++
Osteosarcoma is the most common
malignant primary bone tumor in children and adolescents.Osteosarcoma’s
destruction of normal bone architecture and its production of malignant
osteoid can permit its identification from skeletal remains, allowing
the recognition that it is an ancient disease. Among the earliest
malignant bone tumor described in humans, it was presumed to be
identified in the humerus of a male Celt from 800 to 600 BC.1 A
probable osteosarcoma dates back to 250 AD in the
pelvis of a young individual from Ancient Egypt. A definite osteosarcoma
with a classic sunburst appearance was found in the remains of the
femur of a Peruvian from approximately 1100 to 1200 AD.1 The
term osteosarcoma was introduced by Alexis Boyer
(1757–1833), and the first large clinical-pathological
description of sarcomas of bone was performed by Samuel Weissel
Gross (1837–1889).2 In this description,
the tendency for hematogenous and not lymphatic dissemination, as
well as the occurrence of skip metastases, led to the suggestion
that amputation be performed at a distance beyond the primary lesion.2
++
The diagnosis of osteosarcoma can be made based on histologic
examination of pathologic material, staging can be performed with
imaging procedures, and multimodality therapy including chemotherapy and
surgery successfully treat the majority of patients. Much information
has been acquired about the natural history and biology of this
disease. Despite all of these advances, osteosarcoma remains enigmatic. The
biology of the tumor is incompletely understood, and recent trials
modifying therapy have failed to produce further advances. Patients
with localized disease have a 5-year survival of at least 70%;
patients with metastatic or recurrent disease have a < 20% chance
of long-term survival despite aggressive therapies. These figures
have changed little in the past 2 decades.3-6 A challenge
over the next few years will be to develop strategies to understand
better the biology and behavior of this tumor, to facilitate further
advances in its treatment. The objective of this chapter is to review
what is known about osteosarcoma, including its epidemiology, etiology,
biology, presentation, evaluation, staging, pathology, treatment,
and future approaches. This will establish a context in which emerging
strategies are being developed which may change the outlook for
patients with this disease.
+++
Epidemiology/Etiology
++
Several features characterize the epidemiology of osteosarcoma
and have been taken as providing some clues as to its pathogenesis. Osteosarcoma
has a bimodal age distribution with the first peak in the second decade
of life and the second among older adults. The approximate incidence
of osteosarcoma is 4.8 per million children younger than 20 years
of age.7 There is some variability in the annual incidence
rate as shown in eFigure 453.1. The incidence
by age is as low as 0.3 per million in children under the age of
5 years, 2.8 per million between the ages of 5 and 9 years, 8.3
per million between the ages of 10 and 14 years, and 9.4 per ...