Page 550 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

528 PART IV Specific Malignancies in the Small Animal Patient

Metastasis is very common and arises early in the course of the The signs associated with axial skeletal OSA are site dependent.
disease, although usually subclinically. Although less than 15% Signs vary from localized swelling with or without lameness (scap-
ular, pelvic, or rib sites) to dysphagia (oral sites), exophthalmos and
of dogs have radiographically detectable pulmonary or osseous
VetBooks.ir metastasis at presentation, approximately 90% will die within 1 pain on opening the mouth (caudal mandibular or orbital sites),
facial deformity and nasal discharge (sinus and nasal cavity sites),
year (median ST [MST] of 19 weeks) with metastatic disease,
usually to the lungs, when amputation is the only treatment. 2,16 and hyperesthesia with or without neurologic signs (spinal sites).
Metastasis via the hematogenous route is most common; how- Dogs with tumors arising from ribs usually present because of a
ever, on rare occasions, metastasis to the regional lymph node palpable, variably painful mass. Respiratory signs are uncommon
(LN) may occur. 113 Although the lung is the most commonly even when the lesions have large intrathoracic components; malig-
reported site for metastasis, metastasis to bones or other soft nant pleural effusion is quite rare. Dogs rarely have respiratory
tissue sites occurs with some frequency. 114 An increase in the signs as the first clinical evidence of pulmonary metastasis; rather,
incidence of bone metastasis after systemic chemotherapy has their first signs are usually nonspecific. With radiographically
also been documented in humans and is suspected in dogs. 115,116 detectable pulmonary metastasis, dogs may remain asymptomatic
Suspected synchronous regional bone metastases (skip metas- for many months, but most dogs develop decreased appetite and
tases) has also been reported. 117 Advanced imaging modali- nonspecific signs such as malaise within 1 month. Hypertrophic
ties, including bone scintigraphy, magnetic resonance imaging osteopathy may develop in dogs with pulmonary metastasis.
(MRI), computed tomography (CT), and positron emission
tomography (PET)/CT scans, can aid in detection of occult skip Systemic Alterations
metastases. 118,119 Some differences in metastatic behavior have Alterations in energy expenditure, protein synthesis, urinary
been observed based on the anatomic location of the primary nitrogen loss, and carbohydrate flux have been documented in
OSA site as well as anatomic skeletal size. For appendicular OSA dogs with OSA, similar to humans with neoplasia. 128 Changes
arising from less common sites, including the ulna, retrospec- in resting energy expenditure as well as protein and carbohydrate
tive investigations suggest that OSA behavior may be slightly metabolism have been documented in dogs with OSA. These
less metastatic; however, more thorough studies are necessary to changes were evident even in dogs that did not have clinical signs
draw firmer conclusions. 120,121 Primary OSA arising from axial of cachexia. 128 Although weight loss can occur during therapy
sites, such as mandible and calvarium, may have a less aggressive for OSA, this has not been associated with worse outcomes. 129
metastatic behavior too, although contradictory evidence exists Systemic metabolic derangements reported for dogs with OSA
as local tumor recurrence and subsequent regional disease fail- include lower chromium and zinc levels, lower iron and iron bind-
ure might lead to early death and underestimation of the true ing capacity, and increased ferritin levels compared with normal
metastatic potential of OSA arising from these sites. 122–125 In dogs. 130
addition to primary tumor location, metastatic phenotype of
OSA might be influenced by breed, size, or, more likely, genet- Diagnostic Techniques and Workup
ics associated with small breed dogs. One recent investigation
described the outcomes of 51 small breed dogs diagnosed with Radiology
appendicular OSA and identified no difference in MSTs between Initial evaluation of the primary site involves interpretation of
dogs treated with amputation alone versus curative-intent ther- good quality radiographs taken in lateral and craniocaudal projec-
apy (local treatment and adjuvant chemotherapy). 126 Although tions. Special views may be necessary for lesions occurring in sites
preliminary in nature, these observational findings might sug- other than in the appendicular skeleton. The overall radiographic
gest that the biologic behavior and associated metastatic poten- abnormality of bone varies from mostly bone lysis to almost
tial of appendicular OSA is divergent between dogs of differing entirely osteoblastic or osteogenic changes. There is an entire spec-
skeletal size. trum of changes between these two extremes, and the appearance
of primary bone tumors can be quite variable. There are some
History and Clinical Signs features, however, that are commonly seen. Cortical lysis is a fea-
ture of primary bone tumors and may be severe enough to leave
Dogs with appendicular OSA generally present with a lameness obvious areas of discontinuity of the cortex leading to pathologic
and swelling at the primary site. There may be a history of mild fracture. There is often soft tissue extension with an obvious soft
trauma just before the onset of lameness. This history can often tissue swelling, and new bone (tumor or reactive bone) may form
lead to misdiagnosis of an orthopedic or soft tissue injury. The in these areas in a palisading pattern perpendicular or radiating
lameness worsens and a moderately firm to soft, variably painful from the axis of the cortex (i.e., sunburst). As the tumor invades
swelling may arise at the primary site. Dogs may present with acute, the cortex, the periosteum is elevated, and new bone is laid down
severe lameness associated with pathologic fractures, although by the cambium layer providing a triangular appearing deposition
pathologic fractures account for less than 3% of all fractures. 127 of dense new bone on the cortex at the periphery of the lesion.
Up to 60% of these dogs are lame for a period before presenta- This periosteal new bone has been called Codman triangle, but
tion. 107 Large and giant breed dogs that present with lameness or this is not pathognomonic for OSA. OSA rarely crosses articu-
localized swelling at metaphyseal sites should be evaluated with lar cartilage, and primary lesions usually remain monostotic. The
OSA as a likely diagnosis. The pathophysiology of OSA pain is tumors may extend into periarticular soft tissues, however, and
unclear but may be mediated by loss of mechanical bone strength adjacent bones are at risk because of extension through adjacent
resulting in microfractures, infiltration or compression of nerves, soft tissue structures. Other radiographic changes associated with
and the chemotaxis of immune cells with subsequent secretion of primary bone tumors include loss of the fine trabecular pattern in
cytokines and proteases resulting in inflammatory pain. OSA cells the metaphysis, a long transition zone at the periphery of the med-
have also been shown to secrete nociceptive ligands potentially ullary extent of the lesion (rather than a sharp sclerotic margin),
resulting in pain generation. 97 or areas of fine punctate lysis. Any one or combinations of these