <10 yr of age, Ewing sarcoma is more common than osteosarcoma. Both tumor types are most likely to occur in the second decade of life.

TABLE 501-1 -- Comparison of Features of Osteosarcoma and the Ewing Family of Tumors
FEATURE OSTEOSARCOMA EWING FAMILY OF TUMORS
Age Second decade Second decade
Race All races Primarily whites
Sex (M : F) 1.5 : 11.5 : 1
Cell Spindle cell–producing osteoid Undifferentiated small round cell, probably of neural origin
Predisposition Retinoblastoma, Li-Fraumeni syndrome, Paget disease, radiotherapy None known
Site Metaphyses of long bones Diaphyses of long bones, flat bones
Presentation Local pain and swelling; often, history of injury Local pain and swelling; fever
Radiographic findings Scleroticdestruction (less commonly lytic); sunburst pattern Primarily lytic, multilaminar periosteal reaction (“onion skinning”)
Differential diagnosis Ewing sarcoma, osteomyelitis Osteomyelitis, eosinophilic granuloma, lymphoma, neuroblastoma, rhabdomyosarcoma
Metastasis Lungs, bones Lung, bones
Treatment Chemotherapy Chemotherapy
Ablative surgery of primary tumor Radiotherapy and/or surgery ofprimary tumor
Outcome Without metastases: 70% cured; with metastases at diagnosis, ≤20% survival Without metastases: 60% cured; with metastases at diagnosis, 20–30% survival

Figure 501-1 A, Age and skeletal distribution of 1,649 cases of osteosarcoma in the Mayo Clinic files. B, Age and skeletal distribution of 512 cases of Ewing sarcoma in the Mayo Clinic files. (From Unni KK [editor]:Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases, 5th ed. Philadelphia, Lippincott-Raven, 1996. Reprinted by permission of the Mayo Foundation.)


OSTEOSARCOMA

EPIDEMIOLOGY.

The annual incidence of osteosarcoma in the USA is 5.6 cases per million children <15 yr of age. The highest risk period for development of osteosarcoma is during the adolescent growth spurt,suggesting an association between rapid bone growth and malignant transformation. Patients with osteosarcoma are taller than their peers of similar age.

PATHOGENESIS.

Although the cause of osteosarcoma is unknown, certain genetic or acquired conditions predispose patients to development of osteosarcoma. Patients with hereditary retinoblastoma have a significantly increased risk of developingosteosarcoma. The sites of osteosarcoma in these patients initially were thought to be located only in previously irradiated areas, but more recently they have been shown to arise in sites far from the radiation field. Predisposition to development of osteosarcoma in these patients may be related to loss of heterozygosity of the RB gene. Osteosarcoma also occurs in the Li-Fraumeni syndrome, which isa familial cancer syndrome associated with germline mutations of the p53 gene. Kindreds with Li-Fraumeni syndrome have a spectrum of malignancies in 1st-degree relatives, including carcinoma of the breast, soft tissue sarcomas, brain tumors, leukemia, adrenal cortical carcinoma, and other malignancies. Rothmund-Thomson syndrome is a rare syndrome associated with short stature, skin telangiectasia,small hands and feet, hypoplastic or absent thumbs, and a high risk of osteosarcoma. Osteosarcoma also can be induced by irradiation for Ewing sarcoma, craniospinal irradiation for brain tumors, or high-dose irradiation for other malignancies. Other benign conditions that can be associated with malignant transformation to osteosarcoma include Paget disease, enchondromatosis, multiple hereditary...