Page 549 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 25 Tumors of the Skeletal System 527

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a

c
b
d

a

A B
• Fig. 25.1 (A) Gross, longitudinally split specimen of a proximal femoral osteosarcoma lesion in a dog
showing cortical destruction, soft tissue, and osteoid neoplastic components. (B) Lateral radiograph of a
proximal femoral osteosarcoma lesion from the case in part A. Radiographic features include (a) Codman
triangle, (b) cortical lysis, (c) loss of trabecular pattern in the metaphases, and (d) tumor extension into the
soft tissues in a sunburst pattern.

that upregulation of Notch signaling might contribute to OSA histologic pattern may vary between tumors or even within the
pathogenesis; however, an inverse relationship between Notch/ same tumor. There are many histologic subclassifications of OSA,
HES1 with survival outcomes was identified, indicating that other which are based on the type and amount of matrix and character-
mechanisms that do not alter HES1 expression might be respon- istics of the cells: osteoblastic, chondroblastic, fibroblastic, poorly
90
sible for driving OSA aggressive biology. differentiated, and telangiectatic. Alkaline phosphatase staining
on histopathologic and aspiration cytology specimens has been
Additional Pathways shown to aid in differentiating OSA from other connective tissue
In addition to various growth and survival pathways that potentially tumors. 101–103 In dogs, it has not been well established that there
contribute to OSA pathogenesis, the ability of OSA cells to inter- is a difference in the biologic behavior of the different histologic
act with their immediate microenvironment found in bone and subclassifications or histologic grades. Some investigations indicate
lung tissues likely influences OSA progression and metastases. Tis- that histologic grade is predictive of behavior, whereas other stud-
sue invasion and focal osteolysis are hallmark characteristics of OSA, ies cast doubt on the predictive value of routine histologic grad-
and local disease progression is promoted by several OSA-associated ing. 104,105 Newer techniques designed to recognize molecular or
proteins including matrix metalloproteinases, receptor activator of genetic alterations are being evaluated to determine their potential
NF-κB ligand, lysosomal cathepsin K, endothelin-1, and transform- use in predicting behavior of OSA. 106 The degree of aneuploidy of
ing growth factor β. 91–97 Similar to the ability of OSA cells to invade primary and metastatic tumors, as measured by flow cytometry, is
local tissues, specific proteins have been identified to participate in the potentially indicative of biologic behavior. OSA has very aggres-
75
progression of canine OSA metastasis including ezrin, a cytoskeletal sive local effects and causes lysis, bone production, or both (Fig.
98
linker protein, and CXCR4, 99,100 a chemokine receptor. 25.1). Pathologic fracture at presentation in people and dogs with
OSA does not preclude limb salvage surgery (LSS) and does not
Pathology and Natural Behavior carry a worse prognosis than patients without fracture at presenta-
tion; 107–110 however, dogs presenting with pathologic fracture or
OSA is a malignant mesenchymal tumor of primitive bone cells. high risk for pathologic fracture are poor candidates for treatment
These cells produce an extracellular matrix of osteoid, and the with stereotactic radiotherapy (SRT) and concurrent surgical sta-
presence of tumor osteoid is the basis for the histologic diagno- bilization given the high rate for major local complications such as
sis and differentiating OSAs from other sarcomas of bone. The infection and implant failure. 111,112