10: Aggressive Bone Disease


CHAPTER 10
Aggressive Bone Disease


Erin Porter1 and Nathan C. Nelson2


1 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA


2 Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA


Introduction


Radiographs are often the first diagnostic step when evaluating dogs and cats presenting with orthopedic pain, swelling, and/or lameness. Although not definitive, radiographic findings are supportive of a likely diagnosis when attempting to differentiate neoplastic, inflammatory, and benign bone diseases. The former two types of bone disease (neoplastic and inflammatory disease) tend to cause an aggressive radiographic appearance, whereas benign bone diseases cause a nonaggressive (or benign) radiographic appearance. This chapter will describe radiographic features that define an aggressive versus nonaggressive process.


The patient’s signalment, history, clinical signs, and physical exam findings combined with the radiographic appearance allow creation of a prioritized differential list and formulation of an appropriate diagnostic plan. In addition to the initial radiographic study, it is important to evaluate for changes in the lesion or lesions over time to assess rate of disease progression or healing. Aggressive bone diseases tend to progress rapidly, whereas nonaggressive (benign) diseases remain static or regress (Figure 10.1). Screening of other organs, such as the lungs and draining lymph nodes, is also critical in determination of concurrent sites and/or staging if aggressive disease is suspected. Serologic and PCR analyses can evaluate for fungal and other types of infectious processes. Though history/signalment and radiographic appearance allow prioritization of differential diagnoses, in most cases a definitive diagnosis requires histopathologic evaluation of bone samples and culture if necessary.

Photos depict initial lateral projection (A) and recheck lateral projection 4 days later (B) of the proximal humerus in a 9-month-old boxer with acute left limb lameness due to clostridial osteomyelitis.

FIGURE 10.1 Initial lateral projection (A) and recheck lateral projection 4 days later (B) of the proximal humerus in a 9‐month‐old boxer with acute left limb lameness due to clostridial osteomyelitis. There is lysis seen on the later image (arrow) not identified on initial radiographs. This rapid change over a short period is characteristic of aggressive bone disease.


Radiographic Features of Bone Disease


Bone is composed of metabolically active tissue, which continually remodels throughout life. Cells called osteoblasts make osteoid, a matrix that mineralizes over time to become bone. Osteoblasts are embedded in the osteoid matrix and become osteocytes, which maintain the bone matrix. Osteoclasts break down and resorb bone via enzymatic activity. A fine balance between osteoclastic and osteoblastic activity occurs constantly, on a microscopic level, to maintain the normal homeostasis of bone, and allows bone to remodel and adapt to stress. Osteoclastic and osteoblastic activity, if severe enough, will result in radiographically apparent osteolytic or proliferative change respectively.


Aggressive bone diseases (neoplasia and osteomyelitis) rapidly disrupt the homeostasis of bone. These diseases can range from almost exclusively osteolytic to almost exclusively osteoproliferative; however, the most common radiographic appearance consists of a combination of both. The extent of osseous proliferation or osteolysis cannot differentiate neoplastic or inflammatory bone disease, as their appearance overlaps. Nonaggressive (benign) bone diseases (such as panosteitis, cysts, osteophytes) tend to remodel more slowly and consist entirely of bone proliferation or bone resorption.


As with all radiographic findings, aggressive and nonaggressive bone diseases are characterized using a Roentgen approach: number, location, size, shape, margination, and opacity. When evaluating a lesion, the reviewer should ask the following questions:



  • Number: how many lesions are there? Is a single bone (monostotic) or are multiple bones (polyostotic) affected?
  • Location: is the axial or appendicular skeleton affected? If appendicular, which portion of the bone is affected (diaphysis, metaphysis, epiphysis)? Does the lesion cross a joint space?
  • Size/shape: how extensive is the lesion? Are multiple portions of a long bone affected? Is there a sharply demarcated or poorly demarcated zone of transition between the lesion and adjacent, normal‐appearing bone?
  • Margination: are the margins of the lysis or proliferation smooth and well defined, or irregular and poorly defined? Are the margins continuous or interrupted?
  • Opacity: is there increased or decreased mineral opacity, or a combination of both? If opacity is decreased, what type of lysis is present?

Evaluation of margins, opacity, shape, and size is central to determining if a lesion is likely to be aggressive. Aggressive bone lesions most often have some combination of increased and decreased mineral opacity, with ill‐defined, irregular margins and a long zone of transition between the lesion and normal bone. The number and location of the lesion(s) are helpful for developing a differential diagnosis list once the lesion is characterized as aggressive or nonaggressive.


Zone of Transition


The zone of transition between an osseous lesion and adjacent, normal bone can help to differentiate aggressive from nonaggressive disease processes. Lesions that are sharply demarcated from adjacent, normal‐appearing bone are described as having a “short” zone of transition, and tend to be benign in nature. Examples would be a healing fracture, bone cyst, or cyst‐like lesion at the margin of a joint (see Chapter 8, Figure 8.8). Conversely, aggressive lesions tend to have a poorly demarcated or “long” zone of transition between diseased and normal bone (Figure 10.2).

Photos depict lateral (A) and craniocaudal (B) radiographs of a dog with proximal humeral osteosarcoma.

FIGURE 10.2 Lateral (A) and craniocaudal (B) radiographs of a dog with proximal humeral osteosarcoma. A long zone of transition is identified at the distal aspect of the lesion; the periosteal reaction (arrows) tapers distally, becoming less severe. Similarly, medullary lysis becomes less severe at the distal aspect of the lesion.


Determining the complete extent of pathology in a bone can be clinically imperative, particularly for planning surgical procedures, such as limb‐sparing or complete or partial limb amputations. When planning such surgical procedures, other imaging modalities such as nuclear scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) may be useful to more accurately demarcate the lesion margins (Figure 10.3). For estimating the extent of intramedullary osteosarcoma, MRI has been shown to be more accurate than both CT and radiographs, which largely overestimate the extent of osseous neoplasia in dogs [1].

Photos depict lateral radiograph (A) and magnified image of the distal radius (B) in a dog with osteosarcoma.

FIGURE 10.3 Lateral radiograph (A) and magnified image of the distal radius (B) in a dog with osteosarcoma. A bone scan (C) was also performed. There is moth‐eaten lysis (arrow) and irregular bony proliferation. On bone scan of the same patient, there is intense distal radial uptake (closed arrowhead) which extends more proximally than is apparent on radiographs due to greater sensitivity of bone scan for early/mild bone turnover.


Increased Mineral Opacity and Periosteal Proliferation


Increased mineral opacity can be due to medullary sclerosis, superimposed periosteal proliferation, or a combination of both. Medullary sclerosis does occur with nonaggressive etiologies, such as panosteitis and bone infarction, but is common with osteomyelitis and neoplasia. When periosteal proliferation is present, it can be difficult to determine whether the increased mineral opacity is due to medullary sclerosis or superimposition of the overlying periosteal proliferation. Orthogonal radiographic projections can help to make this differentiation.


The periosteum can be stimulated to react by many causes, including trauma or strain at the attachment of soft tissue structures (e.g., ligaments and joint capsules), invasion by neoplastic cells, infection, and vascular etiologies. In general, the appearance of the periosteal proliferation depends on the intensity and duration of the insult. High‐intensity, rapidly progressing processes result in a more aggressive appearance and less intense, more slowly progressing processes have a less aggressive appearance [2]. Some of the described types of periosteal proliferation, listed from least to most aggressive in appearance, include thin, solid, thick, irregular, septated, laminated or onionskin, sunburst, hair‐on‐end, and disorganized/amorphous (Figure 10.4).

Photos depict examples of periosteal reaction, from most benign to most aggressive.

FIGURE 10.4 Examples of periosteal reaction, from most benign to most aggressive. Lateral projection of the tibia (A) showing a healing fracture with smooth periosteal reaction (arrows). Lateral radiograph of the elbow (B) showing irregular periosteal proliferation (white closed arrowhead). Craniocaudal radiograph of the tibia (C) showing a laminated periosteal reaction (black open arrowhead) and sunburst periosteal reaction (white open arrowhead). Lateral radiograph of the antebrachium (D) showing amorphous periosteal reaction (black closed arrowhead).


Another type of periosteal proliferation, a Codman triangle, is formed when the periosteum is elevated and separated from the underlying cortex by subperiosteal bone formation, creating a triangular shape at the margin of the periosteal elevation (Figure 10.5). A Codman triangle is most often associated with aggressive bone diseases; however, it is not pathognomonic, and may be seen with nonaggressive diseases as well.

Photos depict craniocaudal projection of a distal radial osteosarcoma showing the Codman triangle (arrowheads) where the periosteal reaction smooths toward normal cortical bone.

FIGURE 10.5 Craniocaudal projection of a distal radial osteosarcoma showing the Codman triangle (arrowheads) where the periosteal reaction smooths toward normal cortical bone.


Attempting to categorize the type of periosteal proliferation using specific terminology for every lesion can be confusing, and much overlap exists between nonaggressive and aggressive types of proliferation. However, the type of periosteal proliferation can be suggestive of certain diseases. When evaluating periosteal proliferation, it is most important to first identify its presence and, secondly, recognize that in general, smooth, continuous, well‐defined proliferation tends to result from less aggressive/benign etiologies, while irregular, poorly defined, interrupted periosteal proliferation tends to be formed by more aggressive etiologies.


Osteolysis


Osteolysis is the resorption of bone by osteoclasts, a normal part of bone formation and remodeling. Excessive osteolysis can occur with both benign and aggressive bone diseases. Regardless of the etiology, approximately 50% of the mineral content of bone has to be lost before lysis becomes radiographically apparent [3]. Radiographically, the margins, extent, and zone of transition of any region of lysis should be carefully evaluated. Similar to periosteal proliferation, well‐defined lysis tends to be less aggressive, while poorly defined lytic lesions indicate more aggressive processes.


Three basic patterns of osteolysis have been described and, in order of least to most aggressive, include the following: geographic, moth‐eaten, and permeative lysis. As with periosteal proliferation, there is overlap between the different types of lysis and they do not definitively indicate one disease process over another, but the nature of the lysis may help to form a list of prioritized differential diagnoses (Figure 10.6).



  • Geographic lysis is characterized by well‐defined regions of decreased mineral opacity that do not usually involve the cortex. Geographic lysis is commonly caused by nonaggressive pathology such as bone cysts or cyst‐like lesions, and synovial hyperplasia.
  • Moth‐eaten lysis is characterized by multifocal, small regions of decreased mineral opacity that become confluent with each other and have indistinct margins and a long zone of transition. Aggressive disease processes, such as neoplasia and osteomyelitis, typically cause moth‐eaten lysis.
  • Permeative lysis is characterized by a conglomeration of pinpoint regions of decreased mineral opacity, which are indistinguishable from one another, with indistinct margins and a long zone of transition. Permeative lysis is almost always seen with aggressive disease processes.
Photos depict lateral projection of the radius/ulna (A) showing an area of geographic lysis of the radius (arrow). This has a benign appearance. Ventrodorsal projection of the pelvis (B) showing diffuse moth-eaten lysis of the left pelvis due to osteosarcoma; there are large areas of lysis throughout this area. Lateral projection of the femur (C) showing areas of permeative lysis (arrowhead) above a larger area of moth-eaten lysis (arrow), due to osteosarcoma.

FIGURE 10.6 Lateral projection of the radius/ulna (A) showing an area of geographic lysis of the radius (arrow). This has a benign appearance. Ventrodorsal projection of the pelvis (B) showing diffuse moth‐eaten lysis of the left pelvis due to osteosarcoma; there are large areas of lysis throughout this area. Lateral projection of the femur (C) showing areas of permeative lysis (arrowhead) above a larger area of moth‐eaten lysis (arrow), due to osteosarcoma.


Osteolysis may involve the trabecular, endosteal, and/or cortical bone. Endosteal lysis can result in cortical deformation, which can cause compensatory bone to form on the periosteal surface, resulting in expansion of the affected portion of bone. This can occur with both malignant and nonmalignant diseases such as bone cysts, fibrous dysplasia, retained cartilage, and neoplasia [4].


When lysis weakens the cortex of diseased bones, pathologic fractures may develop (Figure 10.7). Therefore, on radiographic examinations, the cortices in the region of any osseous abnormality should be carefully evaluated for any areas of thinning or discontinuity. Pathologic fractures can be extremely subtle radiographically. Abnormalities, such as bone edema, a nonspecific finding, can indicate microfractures and early bone trauma, and may be seen earlier on MR images than radiographs [2].

Photos depict lateral (A) and craniocaudal (B) radiographs of a distal tibial osteosarcoma with pathologic fracture (arrowheads).

FIGURE 10.7 Lateral (A) and craniocaudal (B) radiographs of a distal tibial osteosarcoma with pathologic fracture (arrowheads). No periosteal reaction is seen, but this aggressive lesion is characterized by moth‐eaten lysis (arrows).


On occasion, pathologic fractures are the reason for initial presentation, with no clinical history of prior disease. When a patient presents with an acute fracture and history of minimal/no trauma, or a history of trauma that seems disproportionate in severity to the clinical presentation, radiographs should be highly scrutinized for evidence of an underlying aggressive lesion at the fracture site. The examiner should be aware that the radiographic findings can be as subtle as mildly ill‐defined fracture margins or faint periosteal proliferation near the fracture site.


In some cases, the degree of bone lysis or periosteal proliferation is insufficient to allow a confident diagnosis of an underlying aggressive lesion in a fractured bone. In these cases, CT of the affected limb should be considered. CT is more sensitive in detecting underlying bone loss and subtle periosteal reaction than radiographs. For that reason, it will often allow a more confident diagnosis of an aggressive, pathologic fracture if screening radiographs are equivocal.


Differentials for Aggressive Bone Disease


Neoplasia and bone infection (osteomyelitis) are the two primary differentials for aggressive bone disease, and cannot be differentiated from each other based on radiographic characteristics alone. Additionally, both neoplastic and infectious bone disease may present with similar clinical signs, such as pain, lameness, local swelling, and/or neurologic signs ranging from ataxia to paralysis.


When differentiating between osseous neoplasia and osteomyelitis, the patient’s signalment and history should be considered. Lesion number and location, including whether it is polyostotic or monostotic, axial or appendicular skeletal location, and whether the epiphyseal, metaphyseal, or diaphyseal portion of any long bone is affected, should also be taken into consideration. For example, primary osseous neoplasia, such as osteosarcoma, tends to be monostotic and affect the metaphyseal region of long bones in older dogs, while metastatic neoplasia is more likely to be middiaphyseal and polyostotic (Figure 10.8). Fungal osteomyelitis typically has a polyostotic distribution in the axial or appendicular skeleton with a history of travel to endemic regions.

Photos depict figure lateral (A), craniocaudal (B) and magnified craniocaudal (C) radiograph of a dog with metastatic neoplasia to the femur.

FIGURE 10.8 Figure lateral (A), craniocaudal (B) and magnified craniocaudal (C) radiograph of a dog with metastatic neoplasia to the femur. There are aggressive lesions in the middiaphysis (arrow) and proximal diaphysis (arrowhead) in the area of the nutrient foramen. There is a long zone of transition and irregular periosteal response. This location is more consistent with spread of an aggressive lesion (in this case neoplasia) to the femur rather than a primary osseous neoplasm.


When an aggressive lesion is identified, other organs should be screened for disease. Screening may include cytologic or histologic evaluation of draining lymph nodes, thoracic radiographs (including right and left lateral as well as orthogonal projections), and evaluation for other sites of osseous involvement. Nuclear scintigraphy, an imaging modality which utilizes a radiopharmaceutical (phosphate analog labeled with radioactive technetium‐99m) to indicate areas of rapid bone turnover, is more sensitive than radiographs for early detection of skeletal lesions and can be used to detect osseous metastasis [5]. Finally, other diagnostics such as serologic and PCR analysis for fungal and other infectious agents, and histopathology and culture of samples of the affected bone should be performed to confirm the suspected diagnosis.


Primary Osseous Neoplasia


Osteosarcoma is responsible for up to 85% of skeletal malignancies, and is the most common primary bone neoplasia dogs and cats. It most commonly affects large‐ and giant‐breed dogs, and has a bimodal distribution, with a small peak in 18–24‐month‐old dogs, but the majority of affected animals are middle aged and older. The most commonly affected locations include the proximal humeral and distal radial metaphyses in the thoracic limb, and the distal femoral and proximal tibial metaphyses in the pelvic limb, leading to the expression “away from the elbow, toward the knee (stifle).” However, the distal tibial metaphysis is also commonly affected.


The anatomic distribution of osteosarcoma is different in small‐breed dogs and cats compared to large‐breed dogs. In small dogs, osteosarcoma more frequently affects the axial skeleton [6, 7], and in cats it tends to be equally distributed between the axial and appendicular skeleton, with appendicular lesions more commonly affecting the thoracic limbs in dogs and pelvic limbs in cats [8, 9

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Jul 15, 2023 | Posted by in ANIMAL RADIOLOGY | Comments Off on 10: Aggressive Bone Disease

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