Fig. 21.16 ). The tumor frequently breaks through the cortex and lifts the periosteum, resulting in reactive subperiosteal bone formation. The triangular shadow between the cortex and raised ends of periosteum, known radiographically as Codman triangle, is indicative of an aggressive tumor, but is not pathognomonic of osteosarcoma.
Approximately 70% of osteosarcomas have acquired genetic abnormalities such as complex structural and numerical chromosomal aberrations. Molecular studies have shown that these tumors usually have mutations in well-known tumor suppressors and oncogenes: • RB is a critical negative regulator of the cell cycle. Patients with germline mutations in RB have a 1000-fold increased risk of osteosarcoma, and somatic RB mutations are present in up to 70% of sporadic osteosarcomas.
Fig.21.15Osteoidosteomacomposedofhaphazardlyinterconnectingtra-beculaeofwovenbonethatarerimmedbyprominentosteoblasts.Theintertrabecularspacesarefilledbyvascularizedlooseconnectivetissue.
Fig.21.16Distalfemoralosteosarcomawithprominentboneformationextendingintothesofttissues.Theperiosteum,whichhasbeenlifted,haslaiddownatriangularshellofreactiveboneknownasaCodmantriangle(arrow).
TP53 is a gene whose product functions as the guardian of genomic integrity by promoting DNA repair and apoptosis of irreversibly damaged cells. Patients with Li-Fraumeni syndrome, who have germline TP53 gene mutations, have a greatly elevated incidence of osteosarcoma, and abnormalities that interfere with p53 function are common in sporadic tumors.
CDKN2A is inactivated in many osteosarcomas. This gene encodes two tumor suppressors, p16 (a negative regulator of cyclin-dependent kinases) and p14 (which augments p53 function).
MDM2 and CDK4, which are cell cycle regulators that inhibit p53 and RB function, respectively, are overexpressed in many low-grade osteosarcomas.
It also is noteworthy that osteosarcomas peak in incidence around the time of the adolescent growth spurt and occur most frequently in the region of the growth plate in bones with the fastest growth. The increased proliferation at these sites may predispose to osteosarcoma development.
MORPHOLOGYOsteosarcomasarebulkytumorsthataregritty,gray-white,andoftencontainareasofhemorrhageandcysticdegeneration(
Fig.21.17 ).Thetumorsfrequentlydestroythesurroundingcorticesandproducesofttissuemasses.Theyspreadextensivelyinthemedullarycanal,infiltratingandreplacingthemarrow.
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Fig.21.17Osteosarcomaoftheproximaltibia.Thetan-whitetumorfillsmostofthemedullarycavityofthemetaphysisandproximaldiaphysis.Ithasinfiltratedthroughthecortex,liftedtheperiosteum,andformedsofttissuemassesonbothsidesofthebone.
Infrequentlytheypenetratetheepiphysealplateorenterthejoint.
Fig.21.18 ).Theneoplasticboneusuallyhasafine,lacelikeconfigurationbutalsomaybedepositedinbroadsheetsorasprimitivetrabeculae.Thetumorcellsvaryinsizeandshape(pleomorphic) andfrequentlyhavelargehyperchromaticnuclei.Bizarretumorgiantcells,vascularinvasion,andnecrosisarecommon.Mitoticactivityishigh,includingabnormalforms(e.g.,tripolarmitoses).